Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 70
Filter
Add more filters

Complementary Medicines
Country/Region as subject
Publication year range
1.
J Biomol Struct Dyn ; : 1-17, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-37997953

ABSTRACT

Cordyceps militaris has been long known for valuable health benefits by folk experience and was recently reported with diabetes-tackling evidences, thus deserving extending efforts on screening for component-activity relationship. In this study, experiments were carried out to find the evidence, justification, and input for computations on the potential against diabetes-related protein structures: PDB-4W93, PDB-3W37, and PDB-4A3A. Liquid chromatography identified 14 bioactive compounds in the ethyl acetate extract (1-14) and quantified the contents of cordycepin (0.11%) and adenosine (0.01%). Bioassays revealed the overall potential of the extract against α-amylase (IC50 = 6.443 ± 0.364 mg.mL-1) and α-glucosidase (IC50 = 2.580 ± 0.194 mg.mL-1). A combination of different computational platforms was used to select the most promising candidates for applications as anti-diabetic bio-inhibitors, i.e. 1 (ground state: -888.49715 a.u.; dipole moment 3.779 Debye; DS¯ -12.3 kcal.mol-1; polarizability 34.7 Å3; logP - 1.30), 10 (ground state: -688.52406 a.u.; dipole moment 5.487 Debye; DS¯ -12.6 kcal.mol-1; polarizability 24.9 Å3; logP - 3.39), and 12 (ground state: -1460.07276 a.u.; dipole moment 3.976 Debye; DS¯ -12.5 kcal.mol-1; polarizability 52.4 Å3; logP - 4.39). The results encourage further experimental tests on cordycepin (1), mannitol (10), and adenosylribose (12) to validate their in-practice diabetes-related activities, thus conducive to hypoglycemic applications.Communicated by Ramaswamy H. Sarma.

2.
Death Stud ; 44(3): 131-140, 2020.
Article in English | MEDLINE | ID: mdl-30523741

ABSTRACT

This study endeavors to investigate how healthcare workers, equipped with expressive arts methods, could foster life-death education for the elderly. Forty-nine older adults aged 60 or above joined a 10-session expressive arts-based life-death education program that was led by social workers equipped with expressive arts methods. An ethnographic research approach, with a post-treatment focus group (n = 17), was conducted with the participants. The results showed that expressive arts methods could enhance reorganization of life experiences, promote dealing with ambivalent emotion regarding life-death issues, improve communicating life-death issues with family members, and induce ideas to prepare for death.


Subject(s)
Art Therapy/methods , Attitude to Death , Aged , Attitude to Death/ethnology , Emotions , Female , Focus Groups , Humans , Male , Middle Aged , Qualitative Research , Social Work/methods
4.
Am J Hosp Palliat Care ; 35(9): 1207-1214, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29621892

ABSTRACT

In the recent decades, expressive arts (EXA) has been used in end-of-life care (EOLC) for facilitating the quality of life of the patients and the caregivers. However, it may not be practical for every EOLC service to dispense EXA activities solely by extensively trained art therapy specialists. There is currently a lack of brief training for nonart therapists, which may have stifled the application of the techniques in clinical settings. The current study therefore described and evaluated the effectiveness of a 2-day EXA training workshop in enhancing practice, knowledge, and self-competence among health and social care professionals working in EOLC using a mixed-method approach. The quantitative findings show significant improvement in perceived competence of providing services per holistic and person-centered EOLC objectives, nonpharmaceutical management of symptoms, and evidence-based psychosocial care as well as self-competence in death work (SCDW) after the workshop. The qualitative findings corroborated the quantitative results by suggesting that the improvement in competence could be associated with enhanced communication, meaning reconstruction, and therapeutic relationship with the clients as well as the improvement in mood, socialization, and self-esteem among the clients through the learned EXA activities. Our findings support the efficacy of a brief training of EXA activities for nonart therapists in enhancing multifaceted intervention competence. Further research on brief training will be needed to promote the use of EXA activities in the EOLC context.


