An integrated transcriptomics and network pharmacology approach to explore the mechanism of Wang-Bi tablet against SAPHO syndrome.

BACKGROUND: SAPHO syndrome is recognized as a rare entity with damage to skin and bones due to inflammation. Currently, the treatment for SAPHO syndrome is still a challenge in clinical practice. In this study, an integrated transcriptomics and network pharmacology approach was applied to explore the therapeutic effect and mechanism of Wang-Bi tablet (WBT) on SAPHO syndrome. METHODS: The main components of WBT and their targets, as well as the targets of SAPHO syndrome, were collected from databases. Network visualization was performed using Cytoscape software. The GO and KEGG enrichment analysis was executed by David dataset. Then, the molecular mechanism of WBT improving SAPHO syndrome was validated by transcriptomics of peripheral blood neutrophils in SAPHO syndrome. Finally, the above results were validated by molecular docking. RESULTS: The Network Pharmacology results showed there are 152 core targets for WBT treatment on SAPHO syndrome. RNA-seq data showed 442 differentially expressed genes (DEGs) in peripheral blood neutrophils of SAPHO patients. Intriguingly, NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway were included in the enrichment results of network pharmacology and RNA-seq. Moreover, we verified that the core components of WBT have good affinity with the core targets of NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway by molecular docking. CONCLUSIONS: This study illustrated that the possible mechanisms of WBT against SAPHO syndrome may be related to NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway, and further experiments are needed to prove these predictions.

Gender Modifies the Association of Cognition With Age-Related Hearing Impairment in the Health and Retirement Study.

Introduction: Despite growing recognition of hearing loss as a risk factor for late life cognitive disorders, sex and gender analysis of this association has been limited. Elucidating this is one means to advocate for holistic medicine by considering the psychosocial attributes of people. With a composite Gender Score (GS), we aimed to assess this among aging participants (50+) from the 2016 Health and Retirement Study (HRS) cohort. Methods: The GS was derived from gender-related variables in HRS by factor analyses and logistic regression, ranging from 0 (toward masculinity) to 100 (toward femininity). GS tertiles were also used to indicate three gender types (GS tertile 1: lower GS indicates masculinity; GS tertile 2: middle GS indicates androgyny; GS tertile 3: higher GS indicates femininity). Univariate followed by multiple logistic regressions were used to estimate the Odds Ratio (OR) and 95% confidence intervals (CI) of cognitive impairment (assessed by adapted Telephone Interview for Cognitive Status) from hearing acuity, as well as to explore the interactions of sex and gender with hearing acuity. The risk of cognitive impairment among hearing-impaired participants was assessed using multivariable models including sex and gender as exposure variables. Results: Five variables (taking risks, loneliness, housework, drinking, and depression) were retained to compute the GS for each participant. The distribution of GS between sexes partly overlapped. After adjusting for confounding factors, the OR for cognitive impairment associated with hearing impairment was significantly higher (OR = 1.65, 95% CI: 1.26, 2.15), and this association was not modified by female sex (OR = 0.77, 95% CI: 0.46, 1.27), but by androgynous gender (OR = 0.44, 95% CI: 0.24, 0.81). In the multivariable models for participants with hearing impairment, androgynous and feminine gender, as opposed to female sex, was associated with lower odds of cognitive impairment (OR of GS tertile 2 = 0.59, 95% CI: 0.41, 0.84; OR of GS tertile 3 = 0.60, 95% CI: 0.41, 0.87; OR of female sex = 0.78, 95% CI: 0.57, 1.08). Conclusions: Hearing impairment was associated with cognitive impairment among older people, and this association may be attenuated by a more feminine GS.

Berberine in the treatment of metabolism-related chronic diseases: A drug cloud (dCloud) effect to target multifactorial disorders.

