ABSTRACT
OBJECTIVE: Endometriosis, defined as the growth of endometrial glands and stromal cells in a heterotopic location under the cyclic influence of ovarian hormones, is a common gynecological disorder manifested by chronic pelvic pain and infertility. In traditional Chinese medicine, endometriosis is characterized by stagnation of vital energy (qi) and blood stasis. Guizhi Fuling Wan (GFW) was first described in Chinese canonical medicine to treat disorders associated with stagnation of qi and blood stasis, including endometriosis. Therefore, the current study aimed to test the effects of combining GFW with western medicine on the suppression of endometriosis. MATERIALS AND METHODS: Endometriosis was generated by suturing endometrial tissue on the peritoneal wall of C57BL/6JNarl mice. The mice were subsequently treated with either GFW or current hormonal therapies or in combination for 28 days. RESULTS: Endometriosis development was inhibited by GFW, Gestrinone, Visanne, GFW + Gestrinone or GFW + medroxyprogesterone acetate (MPA). The expression of intercellular adhesion molecule 1 (ICAM-1) was inhibited by GFW, Gestrinone, MPA, Visanne, GFW + Gestrinone, GFW + MPA and GFW + Visanne. Vascular endothelial growth factor (VEGF) expression was inhibited by GFW, Gestrinone, Visanne, GFW + Gestrinone and GFW + MPA. Both ICAM-1- and VEGF-reducing effects of GFW were attenuated by western medicines. Administration of GFW, MPA, Visanne, GFW + MPA and GFW + Visanne also correspondingly reduced macrophage population in peritoneal fluid. GFW, MPA, Visanne, GFW + MPA and GFW + Visanne enhanced B-cell population in peritoneal fluid. CONCLUSION: The current study reveals the therapeutic effects of GFW on endometriosis. However, the combination of GFW and current hormonal therapies potentially impedes the efficacy of each individual agent in treating endometriosis.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Endometriosis/drug therapy , Gestrinone/therapeutic use , Intercellular Adhesion Molecule-1/drug effects , Medroxyprogesterone Acetate/therapeutic use , Vascular Endothelial Growth Factor A/drug effects , Animals , Female , Mice , Mice, Inbred C57BLABSTRACT
In vitro testing of drug compounds on cell models during the drug development process represents an indispensable step in the initial screening process. Although drug testing on three-dimensional (3D) cultured cells may provide a more accurate prediction of drug efficacy, it is relatively costly and time-consuming to perform compared with conventional 2D cultures due to the thick z-axis of the 3D models. In this study, we have presented a microfluidic platform with integrated pneumatic valves for producing a thin-gel 3D cell culture-based combinatorial drug screening array (3D-µCDS array). The multilayer architecture and microfluidic layout has a smaller device footprint than a single-layer microfluidic channel arrangement, making it well suited to scaling up for high-throughput combinatorial drug screening on 3D cell model. We performed 8 × 8 combination drug screening experiments with the device using two anti-cancer drugs (doxorubicin and paclitaxel) on MDA-MB-231 and MCF-7 breast cancer cell lines for demonstration. Our results indicate that our 3D-µCDS array device allows the successful screening of multiple drug combinations while reducing the operation time and the number of sample/reagents required, making it an ideal tool for general combinatorial drug screening, as well as for applications using valuable tissues and clinical samples.
Subject(s)
Cell Culture Techniques/methods , Combinatorial Chemistry Techniques , Drug Evaluation, Preclinical , Microfluidics/methods , Animals , Collagen/pharmacology , Diffusion , Equipment Design , Extracellular Matrix/chemistry , Fluorescence , Gels/chemistry , High-Throughput Screening Assays , Humans , Inhibitory Concentration 50 , Microfluidics/instrumentation , Rats , Tumor Cells, CulturedABSTRACT
BACKGROUND: Long-term, sustained progress is necessary in drop foot rehabilitation. The necessary inconvenient body training movements, the return trips to the hospital and repetitive boring training using functional electrical stimulation (FES) often results in the patient suspending their training. The patient's drop foot rehabilitation will not progress if training is suspended. OBJECTIVE: A fast spread, highly portable drop foot rehabilitation training device based on the smart phone is presented. This device is combined with a self-made football APP and feedback controlled FES. The drop foot patient can easily engage in long term rehabilitation training that is more convenient and interesting. METHODS: An interactive game is established on the smart phone with the Android system using the originally built-in wireless communications. The ankle angle information is detected by an external portable device as the game input signal. The electrical stimulation command to the external device is supplemented with FES stimulation for inadequate ankle efforts. RESULTS: After six-weeks training using six cases, the results indicated that this training device showed significant performance improvement (p< 0.05) in the patient's ankle dorsiflexion strength, ankle dorsiflexion angle, control timing and Timed Up and Go. CONCLUSIONS: Preliminary results show that this training device provides significant positive help to drop foot patients. Moreover, this device is based on existing and universally popular mobile processing, which can be rapidly promoted. The responses of clinical cases also show this system is easy to operate, convenient and entertaining. All of these features can improve the patient's willingness to engage in long term rehabilitation.