Subject(s)
Art Therapy/education , Health Personnel/education , Inservice Training/organization & administration , Social Workers/education , Terminal Care/organization & administration , Adolescent , Adult , Clinical Competence , Communication , Emotions , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Patient-Centered Care/organization & administration , Quality of Life , Self Concept , Young Adult
5.
Dis Esophagus ; 30(9): 1-8, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28859363

ABSTRACT

Optimal interval between neoadjuvant chemoradiotherapy (CRT) and surgery is not elucidated for esophageal squamous carcinoma. The aim of this study is to evaluate the impact of this time interval on patient outcome. Patients treated with neoadjuvant CRT followed by surgery between 2002 and 2009 were analyzed. Patients were divided into two groups based on the median interval to surgery (64 days): A  64 days (n = 53). A second analysis was performed by re-classifying patients into three interval groups: A* ≤ 40 days (n = 16); B* 41-80 days (n = 60); C* > 80 days (n = 31). Operative outcome, pathological data, and long-term survival were analyzed. One hundred and seven (n = 107) patients were analyzed. Five patients (9.4%) in group B had an anastomotic leak compared with no leakage from group A (P < 0.021). The complete pathological response was comparable in groups A and B (35% vs. 24.5%, p = 0.23). R0 was significantly lower in group A* (A*: 56.3%, B*: 90%, C*: 74.2%, P = 0.006). In patients with R0 resection, 5-year survival was significantly better in group A than B (71.7% vs. 51%, P = 0.032) and in group A* (A* 100% vs. B* 60.2% & C* 48.3%; A* vs. B*, P = 0.036; A* vs. C*, P = 0.019). Complete pathological response was an independent predictor of survival. Early surgery with R0 resection following neoadjuvant CRT may lead to a better outcome. Further prospective studies are still necessary to provide better insight into the issue. At present, timing of surgery should be individualized and performed at the earliest opportunity.


Subject(s)
Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/therapy , Esophagectomy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy, Adjuvant , Cisplatin/administration & dosage , Esophagectomy/adverse effects , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm, Residual , Retrospective Studies , Survival Rate , Time Factors , Treatment Outcome , Young Adult
6.
Hong Kong Med J ; 23(1): 54-62, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27966431

ABSTRACT

INTRODUCTION: The use of adjuvant chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) has been shown to improve the outcome of patients with gastric cancer. There are limited data on the tolerability of S-1 in Chinese patients. In this multicentre retrospective study, we assessed the toxicity profile in local patients. METHODS: Patients with stage II-IIIC gastric adenocarcinoma who had undergone curative resection and who had received S-1 adjuvant chemotherapy were included in the study. Patient demographics, tumour characteristics, chemotherapy records, as well as biochemical, haematological, and other toxicity profiles were extracted from medical charts. Potential factors associated with grade 2-4 toxicities were identified. RESULTS: Adjuvant S-1 was administered to 30 patients. Overall, 19 (63%) patients completed eight cycles. The most common grade 3-4 adverse events included neutropaenia (10%), anaemia (6.7%), septic episode (16.7%), diarrhoea (6.7%), hyperbilirubinaemia (6.7%), and syncope (6.7%). Dose reductions were made in 22 (73.3%) patients and 12 (40.0%) patients had dose delays. Univariate analyses showed that patients who underwent total gastrectomy were more likely to experience adverse haematological events (P=0.034). Patients with nodal involvement were more likely to report adverse non-haematological events (P=0.031). Patients with a history of regular alcohol intake were more likely to have earlier treatment withdrawal (P=0.044). Lower body weight (P=0.007) and lower body surface area (P=0.017) were associated with dose interruptions. CONCLUSIONS: The tolerability of adjuvant S-1 in our patient population was similar to that in other Asian patient populations. The awareness of S-1-related toxicities and increasing knowledge of potential associated factors may enable optimisation of S-1 therapy.


