John W. M. Yuen

Telomerase-Associated Apoptotic Events by Mushroom Ganoderma lucidum on Premalignant Human Urothelial Cells

The chemopreventive effects of Ganoderma lucidum was tested, using a tumorigenic transformable human urothelial cell (HUC-PC) model. These in vitro data show that G. lucidum can inhibit the viability and growth of HUC-PC. This could be explained by a concomitant induction of apoptosis and inhibition of telomerase activity. Significant exteriorization of phosphatidylserine was detected by Annexin-V on cell surface, and the cells subsequently lost membrane integrity for uptake of 7-amino-actinomycin D dye. Additionally, the levels of hydrogen peroxide and 8-hydroxy-2′-deoxyguanosine (8-OHdG) production of the apoptotic cells were significantly increased. The induction of apoptosis and suppression of telomerase activity help to explain the anti-HUC-PC growth properties; however, the induction of oxidative stress requires further study. This study strongly suggests that G. lucidum is a potential source of chemopreventive agents for bladder cancer based on its effectiveness in controlling the premalignant urothelial cell growth and carcinogen-induced transformation.

Guasha-induced hepatoprotection in chronic active hepatitis B: A case study

BACKGROUND Heme oxygenase-1 (HO-1) has demonstrated hepatoprotective effect in animal hepatitis models. HO-1 was also reported to be upregulated with Guasha, an ancient therapeutic technique which applies instrument assisted press-stroking to treat many disorders. METHODS We report a case on the changes of liver function, plasma HO-1 and T-helper (Th) cytokine balance in a chronic active hepatitis B carrier before and after Guasha. The patient presented with increased activities of liver enzymes (ALT and AST), indicating inflammatory damage in liver before Guasha. RESULTS Forty-eight hours after receiving Guasha, the patient showed changes in a number of serum markers: a decline of liver enzymes (ALT and AST) indicating reduced chronic inflammation, an elevated plasma HO-1, and a modulation of T-helper (Th)1/Th2 balance. CONCLUSIONS Guasha was shown to transiently reduce the inflammatory markers of liver injury in human, together with an enhancement of HO-1 which might be responsible for the hepatoprotective action.

The initial and subsequent inflammatory events during calcium oxalate lithiasis.

BACKGROUND Crystallization is believed to be the initiation step of urolithiasis, even though it is unknown where inside the nephron the first crystal nucleation occurs. METHODS Direct nucleation of calcium oxalate and subsequent events including crystal retention, cellular damage, endocytosis, and hyaluronan (HA) expression, were tested in a two-compartment culture system with intact human proximal tubular HK-2 cell monolayer. RESULTS Calcium oxalate dihydrate (COD) was nucleated and bound onto the apical surface of the HK-2 cells under hypercalciuric and hyperoxaluric conditions. These cells displayed mild cellular damage and internalized some of the adhered crystals within 18h post-COD-exposure, as revealed by electron microscopy. Prolonged incubation in complete medium caused significant damage to disrupt the monolayer integrity. Furthermore, hyaluronan disaccharides were detected in the harvested media, and were associated with HAS-3 mRNA expression. CONCLUSION Human proximal cells were able to internalize COD crystals which nucleated directly onto the apical surface, subsequently triggering cellular damage and HAS-3 specific hyaluronan synthesis as an inflammatory response. The proximal tubule cells here demonstrate that it plays an important role in facilitating urolithiasis via endocytosis and creating an inflammatory environment whereby free hyaluronan in tubular fluid can act as crystal-binding molecule at the later segments of distal and collecting tubules.

The differential immunological activities of Ganoderma lucidum on human pre-cancerous uroepithelial cells

AIMS OF THE STUDY Ganoderma lucidum is active to stimulate immunological effector cells, but the effects on uroepithelial cells have never been explored. The present study compared the expression of major cytokines induced by the water (GLw) and ethanol (GLe) extracts of G. lucidum. MATERIALS AND METHODS The pre-cancerous human uroepithelial cell (HUC-PC) line was employed. A total of 15 cytokines, including major Th1/Th2 cytokines and chemokines, were measured in the complete media after 24h incubation with GLw and GLe. Additionally, the following assays were performed: cytotoxicity, apoptosis, migration of neutrophils, and nuclear factor-kappaB (NF-κB) DNA binding activity. RESULTS GLe inhibited the growth of HUC-PC cells through apoptosis. Interleukins IL-2, IL-6, and IL-8 were significantly up-regulated by GLe in dose-dependent manners, but not by GLw. However, MCP-1 level was significantly increased by GLw but was oppositely reduced by GLe. Furthermore, the elevation of cytokine expression was correlated with the enhancement of p50/p65 NF-κB activity induced by GLe. The elevated IL-8 levels in GLe-treated cells were also correlated with the migration of neutrophils. CONCLUSIONS GLe and GLw exhibited different immunological activities on the HUC-PC cells. In particular, the activities of GLe may favor the clearance of high risk urothelial cells, suggesting potent chemopreventive ingredients are extractable by ethanol from G. lucidum.

Prevention and treatment of allergic inflammation by an Fcγ-Der f2 fusion protein in a murine model of dust mite-induced asthma

The immunoglobulin E (IgE) high-affinity receptor FcεRI expressed on mast cells and basophils plays a critical role in triggering allergic disease. The co-aggregation of the FcεRI and FcγRIIb receptors is inhibitory to FcεRI signaling and holds great potential for the treatment of IgE-mediated allergies. In China, Dermatophagoides farinae is a common anaphylaxis trigger. Therefore, in this study, the FcγRIIb-mediated immunomodulating activity of recombinant Fcγ-Der f2 fusion protein was tested in a Der f2-allergic murine model. Following the treatment, bronchoalveolar lavage fluid (BALF) was collected to measure the expression of several Th1/Th2-type cytokines (IL-5, TNF-α, IL-12p70, IL-4, IL-10, IFN-γ and IL-18) and histamine, while blood was used to detect the specific IgE and IgG-types anti-Der f2 antibodies, for measurement. In contrast to the saline-treated allergic mice, the levels of Der f2-specific IgE, cytokines and histamine were lowered in the Fcγ-Der f2-treated allergic mice, in addition to the rare inflammatory cell infiltration in the airways and blood vessels revealed by histopathological examination. The recombinant Fcγ-Der f2 protein was demonstrated to function as an effective immunotherapeutic agent, suggesting that chimeric human Fcγ-allergen proteins could be used in the development of antigen-specific immunotherapy for human allergic diseases.

Nutritional and immunological characteristics of fresh and refrigerated stored human milk in Hong Kong: a pilot study.

BACKGROUND The nutritional and immunological qualities of human milk from Hong Kong mothers were profiled. METHODS A total of 25 colostrum (≤ 3 days postpartum) and 11 mature (30-45 days postpartum) milk specimens were collected from healthy Chinese women in Hong Kong. Parameters including total protein, whey, casein, triglycerides, lactose, lysozyme, secretory immunoglobulin A, lactoferrin and antibacterial activity of human milk were quantified. RESULT Breast milk of Hong Kong Chinese mothers is nutritionally comparable to that of western mothers for colostrum and mature milk, with protein (25.0±11.3 g/l vs 10.1±1.4 g/l) and lactose (44.2±7.5 g/l vs 66.6±5.5 g/l) for growth and energy supply in infants, respectively. The milk of Hong Kong mothers is however characterized by its exceptionally high levels of sIgA (806.3±792.6 mg/dl and 1545.9±334.6 mg/dl) and low levels of triglycerides (10.8±9.3 mmol/l and 11.1±7.7 mmol/l). The human milk in Hong Kong was also shown to be superior to bovine formula milk, particularly in terms of lower total protein level, the high whey to casein protein ratio, rich immunological active contents, and significant antibacterial activity against 2 common Escherichia coli strains. CONCLUSIONS Preliminary data also indicated that mature milk could be refrigerated for at least 3 days in order to maintain the major nutritional constituents and antibacterial activity.

Methicillin-Resistant Staphylococcus aureus (MRSA) Contamination in Bedside Surfaces of a Hospital Ward and the Potential Effectiveness of Enhanced Disinfection with an Antimicrobial Polymer Surfactant

The aim in this study was to assess the effectiveness of a quaternary ammonium chloride (QAC) surfactant in reducing surface staphylococcal contamination in a routinely operating medical ward occupied by patients who had tested positive for methicillin-resistant Staphylococcus aureus (MRSA). The QAC being tested is an antibacterial film that is sprayed onto a surface and can remain active for up to 8 h. A field experimental study was designed with the QAC plus daily hypochlorite cleaning as the experimental group and hypochlorite cleaning alone as the control group. The method of swabbing on moistened surfaces was used for sampling. It was found that 83% and 77% of the bedside surfaces of MRSA-positive and MRSA-negative patients respectively were contaminated with staphylococci at 08:00 hours, and that the staphylococcal concentrations increased by 80% at 1200 h over a 4-hour period with routine ward and clinical activities. Irrespective of the MRSA status of the patients, high-touch surfaces around the bed-units within the studied medical ward were heavily contaminated (ranged 1 to 276 cfu/cm2 amongst the sites with positive culture) with staphylococcal bacteria including MRSA, despite the implementation of daily hypochlorite wiping. However, the contamination rate dropped significantly from 78% to 11% after the application of the QAC polymer. In the experimental group, the mean staphylococcal concentration of bedside surfaces was significantly (p < 0.0001) reduced from 4.4 ± 8.7 cfu/cm2 at 08:00 hours to 0.07 ± 0.26 cfu/cm2 at 12:00 hours by the QAC polymer. The results of this study support the view that, in addition to hypochlorite wiping, the tested QAC surfactant is a potential environmental decontamination strategy for preventing the transmission of clinically important pathogens in medical wards.

