Chemical constituents from the medicinal herb-derived fungus Chaetomium globosum Km1226.

BACKGROUND: Endophytic fungi have proven to be a rich source of novel natural products with a wide-array of biological activities and higher levels of structural diversity. RESULTS: Chemical investigation on the liquid- and solid-state fermented products of Chaetomium globosum Km1226 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-14. Their structures were determined by spectroscopic analysis as three previously undescribed C13-polyketides, namely aureonitol C (1), mollipilins G (2), and H (3), along with eleven known compounds 4-14. Among these, mollipilin A (5) exhibited significant nitric oxide production inhibitory activity in LPS-induced BV-2 microglial cells with an IC50 value of 0.7 ± 0.1 µM, and chaetoglobosin D (10) displayed potent anti-angiogenesis property in human endothelial progenitor cells (EPCs) with an IC50 value of 0.8 ± 0.3 µM. CONCLUSIONS: Three previously unreported compounds 1-3 were isolated and identified. Mollipilin A (5) and chaetoglobosin D (10) could possibly be developed as anti-inflammatory and anti-angiogenic lead drugs, respectively.

Critical role of heme oxygenase-1 in chaetoglobosin A by triggering reactive oxygen species mediated mitochondrial apoptosis in colorectal cancer.

The incidence rate of colorectal cancer (CRC) has been increasing and poses severe threats to human health worldwide and developing effective treatment strategies remains an urgent task. In this study, Chaetoglobosin A (ChA), an endophytic fungal metabolite from the medicinal herb-derived fungus Chaetomium globosum Km1126, was identified as a potent and selective antitumor agent in human CRC. ChA induced growth inhibition of CRC cells in a concentration-dependent manner but did not impair the viability of normal colon cells. ChA triggered mitochondrial intrinsic and caspase-dependent apoptotic cell death. In addition, apoptosis antibody array analysis revealed that expression of Heme oxygenase-1 (HO-1) was significantly increased by ChA. Inhibition of HO-1 increased the sensitivity of CRC cells to ChA, suggesting HO-1 may play a protective role in ChA-mediated cell death. ChA induced cell apoptosis via the induction of reactive oxygen species (ROS) and ROS scavenger (NAC) prevented ChA-induced cell death, mitochondrial dysfunction, and HO-1 activation. ChA promoted the activation of c-Jun N-terminal kinase (JNK), and co-administration of JNK inhibitor or siRNA markedly reversed ChA-mediated apoptosis. ChA significantly decreased the tumor growth without eliciting any organ toxicity or affecting the body weight of the CRC xenograft mice. This is the first study to demonstrate that ChA exhibits promising anti-cancer properties against human CRC both in vitro and in vivo. ChA is a potential therapeutic agent worthy of further development in clinical trials for cancer treatment.

Electroacupuncture Promotes Neuroplasticity of Central Auditory Pathway: An Auditory Evoked Potentials Study.

Our previous studies found that electroacupuncture at the right Zhongzhu acupoint (TE3) can enhance auditory recovery in rats with noise-induced hearing loss. Here, we investigated the changes in auditory brainstem response (ABR) and long late latency (LLR) evoked potential to explain the mechanisms of electroacupuncture at TE3. The auditory evoked potentials were recorded, including ABR and LLR, at baseline and on day 3 (D3), D5, and D8 after baseline. The 2-Hz electroacupuncture at the right TE3 was applied on D3, D4, and D5 in the electroacupuncture group but not in the control group. In ABR, compared with the control group, the latency shift of waves I (0.298 ± 0.033 vs -0.045 ± 0.057 ms), III (0.718 ± 0.038 vs -0.163 ± 0.130 ms), and V (1.160 ± 0.082 vs -0.207 ± 0.138 ms) on D3 (all p < 0.01) and of wave V (0.616 ± 0.433 vs -0.352 ± 0.209 ms, p < 0.05) on D5 was greater in the electroacupuncture group than that in the control group. Moreover, the interpeak latency shift of I-III (0.420 ± 0.041 vs -0.118 ± 0.177 ms) and I-V (0.863 ± 0.088 vs -0.162 ± 0.156 ms) on D3 (both p < 0.05) and of III-V (0.342 ± 0.193 vs -0.190 ± 0.110 ms) and I-V (0.540 ± 0.352 vs -0.343 ± 0.184 ms) on D5 (both p < 0.05) was greater in the electroacupuncture group than that in the control group. In LLR, the latency shift of P0 was greater in the electroacupuncture group than in the control group on D3 (3.956 ± 2.975 vs -1.178 ± 1.358 ms, p < 0.01) and D5 (2.200 ± 1.889 vs -0.311 ± 1.078 ms, p < 0.05). These findings indicate that electroacupuncture at the right TE3 can modulate the neuroplasticity of the central auditory pathway, including the brain stem and the primary and secondary auditory cortex.