Subject(s)
Adenocarcinoma/therapy , Antimetabolites, Antineoplastic/administration & dosage , Chemotherapy, Adjuvant , Oxonic Acid/administration & dosage , Stomach Neoplasms/therapy , Tegafur/administration & dosage , Adult , Aged , Aged, 80 and over , Anemia/etiology , Antimetabolites, Antineoplastic/adverse effects , Chemotherapy, Adjuvant/adverse effects , Drug Combinations , Female , Follow-Up Studies , Gastrectomy , Hong Kong , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neutropenia/etiology , Oxonic Acid/adverse effects , Retrospective Studies , Risk Factors , Survival Analysis , Tegafur/adverse effects , Treatment Outcome
7.
Int J Colorectal Dis ; 31(5): 1031-1038, 2016 May.
Article in English | MEDLINE | ID: mdl-27041554

ABSTRACT

PURPOSE: Hyperbaric oxygen treatment (HBOT) has been found to improve the healing of poorly oxygenated tissues. This study aimed to investigate the influence of HBOT on the healing in ischemic colorectal anastomosis. METHODS: Forty Wistar rats were randomly divided into a treatment group that received HBOT for 10 consecutive days (7 days before and 3 days after surgery), or in a control group, which did not receive the therapy. Colectomy with an ischemic anastomosis was performed in all rats. In each group, the rats were followed for 3 or 7 days after surgery to determine the influence of HBOT on anastomotic healing. RESULTS: Five rats from each group died during follow-up. No anastomotic dehiscence was seen in the HBOT group, compared to 37.5 % and 28.6 % dehiscence in the control group on postoperative day (POD) 3 and 7, respectively. The HBOT group had a significantly higher bursting pressure (130.9 ± 17.0 mmHg) than the control group (88.4 ± 46.7 mmHg; p = 0.03) on POD 3. On POD 3 and POD 7, the adhesion severity was significantly higher in the control groups than in the HBOT groups (p < 0.005). Kidney function (creatinine level) of the HBOT group was significantly better than of the control group on POD 7 (p = 0.001). Interestingly, a significantly higher number of CD206+ cells (marker for type 2 macrophages) was observed in the HBOT group at the anastomotic area on POD 3. CONCLUSION: Hyperbaric oxygen enhanced the healing of ischemic anastomoses in rats and improved the postoperative kidney function.


Subject(s)
Colon/surgery , Hyperbaric Oxygenation , Rectum/surgery , Wound Healing , Abdominal Abscess/blood , Abdominal Abscess/complications , Abdominal Abscess/etiology , Anastomosis, Surgical/adverse effects , Anastomotic Leak/blood , Anastomotic Leak/etiology , Animals , Cell Count , Creatinine/blood , Macrophages/pathology , Male , Rats, Wistar , Surgical Wound Dehiscence/blood , Surgical Wound Dehiscence/complications , Surgical Wound Dehiscence/etiology , Tissue Adhesions/blood , Tissue Adhesions/complications , Tissue Adhesions/pathology
8.
Int J Mol Med ; 35(2): 503-10, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25482299

ABSTRACT

Aspergillus niger (A. niger) is a common species of Aspergillus molds. Cutaneous aspergillosis usually occurs in skin sites near intravenous injection and approximately 6% of cutaneous aspergillosis cases which do not involve burn or HIV-infected patients are caused by A. niger. Biomaterials and biopharmaceuticals produced from microparticle-based drug delivery systems have received much attention as microencapsulated drugs offer an improvement in therapeutic efficacy due to better human absorption. The frequently used crosslinker, glutaraldehyde, in gelatin-based microencapsulation systems is considered harmful to human beings. In order to tackle the potential risks, agarose has become an alternative polymer to be used with gelatin as wall matrix materials of microcapsules. In the present study, we report the eco-friendly use of an agarose/gelatin-based microencapsulation system to enhance the antifungal activity of gallic acid and reduce its potential cytotoxic effects towards human skin keratinocytes. We used optimal parameter combinations, such as an agarose/gelatin ratio of 1:1, a polymer/oil ratio of 1:60, a surfactant volume of 1% w/w and a stirring speed of 900 rpm. The minimum inhibitory concentration of microencapsulated gallic acid (62.5 µg/ml) was significantly improved when compared with that of the original drug (>750 µg/ml). The anti-A. niger activity of gallic acid -containing microcapsules was much stronger than that of the original drug. Following 48 h of treatment, skin cell survival was approximately 90% with agarose/gelatin microcapsules containing gallic acid, whereas cell viability was only 25-35% with free gallic acid. Our results demonstrate that agarose/gelatin-based microcapsules containing gallic acid may prove to be helpful in the treatment of A. niger-induced skin infections near intravenous injection sites.