Berberine (BBR) is a multi-target drug (MTD) that has proven effective in the treatment of metabolism-related chronic diseases (CDs). However, the mode of action (MOA) of BBR remains to be clarified. At a cellular level, the inhibitory effect of BBR on mitochondrial enzymes is probably responsible for many of its biological activities, including the activation of low-density lipoprotein receptor (LDLR), AMP-activated protein kinase (AMPK) and insulin receptor (InsR); these biological activities contribute to ameliorate peripheral blood metabolic profiles, e.g. by reducing plasma lipids and glucose levels, thus improving signs and symptoms of metabolic disorders. In this perspective, BBR acts as a targeted therapy. However, it also exerts pleiotropic systemic activities on some root causes of CDs that include antioxidant / anti-inflammatory effects and modifications of gut microbiota composition and metabolism, which may also contribute to its disease-modifying effects. After reviewing the different MOA of BBR, here we propose that BBR acts through a drug-cloud (dCloud) mechanism, as different to a drug-target effect. The dCloud here is defined as a group of terminal molecular events induced by the drug (or/and related metabolites), as well as the network connections among them. In this scenario, the therapeutic efficacy of BBR is the result of its dCloud effect acting on symptoms/signs as well as on root causes of the diseases. The dCloud concept is applicable to other established MTDs, such as aspirin, metformin, statins as well as to nutrient starvation, thus providing a novel instrument for the design of effective therapies against multifactorial metabolism-related CDs.

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents.

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.

Prevention and treatment of cancer targeting chronic inflammation: research progress, potential agents, clinical studies and mechanisms.

Numerous experimental and clinical studies indicate that chronic inflammation is closely related to the initiation, progression, and spread of cancer, in which proinflammatory cytokines, such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α), and transcription factors, such as nuclear factor-κB (NF-κB), and signal transducer and activator of transcription 3 (STAT3), play pivotal roles. Stimulated by proinflammatory cytokines, NF-κB and STAT3 can modulate the expression of target genes, most of which are oncogenic ones, and promote the survival, proliferation, invasion, and metastasis of cancer cells. Now it is generally accepted that inflammation-related molecules and pathways are useful targets for the prevention and treatment of cancer. In this review, we summarize the relationship between chronic inflammation and cancer and describe some potentially useful agents including aspirin, meformin, statins, and some natural products (green tea catechins, andrographolide, curcumin) for their cancer prevention and treatment activities targeting chronic inflammation. The results of typical clinical studies are included, and the influences of these agents on the proinflammatory cytokines and inflammation-related pathways are discussed. Data from the present review support that agents targeting chronic inflammation may have a broad application prospect for the prevention and treatment of cancer in the future.

Meniett Therapy for Ménière's Disease: An Updated Meta-analysis.

OBJECTIVE: To re-evaluate the efficacy of Meniett therapy for the treatment of Ménière's disease (MD). DATA SOURCES: PubMed, Embase, Cochrane Library, Clinicaltrials.gov, ChiCTR, and the CNKI database were searched for articles in English and Chinese published before August 31, 2015. STUDY SELECTION: Included in this meta-analysis were studies that dealt with outcomes of Meniett therapy for the treatment of MD, including randomized controlled clinical trials, case-control studies, and prospective or retrospective cohort studies, with sample sizes of ≥ 10 subjects. DATA EXTRACTION: Keywords included endolymphatic hydrops, Ménière's disease, pressure, Meniett, and transtympanic micropressure treatment. DATA SYNTHESIS: Fourteen studies were included, involving a total of 345 MD patients. Data were analyzed using the Meta package in R. Dichotomous outcomes were expressed as risk ratios with 95% confidence intervals, and weighted mean differences with 95% confidence intervals were used to present continuous outcomes. Heterogeneity of the included studies was quantitatively assessed by χ(2) and I tests. Fixed-effects models were used for I(2) <50%; otherwise, random-effects models were used. Funnel plots were constructed to test the publication bias. CONCLUSION: This study showed that Meniett therapy may prevent vertigo attacks and substantially reduce its frequency in MD patients. It may also alleviate the functional deficit. The impact of Meniett therapy on hearing remains uncertain. The optimal effect might maintain for approximately 18 months. This meta-analysis suggested that Meniett therapy may be a useful second-line therapy in the treatment of MD.

