Sulforaphane (1-isothiocyanato-4-(methylsulfinyl)-butane), belonging to a family of natural compounds that are abundant in broccoli, has received significant therapeutic interest in recent years. However, the molecular basis of its effects remains to be elucidated. In this study, we attempt to determine whether sulforaphane regulates the inflammatory response in an ovalbumin (OVA)-induced murine asthma model. Mice were sensitized with OVA, treated with sulforaphane, and then challenged with OVA. Sulforaphane administration significantly alleviated the OVA-induced airway hyperresponsiveness to inhaled methacholine. Additionally, sulforaphane suppressed the increase in the levels of SOCS-3 and GATA-3 and IL-4 expression in the OVA-challenged mice. Collectively, our results demonstrate that sulforaphane regulates Th2 immune responses. This sutdy provides novel insights into the regulatory role of sulforaphane in allergen-induced Th2 inflammation and airway responses, which indicates its therapeutic potential for asthma and other allergic diseases.
Kobet, Robert A.;Pan, Xiaoping;Zhang, Baohong;Pak, Stephen C.;Asch, Adam S.;Lee, Myon-Hee
Biomolecules & Therapeutics
/
제22권5호
/
pp.371-383
/
2014
The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.
Neural progenitor cells (NPCs) differentiate into astrocytes, neurons and oligodendrocytes, which is controlled by various factors in brain. Recent evidences suggest that small molecules modulating the proliferation and differentiation of NPCs may have therapeutic value as well as the potential use as chemical probes. Phylligenin is a lignan with anti-inflammatory activity that is isolated from the fruits of Forsythia koreana. We investigated effects of phylligenin on proliferation and differentiation of NPCs. Treatment of phylligenin decreased the number of proliferating NPCs in culture without effects on the differentiation and survival of neural cells such as neurons and astrocytes. To examine the mechanism of the decreased NPCs number, we performed cell cycle analysis. Proliferation of NPCs was decreased via G1-S transition block by phylligenin treatment, and it was mediated by the increase of p21 level. However, phylligenin did not induce apoptosis of NPCs as determined by TUNEL assay and PARP cleavage. We also found that viability of glioma cell lines such as C6 and U87MG glioma cells, but not that of primary neuron and astrocyte, was inhibited by phylligenin. These results suggest that phylligenin selectively inhibits proliferation of rapidly growing cells such as neural stem cells and glioma cells. Given that the possible role of brain tumor stem cells in the pathology of brain cancers, the inhibitory effects of phylligenin might be useful in the development of new therapeutic agents against brain cancers.
The production of therapeutic proteins from transgenic animals is one of the most important successes of animal biotechnology. Milk is presently the most mature system for production of therapeutic proteins from a transgenic animal. Specifically, ${\beta}$-casein is a major component of cow, goat and sheep milk, and its promoter has been used to regulate the expression of transgenic genes in the mammary gland of transgenic animals. Here, we cloned the porcine ${\beta}$-casein gene and analyzed the transcriptional activity of the promoter and intron 1 region of the porcine ${\beta}$-casein gene. Sequence inspection of the 5'-flanking region revealed potential DNA elements including SRY, CdxA, AML-a, GATA-3, GATA-1 and C/EBP ${\beta}$. In addition, the first intron of the porcine ${\beta}$-casein gene contained the transcriptional enhancers Oct-1, SRY, YY1, C/EBP ${\beta}$, and AP-1, as well as the retroviral TATA box. We estimated the transcriptional activity for the 5'-proximal region with or without intron 1 of the porcine ${\beta}$-casein gene in HC11 cells stimulated with lactogenic hormones. High transcriptional activity was obtained for the 5'-proximal region with intron 1 of the porcine ${\beta}$-casein gene. The ${\beta}$-casein gene containing the mutant TATA box (CATAAAA) was also cloned from another individual pig. Promoter activity of the luciferase vector containing the mutant TATA box was weaker than the same vector containing the normal TATA box. Taken together, these findings suggest that the transcription of porcine ${\beta}$-casein gene is regulated by lactogenic hormone via intron 1 and promoter containing a mutant TATA box (CATAAAA) has poor porcine ${\beta}$-casein gene activity.
Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in older men. WSY-0702 is the extracted from the traditional medicinal plant; Seoritae, and it has effects of anti-obesity, chronic cervical pain, and anti-oxidant. The present study aimed to investigate the therapeutic potential of WSY-0702 in the prevention and treatment of BPH. Several parameters including inflammatory mediators, hormones, and oxidative stress (OS) have been considered to play a role in the development of BPH. Prostate tissue damage and OS may lead to compensatory cellular proliferation with resulting hyperplastic growth. An in vitro study showed that proliferation inhibited the human prostate epithelial cell line RWPE-1 in a dose-dependent manner. In cell line, the cell cycle at the G2/M and G0/G1 phase and downregulated the expression of CyclineB1 (CCNB1) and CyclineD1 (CCND1). In addition, we measured the $H_2O_2$-induced OS damage using RWPE-1 cells. We examined the relative expression of protein involved in the regulation of prostate apoptosis: transforming growth factor (TGF)-${\beta}$, a negative growth factor able to induced prostate apoptosis under physiological conditions. These results suggest that WSY-0702 that can inhibit the growth of prostate epithelial cell by a mechanism that may involve arresting the cell cycle and downregulating CCNB1 and CCND1 expression. In addition, WSY-0702 exposure resulted in significant protective effects in $H_2O_2$-stressed PWPE-1 cells by reduction in TGF-${\beta}$ levels.
Imperata cylindrica, a tall tufted grass which has multiple pharmacological applications is one of the key ingredients in various traditional medicinal formula used in India. Previous reports have shown that I. cylindrica plant extract inhibited cell proliferation and induced apoptosis in various cancer cell lines. To our knowledge, no studies have been published on the effect of I. cylindrica leaf extract on human oral cancers. The present study was undertaken in order to evaluate the anticancer properties of the leaf extract of I. cylindrica using an oral squamous cell carcinoma cell line SCC-9 as an in vitro model system. A methanol extract from dried leaves of I. cylindrica (ICL) was prepared by standard procedures. Effects of the ICL extract on the morphology of SCC-9 cells was visualized by microscopy. Cytotoxicity was determined by MTT assay. Effects of the ICL extract on colony forming ability of SCC-9 cells was evaluated using clonogenic assay. Cell cycle analysis was performed by flow cytometry and induction of apoptosis was determined by DNA fragmentation assay. The ICL extract treatment caused cytotoxicity and induced cell death in vitro in SCC-9 cells in a dose-dependent manner. This treatment also significantly reduced the clonogenic potential and inhibited cell proliferation by arresting the cell cycle in the G2/M phase. Furthermore, DNA fragmentation assays showed that the observed cell death was caused by apoptosis. This is the first report showing the anticancer activity of the methanol extracts from the leaves of I. cylindrica in human oral cancer cell line. Our data indicates that ICL extract could be considered as one of the lead compounds for the formulation of anticancer therapeutic agents to treat/manage human oral cancers. The natural abundance of I. cylindrica and its wide geographic distribution could render it one of the primary resource materials for preparation of anticancer therapeutic agents.
Objectives : Contents regarding Qiuzimen as found in Beijiqianjinyaofang and Qianjinyifang were studied for their potentialities to be applied to infertility clinics. Methods : The contents on Qiuzimen in Beijiqianjinyaofang and Qianjinyifang are pondered upon after dividing into two categories of medical theory and therapeutic principle, and other related texts and dissertations are further studied to discover a potential subject matter in being applied to today's modern clinics. Results : 1. In medical theory, Sunsimiao picked five overexertions and seven damages as the main medical cause of infertility. For remedy, he established four common formula, which are: chinjasan, bakchotangpotang, suppository, and haseog(cheon)moondongwhan. 2. There are total of thirteen types of formula described in the Qiuzimen in Beijiqianjinyaofang and Qianjinyifang, and five acupuncture points are used in the moxibustion method. After analyzing the herbs that were used six or more times, it was discovered that medicines were used to tonify the viscera of heart and kidney that are damaged through five overexertions and seven damages. In moxibustion method, different points such as CV4, LR14, pomoon, cheonmoon, and KI2, which is the point for kidney meridian were used in order to tonify the uterus through lower abdomen area and reproductive organs. 3. Qiuzimen has not only had a great impact on the infertility treatment as found in Furendaquanliangfang, which is the first gynecology text in Song dynasty, but it also had a continuous impact on medical texts in Ming and Qing dynasty. 4. The infertility therapeutic principle and approach method as found in the Qiuzimen are still relevant in today's modern infetility treatment. Conclusions : In the Qiuzimen of Beijiqianjinyaofang and Qianjinyifang, the problem of infertility is viewed as the whole body's problem, namely a type of defective disease caused by five overexertions and seven damages, the view of which should be applied to today's modern clinics.
