Combination of Fushengong decoction with Western medicine on patients with chronic renal failure: An observational study.

Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-ß1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography-mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-ß1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-ß, which are closely related to the pathogenesis of CRF. Protein-protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-ß, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).

Therapeutic potential of icariin in rats with letrozole and high-fat diet-induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by reproductive, endocrine, and metabolic disorders. Icariin has been shown to regulate endocrine and metabolic imbalances. This study aimed to determine the therapeutic effect and pharmacological mechanism of icariin in PCOS rats. Rats were fed a high-fat diet and gavaged with letrozole to induce PCOS. Thirty-six female rats were randomly divided into four groups: control, model, low-dose, and high-dose icariin. After 30 days of treatment, we evaluated the therapeutic effects on weight and diet, sex hormone levels, ovarian morphology, estrous cycle, inflammatory factors, and indicators of glucolipid metabolism. Combined with the ovarian transcriptome, we verified the key markers of apoptosis and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway by RT-qPCR for mRNA level, western blot, and immunohistochemistry for protein expression. Icariin significantly improved ovarian function and reproductive endocrine disorders by regulating sex hormones, restoring the estrous cycle, and reducing ovarian morphological damage in PCOS rats. Icariin-treated rats had lower weight gain and reduced triglycerides, fasting insulin, HOMA-IR, TNF-α, and interleukin-6 with higher high-density lipoprotein cholesterol levels than PCOS rats. TUNEL staining showed icariin improved apoptosis in the ovaries. This was supported by an increase in Bcl2 and a decrease in Bad and Bax. Icariin decreased the ratios of p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3, and p-STAT5a/STAT5a, decreased IL-6, gp130 expression, and increased cytokine-inducible SH2-containing protein (CISH) and suppressor of cytokine signaling 1 (SOCS1) expression. The pharmacological mechanism may be related to the reduction in ovarian apoptosis and inhibition of the IL-6/gp130/JAK2/STATs pathway.

Metabolomics combined with network pharmacology to explore the mechanisms of modified Guishen pill to ameliorate polycystic ovary syndrome.

BACKGROUND: The modified Guishen pill (MGP) has a prominent therapeutic effect on polycystic ovary syndrome (PCOS). However, its mechanism is still unclear. This study aimed to uncover the mechanism of MGP for PCOS treatment through a comprehensive strategy integrating metabolomics and network pharmacology. METHODS: A letrozole-induced PCOS model was used to evaluate ovarian function in rats. Plasma metabolomics was used to authenticate differential metabolites and enriched related pathways using the MetaboAnalyst platform. Network pharmacology was utilized to explore the endogenous targets of MGP treatment for PCOS. Finally, the potential targets and related biological functions were verified experimentally. RESULTS: MGP improved PCOS symptoms by regulating abnormal levels of sex hormones and alleviating ovarian pathological changes in rats; fifty-four potential differential metabolites involved in MGP treatment for PCOS, and the hub genes derived from network pharmacology were consistent with the metabolomic analysis results to varying degrees. The comprehensive analysis identified that a key novel target for endothelial nitric oxide synthase (eNOS/NOS3), five key metabolites (ornithine, citrulline, l-glutamic acid, acetylornithine, and hydroxyproline), and one pathway (arginine and proline metabolism) were related to the therapy of PCOS with MGP. Subsequently, we verified the localization and expression of eNOS in the ovaries, and it significantly improved insulin resistance, apoptosis, and oxidative stress in letrozole-induced PCOS rats. CONCLUSION: Our work reveals the complex mechanism of MGP therapy for PCOS. This study is a successful paradigm for elucidating the pharmacological mechanism of the traditional Chinese medicine compound.

The biological function of metazoan-specific subunit nuclear factor related to kappaB binding protein of INO80 complex.

The INO80 chromatin remodeling complex plays an essential role in the regulation of gene transcription, which participate in a variety of important biological processes in cells including DNA repair and DNA replication. Difference from the yeast INO80 complex, metazoan INO80 complex have the specific subunit G, which is known as nuclear factor related to kappaB binding protein (NFRKB). Recently, NFRKB has been received much attention in many aspects, such as DNA repair, cell pluripotency, telomere protection, and protein activity regulation. To dig the new function of metazoan INO80 complex, a better understanding of the role of NFRKB is required. In this review, we provide an overview of the structure and function of NFRKB and discuss its potential role in cancer treatment and telomere regulation. Overall, this review provides an important reference for further research of the INO80 complex and NFRKB.

[Effects of electro-acupuncture on expression of triggering receptor expressed on myeloid cells 1 in ankle joint synovial tissue of acute gouty arthritis rats].