Gastrodin Ameliorates Oxidative Stress and Proinflammatory Response in Nonalcoholic Fatty Liver Disease through the AMPK/Nrf2 Pathway.

This study was designed to investigate the antioxidative, antiinflammatory and metabolism-regulating effects of gastrodin (GSTD) in the treatment of nonalcoholic fatty liver disease (NAFLD). Oleic acid (OA) was used to induce steatosis in HL-7702 cells; a high-fat or high-fat and high-cholesterol diet was used to induce NAFLD in mice and rats. Our results showed that GSTD significantly increased hepatic superoxide dismutase (SOD) but decreased reactive oxygen species (ROS)/malondialdehyde (MDA) and reduced the mRNA levels of proinflammatory cytokines both in vitro and in vivo. GSTD promoted the phosphorylation of nuclear factor erythroid-2-related factor-2 (Nrf2) at serine (Ser) 40, stimulated its nuclear translocation and increased hepatic expression of heme oxygenase-1 (HO-1). GSTD activated AMP-activated protein kinase (AMPK), suppressed hepatic steatosis, lowered serum triglyceride (TG)/glucose and decreased body weight gain in animals with NAFLD. The stimulating effects of GSTD on the Nrf2 pathway as well as its antioxidative/antiinflammatory activities were abolished by compound C in OA-treated HL-7702 cells. In summary, our results demonstrate that GSTD activates the AMPK/Nrf2 pathway, ameliorates oxidative stress/proinflammatory response and improves lipid metabolism in NAFLD. Our findings may support the future clinical application of GSTD for the treatment of NAFLD to reduce hepatic steatosis, oxidative stress and proinflammatory response.

[Analysis on allergen of clinical allergic rhinitis patients in north-west mountain area of Hubei Province].

OBJECTIVE: To investigate the main inhaled allergens and the difference of that between city and rural suburbs in patients with allergic rhinitis in the mountain region of the northwest Hubei province and to provide epidemiological basis for prevention and treatment in the region. METHOD: Eight hundred and thirty-five cases who were diagnosed as allergic rhinitis with standardized allergens in Taihe Hospital of Hubei University of Medicine from Sep 2009 and Dec 2011 were studied. The data of allergens and the distribution of the patients were recorded and analyzed. χ2-test were used to analyze the data. RESULT: The top 7 of inhaled allergens were house dust mites (89.6%), dust mites (86.0%), tropical mites (56.9%), croton bug (18.8%), felon herb (8.1%), the cat hair (8.1%) and fine chain alternata bacteria (9.5%), Two main kinds of allergen in three different area are with no obvious difference (P > 0.05). CONCLUSION: In northwest Hubei Province, the highest rate of inhaled allergens was dust mites, which are approximate in different age groups and different regions, especially in the city.

Learning from berberine: Treating chronic diseases through multiple targets.

Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine (BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR's molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.

Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus.

Oxidative stress and inflammation are proved to be critical for the pathogenesis of diabetes mellitus. Berberine (BBR) is a natural compound isolated from plants such as Coptis chinensis and Hydrastis canadensis and with multiple pharmacological activities. Recent studies showed that BBR had antioxidant and anti-inflammatory activities, which contributed in part to its efficacy against diabetes mellitus. In this review, we summarized the antioxidant and anti-inflammatory activities of BBR as well as their molecular basis. The antioxidant and anti-inflammatory activities of BBR were noted with changes in oxidative stress markers, antioxidant enzymes, and proinflammatory cytokines after BBR administration in diabetic animals. BBR inhibited oxidative stress and inflammation in a variety of tissues including liver, adipose tissue, kidney and pancreas. Mechanisms of the antioxidant and anti-inflammatory activities of BBR were complex, which involved multiple cellular kinases and signaling pathways, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2) pathway, and nuclear factor- κ B (NF- κ B) pathway. Detailed mechanisms and pathways for the antioxidant and anti-inflammatory activities of BBR still need further investigation. Clarification of these issues could help to understand the pharmacology of BBR in the treatment of diabetes mellitus and promote the development of antidiabetic natural products.