Subject(s)
Antifungal Agents/pharmacology , Aspergillosis/drug therapy , Aspergillus niger/growth & development , Dermatomycoses/drug therapy , Gallic Acid/pharmacology , Gelatin/pharmacology , Sepharose/pharmacology , Antifungal Agents/chemistry , Capsules , Cells, Cultured , Drug Evaluation, Preclinical , Gallic Acid/chemistry , Gelatin/chemistry , Humans , Keratinocytes/cytology , Keratinocytes/metabolism , Sepharose/chemistry
9.
Colloids Surf B Biointerfaces ; 117: 277-83, 2014 May 01.
Article in English | MEDLINE | ID: mdl-24657927

ABSTRACT

Gelatin/Collagen-based matrix and reservoir nanoparticles require crosslinkers to stabilize the formed nanosuspensions, considering that physical instability is the main challenge of nanoparticulate systems. The use of crosslinkers improves the physical integrity of nanoformulations under the-host environment. Aldehyde-based fixatives, such as formaldehyde and glutaraldehyde, have been widely applied to the crosslinking process of polymeric nanoparticles. However, their potential toxicity towards human beings has been demonstrated in many previous studies. In order to tackle this problem, D-glucose was used during nanoparticle formation to stabilize the gelatin/collagen-based matrix wall and reservoir wall for the deliveries of Calendula officinalis powder and oil, respectively. In addition, therapeutic selectivity between malignant and normal cells could be observed. The C. officinalis powder loaded nanoparticles significantly strengthened the anti-cancer effect towards human breast adenocarcinoma MCF7 cells and human hepatoma SKHep1 cells when compared with the free powder. On the contrary, the nanoparticles did not show significant cytotoxicity towards normal esophageal epithelial NE3 cells and human skin keratinocyte HaCaT cells. On the basis of these evidences, D-glucose modified gelatin/collagen matrix nanoparticles containing C. officinalis powder might be proposed as a safer alternative vehicle for anti-cancer treatments.


Subject(s)
Calendula/chemistry , Collagen/chemistry , Drug Delivery Systems , Gelatin/chemistry , Glucose/chemistry , Nanoparticles/chemistry , Plant Extracts/pharmacology , Animals , Antineoplastic Agents/pharmacology , Cell Death/drug effects , Cell Survival/drug effects , Humans , Keratinocytes/cytology , Keratinocytes/drug effects , MCF-7 Cells , Nanoparticles/ultrastructure , Particle Size , Plant Oils/pharmacology , Powders , Spectroscopy, Fourier Transform Infrared , Sus scrofa
10.
Complement Ther Med ; 21(4): 348-57, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23876566

ABSTRACT

OBJECTIVES: Previous studies have identified different, but highly correlated variables explaining the effects of mindfulness training. Many of them are limited by tautological explanation. Under the framework of the mind-body connection, mindfulness training cultivates body awareness and promotes self-management of illness. Stagnation, a concept from Chinese medicine, may help explain the mechanism of change in mindfulness training. METHODS: Individuals with depressive and anxiety symptoms (n=82) were randomized to either a Compassion-Mindfulness Therapy (C-MT) program or a waitlist control condition. The effect of stagnation as a mediator was investigated for dependent variables including depression, anxiety, and other physical and mental health variables. MAJOR OUTCOME MEASURES: Depression, anxiety, stagnation, physical distress, daily functioning, positive affect, negative affect. RESULTS: Compared with the participants in the control group, those who completed C-MT demonstrated significant decreases in depression, F(1, 78)=15.67, p<.001, anxiety, F(1, 78)=7.72, p<.001, stagnation, F(1, 78)=4.96, p<.001, and other body-mind-spirit well-being measures. After entering the change in stagnation as the mediator, the effect of treatment reduced: depression (.35-.22), anxiety (.33-.05), and same patterns in other three secondary measures. The Sobel test was administered and significant reductions between group and depression (z=2.18, p=.029), anxiety (z=2.21, p=.027), and three secondary other measures (p<.05) were indicated. CONCLUSION: The study provides initial support for the role of stagnation in mediating changes in mindfulness training. It adds evidence to body-mind nondualism and offers new possibilities in studying treatment process and change mechanism.


Subject(s)
Anxiety/therapy , Cognitive Behavioral Therapy/methods , Depression/therapy , Medicine, Chinese Traditional/methods , Mindfulness , Adult , Female , Humans , Male , Middle Aged
11.
Cell Death Dis ; 4: e720, 2013 Jul 11.
Article in English | MEDLINE | ID: mdl-23846222

ABSTRACT

Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump, leading to autophagy induction through the activation of the Ca(2+)/calmodulin-dependent kinase kinase-AMP-activated protein kinase-mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells.


Subject(s)
Antineoplastic Agents/pharmacology , Autophagy/drug effects , Oleanolic Acid/analogs & derivatives , Saponins/pharmacology , Sarcoplasmic Reticulum Calcium-Transporting ATPases/antagonists & inhibitors , Adenylate Kinase/metabolism , Animals , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Autophagy-Related Protein 7 , Beclin-1 , Binding Sites , Calcium/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism , Cell Line, Tumor , Class III Phosphatidylinositol 3-Kinases/metabolism , Membrane Proteins/metabolism , Mice , Models, Molecular , Oleanolic Acid/pharmacology , Signal Transduction , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/metabolism , Ubiquitin-Activating Enzymes/metabolism , Unfolded Protein Response/drug effects
12.
Curr Med Chem ; 19(32): 5513-23, 2012.
Article in English | MEDLINE | ID: mdl-22876919

ABSTRACT

In obesity, the expansion of dysfunctional adipose tissue leads to augmented production of pro-inflammatory adipokines that mediate metabolic changes through their paracrine and/or endocrine actions. By contrast, the secretion and plasma concentration of adiponectin, an adipokine with cardiovascular protective, anti-diabetic and anti-inflammatory properties, are markedly decreased in obesity and its related pathologies. Epidemiological studies on different ethnic groups have identified hypoadiponectinemia as an independent risk factor for type 2 diabetes, hypertension, coronary heart disease and several types of cancers. In animals, replenishment of recombinant adiponectin or transgenic expression of adiponectin can reverse these obesity-related pathological conditions. Although there is currently no direct clinical evidence demonstrating that adiponectin is effective in treating obesity-related cardiometabolic diseases, therapeutic benefits of several anti-diabetic and cardiovascular drugs, such as the agonists of peroxisome proliferator-activated receptor (PPAR) γ and PPAR α and statins, are associated with increased plasma adiponectin in humans. In addition, a number of medicinal herbs and natural compounds with beneficial effects on cardiometabolic diseases, have been shown to increase adiponectin secretion in adipocytes. This review highlights recent advances on multiple beneficial effects of adiponectin and discusses the potential therapeutic interventions for obesity-related cardiometabolic syndromes by targeting adiponectin.


Subject(s)
Adiponectin/metabolism , Obesity/metabolism , Adiponectin/chemistry , Animals , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Humans , Metabolic Diseases/etiology , Metabolic Diseases/metabolism , Obesity/complications , Signal Transduction
14.
Acta Psychiatr Scand ; 126(6): 440-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22533702

ABSTRACT

OBJECTIVE: To investigate the impact of a Western mental health training course for Traditional Chinese Medicine (TCM) practitioners. METHOD: A combined qualitative and quantitative approach was applied to examine the changes in the TCM practitioners' clinical practice characteristics and attitudes. Focus groups and structured questionnaire surveys were conducted to compare their responses before and after the Course. RESULTS: After a 10-week training course conducted by psychiatrists and family physicians, there were significant changes in confidence of the TCM practitioners for diagnosis (33% being confident before the Course vs. 76% after the Course) and management (24% vs. 55%) of common mental health problems. The causal effects of better classifications to recognition of mental health problems were explained by the qualitative responses. Proportion of TCM practitioners being confident of referring mental health patients to other healthcare professionals doubled from 25% to 50% after the Course. Nonetheless, there was no significant change in percentage of these patients being recommended to Western doctors owing to a lack of formal referral channel. CONCLUSIONS: Western mental health training for TCM practitioners has positive impact on their clinical practice. However, the practical barriers in making referrals highlight the need of closer collaboration between conventional and traditional medicine.


