Chaihu-Longgu-Muli decoction improves sleep disorders by restoring orexin-A function in CKD mice.

Introduction: Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the "Treatise on Febrile Diseases" written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing. While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, anxiety and dementia, its mechanisms remain unclear. Methods: In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia, An adenine diet-induced chronic kidney disease (CKD) model was established in mice, Furthermore, we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice, as well as the production of insomnia related regulatory proteins and inflammatory factors. Results: CLMD significantly improved circadian rhythm and sleep disturbance in CKD mice. The insomnia related regulatory proteins, Orexin, Orexin R1, and Orexin R2 in the hypothalamus of CKD mice decreased significantly, while Orexin and its receptors increased remarkably after CLMD intervention. Following administration of CLMD, reduced neuron loss and improved learning as well as memory ability were observed in CKD mice. And CLMD intervention effectively improved the chronic inflflammatory state of CKD mice. Discussion: Our results showed that CLMD could improve sleep and cognitive levels in CKD mice. The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK, which further inhibits NF-κB downstream signaling pathways, thereby improving the disordered inflammatory state in the central and peripheral system. However, More research is required to confirm the clinical significance of the study.

Reduced antioxidant and anti-inflammatory effects of propofol at high-dose on morbidly obese patients.

This study was aimed to investigate differences in antioxidant and anti-inflammatory effects of propofol at two commonly used dosing schedules on morbidly obese patients. Twenty-two morbidly obese patients were randomly divided into two groups, namely, TBW (dosing based on total body weight) and LBW (dosing based on lean body weight) groups. Three biomarkers, i.e. superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) were measured as indicators of the level of oxidation stress reaction. Pro-inflammatory cytokines including Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were used to describe the degree of inflammation. Plasma levels of SOD, MDA and NO were increased and reached a peak value 0.5h after anesthesia induction, but the increase was smaller in the LBW group compared with the TBW group. Besides, plasma concentrations of IL-6 and IL-8 were also increased and attained a peak level 0.5h after anesthesia induction, but the increase was higher in the TBW group compared with the LBW group. The LBW-based dosing of propofol had more potent antioxidant and anti-inflammatory effects than the TBW-based dosing during anesthesia induction period on morbidly obese patients. This study provided a dosing recommendation of propofol for morbidly obese patients.

Kuntai capsules improve glucolipid metabolism in patients with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: The aim of this study was to observe the effect and safety of Heyan Kuntai Capsule (HYKT) on glucose and lipid metabolism in patients with polycystic ovary syndrome (PCOS). METHODS: Hundred patients with PCOS were randomly divided into HYKT group (n = 50) and placebo groups (n = 50) in which the individuals were treated with HYKT and its placebo continuously for 6 months. Meanwhile, all participants received health education (such as exercise and diet). The primary outcomes were serum sex hormone levels, a series of blood lipid, fasting and postprandial 2 hours blood glucose. Body mass index (BMI), waist-hip ratio (WHR), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and insulin-sensitive index (ISI) were also observed. In addition, adverse events were recorded to evaluate the drug safety. RESULTS: After treatment, the BMI and WHR of all the patients were decreased. The fasting and postprandial 2 hours blood glucose levels were significantly declined when treated with HYKT, which were not observed in the placebo group. Similarly, serum sex hormones including luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), and testosterone were lowered after treated with HYKT instead of the placebo. Besides, blood lipids outcomes such as total cholesterol, triglyceride, and low-density lipoprotein cholesterol, as well as insulin and HOMA-IR were decreased with significance in HYKT group when compared with those in the placebo group, whereas high-density lipoprotein cholesterol and ISI increased obviously. CONCLUSION: HYKT showed the effect on ameliorating the glucose and lipid metabolism disorder and improving insulin resistance and increase insulin sensitivity of PCOS patients, which is similar to insulin sensitizing agent.

Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFß1.

Transforming growth factor-ß1 (TGFß1) has been identified as a major pathogenic factor underlying the development of diabetic nephropathy (DN). However, the current strategy of antagonizing TGFß1 has failed to demonstrate favorable outcomes in clinical trials. To identify a different therapeutic approach, we designed a mass spectrometry-based DNA-protein interaction screen to find transcriptional repressors that bind to the TGFB1 promoter and identified Yin Yang 1 (YY1) as a potent repressor of TGFB1. YY1 bound directly to TGFB1 promoter regions and repressed TGFB1 transcription in human renal mesangial cells. In mouse models, YY1 was elevated in mesangial cells during early diabetic renal lesions and decreased in later stages, and knockdown of renal YY1 aggravated, whereas overexpression of YY1 attenuated glomerulosclerosis. In addition, although their duration of diabetic course was comparable, patients with higher YY1 expression developed diabetic nephropathy more slowly compared to those who presented with lower YY1 expression. We found that a small molecule, eudesmin, suppressed TGFß1 and other profibrotic factors by increasing YY1 expression in human renal mesangial cells and attenuated diabetic renal lesions in DN mouse models by increasing YY1 expression. These results suggest that YY1 is a potent transcriptional repressor of TGFB1 during the development of DN in diabetic mice and that small molecules targeting YY1 may serve as promising therapies for treating DN.

Ginkgetin exerts anti-inflammatory effects on cerebral ischemia/reperfusion-induced injury in a rat model via the TLR4/NF-κB signaling pathway.