Tetrandrine potentiates the hypoglycemic efficacy of berberine by inhibiting P-glycoprotein function.

This study was designed to improve the absorption and hypoglycemic efficacy of berberine (BBR), which is a substrate of P-glycoprotein (P-gp), by combination with a P-gp inhibitor tetrandrine (Tet). Flow cytometry and LC-MS/MS were used to determine the cellular efflux or retention of chemicals. Pharmacokinetic study was performed in ICR mice following oral administration of the study compounds. The hypoglycemic efficacies of the compounds were evaluated in diabetic KK-Ay mice. In the in vitro experiments, Tet significantly inhibited the efflux and increased the uptake of P-gp substrates rhodamine-123 as well as BBR in MCF7/DOX cells and Caco-2 intestinal cells. Meanwhile, Tet greatly reduced the expression of P-gp in Caco-2 cells. The inhibition of BBR efflux by Tet was translated into improved pharmacokinetics in vivo. When co-administered, Tet dose-dependently increased the average maximum concentration (C(max)) and area under concentration-time curve (AUC0₋24) of BBR in mice. Tet itself had no impact on glucose metabolism. However, it greatly potentiated the hypoglycemic efficacy of BBR in diabetic KK-Ay mice. In addition, we found that Tet had moderate inhibitory effect on the catalytic activity of CYP3A4, which played a role in the bio-transformation of BBR, and this may also take part in the improvement of the pharmacokinetics of BBR. In summary, combination with P-gp inhibitors such as Tet can improve the pharmacokinetics and hypoglycemic efficacy of BBR greatly; this implicates a feasible strategy for exploring the therapeutic effects of BBR and other pharmaceuticals which are substrates of P-gp.

Reversible neurotoxicity of kanamycin on dorsal cochlear nucleus.

The time course of aminoglycoside neurotoxic effect on cochlear nucleus is still obscure. We examined dynamic pathological changes of dorsal cochlear nucleus (DCN) and investigated whether apoptosis or autophagy was upregulated in the neurotoxic course of kanamycin on DCN after kanamycin treatment. Rats were treated with kanamycin sulfate/kg/day at a dose of 500mg by subcutaneous injection for 10 days. Dynamic pathological changes, neuron density and neuron apoptosis of the DCN were examined at 1, 7, 14, 28, 56, 70 and 140 days after kanamycin treatment. The expressions of JNK1, DAPK2, Bcl-2, p-Bcl-2, Caspase-3, LC3B and Beclin-1 were also detected. Under transmission electron microscopy, the mitochondrial swelling and focal vacuoles as well as endoplasmic reticulum dilation were progressively aggravated from 1 day to 14 days, and gradually recovered from 28 days to 140 days. Meanwhile, both autophagosomes and autolysosomes were increased from 1 day to 56 days. Only few neurons were positive to the TUNEL staining. Moreover, neither the expressions of caspase-3 and DAPK2 nor neurons density of DCN changed significantly. LC3-II was drastically increased at 7 days. Beclin-1 was upgraded at 1 and 7 days. P-Bcl-2 increased at 1, 7, 14 and 28 days. JNK1 increased at 7 days, and Bcl-2 was downgraded at 140 days. LC3-B positive neurons were increased at 1, 7 and 14 days. These data demonstrated that the neurons damage of the DCN caused by kanamycin was reversible and autophagy was upregulated in the neurotoxic course of kanamycin on DCN through JNK1-mediated phosphorylation of Bcl-2 pathway.