Anti-Epstein-Barr Viral Agents from the Medicinal Herb-Derived Fungus Alternaria alstroemeriae Km2286.

Chromatographic separation on the liquid-state fermented products produced by the fungal strain Alternaria alstroemeriae Km2286 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-9. Structures were determined by spectroscopic analysis as four undescribed perylenequinones, altertromins A-D (1-4), along with altertoxin IV (5), altertoxin VIII (6), stemphyperylenol (7), tenuazonic acid (8), and allo-tenuazonic acid (9). Compounds 1-6 exhibited antiviral activities against Epstein-Barr virus (EBV) with EC50 values ranging from 0.17 ± 0.07 to 3.13 ± 0.31 µM and selectivity indices higher than 10. In an anti-neuroinflammatory assay, compounds 1-4, 6, and 7 showed inhibitory activity of nitric oxide production in lipopolysaccharide-induced microglial BV-2 cells, with IC50 values ranging from 0.33 ± 0.04 to 4.08 ± 0.53 µM without significant cytotoxicity. This is the first report to describe perylenequinone-type compounds with potent anti-EBV and anti-neuroinflammatory activities.

Effect of Electroacupuncture on Noise-Induced Hearing Loss in Rats.

Acupuncture has long been used to relieve some inner ear diseases such as deafness and tinnitus. The present study examined the effect of electroacupuncture (EA) on noise-induced hearing loss (NIHL) in animals. A NIHL rat model was established. Electroacupuncture pretreatment at 2 Hz or posttreatment at the right Zhongzhu (TE3) acupoint was applied for 1 hour. Auditory thresholds were measured using auditory brainstem responses (ABRs), and histopathology of the cochlea was examined. The results indicated that the baseline auditory threshold of ABR was not significantly different between the control (no noise), EA-only (only EA without noise), noise (noise exposure only), pre-EA (pretreating EA then noise), and post-EA (noise exposure then posttreating with EA) groups. Significant auditory threshold shifts were found in the noise, pre-EA, and post-EA groups in the immediate period after noise exposure, whereas auditory recovery was better in the pre-EA and post-EA groups than that in the noise group at the three days, one week (W1), two weeks (W2), three weeks (W3), and four weeks(W4) after noise stimulation. Histopathological examination revealed greater loss of the density of spiral ganglion neurons in the noise group than in the control group at W1 and W2. Although significant loss of spiral ganglion loss happened in pre-EA and post-EA groups, such loss was less than the loss of the noise group, especially W1. These results indicate that either pretreatment or posttreatment with EA may facilitate auditory recovery after NIHL. The detailed mechanism through which EA alleviates NIHL requires further study.

Back massage intervention for improving health and sleep quality among intensive care unit patients.

