Exploring brusatol as a new anti-pancreatic cancer adjuvant: biological evaluation and mechanistic studies.

Pancreatic cancer is highly resistant to chemotherapeutic agents and is known to have a poor prognosis. The development of new therapeutic entities is badly needed for this deadly malignancy. In this study, we demonstrated for the first time that brusatol, a natural quassinoid isolated from a Chinese herbal medicine named Bruceae Fructus, possessed potent cytotoxic effect against different pancreatic adenocarcinoma cell lines. Its anti-pancreatic cancer effect was comparable to that of the first-line chemotherapeutic agents such as gemcitabine and 5-fluorouracil, with a more favorable safety profile. In addition, brusatol showed a synergistic anti-proliferative effect toward PANC-1 and Capan-2 cell lines when combined with gemcitabine or 5-fluorouracil. The results of flow cytometry suggested that brusatol combination treatment with gemcitabine or 5-fluorouracil was able to cause cell cycle arrest at G2/M phase, and accentuate apoptosis in PANC-1 cells. Moreover, brusatol deactivated gemcitabine/5-fluorouracil-induced NF-κB activation. Western blot analysis and qRT-PCR results showed that brusatol significantly down-regulated the expression of vimentin and Twist, and markedly stimulated the expression of E-cadherin, the key regulatory factors of the epithelial-mesenchymal transition process. Furthermore, treatment with combination of brusatol and gemcitabine or 5-fluorouracil significantly reduced in vivo tumor growth when compared with treatment of either brusatol or gemcitabine/5-fluorouracil alone. Taken together, these results have amply demonstrated that brusatol is a potent anti-pancreatic cancer natural compound, and the synergistic anti-pancreatic cancer effects of brusatol and gemcitabine/5-fluorouracil observed both in vitro and in vivo are associated with the suppression of epithelial-mesenchymal transition process, indicating that brusatol is a promising adjunct to the current chemotherapeutic regimen.

Electroacupuncture and splinting versus splinting alone to treat carpal tunnel syndrome: a randomized controlled trial.

BACKGROUND: The effectiveness of acupuncture for managing carpal tunnel syndrome is uncertain, particularly in patients already receiving conventional treatments (e.g., splinting). We aimed to assess the effects of electroacupuncture combined with splinting. METHODS: We conducted a randomized parallel-group assessor-blinded 2-arm trial on patients with clinically diagnosed primary carpal tunnel syndrome. The treatment group was offered 13 sessions of electroacupuncture over 17 weeks. The treatment and control groups both received continuous nocturnal wrist splinting. RESULTS: Of 181 participants randomly assigned to electroacupuncture combined with splinting (n = 90) or splinting alone (n = 91), 174 (96.1%) completed all follow-up. The electroacupuncture group showed greater improvements at 17 weeks in symptoms (primary outcome of Symptom Severity Scale score mean difference [MD] -0.20, 95% confidence interval [CI] -0.36 to -0.03), disability (Disability of Arm, Shoulder and Hand Questionnaire score MD -6.72, 95% CI -10.9 to -2.57), function (Functional Status Scale score MD -0.22, 95% CI -0.38 to -0.05), dexterity (time to complete blinded pick-up test MD -6.13 seconds, 95% CI -10.6 to -1.63) and maximal tip pinch strength (MD 1.17 lb, 95% CI 0.48 to 1.86). Differences between groups were small and clinically unimportant for reduction in pain (numerical rating scale -0.70, 95% CI -1.34 to -0.06), and not significant for sensation (first finger monofilament test -0.08 mm, 95% CI -0.22 to 0.06). INTERPRETATION: For patients with primary carpal tunnel syndrome, chronic mild to moderate symptoms and no indication for surgery, electroacupuncture produces small changes in symptoms, disability, function, dexterity and pinch strength when added to nocturnal splinting. TRIAL REGISTRATION: Chinese Clinical Trial Register no. ChiCTR-TRC-11001655 (www.chictr.org.cn/showprojen.aspx?proj=7890); subsequently deposited in the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-TRC-11001655).