[Jinsangsanjie capsule for treating vocal fold polyps and vocal nodules].

OBJECTIVE: To investigate therapeutic effects of Jinsangsanjie capsule on vocal fold polyps and vocal nodules. METHOD: Seventy-five patients with vocal fold polyps and vocal nodules were treated by taking Jinsangsanjie capsule orally. After the therapeutic course, they were all followed up for 1 month. RESULT: The effective rate of vocal nodule group was 93.8%, the effective rate of vocal fold polyp group was 89.7%, the effective rate of vocal nodule with acute congestion group was 100%, the effective rate of vocal fold polyp with acute congestion group was 100%, and the effective rate of hypertrophy of vocal cords with chronic congestion group was 66.7%. CONCLUSION: Jinsangsanjie capsule has definite efficacy for treatment of vocal fold polyps and vocal nodules and deserved to be recommended.

[Clinical effectiveness and safety of sanchi tong shu capsule in the treatment of aural vertigo: a multi-center randomized controlled clinical trial].

OBJECTIVE: To evaluate the clinical effectiveness and safety of Sanchi Tong Shu capsule in the treatment of common aural vertigo. METHOD: A multi-center randomized controlled trial was designed to study 206 vertigo patients who were randomly allocated into one of the two groups. One group was treated with Sanchi Tong Shu capsule for 14 days, another group was treated with betahistine mesilate tablets for 14 days. RESULT: The clinical effectiveness rates of the two groups were 84.86% and 90.92% respectively according to FAS analysis and 84.76%, 90.92% respectively according to PPS analysis. No statistic significance difference was found between the two groups (P > 0.05). After 14 days treatment, total DHI and all the subsection (including body, emotion and function) scores of the two groups were all decreased compared with treatment before (P < 0.01). Compared the difference value of the total DHI and subsection scores before and after treatment, the two groups have no difference (P > 0.05). The adverse effective rate of the two groups were 3.29% and 7.84% respectively and there was no statistic difference between the two groups (P > 0.05). CONCLUSION: Sanchi Tong Shu capsule is a safe and effective drug for the treatment of common aural vertigo.

Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression.

Our previous work demonstrated that berberine (BBR) increases insulin receptor (InsR) expression and improves glucose utility both in vitro and in animal models. Here, we study the InsR-up-regulating and glucose-lowering activities of BBR in humans. Our results showed that BBR increased InsR messenger RNA and protein expression in a variety of human cell lines, including CEM, HCT-116, SW1990, HT1080, 293T, and hepatitis B virus-transfected human liver cells. Accordingly, insulin-stimulated phosphorylations of InsR beta-subunit and Akt were increased after BBR treatment in cultured cells. In the clinical study, BBR significantly lowered fasting blood glucose (FBG), hemoglobin A(1c), triglyceride, and insulin levels in patients with type 2 diabetes mellitus (T2DM). The FBG- and hemoglobin A(1c)-lowering efficacies of BBR were similar to those of metformin and rosiglitazone. In the BBR-treated patients, the percentages of peripheral blood lymphocytes that express InsR were significantly elevated after therapy. Berberine also lowered FBG effectively in chronic hepatitis B and hepatitis C patients with T2DM or impaired fasting glucose. Liver function was improved greatly in these patients by showing reduction of liver enzymes. Our results confirmed the activity of BBR on InsR in humans and its relationship with the glucose-lowering effect. Together with our previous report, we strongly suggest BBR as an ideal medicine for T2DM with a mechanism different from metformin and rosiglitazone.

[Individualized integrated therapy on patients with vertigo].