BACKGROUND: A massage may relax muscles, improve blood circulation and reduce pain and anxiety while also improving sleep quality by increasing comfort. However, there is little research on whether a back massage improves sleep quality in intensive care unit (ICU) patients. AIMS AND OBJECTIVES: This study examined the effects of a back massage on improving vital signs, sleep quality, anxiety and depression among ICU patients. DESIGN: Adopting a quasi-experimental design, convenience sampling was used to recruit ICU patients from a medical centre in Southern Taiwan. The experimental group received back massages for three consecutive days (n = 30), while controls received usual care (n = 30). METHODS: The Verran and Snyder-Halpern Scale and the Hospital Anxiety and Depression Scale were used, and subjective and objective sleep time (wrist actigraphy and sleep duration from nurse observations) was recorded. The effect of the intervention was examined using a generalized estimating equation model with a robust standard error and an exchangeable working correlation matrix adjusting for time. RESULTS: The results show that subjective sleep quality scores in ICU patients were low. Mean observed sleep time (measured by nurses) was 3·9 h, but mean sleep time measured using wrist actigraphy was 5·9 h. Back massages improved breathing in patients, increased sleep quality reflected by both subjective and objective data and were associated with a significant change in anxiety. CONCLUSIONS: These findings suggest that a 10-min back massage can improve sleep quality, sleep duration, breathing and anxiety in ICU patients. RELEVANCE TO CLINICAL PRACTICE: The implementation of a back massage shows positive improvements in the sleep quality of ICU patients. The training and theory of massage interventions should be further applied when developing courses in critical care nursing.

A novel orally available seleno-purine molecule suppresses triple-negative breast cancer cell proliferation and progression to metastasis by inducing cytostatic autophagy.

Patients with triple-negative breast cancer (TNBC) often have a poor prognosis largely due to lack of effective targeted therapy. Using a library of seleno-purines coupled to a high-throughput biochemical enzymatic assays we identified a potent pharmacological enhancer of autophagy (referred herein as SLLN-15) that selectively activated cytostatic macroautophagy/autophagy in TNBC preclinical models. SLLN-15 induced a dose-dependent anti-proliferative activity in the TNBC cell lines MDA-MB-231 and BT-20 via induction of autophagy and autophagic flux. This induction was associated with a selective inhibition of AKT-MTOR signaling. Conversely, rapamycin, a known autophagy inducer and MTOR inhibitor, was unable to duplicate SLLN-15's effect on TNBC cells. Inhibition of autophagy by siRNA-mediated targeting of the autophagy regulators, BECN1, ATG5 and ATG7 or using 3-methyladenine (3-MA), significantly protected against SLLN-15-induced inhibition of cell viability, further supporting that SLLN-15-induced inhibition of cancer cell proliferation was autophagy-dependent. SLLN-15-induced autophagy in TNBC cells was also associated with decreased AURKA expression, decreased AKT phosphorylation and subsequent blockage of the AKT-MTOR pathway. In vivo, oral SLLN-15 revealed a potent anticancer and anti-metastatic activity in mice bearing TNBC. Altogether, this study describes a novel regulator of mammalian autophagy, with potential utility as an experimental therapeutic for TNBCs. Abbreviations: 3-MA: 3-methyladenine; ATG5: autophagy related 5; ATG7: autophagy related 7; AURKA: aurora kinase A; AURKB: aurora kinase B; BECN1: beclin 1; CQ: chloroquine; DMSO: dimethyl sulfoxide; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; ERBB2: erb-b2 receptor tyrosine kinase 2; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PARP1: poly(ADP-ribose) polymerase 1; PI: propidium iodide; SQSTM1/p62: sequestosome 1; TNBC: triple-negative breast cancer.

Prescription patterns of traditional Chinese medicine amongst Taiwanese children: a population-based cohort study.