Objectives: The aim of this study was to review main symptoms of outpatient in Lee young Jun clinics who developed the functional cerebrospinal therapy and to investigate the therapeutic effects on one time application of functional cerebrospinal therapy (FCST). Methods: Patients who visited at least twice at an oriental medical clinic and treated with FCST were included. They were asked to write 216 numeric rating scale (NRS)-based questionnaire about degree of various symptoms at each visit. Prevalence and degree decrease of all reported symptoms were analyzed. Results: Total of 744 outpatients were included. There were fourteen symptoms of which more than half of all patients commonly complained. All symptoms were significantly reduced after one administration of FCST. About four to seven percent of patients reported at least five-point reduction on NRS in each symptom after FCST. Conclusions: FCST might have potential immediate effect on not only TMJ related symptoms, but also diverse kinds of pain, psychological symptoms, and fatigue-related symptoms.
Therapeutic garments are an undeveloped area and yet they have the potential to generate considerable profit for the fashion industry. In traditional Chinese medicine, there are spots and pathways on the body through which energy flows and practitioners consider that disease results when this energy flow is hindered. Clothes which stimulate the spots can therefore potentially help to cure disease. In addition, clothes are worn every day and can therefore offer prolonged treatment certainly in comparison with other treatments. Obesity is a big problem nowadays and one which is caused by poor energy circulation (according to TCM). A garment which stimulates the spots can assist energy flow and therefore cause the wearer to lose weight. In the process, it can also alleviate side effects of obesity such as diabetes and high blood pressure. The was to stimulate spots include acupuncture, acupressure, moxibustion etc. There are lots of products to press spots which improve energy flow both in the Western and Chinese markets. The basic principle of circulation is in fact the same in both Western and Chinese medicine. However, most of these are products are footwear ones because they can easily provide the necessary stimulation to reduce tiredness and improve circulation. For garments, to press the spots effectively it is best to use tight clothes such as corsets and leggings. The important point is to tighten the body and to make energy flow and yet feel comfortable at the same time. Choice of fabric is therefore an important issue. Although the idea has been introduced, it will be necessary to develop a technique which will allow the necessary amount of pressure to be applied. It could be concluded that this area has a lot of possibility for the future but further research will need to be done before the idea becomes workable.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder on the large intestine that has been considered as an incurable not only in Western society but also in Eastern Asia in recent years. Despite enormous efforts to develop novel therapeutics for this disease, strategy using bioactive compounds from natural product is still considered as important. p-hydroxycinnamic acid (HCA) is an intermediate substance found in several plants and has been known to possess anti-inflammation but little evidence is reported whether HCA has an inhibitory effect on intestinal inflammation. In the present study, we observed HCA does not show cytotoxic and apoptotic in HT-29 cells. Quantitative PCR analysis revealed that HCA effectively blocks the activity of HT-29 cells stimulated with TNF-α treatment. HCA inhibits translocation of p65 and MAPK pathways in activated HT-29 cells by TNF-α treatment. Besides, oral administration of HCA attenuates manifestation of DSS-induced inflammatory disease in vivo. Histological analysis exhibited that oral administration of HCA recovers IBD symptoms. The expression of pro-inflammatory cytokines were reduced by oral administration of HCA on intestinal tissues. Therefore, these results suggest that HCA has a potent anti-inflammatory effect on intestinal cells as well as show a therapeutic potential for treating IBD in vivo.
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