OBJECTIVE: To explore the treatment of patients with vertigo by the integrated therapy including the drug, surgery and rehabilitation exercise and to investigate the establishment of individualized integrated therapy on patients with vertigo. METHOD: One hundred and fifty-eight patients with peripheral vestibular vertigo were taken the individualized integrated therapy of vertigo (IITV). In first step of IITV, according to the etiology of vertigo, the therapy protocols were personally designed including drug, surgery or rehabilitation exercise. In second step of IITV, the patients who did not achieve effective treatment were followed-up and status of vestibular compensation and model of sensory organization in stance balance were re-evaluated. Then, the adjusted therapy protocol was designed by using drug, surgery or rehabilitation exercise comprehensively. The outcome assessment methods included the vestibular symptom index (VSI), balance assessment and dizziness handicap inventory (DHI). RESULT: The result of VSI showed that there were significant difference (P < 0.01) between the post-therapy and pre-therapy in the symptoms except the headache. Both results of timed balance test and foam posturography showed that the postural stability was improved after IITV (P < 0.01). The total DHI score improved 15.97 after therapy and there were significant difference (P < 0.01) of total DHI score between the post-therapy and pre-therapy. The total effective rate of IITV was 91.14% in these patients with vertigo. CONCLUSION: To treat patients with vertigo effectively, it was necessary to design the individualized integrated therapy protocol which applied the methods of drug, surgery and rehabilitation exercise comprehensively on the base of etiology of vertigo, status of vestibular compensation and model of sensory organization.

[Idiopathic sudden deafness: the therapeutic evaluation of hyperbaric oxygen treatment].

OBJECTIVE: To further evaluate the therapeutic effect of hyperbaric oxygen (HBO) to idiopathic sudden deafness. METHOD: A total number of 236 medical records of inpatients with idiopathic sudden deafness during 1997-2004 were collected from the Wuhan Union Hospital. Single factor analysis was done to evaluate the therapeutic effect with ten factors with SPSS analysis software. We divided the cases into HBO group and non-HBO group. The logistic regression was used in multivariate analysis. RESULT: Single factor analysis indicated that sex, ear side, presence of tinnitus, inducement and period of treatment had no effect on the prognosis, while age, course, presence of vertigo, a sensorineural hearing loss history with the other ear, degree of deafness had some effect on the prognosis. Multivariate analysis indicated: the effective (hearing threshold has elevated above 15 dB) ratio of HBO group comparing to the control group (non-HBO group), the difference was significant (P<0.01). CONCLUSION: The first visit after 14 days, the presence of vertigo, a sensorineural hearing loss history with the other ear and complete deafness may imply poor prognosis. HBO is effective for sudden deafness.

[Vestibular evoked myogenic potentials in normal young people].

OBJECTIVE: To observe the positive rate and other variances of the vestibular evoked myogenic potentials (VEMP)in normal young people. METHOD: Fifty-two normal young people aged from 21-22 years old including 31 males and 21 females were investigated. Intense clicks were given to one test ear and EMG was recorded from ipsilateral side. RESULT: VEMPs were presented in both ears in 47 subjects, absent in either of the two ears in 5 subjects. Variances averaged from all 94 positive ears were as follows (mean +/- standard deviation): latencies for p1 (15.97 +/- 3.22) ms, latencies for n2 (24.41+/- 2.46) ms, interval time between p1 and n2 (8.41 +/- 2.06) ms, amplitude (33.27 +/- 14.37) microV, threshold (93.67 +/- 5.20) dB nHL. Inter-subject variances averaged from 47 normal subjects were as follows:latencies for p1 (0.97 +/- 1.31) ms, latencies for n2 (1.23 +/- 1.30) ms, interval time between p1 and n2 (0.95 +/- 1.21) ms, amplitude (10.04 +/- 11.88) microV, threshold (2.29 +/- 2.56) dB nHL. There were no significant difference between males and females. CONCLUSION: VEMP can be recorded in most normal subjects. VEMP may travel along the hypothesized response pathway from the vestibular sacculus to the inferior vestibular nerve, vestibular nucleus, and lateral vestibulospinal tract to the SCM muscle. VEMP recording could become an attractive method for testing otolithic receptors and vestibulospinal pathways.

Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins.

We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs.