Nowadays, depression is a serious psychological disorder that causes extreme economic loss and social problems. Previously, we discovered that the water extract of Gastrodia elata Blume (WGE) improved depressive-like behavior by influencing neurotransmitters in rats subjected to the forced swimming test. To elucidate possible mechanisms, in the present study, we performed a proteomics and bioinformatics analysis to identify the related pathways. Western blot-validated results indicated that the core protein network modulated by WGE administration was closely associated with down-regulation of the Slit-Robo pathway, which modulates neuronal cytoskeletal remodeling processes. Although Slit-Robo signaling has been well investigated in neuronal development, its relationship with depression is not fully understood. We provide a potential hint on the mechanism responsible for the antidepressive-like activity of WGE. In conclusion, we suggest that the Slit-Robo pathway and neuronal cytoskeleton remodeling are possibly one of the pathways associated with the antidepressive-like effects of WGE.
This study investigated the protective properties of garlic essential oil (GEO) and its major organosulfur component (diallyl disulfide, DADS) against the development of nonalcoholic fatty liver disease (NAFLD). C57BL/6J mice were fed a normal or high-fat diet (HFD) with/without GEO (25, 50, and 100 mg/kg) or DADS (10 and 20 mg/kg) for 12 weeks. GEO and DADS dose-dependently exerted antiobesity and antihyperlipidemic effects by reducing HFD-induced body weight gain, adipose tissue weight, and serum biochemical parameters. Administration of 50 and 100 mg/kg GEO and 20 mg/kg DADS significantly decreased the release of pro-inflammatory cytokines in liver, accompanied by elevated antioxidant capacity via inhibition of cytochrome P450 2E1 expression during NAFLD development. The anti-NAFLD effects of GEO and DADS were mediated through down-regulation of sterol regulatory element binding protein-1c, acetyl-CoA carboxylase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as stimulation of peroxisome proliferator-activated receptor ? and carnitine palmitoyltransferase-1. These results demonstrate that GEO and DADS dose-dependently protected obese mice with long-term HFD-induced NAFLD from lipid accumulation, inflammation, and oxidative damage by ameliorating lipid metabolic disorders and oxidative stress. The dose of 20 mg/kg DADS was equally as effective in preventing NAFLD as 50 mg/kg GEO containing the same amount of DADS, which demonstrates that DADS may be the main bioactive component in GEO.
To evaluate the associations between cyberbullying behaviors and problematic internet use, and to compare psychopathologic symptoms in victims, perpetrators, and victims-perpetrators of cyberbullying to those in youths who were not involved in cyberbullying. A total of 4531 youths (11-14 years of age) were recruited from elementary and middle schools. Among 4531 youths, 9.7% were involved in cyberbullying; 3.3% were only victims; 3.4% were only perpetrators; and 3.0% were victims-perpetrators. Cyberbullying behaviors were associated with problematic internet use as well as various psychopathologic symptoms. Depressive symptoms were associated with cyberbullying victimization, and rule-breaking behaviors and aggressive behaviors have relevance to cyberbullying perpetration. Greater attention needs to be paid to identify youths earlier who are involved in cyberbullying and prevent serious adverse consequences in them.
Bitter gourd (Momordica charantia L.) is a common vegetable grown widely in Asia that is used as a traditional medicine. The objective of this study was to investigate whether wild bitter gourd possessed protective effects against chronic alcohol-induced liver injury in mice. C57BL/6 mice were fed an alcohol-containing liquid diet for 4 weeks to induce alcoholic fatty liver. Meanwhile, mice were treated with ethanol extracts from four different wild bitter gourd cultivars: Hualien No. 1', Hualien No. 2', Hualien No. 3' and Hualien No. 4'. The results indicated that the daily administration of 500 mg kg body weight(-1) of a Hualien No. 3' extract (H3E) or a Hualien No. 4' extract (H4E) markedly reduced the steatotic alternation of liver histopathology. In addition, the activation of serum aminotransferases (AST and ALT) and the accumulation of hepatic TG content caused by alcohol were ameliorated. The hepatoprotective effects of H3E and H4E involved the enhancement of the antioxidant defence system (GSH, GPx, GRd, CAT and SOD), inhibition of lipid peroxidation (MDA) and reduction of pro-inflammatory cytokines (TNF-?, IL-1? and IL-6) in the liver. Moreover, H3E and H4E supplementation suppressed the alcohol-induced elevation of CYP2E1, SREBP-1, FAS and ACC protein expression. These results demonstrated that ethanol extracts of Hualien No. 3' and Hualien No. 4' have beneficial effects against alcoholic fatty liver, in which they attenuate oxidative stress and inflammatory responses.