Subject(s)
Family Practice/standards , Medicine, Chinese Traditional/standards , Physicians, Family/education , Psychiatry/education , Adult , Focus Groups , Follow-Up Studies , Humans , Medicine, Chinese Traditional/psychology , Qualitative Research , Western World
15.
Curr Cancer Drug Targets ; 11(3): 254-84, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21247382

ABSTRACT

The proteasome has emerged as an important clinically relevant target for the treatment of hematologic malignancies. Since the Food and Drug Administration approved the first-in-class proteasome inhibitor bortezomib (Velcade) for the treatment of relapsed/refractory multiple myeloma (MM) and mantle cell lymphoma, it has become clear that new inhibitors are needed that have a better therapeutic ratio, can overcome inherent and acquired bortezomib resistance and exhibit broader anti-cancer activities. Marizomib (NPI-0052; salinosporamide A) is a structurally and pharmacologically unique ß-lactone-γ-lactam proteasome inhibitor that may fulfill these unmet needs. The potent and sustained inhibition of all three proteolytic activities of the proteasome by marizomib has inspired extensive preclinical evaluation in a variety of hematologic and solid tumor models, where it is efficacious as a single agent and in combination with biologics, chemotherapeutics and targeted therapeutic agents. Specifically, marizomib has been evaluated in models for multiple myeloma, mantle cell lymphoma, Waldenstrom's macroglobulinemia, chronic and acute lymphocytic leukemia, as well as glioma, colorectal and pancreatic cancer models, and has exhibited synergistic activities in tumor models in combination with bortezomib, the immunomodulatory agent lenalidomide (Revlimid), and various histone deacetylase inhibitors. These and other studies provided the framework for ongoing clinical trials in patients with MM, lymphomas, leukemias and solid tumors, including those who have failed bortezomib treatment, as well as in patients with diagnoses where other proteasome inhibitors have not demonstrated significant efficacy. This review captures the remarkable translational studies and contributions from many collaborators that have advanced marizomib from seabed to bench to bedside.


Subject(s)
Antineoplastic Agents/therapeutic use , Lactones/therapeutic use , Neoplasms/drug therapy , Protease Inhibitors/therapeutic use , Proteasome Inhibitors , Pyrroles/therapeutic use , Animals , Drug Evaluation, Preclinical , Humans , Neoplasms/metabolism , Proteasome Endopeptidase Complex/metabolism
16.
Phytother Res ; 24(7): 1056-64, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19960426

ABSTRACT

Psoriasis is a skin disease associated with hyperproliferation and aberrant differentiation of keratinocytes. Our previous studies have identified the root of Rubia cordifolia L. as a potent antiproliferative and apoptogenic agent in cultured HaCaT cells (IC(50) 1.4 microg/ml). In the present study, ethanolic extract of Radix Rubiae was fractioned sequentially with hexane, ethyl acetate (EA), n-butanol and water. EA fraction was found to possess most potent antiproliferative action on HaCaT cells (IC(50) 0.9 microg/ml). Mechanistic study revealed that EA fraction induced apoptosis on HaCaT cells, as it was capable of inducing apoptotic morphological changes. Annexin V-PI staining assay also demonstrated that EA fraction significantly augmented HaCaT apoptosis. In addition, EA fraction decreased mitochondrial membrane potential in a concentration- and time-dependent manner. The standardized EA fraction was formulated into topical gel and its keratinocyte-modulating action was tested on mouse tail model. EA fraction dose-dependently increased the number and thickness of granular layer and epidermal thickness on mouse tail skin, indicative of the keratinocyte differentiation-inducing activity. Taking the in vitro and in vivo findings together, the present preclinical study confirms that EA fraction is a promising antipsoriatic agent warranting further development for psoriasis treatment.