BACKGROUND: Traditional Chinese medicine (TCM) has been used by Chinese patients and in many other countries worldwide. However, epidemiological reports and prescription patterns on children are few. METHODS: A cohort of 178,617 children aged 18 and under from one million randomly sampled cases of the National Health Insurance Research Database was analyzed for TCM prescription patterns. SAS 9.1 was applied and descriptive medicine utilization patterns were presented. RESULTS: The cohort included 112,889 children treated by TCM, with adolescents (12- to 18-year-olds) as the largest group. In the children's TCM outpatient visits, Chinese herbal remedies were the main treatment. The top three categories of diseases treated with Chinese herbal remedies were respiratory system; symptoms, signs, and ill-defined conditions; and digestive system. The top three categories using acupuncture were: injury and poisoning, diseases of the musculoskeletal system and connective tissue, and diseases of the respiratory system. Of the top ten herbal medicines prescribed by TCM physicians, the top nine herbal formulae and the top ten single herbs were associated with diseases of the respiratory system. CONCLUSION: This study identified patterns of TCM prescriptions for children and common disease categories treated with TCM. The results provide a useful reference for health policy makers and for those who consider the usage of TCM for children.

Effect of Laser Acupuncture on Anthropometric Measurements and Appetite Sensations in Obese Subjects.

Purpose. A patient-assessor-blinded, randomized, sham-controlled crossover trial was performed to investigate the effectiveness of laser acupuncture on anthropometric measurements and appetite sensation in obese subjects. Methods. Fifty-two obese subjects were randomly assigned to either the laser acupuncture group or the sham laser acupuncture group. Subjects within each group received the relevant treatment three times a week for 8 weeks. After a two-week washout period, the subjects then received the treatment of the opposite group for another 8 weeks. BMI, body fat percentage, waist-to-hip ratio (WHR), waist circumference, hip circumference, and appetite sensations were measured before and after 8 weeks of treatment. Results. BMI, body fat percentage, WHR, waist circumference, and hip circumference decreased significantly (p < 0.05) in the laser acupuncture group compared to baseline but there was no decrease in those variables in the sham laser acupuncture group. Laser acupuncture significantly improved scores on the fullness, hunger, satiety, desire to eat, and overall well-being relative to the baseline (p < 0.05). Conclusions. Laser acupuncture is well tolerated and improves anthropometric measurements and appetite sensations in obese subjects.

Effect of laser acupuncture on obesity: study protocol for a randomized controlled trial.

BACKGROUND: Obesity-related diseases have a profound economic impact on health care systems. Laser acupuncture has been shown to have beneficial effects on obesity. However, to our knowledge, those trials were either non-randomized, non-blinded or included low-calorie diet control. We have, therefore, designed a patient-assessor-blinded, randomized, sham-controlled crossover trial to investigate the significance of laser acupuncture on obesity. METHODS/DESIGN: 104 subjects above 20 years of age with a body mass index (BMI) of over 25 kg/m(2) will be divided into 2 groups: experimental and control. Each subject will receive the treatment relevant to their group 3 times a week for 8 weeks. After 8 weeks of treatment the subject will enter a 2-week washout period, after which the subjects will switch groups. Measurements will include BMI, body fat percentage, waist-to-hip ratio (WHR), waist circumference, hip circumference, skinfold thickness, thigh circumference, body fat, blood pressure, heart rate, hunger and the 36-item Short-Form Health Survey (SF-36). DISCUSSION: The results of this study will provide the basis for future large-scale multicenter trials investigating the effects of laser acupuncture on obesity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02167308 ; registration date: 14 June 2014.

GnRH mRNA levels in male three-spined sticklebacks, Gasterosteus aculeatus, under different reproductive conditions.