Head and neck cancer is a critical global health problem and approximately 650,000 patients per year are diagnosed with this type of cancer. In addition, head and neck cancer exhibits a high recurrence rate, readily causing second primary cancers in other locations, often yielding a poor prognosis. Current medical and surgical treatment options result in considerable impairment of speaking and swallowing functions, with side effects such as nausea, vomiting, bone marrow suppression, and renal damage, thereby impairing patients' quality of life. Thus, developing a prevention and therapeutic intervention strategy for head and neck cancer is vital. Phytochemicals have been shown to have a unique ability to protect cells from damage and modulation of cell repair. The chemopreventive activities of phytochemicals have also been demonstrated to be associated with their antioxidant properties and the induction and stimulation of intercellular communication via gap junctions, which play a role in the regulation of cancer cell cycle, differentiation, apoptosis, and stagnate cancer cell growth. Phytochemicals can also regulate cancer cell signaling pathways, reduce the invasion and metastasis of cancer cells, and protect normal cells during treatment, thus reducing the damage caused by chemotherapy and radiotherapy. The most studied of the chemopreventive effects of phytochemicals are the carotenoids and phenolics. In this review, we investigated the multiple mechanisms of carotenoids and polyphenols (PPs) for use in preventing head and neck cancer, reducing the side effects of chemotherapy and radiotherapy, improving patient survival rates, and reducing the occurrence rate of second primary cancers.
Fatty liver is significantly associated with hepatic cirrhosis and liver cancer. Excessive alcohol consumption causes alcoholic fatty liver disease (AFLD). Ginger has been reported to exhibit antioxidant potential and hepatoprotective activity. In the present study, a mouse model for AFLD was developed by employing male C57BL/6 mice that were fed an alcohol-containing liquid diet (Lieber-DeCarli diet) ad libitum. In the treatment groups, ginger essential oil (GEO) and citral were orally administered every day for 4 weeks. Serum biochemical analysis, antioxidant enzyme activity analysis, and histopathological evaluation revealed that GEO and citral exhibited hepatoprotective activity against AFLD. Metabolites in serum samples were profiled by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS). Metabolomic data indicated the amounts of metabolites such as d-glucurono-6,3-lactone, glycerol-3-phosphate, pyruvic acid, lithocholic acid, 2-pyrocatechuic acid, and prostaglandin E1 were increased after alcohol administration, but the levels were recovered in treatment groups. The analysis indicated that ginger possesses hepatoprotective properties against AFLD. Furthermore, these metabolites can serve as early noninvasive candidate biomarkers in the clinical application of AFLD for health management.
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer globally and ranks first among the cancer-related mortalities in Taiwan. This study aims to understand the modes of cell death mechanism induced by allicin, a major phytochemical of crushed garlic, in human hepatoma cells. Our earlier study indicated that allicin induced autophagic cell death in human HCC Hep G2 (p53(wild type)) cells, whereas in the present study, allicin induced apoptotic cell death through caspase-dependent and caspase-independent pathways by reactive oxygen species (ROS) overproduction in human HCC Hep 3B (p53(mutation)) cells. To gain insight into the cell death mechanism in p53 knocked down Hep G2, we silenced the p53 gene using siRNA-mediated silencing. Allicin treatment induced apoptotic cell death in p53 knocked down Hep G2 cells similar to that of Hep 3B cells. These results suggest that allicin induced cell death in human hepatoma cells through either autophagy or apoptosis and might be a potential novel complementary gene therapeutic agent for the treatment of apoptosis-resistant cancer cells.
Candida spondylitis is relatively uncommon and is usually encountered as an opportunistic infection. We analyzed the MRI characteristics of biopsy-proven cases of Candida spondylitis, and compared the findings with bacterial or tuberculous spondylitis.