Subject(s)
Electric Stimulation Therapy , Football , Gait Disorders, Neurologic/rehabilitation , Mobile Applications , Smartphone , Adult , Aged , Aged, 80 and over , Electric Stimulation Therapy/methods , Electric Stimulation Therapy/psychology , Humans , Middle Aged , Patient ComplianceABSTRACT
The human enteroendocrine L cell line NCI-H716, expressing taste receptors and taste signaling elements, constitutes a unique model for the studies of cellular responses to glucose, appetite regulation, gastrointestinal motility, and insulin secretion. Targeting these gut taste receptors may provide novel treatments for diabetes and obesity. However, NCI-H716 cells are cultured in suspension and tend to form multicellular aggregates, preventing high-throughput calcium imaging due to interferences caused by laborious immobilization and stimulus delivery procedures. Here, we have developed an automated microfluidic platform that is capable of trapping more than 500 single cells into microwells with a loading efficiency of 77% within two minutes, delivering multiple chemical stimuli and performing calcium imaging with enhanced spatial and temporal resolutions when compared to bath perfusion systems. Results revealed the presence of heterogeneity in cellular responses to the type, concentration, and order of applied sweet and bitter stimuli. Sucralose and denatonium benzoate elicited robust increases in the intracellular Ca(2+) concentration. However, glucose evoked a rapid elevation of intracellular Ca(2+) followed by reduced responses to subsequent glucose stimulation. Using Gymnema sylvestre as a blocking agent for the sweet taste receptor confirmed that different taste receptors were utilized for sweet and bitter tastes. This automated microfluidic platform is cost-effective, easy to fabricate and operate, and may be generally applicable for high-throughput and high-content single-cell analysis and drug screening.
Subject(s)
High-Throughput Screening Assays/methods , Lab-On-A-Chip Devices , Receptors, G-Protein-Coupled/metabolism , Single-Cell Analysis/methods , Taste Perception/drug effects , Time-Lapse Imaging/methods , Calcium/agonists , Calcium/metabolism , Calcium Signaling/drug effects , Cell Line , Enteroendocrine Cells/cytology , Enteroendocrine Cells/drug effects , Enteroendocrine Cells/metabolism , Glucose/antagonists & inhibitors , Glucose/pharmacology , Gymnema sylvestre/chemistry , High-Throughput Screening Assays/instrumentation , Humans , Models, Biological , Plant Extracts/chemistry , Plant Extracts/pharmacology , Quaternary Ammonium Compounds/pharmacology , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/antagonists & inhibitors , Single-Cell Analysis/instrumentation , Sucrose/analogs & derivatives , Sucrose/pharmacology , Taste/drug effects , Taste/physiology , Taste Perception/physiology , Time-Lapse Imaging/instrumentationABSTRACT
PURPOSE: Many patients who suffer from spinal cord injuries with paraplegia cannot recover to walk independently. They need to use a special walking orthoses to support their body to walk properly. Traditionally, long leg braces (LLB) were fitted to patients for walking. Unfortunately, the results were not satisfactory as this device supplies adequate support with less than optimum mobility. This study used the latest reciprocating gait orthosis (RGO) combined with functional electrical stimulation (FES). This combination provides a greater support range while applying assistant mechanical walking structures. The FES co-ordination helps restore natural walking abilities that the paralysed patient has lost. METHOD: This study developed a walking orthosis with FES, using FES to stimulate specific muscles (quadriceps, hamstring) in the paralysed patients' lower limbs. The proposed method can achieve the benefits of physical therapeutics while paralysed patients can achieve the purpose of walking. The FES is designed with control buttons on the walking orthosis. A patient can control the left or right leg in walking and speed control via the control buttons. RESULTS: Several practical tests were conducted on the new walking orthosis. A 25-year-old female paralysed patient (L1 complete spinal cord injury) used traditional LLB, RGO and RGO with FES to proceed with walking rehabilitation and clinical assessment. Heart rate difference (HRdifference), mean blood pressure (MBPdifference), walking speed, length of steps, number of steps and oxygen consumption comparisons were made before and after walking. The results show that RGO and RGO with FES were both better than LLB. However, the differences between RGO and RGO with FES in HRdifference, MBPdifference, and walking speed were not significant. This is because the patient's right leg reaction to the electrical stimulation was relatively low. DISCUSSION AND CONCLUSIONS: In general, RGO can help the patient achieve quicker and more independent walking. The combination of RGO and FES can increase the effectiveness of RGO for more mobile aid. These two walking orthoses are better than traditional LLB. Both methods provide patients who suffer from paraplegia with better choices.