“Aging males” symptoms and general health of adult males: a cross-sectional study

Abstract A cross-sectional study was conducted to explore the prevalence and severity of health-related complaints perceived by adult males of Hong Kong by using the Hong Kong Traditional Chinese versions of the Aging males’ symptoms (AMS) scale and the 5-dimensional and 3-level European Quality of life (EQ-5D-3L) questionnaire. A total of 825 adult males aged 40 years or above were surveyed, and observed that 80% of the population was living with little-to-mild levels of aging symptoms with mean total scores ranged between 26.02 ± 7.91 and 32.99 ± 7.91 in different age groups. Such symptoms were correlated with age, especially for the somato-vegetative and sexual symptoms. The most severe AMS symptoms were observed in the oldest age group at 70 years or above, with 76%, 34% and 70% living with moderate-to-severe levels of somato-vegetative, psychological and sexual symptoms, respectively. The result was highly correlated with the EQ-5D-3L questionnaire. Secondly, the Hong Kong Aging males’ symptoms (AMS) scale was shown to have good reliability with test–retest coefficient at 0.79 (ranged 0.66–0.87) and Cronbach’s alpha coefficient at 0.88 (ranged 0.70–0.84). In summary, the population of Hong Kong male adults was commonly living with little-to-mild levels of aging symptoms, whereas their severity was correlated with age.

A survey on the prevalence and utilization characteristics of gua sha in the Hong Kong community

OBJECTIVE To conduct a community-based survey to describe the demographics, experience, and utilization variables among the users of gua sha living in Hong Kong. METHOD A total of 3209 adult respondents were surveyed by using a short Chinese questionnaire. RESULTS Gua sha was found to have a one-year prevalence of 22.7% and four-week prevalence of 6.6%. The users were seen to be old of age and less educated. The majority believed that gua sha is beneficial to health, practiced in non-regular basis, and mainly employed for treating illnesses. For both male and female, the top two common illnesses to be treated were the respiratory and pain problems, which accounting for 74% of all users. Other illnesses included nervousness, heat stroke, fever, infection, dizziness, diarrhoea and vomiting, oedema, and constipation. As practiced by most respondents, unidirectional pressured stroking was applied repeatedly on the lubricated skin surface at the back region using various smooth-edged tools typically spoons. Almost all users reported the occurrence of skin blemishing and subsequently faded within 7 days after the gua sha treatment. CONCLUSION The general population of Hong Kong was found to have high prevalence of gua sha usage. The utilization characteristics as reported by the users were generally aligned with the current scientific knowledge, in particular the treatment procedures and response.

Synergistic Cytotoxic Effects of Ganoderma lucidum and Bacillus Calmette Guérin on Premalignant Urothelial HUC-PC Cells and Its Regulation on Proinflammatory Cytokine Secretion

Bacillus Calmette-Guérin (BCG) is conventionally used as an adjuvant immunotherapy to reduce the recurrence of bladder cancer. To address the issues of efficacy and safety, an ethanol extract of Ganoderma lucidum (GLe) was evaluated for its interaction with BCG. In a model of premalignant human uroepithelial cells (HUC-PC), GLe exerted immediate cytotoxic effects while BCG showed a delayed response, given that both were immunological active in inducing the secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1 (MCP-1). Synergistic cytotoxic effects were observed when cells were either coincubated with both drugs or firstly preincubated with GLe. Synergism between GLe and BCG was demonstrated to achieve a complete cytostasis in 24 hours, and such effects were progressed in the subsequent 5 days. However, the pretreatment of GLe resulted in suppression of IL-6, IL-8, and MCP-1 secretions without affecting the cytotoxicity. Given that numerous proinflammatory cytokines are associated with the high side effects toll of BCG, results herein suggested the potential implications of GL to supplement the BCG immunotherapy in bladder cancer, for better efficacy and reducing side effects.