To assess the potential risk of human exposure to carcinogenic leucomalachite green (LMG) due to fish consumption, the probabilistic risk assessment was conducted for adolescent, adult and senior adult consumers in Taiwan. The residues of LMG with the mean concentration of 13.378±20.56?gkg(-1) (BFDA, 2009) in fish was converted into dose, considering fish intake reported for three consumer groups by NAHSIT (1993-1996) and body weight of an average individual of the group. The lifetime average and high 95th percentile dietary intakes of LMG from fish consumption for Taiwanese consumers were estimated at up to 0.0135 and 0.0451?gkg-bw(-1)day(-1), respectively. Human equivalent dose (HED) of 2.875mgkg-bw(-1)day(-1) obtained from a lower-bound benchmark dose (BMDL10) in mice by interspecies extrapolation was linearly extrapolated to oral cancer slope factor (CSF) of 0.035 (mgkg-bw(-1)day(-1))(-1) for humans. Although, the assumptions and methods are different, the results of lifetime cancer risk varying from 3×10(-7) to 1.6×10(-6) were comparable to those of margin of exposures (MOEs) varying from 410,000 to 4,800,000. In conclusions, Taiwanese fish consumers with the 95th percentile LADD of LMG have greater risk of liver cancer and need to an action of risk management in Taiwan.
Rice body formation in a joint or bursa is a rare condition, and is usually associated with rheumatoid arthritis or tuberculous arthritis. Here we describe a case of multiple rice body formation in a shoulder joint and in adjacent bursae, which was confirmed to be due to septic arthritis by Candida species. To the best of our knowledge, rice body formation in Candida septic arthritis in an immune-competent patient has not been previously reported.
In traditional Chinese medicine, hot- and cold-attribute of food ingredients are a major part of dietary therapy. The aim of this study was to establish a suitable scientific methodology to define the attributes of food ingredients by investigating the relationship between food attributes and the physiological signals produced in healthy young subjects with different constitutions. Thirty subjects were grouped into hot and cold constitutions by Chinese medical doctors. Every subject took water, aged ginger tea and coconut water, which are well recognized as having neutral-, hot- and cold-attribute, respectively, on different visits. The different physiological signals induced by the samples were observed using skin and axillary temperature sensors, a heart rate variability analyzer and a laser Doppler anemometer. We found that the capillary red blood cell (RBC) velocity in nail fold microcirculation (NFM) of the subjects with hot constitution accelerated significantly after taking the hot-attribute aged ginger tea, which might be the result of elevated vagal activity leading to arteriole dilation in these subjects. In contrast, in subjects with cold constitution, capillary RBC velocity decelerated significantly and skin temperature decreased markedly after taking the cold-attribute coconut water, which might have been induced by sympathetic nerve activation causing the arteriole to be constricted. Accordingly, the use of capillary RBC velocity of NFM measured by laser Doppler anemometer may be a promising way to classify attributes of food ingredients commonly used in Chinese medicine dietary therapy in accordance with different personal constitutions.
This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0?g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18?mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming.
Currently, liver cancer is a leading cause of cancer-related death in the world. Hepatocellular carcinoma is the most common type of liver cancer. Previously, it was reported that blazeispirol A (BA) is the most active antihepatoma compound in an ethanolic extract of Agaricus blazei fermentation product. The aim of this study was to understand the antihepatoma mechanism of BA in human liver cancer Hep 3B cells. The results showed that BA inhibited the growth of Hep 3B cells and increased the percentage of cells in sub-G1 phase in a concentration- and time-dependent manner. In addition, BA treatment resulted in DNA fragmentation, caspase-9 and caspase-3 activations, poly(ADP-ribose)polymerase (PARP) degradation, down-regulation of Bcl-2 and Bcl-xL expressions, up-regulation of Bax expression, and disruption of the mitochondrial membrane potential (MMP) in Hep 3B cells. Furthermore, z-VAD-fmk, a caspase inhibitor, did not enhance the viability of BA-treated Hep 3B cells, and BA induced the release of HtrA2/Omi and apoptosis-inducing factor (AIF) from mitochondria into the cytosol. These findings suggested that BA with novel chemopreventive and chemotherapeutic potentials causes both caspase-dependent and caspase-independent cell death in Hep 3B cells.
Liver fibrosis is chronic liver damage usually caused by alcohol, viruses or other toxins and is characterised by an excessive accumulation of extracellular matrix proteins such as collagen. The aim of this study was to establish an animal model of chronic liver damage and investigate molecular mechanisms of silymarin hepatoprotective effects.
