Traditional Chinese Medicine as an adjunct therapy in the treatment of idiopathic membranous nephropathy: A systematic review and meta-analysis.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults involving multiple targets and factors. The effect of conservative nonimmunosuppressive or immunosuppressive therapies is unsatisfactory and with many side effects. Traditional Chinese medicine (TCM) can regulate immune function and improve kidney function. PURPOSE: To evaluate the total effective rate, curative rate, recurrence rate and adverse events of TCM alone or TCM as an adjunctive therapy for IMN. METHODS: Randomized controlled trials (RCT) comparing either TCM alone or the combination of TCM to western medicine (WM) therapies for patients with IMN were retrieved by searching English and Chinese database. Risk of bias summary was used to assess the methodological quality of eligible studies. Dichotomous data were presented using odds ratios (OR). The primary outcome measure was the total effective rate. Secondary outcomes included curative rate, recurrence rate and adverse events. RESULTS: 29 RCTs involving 1883 participants met the inclusion criteria. There was no statistically significant difference between the therapy of TCM alone and WM on the total effective rates (OR: 2.00; 95% CI: 0.80-4.98; P = 0.14) and curative rate (OR: 1.66; 95%CI: 0.66-4.22; p = 0.28). However, compared to basic treatment or immunosuppressive therapies alone, results showed that TCM as an adjunctive therapy had beneficial effects on the total effective rate (OR: 2.59; 95% CI: 1.38-4.86; P = 0.003 and OR: 3.01; 95% CI: 2.25-4.04; P < 0.00001) and curative rate (OR: 3.01; 95%CI: 1.24-7.28; p = 0.01 and OR: 1.73; 95%CI: 1.10-2.71; p = 0.02). In addition, the combination of TCM treatment could reduce the recurrence rate (OR: 0.28; 95% CI: 0.12-0.68; P = 0.004) and adverse reactions (OR: 0.38; 95% CI: 0.27-0.54; p < 0.00001). CONCLUSION: The results indicate that TCM is well-tolerated for the treatment of IMN. However, there remains a need for large-scale and high-quality trials.

Safety, tolerability, pharmacokinetics, and food effect of baicalein tablets in healthy Chinese subjects: A single-center, randomized, double-blind, placebo-controlled, single-dose phase I study.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis (Huang-Qin in Chinese) is a dry root of the perennial herb Scutellaria baicalensis Georgi, which has been used extensively in current prescriptions. Scutellaria baicalensis is an herb high in flavonoids, and baicalein is the one flavonoid found in the highest amount in Scutellaria baicalensis. AIM OF THE STUDY: Influenza virus could cause mild respiratory tract illness to severe pneumonia and even death. Baicalein has been proved to be one of the effective components against the influenza virus. However, there have been few reports on human trials of baicalein. The purpose of this study was to evaluate the safety of baicalein in vivo and analyze its pharmacokinetic characteristics. MATERIALS AND METHODS: Three randomized studies were conducted to evaluate the pharmacokinetics (PK), safety, tolerability, and food effects of baicalein tablets. In the 7-month single-dose safety study, 60 subjects were enrolled and randomized to receive 100-800 mg baicalein tablets or placebo. In the single-dose PK study, 40 subjects were enrolled and randomized to receive 200 mg, 400 mg, 600 mg, 800 mg baicalein tablets. In the study of food effect on PK of baicalein, an additional 10 subjects were enrolled in the 400 mg group, this part of the trial lasted for 7 months. Blood and urine samples for PK analysis were collected at a pre-specified time. PK properties in both fasted and fed states were evaluated, as well as safety and tolerability. RESULTS: Among the 80 subjects who were evaluable for the single-dose safety and tolerability, 56 adverse events (AEs) were observed in 32/80 subjects, of which 49 events were from 28/68 subjects in baicalein group and 7 events were from 4/12 subjects in placebo group. All AEs were mild and resolved without any medical intervention. The most common AEs were elevated high-sensitivity C-reactive protein (hs-CRP) level and high triglycerides. After a single administration of baicalein tablets (200 mg, 400 mg, 600 mg, or 800 mg), Cmax were 280.44, 628.80, 845.20, 489.55 ng/mL; AUC0-∞ were 2035.57, 2939.31, 4494.88, and 3754.43 h*ng/mL, respectively. And t1/2z ranged from 7.80 to 14.91 h. The exposure of baicalein and its metabolites increased in a less than dose-proportional manner. CONCLUSION: Baicalein tablets within the studied dose range were safe and well-tolerated in healthy Chinese subjects with no serious or severe adverse effects. Further investigation will be needed to assess the safety and efficacy in the target patients.