Ginkgo biloba, a natural biflavonoid isolated from Ginkgo biloba leaves, is reported to have strong anti-inflammatory and immunosuppressive properties. The aim of this study is to investigate the potential anti-inflammatory mechanisms of ginkgo flavonoids on cerebral ischemia/reperfusion (I/R) injury. Inflammatory-associated cytokines in cerebral ischemic hemispheres were determined by immunohistochemical staining, Western blot and enzyme-like immunosorbent assay (ELISA). Our results indicated that treatment with Ginkgetin significantly restored rat brain I/R-induced neurological deficit scores. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in Ginkgetin treatment group (100 mg/kg) also significantly reduced. The expression inflammation-related protein prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and interleukin-8 (IL-8) was also decreased in Ginkgetin treatment group. However, the expression of interleukin-10 (IL-10) was remarkably increased. Thus, this study demonstrates that Ginkgetin protects neurons from I/R-induced rat injury by down-regulating pro-inflammatory cytokines and blocking the TLR4/NF-κB pathway.

Efficacy of acupuncture on pelvic pain in patients with endometriosis: study protocol for a randomized, single-blind, multi-center, placebo-controlled trial.

BACKGROUND: Endometriosis is a chronic gynecological disease that is characterized by the presence of endometrial tissue outside the uterine cavity. The main symptoms include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. These symptoms impair the lives of most of the women suffering from the disease. Surgical resection of endometriotic lesions is an effective means of treating dysmenorrhea, but the risk of recurrence is high. Western medicine has limited use for treating it due to side effects and ineffectiveness. The purpose of this study is to verify the effectiveness and safety of acupuncture. METHODS/DESIGN: This trial will be carried out in four parts. A total of 106 eligible patients with pelvic pain related to endometriosis will be randomly assigned into two groups, in a 1:1 ratio, as the treatment group or the control group. The participants assigned to the treatment group will be treated with acupuncture treatment at Guanyuan (CV4), Sanyinjiao (SP6), Taichong (LR3), Zhaohai (KI6) and Qichong (ST30) while the control group will receive acupuncture at non-acupoints. The trial will include three menstrual cycles of treatment and three menstrual cycles of follow-up. The primary outcome is pelvic pain that will be assessed by means of a 10-cm visual analog scale (VAS). At each stage, we will evaluate the safety of the acupuncture treatment. DISCUSSION: The study will compare the effectiveness and safety of acupuncture with comfort needles on pelvic pain related to endometriosis in the hope of providing significant evidence for using acupuncture on pelvic pain related to endometriosis. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03125304 . Registered on 30 April 2017.

[Inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine ameliorates hemodynamics and pulmonary histopathology in a porcine model of acute lung injury].

OBJECTIVE: To observe the effect of inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine on the hemodynamics and histopathology in a porcine model of acute lung injury. METHODS: Normal adult pigs were subjected to saline lavage of the bilateral lungs to induce acute lung injury and randomized subsequently into 3 groups for treatment with inhalation of perfluorocarbon, combined inhalation of perfluorocarbon and tetramethylpyrazine, or inhalation of tetramethylpyrazine. The changes of mean arterial pressure (MAP), PetCO(2), mPAP, CVP and PAWP were recorded at different time points following the lung injury, and the lung tissues were sampled for histological observations. RESULTS: The MAP, mPAP, CVP and PAWP all increased significantly in the 3 groups after acute lung injury. Interventions with combined tetramethylpyrazine and perfluorocarbon inhalation significantly improved these indices as compared with inhalation of tetramethylpyrazine or perfluorocarbon alone (P<0.05). The pulmonary pathology was the mildest in the combined inhalation group, and the most severe in tetramethylpyrazine group. CONCLUSION: Combined inhalation of perfluorocarbon and tetramethylpyrazine can effectively improve the oxygenation, reduce pulmonary arterial pressure?and ameliorate lung pathology in pigs with acute lung injury.

Development of randomly amplified polymorphic DNA-sequence characterized amplified region marker for identification of Apocynum venetum LINN. from A. pictum SCHRENK.

Apocynum venetum LINN. is an important Chinese crude drug, and its sibling species A. pictum SCHRENK is a confusable herb which is similar to it. The purpose of this study is to develop DNA molecular markers to distinguish A. venetum from A. pictum through the combinative technologies of bulked segregate analysis (BSA) and randomly amplified polymorphic DNA (RAPD). Two putative markers B08-407 and B03-1368 specific for A. venetum were identified and sequenced. Based on the sequence information, two pairs of primers were designed and synthesized for sequence characterized amplified region (SCAR) markers. But only one primer pair, B03-1368, produced a clear SCAR band in all samples of A. venetum and not in A. pictum. This SCAR marker was found useful for rapid identification of A. venetum from A. pictum.

Synthesis and preliminary in vitro investigation of bivalent ligands containing homo- and heterodimeric pharmacophores at mu, delta, and kappa opioid receptors.

A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured in the [(35)S]GTPgammaS binding assay. The data suggest that the stereochemistry of the pharmacophores, the N-substituents of the pharmacophore, ester linkages, and the spacer length were crucial factors for optimum interactions of such ligands at opioid receptor binding sites. These novel ligands as well as their pharmacological properties will serve as the basis for our continuing investigation of such bivalent ligands as probes of the opioid receptor oligomerization phenomena and for in vivo studies as analgesics.