OBJECTIVE: To investigate the effects of electro-acupuncture (EA) on the expression of triggering receptor expressed on myeloid cell (TREM)l in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. METHODS: Forty male SD rats were randomly divided into 4 groups: normal, AGA, medication and EA group, 10 rats in each group. AGA model was established by induced monosodium urate (MSU) method, except the normal group. Tow days before AGA model was established, normal and AGA groups were lavaged with normal saline (20 ml/kg), medication group was lavaged with colchicine solution (20 ml/kg), EA(1.5-2 Hz, D.-D.wave, 9v; 1-3 rnA) was applied to "Sanyinjiao" (SP6), "jiexi" (ST41) and "Kunlun" (BL60) for 20 min, once daily;continuously for 9 days. Then observed the changes in dysfunction, and the content of TNF-α and IL-lß detected by ELISA, the expression of TREM-l detected by immunohistochemistry and western blot. RESULTS: Compared to the normal group, the AGA group of the dysfunction index increased significantly (P<0.01), the content of TNF-α and IL-lß increased significantly (P<0.05), the expression of TREM-l in synovial tissue increased significantly (P<0.05); the medication and EA groups compared to the AGA group, the dysfunction index decreased significantly (P<0.01), the content of TNF-α and IL-lß decreased significantly (P<0.05), the expression of TREM-l in synovial tissue decreased significantly (P<0.05); there were not statistically significant between the medication and EA group (P>0.05). CONCLUSION: EA treating AGA may be through down-regulating the expression of TREM -1 in synovial tissue.

[Observation on therapeutic effects of acupoint injection of metoclopramide for postsurgical gastroparesis syndrome].

OBJECTIVE: To observe the clinical effects of acupoint injection of metoclopramide for postsurgical gastroparesis syndrome (PGS). METHODS: A total of 46 patients with PGS(from abdominal surgery) were randomly divided into control and acupoint injection groups (n=23 in each group). Patients of the acupoint injection group were treated by injection of Metoclopramide (5 mg+ normal saline) into bilateral Zusanli (ST 36) and Weishu (BL 21) alternatively, while patients of the control group treated by injection of 10 mg of Metoclopramide into the deltoid muscle and gluteus maximus muscle alternatively. The treatment of both groups was conducted once daily for 14 days. A 3-point scale of clinical symptoms (abdominal distension, belching, nausea-vomiting, upper-abdominal distending pain, sour regurgitation and gastric burning sensation) was used to evaluate the therapeutic effect. RESULTS: There were no statistical differences between two groups in clinical symptom scores before the treatment (P>0.05). Following treatment, the clinical symptom scores of both groups were significantly decreased in comparison with pre-treatment (P<0.05) and the scores of the acupoint injection group were significantly lower than those of the control group (P<0.05). Of the 23 PGS patients in the control group and acupoint injection group, 0 and 2 were cured, 5 and 10 were significantly improved, 10 and 9 were improved, 8 and 2 failed, with the effective rates being 65.22% and 91.30%, respectively. CONCLUSION: Acupoint injection of Metoclopramide is effective for improving clinical symptoms of PGS patients.

[Effect of electroacupuncture stimulation of back-shu points on expression of TNF-alpha and lipid peroxidation reaction in the liver tissue in non-alcoholic fatty liver disease rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation (EAS) of back-shu acupoints on expression of tumor necrosis factor-alpha (TNF-alpha) and lipid peroxidase reaction in the liver in non-alcoholic fatty liver disease (NAFLD) rats. METHODS: Wistar rats were randomly divided into normal group (n = 1), model group (n = 10), EAS group (n = 10) and medication group (n = 10). The NAFLD model was established by feeding the animals with high fat diet for 8 weeks. EAS was applied to bilateral "Pishu" (BL 20), "Geshu" (BL 17) and "Shenshu" (BL 23) for 20 min, once daily for 4 weeks. Rats of the medication group were treated by 1% Dongbao Gantai suspension (0.28 g/kg, 20 mL/kg) once daily for 4 weeks. Pathological changes of the liver tissue were observed by microscope after H. E. staining. Hepatic free fatty acid (FFA) content was assayed by using an automatic biochemistry analyzer, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected by penthiobarbituric acid colorimetric method and xanthine oxidase colorimetric method, respectively. The expression of liver TNF-alpha was detected by immunohistochemistry. RESULTS: Compared with the normal group, rats of the model group showed a moderate to severe fatty degeneration of liver cells, significant up-regulation of hepatic TNF-alpha expression, FFA and MDA contents (P < 0.01), and marked down-regulation of SOD activity (P < 0.01). Following 4 weeks' treatment, compared with the model group, liver fatty degeneration was reduced at different degrees in both EAS and medication groups; liver FFA and MDA contents and TNF-alpha expression were significantly down-regulated (P < 0.01, P < 0.05), and hepatic SOD activity was notably increased (P < 0.01, P < 0.05) in both EAS and medication groups, suggesting a reduction of hepatic lipid peroxidation. No significant differences between the EAS and medication groups in the liver FFA and MDA contents, SOD activity and TNF-alpha expression (P > 0.05). CONCLUSION: EA intervention can improve liver fatty degeneration, inhibit high fat induced up-regulation of hepatic TNF-a expression, FFA and MDA contents and down-regulation of SOD activity in non-alcohol fatty liver model rats, which may contribute to its effect in improving NAFLD.