Effects of huoxin formula on the arterial functions of patients with coronary heart disease.

Context: Huoxin formula is a Traditional Chinese Medicine for coronary heart disease (CHD) treatment. Objective: To explore the therapeutic mechanism of the Huoxin formula on arterial functions in CHD patients. Materials and methods: Fifty-eight CHD patients receiving cardiovascular drugs including ß-receptor blocker, statins, and antiplatelet medications or others were randomized into intervention [additionally 13.5 g Huoxin formula granules dissolved in 150 mL warm water per time, twice a day (n = 30)] and control [only cardiovascular drugs (n = 28)] groups. Serum biomarkers (hs-CRP, IL-18, IL-17, TNF-α, MMP-9), and cardiovascular indicators of the common and internal carotid arteries (ICAs) were monitored before and after the treatments. Results: After 3 months of treatment, the increases of intima-media thicknesses (IMT) of the left and right common carotid arteries (CCAs) as well as of the left and right ICAs and the increases of the left and right cardio-ankle vascular index were all significantly (all p < 0.001) less in the intervention than in control group (all p < 0.001). Serum concentrations reductions of hs-CRP, IL-18, IL-17 and MMP9 (all p < 0.001) levels were higher in the intervention compared to the control group, which correlated with the changes of left ICA (hs-CRP: r = 0.581, p = 0.009; IL-18: r = 0.594, p = 0.007; IL-17: r = 0.575, p = 0.006). Discussion and conclusion: Since the Huoxin formula improved arterial functions and reduced inflammatory factor activities in CHD patients, a large-scale clinical trial is warranted.

Omega-3 polyunsaturated fatty acid attenuates traumatic brain injury-induced neuronal apoptosis by inducing autophagy through the upregulation of SIRT1-mediated deacetylation of Beclin-1.

BACKGROUND: Enhancing autophagy after traumatic brain injury (TBI) may decrease the expression of neuronal apoptosis-related molecules. Autophagy-mediated neuronal survival is regulated by the sirtuin family of proteins (SIRT). Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are known to have antioxidative and anti-inflammatory effects. We previously demonstrated that ω-3 PUFA supplementation attenuated neuronal apoptosis by modulating the neuroinflammatory response through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway, leading to neuroprotective effects following experimental traumatic brain injury (TBI). However, no studies have elucidated if the neuroprotective effects of ω-3 PUFAs against TBI-induced neuronal apoptosis are modulated by SIRT1-mediated deacetylation of the autophagy pathway. METHODS: The Feeney DM TBI model was adopted to induce TBI rats. Modified neurological severity scores, the rotarod test, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect Beclin-1 nuclear translocation and autophagy pathway activation. The impact of SIRT1 deacetylase activity on Beclin-1 acetylation and the interaction between cytoplasmic Beclin-1 and Bcl-2 were assessed to evaluate the neuroprotective effects of ω-3 PUFAs and to determine if these effects were dependent on SIRT1-mediated deacetylation of the autophagy pathway in order to gain further insight into the mechanisms underlying the development of neuroprotection after TBI. RESULTS: ω-3 PUFA supplementation protected neurons against TBI-induced neuronal apoptosis via enhancement of the autophagy pathway. We also found that treatment with ω-3 PUFA significantly increased the NAD+/NADH ratio and SIRT1 activity following TBI. In addition, ω-3 PUFA supplementation increased Beclin-1 deacetylation and its nuclear export and induced direct interactions between cytoplasmic Beclin-1 and Bcl-2 by increasing SIRT1 activity following TBI. These events led to the inhibition of neuronal apoptosis and to neuroprotective effects through enhancing autophagy after TBI, possibly due to elevated SIRT1. CONCLUSIONS: ω-3 PUFA supplementation attenuated TBI-induced neuronal apoptosis by inducing the autophagy pathway through the upregulation of SIRT1-mediated deacetylation of Beclin-1.

Strong Near-Infrared Absorbing and Biocompatible CuS Nanoparticles for Rapid and Efficient Photothermal Ablation of Gram-Positive and -Negative Bacteria.

Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common infectious bacteria in our daily life, and seriously affect human's health. Because of the frequent and extensive use of antibiotics, the microbial strains forming drug resistance have become more and more difficult to deal with. Herein, we utilized bovine serum albumin (BSA) as the template to synthesize uniform copper sulfide (CuS) nanoparticles via a biomineralization method. The as-prepared BSA-CuS nanocomposites showed good biocompatibility and strong near-infrared absorbance performance and can be used as an efficient photothermal conversion agent for pathogenic bacteria ablation with a 980 nm laser at a low power density of 1.59 W/cm2. The cytotoxicity of BSA-CuS nanocomposite was investigated using skin fibroblast cells and displayed good biocompatibility. Furthermore, the antibacterial tests indicated that BSA-CuS nanocomposite showed no antibacterial activity without NIR irradiation. In contrast, they demonstrated satisfying killing bacterial ability in the presence of NIR irradiation. Interestingly, S. aureus and E. coli showed various antibacterial mechanisms, possibly because of the different architectures of bacterial walls. Considering the low cost, easy preparation, excellent biocompatibility and strong photothermal convention efficiency (24.68%), the BSA-CuS nanocomposites combined with NIR irradiation will shed bright light on the treatment of antibiotic-resistant pathogenic bacteria.

Dioxin exposure down-regulates nitric oxide synthase and NADPH-diaphorase activities in the hypothalamus of Long-Evans rat.

In this study, we investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) gastric administration on the expression of neuronal nitric oxide synthase (nNOS) and the NADPH-diaphorase (NADPH-d) activities in the brain of the Long-Evans rat. A single dose of TCDD (dissolved in olive oil, 50 microg/kg) or olive oil alone was administered to the rats by gavage. nNOS Western blotting experiment indicated a marked decrease in nNOS immunoreactivity at 1 and 2 weeks after TCDD treatment. NADPH-d histochemistry results showed a marked decrease in the number of NADPH-d stained cell bodies in the paraventricular hypothalamic nucleus, lateral hypothalamic area and perifornical nucleus in the TCDD-treated rats. The present study suggests that TCDD administration down-regulates nitric oxide product in the hypothalamus, which may be partially responsible for TCDD-induced feeding inhibition.

Morphological study of orexin neurons in the hypothalamus of the Long-Evans rat, with special reference to co-expression of orexin and NADPH-diaphorase or nitric oxide synthase activities.

Orexins, novel neuropeptides, are exclusively localized in the hypothalamus and implicated in the regulation of a variety of activities, including food intake and energy balance. Nitric oxide (NO), an unconventional neurotransmitter, is widely present in numerous brain regions including the hypothalamus, and has similar physiological roles to those of the orexins. The present study was undertaken to examine the distribution of orexin neurons and the presence of neuronal nitric oxide synthase (nNOS) in the orexin neurons to clarify whether NO interacts with the orexins in the neuronal regulation activities in the Long-Evans rat. We used two double-labeling methods: nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry in combination with orexin immunohistochemistry, and double-labeling fluorescent immunohistochemistry for orexin and nNOS. The majority of the orexin immunoreactive neurons were localized mainly in the areas of the dorsomedial hypothalamic nucleus (DMN), the dorsal part of the perifornical nucleus (PEF) and lateral hypothalamic area. The orexin immunoreactive cell bodies were medium in size, and triangular, round, elliptic, and fusiform in shape. The sizes and shapes of orexin neurons in the different parts were similar. Cell bodies coexpressing the orexin and nNOS or NADPH-d were present in the areas of the DMN and the PEF, and the nerve fibers containing orexin and nNOS were distributed in the DMN and PEF, arcuate nucleus (ARN) and ventromedial hypothalamic nucleus (VMH). These results provide morphological evidence that there exists a population of nNOS- or NADPH-d-/orexin-coexpressing neurons in the orexinergic cell group in the hypothalamus, and taken together with previous findings, suggest that NO may play a role in the mechanisms by which orexin neurons regulate food intake and energy balance.

Infantile citrullinemia caused by citrin deficiency with increased dibasic amino acids.

In an infant who suffered from prolonged icterus and hepatocellular dysfunction we detected an increase of citrulline and dibasic amino acids in plasma and urine. The amino acid levels along with all the abnormal liver tests normalized upon replacing breast-milk by formula feeding; there was no relapse after human milk was tentatively reintroduced. A novel mutation, a approximately 9.5-kb genomic duplication, was identified in the citrin gene (SLC25A13) resulting in the insertion of exon 15. No mutation was detected in the CAT2A specific exon of the SLC7A2 gene which encodes for the liver transporter of cationic amino acids. This is the first report of infantile citrin deficiency in non-Asian patients.