Patient Perceptions of Expression of Empathy From Chinese Medicine Clinicians in a Chinese Population: A Cross-Sectional Study.

This study aims to examine the level of empathy perceived by patients receiving care from herbalists, acupuncturists and massage therapists and to investigate the factors that influence levels of perceived empathy.Participants who were 18 years or above; able to provide written informed consent; and able to read and write in Chinese without assistance were included. A total of 514 participants sampled from charity and semipublic Chinese medicine (CM) clinics in Hong Kong were recruited to assess levels of empathy perceived during various length of consultations (1-20 minutes) by the Chinese Consultation and Relational Empathy Measure (Chinese CARE). Multiple linear regressions were conducted to evaluate the associations between perceived levels of empathy and the type of CM practitioner consulted and participants' demographic and health characteristics.The average Chinese CARE total score for participants consulting CM practitioners was 34.3 of a maximum of 50. After adjusting for participants' health and demographic characteristics, acupuncturists received the highest ratings (P < 0.001), whereas massage therapists (P < 0.001) scored the lowest of the 3 modalities. Participants receiving social benefits (P = 0.013), those with longer waiting times (P = 0.002), and those with shorter consultation durations (P = 0.020) scored significantly lower on the Chinese CARE.The level of empathy perceived by participants using CM was similar to results found for those in conventional care, in contrast to findings in other geographical settings, where a high level of perceived empathy was a major motivator for participants to choose complementary medicine.

Effect of acupressure in treating urodynamic stress incontinence: a randomized controlled trial.

The efficacy of acupressure therapy in managing urodynamic stress incontinence has not been fully investigated. This study evaluates the effects of a validated acupressure protocol for treating women with urodynamic stress incontinence. A randomized, single-blinded, placebo-controlled trial with a before-and-after study design was conducted. Eighty-one women aged between 18 and 60 were recruited at a urogynecology clinic in an acute hospital in Hong Kong. Participants were randomly assigned to an intervention (acupressure) group, a sham group, or a usual care (control) group. A validated acupressure protocol was employed in the intervention group. The intervention comprised three weekly sessions of 30 minutes each for a total of thirty sessions. Outcome measures included pelvic floor muscle strength, number of episodes of urine leakage over four days, self-reported severity of urine leakage, and responses on the Chinese version of the King's Health Questionnaire. No adverse effects were reported. Five percent of the participants dropped out of the study. Intention-to-treat analysis was conducted, the results indicated significant differences in pelvic floor muscle strength across the three groups (H =7.05, p =0.03) and in self-reported severity of urine leakage between the intervention and control groups (Z = -2.48, p = 0.01). Significant improvement in all domains of the Chinese version of the King's Health Questionnaire was evident in the intervention group. Acupressure is a simple and non-invasive intervention that appears to have positive physiological and psychological effects on women with urodynamic stress incontinence. The findings support acupressure as an intervention option for managing urodynamic stress incontinence in women.

Induction of early apoptosis in human nasopharyngeal carcinoma cells by mTHPC-mediated photocytotoxicity.

OBJECTIVES: In this study, the early apoptotic events elicited by mTHPC-mediated photo-cytotoxicity were explored in a human nasopharyngeal carcinoma cell line (NPC/HK1). METHODS AND MATERIALS: NPC/HK1 cells (5 x 10(3)) were incubated with photosensitizer mTHPC (0.8 microg/ml) in chamber slides for 20h and subjected to light irradiation at 2J/cm(2) (LD(80)). Morphologic changes of treated cells were examined under light microscopy and confocal microscopy at 0-4h after the light irradiation. The early stage of apoptosis was detected by fluorescein-conjugated Annexin V (Annexin V-FITC) assay. Mitochondrial membrane damage and cytochrome c release were determined by flowcytometric analysis. Bcl-2 expression was measured by Western blot analysis. RESULTS: One hour after mTHPC-mediated photodynamic therapy (PDT), microscopic examination showed membrane blebbing and cell shrinkage. Annexin V-FITC assay showed that a considerable number of NPC/HK1 cells became apoptotic. Flowcytometric analysis showed that the cytochrome c was released at 1h after PDT. Bcl-2 expression also declined significantly compared to control groups. CONCLUSIONS: mTHPC-mediated photo-cytotoxicity can effectively induce early apoptotic responses in NPC/HK1 cells which might be modulated by mitochondrial damages and Bcl-2 inhibition.

Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats.

Diabetes mellitus is characterized by hyperglycemia and complications affecting the eye, kidney, nerve and blood vessel. We have previously demonstrated the occurrence of oxidative stress of streptozotocin-induced diabetic rats, preceded by a depletion in the tissue level of glutathione. In this study, when diabetic rats were treated with ginsenoside Re of Panax ginseng C.A. Meyer, there was a significant reduction in blood glucose, total cholesterol and triglyceride levels. On the other hand, oxidative stress has been implicated in the pathogenesis of diabetes and its complications. It was found that treatment by ginsenoside Re restored the levels of both glutathione and malondialdehyde in the eye and kidney to those found in the control rats. This is the first report demonstrating ginsenoside Re has significant antioxidant efficacy in diabetes, and prevents the onset of oxidative stress in some vascular tissues. Our results demonstrated that ginsenoside Re could lower blood glucose and lipid levels, and exerts protective actions against the occurrence of oxidative stress in the eye and kidney of diabetic rats. Our data also provide evidence that ginsenoside Re could be used as an effective antidiabetic agent particularly in the prevention of diabetic microvasculopathy.

Altered expression of serum protein in ginsenoside Re-treated diabetic rats detected by SELDI-TOF MS.

Diabetes mellitus (DM) is now a global health problem, however, its pathogenesis has not yet been fully deciphered. Even though modern medicine has great contribution to the control and treatment of DM, it is still far from success to completely cure the disease. Panax ginseng C.A. Meyer (ginseng) is a well-recognized traditional Chinese medicine for treating DM in Asia. In this study, high throughput proteomic approach has been adopted to investigate the antidiabetic action of 2 weeks' ginsenoside Re (Re, a major component of ginseng) administration to streptozotocin-induced diabetic rats. Employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and bioinformatics, 432 cluster peaks were detected in the samples, among them 293 potential biomarkers were found to have significant differentiations between the DM and control normal rats. When the Re-treated diabetic rats were compared to the untreated ones, a protein peak was detected to have significant alteration corresponding to Re treatment. This specific protein was found to match with C-reactive protein (CRP) in the protein database, and was subsequently validated by ELISA. This is the first study demonstrated that CRP could be altered by Re treatment, indicating that Re may improve diabetes and its complications by alleviation of inflammation.

Potential biomarkers found by protein profiling may provide insight for the macrovascular pathogenesis of diabetes mellitus.

Diabetes mellitus (DM) is an alarming threat to health of mankind, yet its pathogenesis is unclear. The purpose of this study was to find potential biomarkers to serve as indicators for the pathogenesis of DM in a time course manner. Based on our previous findings that oxidative stress occurred at week 8, aorta lysate and sera of 102 streptozotocin (STZ)-induced diabetic and 85 control male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week after STZ injection. The protein profiles were studied employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology in attomole sensitivity range. In the aorta, a multiple biomarker panel was discovered at the 4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3 biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers were all discovered to have 100% classification accuracy rate to differentiate the DM and control groups at all time intervals. Besides, 2 biomarkers were also found to have high classification value at week 12. Comparing the aorta and sera from DM and non-DM rats, a bundle of potential biomarkers with significant changes in peak intensities and high classification values were found. Two of the serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS-PROT knowledgebase. Validation has been conducted using immunoassay kits. These potential biomarkers may provide valuable insight on the pathogenesis of DM and macrovascular complications.

Photodynamic effect of curcumin on NPC/CNE2 cells.