In vertebrates, reproduction is regulated by the brain-pituitary-gonad (BPG) axis, where the gonadotropin-releasing hormone (GnRH) is one of the key components. However, very little is known about the possible role of GnRH in the environmental and feedback control of fish reproduction. To investigate this, full-length gnrh2 (chicken GnRH II) and gnrh3 (salmon GnRH) sequences of male three-spined sticklebacks (Gasterosteus aculeatus), which are clustered with the taxa of the same GnRH type as other Euteleostei, were cloned and annotated. gnrh1 is absent in this species. The mRNA levels of gnrh2 and gnrh3 in the sticklebacks' brain were measured under breeding and post-breeding conditions as well as in castrated and sham-operated breeding fish and castrated/sham-operated fish kept under long-day (LD 16:8) and short-day (LD 8:16) conditions. Fully breeding males had considerably higher mRNA levels of gnrh2 and gnrh3 in the thalamus (Th) and in the telencephalon and preoptic area (T+POA), respectively, than post-breeding males. Sham-operated breeding males have higher gnrh3 mRNA levels than the corresponding castrated males. Moreover, higher gnrh2 mRNA levels in the Th and higher gnrh3 mRNA levels in the T+POA and hypothalamus (HypTh) were also found in long-day sham-operated males than in sham-operated fish kept under an inhibitory short day photoperiod. Nevertheless, gnrh2 and gnrh3 mRNA levels were not up-regulated in castrated males kept under long-day photoperiod, which suggests that positive feedbacks on the brain-pituitary-gonad axis are necessary for this response.

In vitro antioxidant activities, free radical scavenging capacity, and tyrosinase inhibitory of flavonoid compounds and ferulic acid from Spiranthes sinensis (Pers.) Ames.

In this study, ultrasound-assisted extraction (UAE) and other methods of extracting flavonoid compounds and ferulic acid (FA) from S. sinensis were investigated. Five different extraction methods, including water extraction (W), water extraction using UAE (W+U), 75% ethanol extraction (E), 75% ethanol extraction using UAE (E+U), and supercritical CO2 extraction (SFE) were applied in the extraction of bioactive compounds (flavonoids and ferulic acid) in order to compare their efficiency. The highest yield of flavonoids (4.28 mg/g) and ferulic acid (4.13 mg/g) content was detected in the E+U extract. Furthermore, S. sinensis extracts obtained by E+U show high antioxidant activity, and IC50 values of 0.47 mg/mL for DPPH radicals and 0.205 mg/mL for metal chelating activity. The total antioxidant assay shows superoxide radical scavenging capacity and in vitro mushroom tyrosinase inhibition in a dose-dependent manner, suggesting that E+U can be used for extraction of bioactive compounds from S. sinensis.

Local autogenous bone mixed with bone expander: an optimal option of bone graft in single-segment posterolateral lumbar fusion.

BACKGROUND: This was a retrospective study of clinical results for single-segment posterolateral lumbar fusion using local autograft bone with bone expander. METHODS: Sixty-six patients underwent single-segment decompression with instrumented posterolateral fusion. Locally harvested morselized bone from the decompressive site mixed with 2 mL calcium sulfate (OSTEOSET, Wright Medical Technology, Arlington, TN, USA) was used for the fusion at the posterolateral aspect of the lumbar spine. The minimum follow-up period was 15 months. The status of the fusion was evaluated by plain film, flexion-extension view, and fine-cut computed tomography (CT) with coronal reconstruction. Radiographic fusion criteria included less than 5 degrees of angular motion, less than 2 mm of translation, and evidence of bridging bone in the posterolateral lumbar area on the CT scan. The clinical outcome was recorded using VAS score and the ODI. The results were then compared with the result of the other group who had received the same procedure except that a pure autogenous bone graft harvested from the PSIS was used. RESULTS: In the group using local bone and OSTEOSET, the fusion rate was 92.3% by the strict criteria. The VAS scores for leg pain and back pain were decreased in the 2 groups, but there was no significant difference between them. The improvement in the ODI was also similar between the 2 groups. Intraoperative blood loss and the time needed for the operation were significantly decreased in the group using local bone and OSTEOSET as the bone graft. In the group using autogenous bone graft, donor site morbidity was still encountered. CONCLUSIONS: Using local laminectomy bone with calcium sulfate as bone graft is a practical option in posterolateral lumbar fusion with the advantages of less operative time, less blood loss, and avoidance of donor site morbidity.