Subject(s)
Cell Differentiation/drug effects , Cell Proliferation/drug effects , Dermatologic Agents/pharmacology , Keratinocytes/drug effects , Plant Extracts/pharmacology , Rubia/chemistry , Acetates , Administration, Cutaneous , Animals , Cells, Cultured , Dermatologic Agents/administration & dosage , Humans , Male , Mice , Mice, Inbred BALB C , Plant Extracts/administration & dosage , Plant Roots/chemistry , Psoriasis/drug therapy
17.
Anal Chem ; 81(13): 5373-80, 2009 Jul 01.
Article in English | MEDLINE | ID: mdl-19563213

ABSTRACT

We explored two macromolecular scaffolds, bovine serum albumin (BSA) and polyvinyl alcohol (PVA), as chemically complementary platforms for immobilizing small molecule compounds on functionalized glass slides. We conjugated biotin molecules to BSA and amine-derivatized PVA and subsequently immobilized the conjugates on epoxy-functionalized glass slides through reaction of free amine residues on BSA and PVA with surface-bound epoxy groups. We studied binding reactions of such immobilized small molecule targets with solution-phase protein probes using an oblique-incidence reflectivity difference scanning optical microscope. The results showed that both BSA and amine-derivatized PVA were effective and efficient as carriers of small molecules with NHS residues and fluoric residues and for immobilization on epoxy-coated solid surfaces. A significant fraction of the conjugated small molecules retain their innate chemical activity.


Subject(s)
Ligands , Protein Array Analysis/methods , Serum Albumin, Bovine/chemistry , Animals , Biotin/chemistry , Biotin/immunology , Cattle , Immunoglobulin Fab Fragments/chemistry , Immunoglobulin Fab Fragments/immunology , Kinetics , Polyvinyl Alcohol/chemistry , Protein Binding
18.
BJOG ; 116(6): 789-97; discussion 797-8, 2009 May.
Article in English | MEDLINE | ID: mdl-19432567

ABSTRACT

OBJECTIVE: To test the hypothesis that iron supplement from early pregnancy would increase the risk of gestational diabetes mellitus (GDM). DESIGN: Randomised placebo-controlled trial. SETTING: A university teaching hospital in Hong Kong. POPULATION: One thousand one hundred sixty-four women with singleton pregnancy at less than 16 weeks of gestation with haemoglobin (Hb) level between 8 and 14 g/dl and no pre-existing diabetes or haemoglobinopathies. METHODS: Women were randomly allocated to receive 60 mg of iron supplement daily (n= 565) or placebo (n= 599). Oral glucose tolerance tests (OGTTs) were performed at 28 and 36 weeks. Women were followed up until delivery. OUTCOME MEASURES: The primary outcome was development of GDM at 28 weeks. The secondary outcomes were 2-hour post-OGTT glucose levels, development of GDM at 36 weeks and delivery and infant outcomes. RESULTS: There was no significant difference in the incidence of GDM in the iron supplement and placebo groups at 28 weeks (OR: 1.04, 95% confidence interval [CI]: 0.7-1.53 at 90% power) or 36 weeks. Maternal Hb and ferritin levels were higher in the iron supplement group at delivery (P < 0.001 and P= 0.003, respectively). Elective caesarean section rate was lower in the iron supplement group (OR: 0.58, 95% CI: 0.37-0.89). Infant birthweight was heavier (P= 0.001), and there were fewer small-for-gestational-age babies in the iron supplement group (OR: 0.46, 95% CI: 0.24-0.85). CONCLUSION: Iron supplement from early pregnancy does not increase the risk of GDM. It may have benefits in terms of pregnancy outcomes.


Subject(s)
Diabetes, Gestational/chemically induced , Dietary Supplements/adverse effects , Ferrous Compounds/adverse effects , Prenatal Care/methods , Adult , Anemia, Iron-Deficiency/prevention & control , Birth Weight , Delivery, Obstetric/methods , Female , Ferritins/blood , Ferrous Compounds/therapeutic use , Glucose Tolerance Test , Hemoglobins/metabolism , Humans , Infant, Newborn , Pregnancy , Pregnancy Complications, Hematologic/prevention & control , Pregnancy Outcome , Single-Blind Method
19.
Int J Mol Med ; 23(1): 121-9, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19082515