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China. Radiotherapy is the primary treatment of NPC, but the rate of tumor recurrence is significant. Photodynamic therapy (PDT) and the use of natural compounds become one of the new approaches in the investigation of NPC treatment. PDT is an alternate method of cancer treatment while curcumin (CUR) is a compound derived from the traditional Chinese medicinal (TCM) herbs. The purpose of the study focuses on the photodynamic effect of CUR on one of the NPC cell lines, NPC/CNE2. Cytotoxicity and photocytotoxicity of CUR were evaluated by 3-(4,5-dimthyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Uptake kinetics of CUR in NPC/CNE2 was examined by flow cytometry. The mode of cell death induced by CUR was studied by fluorescence microscopy. Summarizing the results, CUR showed dark cytotoxicity as well as photocytotoxic effects on NPC/CNE2 cells. LC50 of CUR in the dark was about 16 microM. The cytotoxicity of CUR was enhanced by the irradiation of visible light and blue filtered light (maximum transmittance at 300 approximately 400 nm) with light doses of 300 kJ/m2 and 60 kJ/m2 respectively. NPC/CNE2 was found to rapidly take up CUR in the first hour of incubation, and the uptake kinetics steadily increased to a plateau level after 20 hr of incubation. Cell shrinkage and membrane bledding appeared under the observation of fluorescence microscopy. Such evidences proved that CUR might induce apoptosis on NPC/CNE2 cells. The preliminary study confirmed that CUR demonstrated dark cytotoxicity and photocytotoxicty to NPC/CNE2. The mode of action is likely to be induced by apoptotic pathway. CUR may be developed as a potential photosensitizer as well as a chemotherapeutic agent in clinical application.

Danshen prevents the occurrence of oxidative stress in the eye and aorta of diabetic rats without affecting the hyperglycemic state.

Oxidative stress has been implicated in the pathogenesis of diabetic complications. We have previously demonstrated the occurrence of oxidative stress in the eye and aorta but not in the kidney of diabetic rats. In the present study we have investigated the effects of danshen, a herb used in traditional Chinese medicine to treat ailments related to diabetic complications, on the onset of oxidative stress in the above tissues. Diabetic rats were treated with 3 g/kg of danshen via oral intubation for 7 weeks. Afterwards, the tissue levels of glutathione (GSH), the primary endogenous antioxidant, and malondialdehyde (MDA), a marker of oxidative stress, were measured. Our results showed that danshen treatment did not alter the hyperglycemic status of the diabetic animals. However, the GSH levels were normalized in both the eye and aorta of the diabetic rats when these rats were administered with danshen. Administration with danshen also restored the level of MDA in the eye and aorta of the diabetic rats to that found in the control rats. These changes, however, were not observed in the kidney where oxidative stress did not occur. These results suggested that oral administration of danshen can effectively prevent the occurrence of oxidative stress in the eye and aorta of the diabetic rats. Furthermore, danshen treatment did not affect the blood glucose concentration of the animals irrespective of their diabetic state. These data therefore provide important information on mode of action of danshen, thereby establishing a basis for this herb to be used as a supportive treatment regime to ameliorate the severity of diabetic complications.

Alterations in antioxidant enzyme activities in the eyes, aorta and kidneys of diabetic rats relevant to the onset of oxidative stress.

Profound changes in antioxidant enzyme activities were observed in a number of vascular tissues during the development of streptozotocin-induced diabetes in rats. In the eyes, there was an increase in superoxide dismutase activity at week 4 of diabetes. However, no difference in superoxide dismutase activity was observed between the control and diabetic animals at week 8. On the other hand, the diabetic state did not seem to affect the catalase activity in the eyes. There was a generalized increase in catalase activity of the eyes from week 4 to week 8 irrespective of the diabetic state. For glutathione peroxidase in the eyes, a decreased activity was observed in the diabetic animals at week 8, but not in week 4. A different pattern of enzyme activity changes was observed in the aorta where an increase in superoxide dismutase activity was observed in the diabetic group at week 4 but not in week 8. On the other hand, an increase in catalase activity was observed only at week 8 but not at week 4. Whereas there was no observed difference between the control and diabetic animals in glutathione peroxidase activity in the aorta, except for a generalized decrease from week 4 to week 8 in both groups of animals. In big contrast to the eyes and aorta where an increase in superoxide dismutase activity was observed at week 4 of diabetes, no change in kidney superoxide dismutase activity was noted at week 4 and a decrease was observed at week 8. A similar pattern of enzyme activity changes was observed for glutathione peroxidase in the kidneys. The catalase activity in the kidneys was not affected at all by the diabetic state at both week 4 and week 8. These results clearly demonstrate the active involvement of these antioxidant enzymes during the development of diabetes, and could be rationalized by the differential response of the tissues towards the different extent of oxidative stress imposed by the diabetic state on the different tissues.