The objective of this study was to investigate the effects of various concentrations and incubation times of water extract of clam (WEC) on glutathione, its antioxidant and the detoxification defense systems in normal and CCl?-induced oxidative damaged primary rat hepatocytes. This study showed that when the hepatocytes were treated with WEC (0.14 ~ 1.68 mg/ml), the intracellular glutathione (GSH) levels, GSH/GSSG ratio, and the activities of GSH-related enzymes (GPx, GRd, and GST) were higher than those in the control at 24 or 48 hour treatments. However, the lactate dehydrogenase (LDH) leakage and microscopic observations did not differ from those of the control. Yet, when the hepatocytes were pretreated with various concentrations of WEC for 24 hours and then exposed to 5 mM carbon tetrachloride (CCl?) for 1 hour, at concentrations of WEC between 0.42 ~ 1.68 mg/ml, the viabilities, intracellular GSH level, and activities of GST and GPx were significantly increased compared to those of the CCl?-treated control group (p < 0.05). In conclusion, WEC could improve the viability and the capabilities of detoxification and antioxidation in hepatocytes by increasing the GSH level and the activities of GSH-related enzymes.
Antrodia camphorata has been recognized to be a traditional Chinese medicine for abdominal pain, diarrhea, and to protect against hepatitis virus infection. Several ingredients derived from A. camphorata possess various pharmacological and biological activities such as antioxidant and anticancer. In this study, its ability to promote immune responses and to exhibited antileukemia activity in WEHI-3 leukemia BALB/c mice were investigated. The results indicated A. camphorata significantly prolonged the survival rate and prevented the body weight loss in leukemia mice. Four mg/kg of A. camphorata treatment significantly decreased the weight of the spleen. Both doses (2 and 4 mg/kg) of A. camphorata did not affect Mac-3 marker in leukocytes. However, the 4 mg/kg of A. camphorata decreased the levels of CD11b and both doses of treatment increased CD3 and CD19. With lipopolysaccharide stimulation, the 4 mg/kg of A. camphorata promoted the significant proliferation of leukocytes; but with concanavalin A stimulation, both doses promoted the significant proliferation of leukocytes. YAC-1 target cells were killed by NK cells from the mice after treatment with A. camphorata at 4 mg/kg in target cells at a ratio of 50:1. The percentage of macrophages with phagocyted at A. camphorata treatment increased, and these effects were in dose-dependent manners.
Antrodia cinnamomea is known for its antihepatoma activity, yet the identity of its active compound was unclear. In this study, a 5-ton fermenter was used to prepare sufficient mycelium of A. cinnamomea for active compound isolation and identification.
Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), extracted from crushed garlic by steam-distillation, have been reported to provide the anticancer activity in several cancer types. However, their mechanisms of effects on skin cancer cells remain unclear. Therefore, we used human melanoma A375 cells and basal cell carcinoma cells as the models to elucidate the effects of these three allyl sulfides. Basal cell carcinoma (BCC) is known to be the most prevalent type of skin cancer, and melanoma is the most lethal form. We found that DATS revealed better growth inhibition of A375 and BCC cells than DADS and DAS did. We further demonstrated that DATS increased intracellular reactive oxygen species (ROS) generation, induced cytosolic Ca(2+) mobilization, and decreased mitochondrial membrane potential (DeltaPsim). Western blot results showed the concordance for the expression of molecules involved in G(2)/M arrest and apoptosis observed by cell cycle and cell viability analysis. Moreover, we detected the activation of p53 pathway in response to the oxidative DNA damage. DATS also displayed selective target of growth inhibition between skin cancer cells and normal keratinocyte HaCaT cells. Taken together, these results suggest that DATS is a potential anticancer compound for skin cancer.
Garlic is viewed as an effective health food against atherosclerosis. In this study, we examined whether diallyl disulfide (DADS) and diallyl trisulfide (DATS) protect endothelial nitric oxide synthase (eNOS) activation against oxidized LDL (ox-LDL) insult and through what mechanism. We found that DADS and DATS reversed the suppression of eNOS Ser1177 phosphorylation by ox-LDL, and wortmannin abolished the reversal by DADS and DATS. Similarly, the inhibition of cellular cGMP and nitric oxide production by ox-LDL was reversed by DADS and DATS (p<0.05). This increase in nitric oxide bioavailability by the allyl sulfides was attenuated by wortmannin. Immunoprecipitation assay revealed that DADS and DATS preserved the interaction of eNOS with caveolin-1 in the membrane. In addition, DADS and DATS suppressed the reduction of the cellular eNOS protein content by ox-LDL. When cycloheximide was added to block protein synthesis, DADS and DATS suppressed eNOS protein degradation similarly to that noted by MG132. Ox-LDL increased chymotrypsin-like proteasome activity, and this increase was inhibited by the allyl sulfides and MG132 (p<0.05). These results suggest that DADS and DATS protect eNOS activity against ox-LDL insult. This protection can be attributed partly to their mediation of phosphatidylinositol 3-kinase/protein kinase B signaling and prevention of eNOS degradation.