ABSTRACT

The anti-cancer effects of the anomalous fruit extract of Gleditsia sinensis (GSE) attributed to its apoptotic activity, telomerase inhibition and anti-angiogenesis in a panel of solid and non-solid tumor cell lines including esophageal squamous cell carcinoma (ESCC) have been intensively investigated by us in previous studies. Cyclooxygenase-2 (COX-2) has been well described as another promising target of cancer therapy for ESCC, and novel therapeutic agents are still being sought which target COX-2 expression. However, the anti-cancer effect of GSE through the suppression of COX-2 expression has not been previously investigated. In the present study, the anti-cancer effects of GSE on eight ESCC cell lines (KYSE 30, KYSE 150, KYSE 450, KYSE 510, KYSE 520, HKESC-3, HKESC-4 and SLMT-1) of Chinese and Japanese origins were first studied by MTS cytotoxicity assays. The effects of GSE on COX-2 expression levels and on the housekeeping form COX-1 were also investigated by multiplex RT-PCR analysis. Moreover, the anti-proliferative effect of GSE on KYSE 510 was also studied by anchorage-independent clonogenicity assay in soft agar. The results showed that GSE induced a dose- and time-dependent cytotoxicity on all of the eight ESCC cell lines and caused positive anti-proliferative action on KYSE 510 in the anchorage-independent clonogenicity assay, suggesting that GSE suppressed the in vitro growth of the ESCC cell lines. More importantly, the MRNA expression levels of COX-2, but not COX-1, in all of the ESCC cell lines were suppressed by GSE in a dose-dependent fashion. The overall results of the present study show that the anti-cancer effect of GSE on the ESCC cell lines is associated with the suppression of COX-2 expression, but not COX-1. Our findings also open a new chapter for the future advancement of GSE as a novel anti-cancer agent or as an adjuvant of traditional cancer treatments.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/drug therapy , Cyclooxygenase 2/genetics , Esophageal Neoplasms/drug therapy , Gleditsia/chemistry , Phytotherapy , Antineoplastic Agents/isolation & purification , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation , Cytotoxins/isolation & purification , Cytotoxins/pharmacology , Esophageal Neoplasms/enzymology , Esophageal Neoplasms/genetics , Fruit/chemistry , Gene Expression Regulation , Humans , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Reverse Transcriptase Polymerase Chain Reaction
20.
Singapore Med J ; 48(12): 1117-21, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18043839

ABSTRACT

INTRODUCTION: Calcium supplementation and pharmacotherapy are recommended in the preventive management of osteoporosis. Many previous studies report of underdiagnosis and undertreatment of osteoporosis among elderly patients with hip fractures. We undertook this study to determine the dietary calcium levels in our local elderly population who were admitted with hip fractures. METHODS: 77 patients, between the ages of 60 and 98 years of age, and admitted to our department between January 2001 and September 2001 for hip fractures, were studied. The dietary calcium intakes of these patients were determined by a food frequency questionnaire and a detailed diet history. Bone mineral density (BMD) studies were performed on 55 of these patients to confirm the diagnosis of osteoporosis. RESULTS: The mean daily calcium intake was found to be 650 mg. Only six of our hip fracture patients (7.8 percent) had a daily calcium intake above the recommended levels of 1,000 mg per day. For the 55 patients who had BMD performed, only one patient had a BMD within the normal range. 34 patients (64.2 percent) had hip T-scores in the osteoporotic range and 18 patients (33.9 percent) had hip T-scores in the osteopenic range. We found that the patients with BMD in the osteoporotic and osteopenic ranges had no significant difference in the dietary calcium intake. CONCLUSION: The dietary calcium intake of our elderly patients with hip fractures is insufficient. They would benefit from dietary education and calcium supplements to prevent deterioration in bone density and subsequent osteoporotic fractures.


Subject(s)
Bone Density/drug effects , Calcium, Dietary/administration & dosage , Fractures, Spontaneous/prevention & control , Hip Fractures/prevention & control , Osteoporosis/prevention & control , Age Factors , Aged , Aged, 80 and over , Bone Density/physiology , Cohort Studies , Dietary Supplements/statistics & numerical data , Female , Fractures, Spontaneous/epidemiology , Fractures, Spontaneous/physiopathology , Geriatric Assessment , Hip Fractures/epidemiology , Hip Fractures/physiopathology , Humans , Male , Middle Aged , Nutritional Requirements , Nutritional Status , Osteoporosis/epidemiology , Osteoporosis/physiopathology , Risk Assessment , Sex Factors , Singapore
SELECTION OF CITATIONS
SEARCH DETAIL