Redox changes precede the occurrence of oxidative stress in eyes and aorta, but not in kidneys of diabetic rats.

Almost all diabetic complications are known to be associated with vascular dysfunctions of different tissues. Oxidative stress, on the other hand, has been implicated in the pathogenesis of diabetes mellitus. Therefore in the present study we have investigated the correlation between redox status and oxidative stress in the eyes, aorta and kidneys of streptozotocin (STZ)-induced diabetic rats. Glutathione (GSH), the primary endogenous antioxidant, and malondialdehyde (MDA), a marker of oxidative stress, were measured in these tissues of diabetic rats at different time points after STZ injection. Our results showed that GSH was reduced significantly in both the eyes and aorta of diabetic rats 8 weeks after STZ injection (43% and 66% of the control, respectively). Furthermore, the depletion of GSH occurred from the first week after STZ injection, and the level remained low as compared with the control rats (both week 1 and week 8: 43% and 66% of the control in the eyes and aorta, respectively). MDA was not increased until week 8 onwards after STZ-injection (177% and 93% of the control in the eyes and aorta, respectively). These changes, however, were not found in the kidneys, in which the GSH was slightly increased and MDA remained comparable to the control rats. These results indicate different tissues respond differently to high glucose conditions as redox changes and oxidative stress occurred only in the eyes and aorta but not in the kidneys of diabetic rats. In addition, the onset of oxidative stress is preceded by a depletion of GSH and probably an exhaustion of the antioxidant defense system. Furthermore, administration of Vitamin E was found to normalize MDA levels in the eyes and aorta but not in the kidneys of diabetic rats. In summary, our results suggest that the underlying mechanism in developing diabetic complications in the eyes and aorta involves the occurrence of oxidative stress, which may not be the case in diabetic kidneys. In addition, Vitamin E may prevent the development of diabetic complications in the eyes and aorta by reducing lipid peroxidation and oxidative damage in the cells.

Effectiveness of auricular therapy on sleep promotion in the elderly.

Sleep disturbances are a particularly common problem in the elderly. The purpose of this study was to examine the effectiveness of auricular therapy on sleep behaviors in the elderly. One hundred and twenty participants of 60 years old or above and who were suffering from sleep disturbances were invited to participate in this study. Eligible participants were randomly allocated to receive auricular therapy using Junci Medulla (Group A = 30), Semen Vaccariae (Group B = 30) or magnetic pearls (Group C = 60). Groups A and B were the control groups, while Group C was the experimental group. Seven auricular points which are thought to have an effect on promoting sleep were selected. The total treatment course lasted for three weeks. Objective measurement using actigraphic monitoring was performed before the therapy commenced, in the middle period of the therapy, and within one week after the therapy had been completed. After the therapy, there were significant differences among the three groups in terms of the nocturnal sleep time (NST) (F(2,117) = 6.84, p < 0.05) and sleep efficiency (SE) (F(2,117) = 7.69, p < 0.05). Significant improvement in the sleep behaviors was observed in the experimental group using magnetic pearls. In a backward multiple regression, the effect of auricular therapy on SE after allowing for age in female participants is of high statistical significance (F(3,106) = 9.04, p < 0.001). The paper concludes that auricular therapy using magnetic pearls is an effective means of improving the quantity and quality of sleep in the elderly.