Depression is one of the most common psychiatric disorders that affects over 10% of individuals. However there is no desirable therapeutic approach nowadays. Thus, looking for an alternative treatment is important. The objectives of this study are to investigate the antidepressant effects of the rhizomes of Gastradia elata B(L), a traditional Chinese medicine, in the animal model forced-swimming test (FST), and to analyze the monoamine content in the rats brain regions in order to better understand the possible mechanisms of the water extract of the rhizomes of Gastrodia elata B(L) (WGE). Subchronic administration of 0.5 or 1.0 mg/kg bw WGE by gavage for 21 consecutive days significantly reduced the immobility duration of rats in the test session of FST as compared to the control group (p < 0.05), with the equivalent effects as the antidepressant drug fluoxetine. The concentration of serotonin (5-HT) in the frontal cortex and dopamine (DA) in striatum were significantly increased after WGE administration (p < 0.05). The ratio of 5-HIAA/5-HT and (DOPAC + HVA)/DA, i.e. the turnover of 5-HT and DA respectively, were also significantly lowered in WGE groups (p < 0.05). In summary, the present study showed that the WGE possesses antidepressant-like effect on rats in the animal model FST, and the possible mechanism may be via regulating both the serotonergic and dopaminergic systems.
The objective of this study was to investigate the cytotoxicity of the ethanolic extract of mycelia from Ganoderma lucidum (EMG) cultivated in a medium containing leguminous plants Glycine max (L.) Merr. and Astragalus membranaceus on human hepatocellular carcinoma cells (Hep 3B) and to isolate the active components from EMG. The results indicated that EMG induced cytotoxicity in a dose- and time-dependent manner, and the cells treated with EMG for 24, 48, and 72 h had IC(50) values of 156.8, 89.9, and 70.1 microg/mL, respectively. Furthermore, EMG was fractionated into seven fractions (F1-F7). We found that F5 and F6 had higher growth inhibitory effects on Hep 3B cells than the other fractions, and F6 possessed enough amounts (about 2.1 g) to carry out a more detailed study. F6 caused a sub-G1 peak rise and DNA fragmentation in Hep 3B cells and was further separated by high-performance liquid chromatography to obtain two active compounds, 9,11-dehydroergosterol peroxide [9(11)-DHEP] (compound 1) and ergosterol peroxide (EP) (compound 2). The IC(50) values of 9(11)-DHEP and EP based on the cell viability of Hep 3B were 16.7 and 19.4 microg/mL, respectively.
Adult stem cells are promising therapeutic reagents for skeletal regeneration. We hope to validate by molecular imaging technologies the in vivo life cycle of adipose-derived multipotent cells (ADMCs) in an animal model of skeletal injury. Primary ADMCs were lentivirally transfected with a fusion reporter gene and injected intravenously into mice with bone injury or sham operation. Bioluminescence imaging (BLI), [(18)F]FHBG (9-(fluoro-hydroxy-methyl-butyl-guanine)-micro-PET, [(18)F]Fluoride ion micro-PET and micro-CT were performed to monitor stem cells and their effect. Bioluminescence microscopy and immunohistochemistry were done for histological confirmation. BLI showed ADMCs traffic from the lungs then to the injury site. BLI microscopy and immunohistochemistry confirmed the ADMCs in the bone defect. Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 (p < 0.05). Systemically administered ADMCs traffic to the site of skeletal injury and facilitate bone healing, as demonstrated by molecular and small animal imaging. Molecular imaging technologies can validate the usage of adult adipose tissue-derived multipotent cells to promote fracture healing. Imaging can in the future help establish therapeutic strategies including dosage and administration route.
Garlic and garlic products are known to induce anti-inflammatory effects, but much of the research to date has focused on the inhibitory effect of garlic on the activity of mononuclear cells/macrophages. The effect of garlic on the balance of the two mutually inhibitory T helper cell subtypes, Th1 and Th2 cells, has hitherto received little attention. We thus studied the effect of supplementation with garlic oil on the activity of Th1 and Th2 cells. Rats were administered by gavage with garlic oil (10 - 200 mg/kg) or corn oil every other day for 2 weeks. Cervical lymph nodes were collected to assay the lymphocyte proliferation rate and the production of Th1 interleukin 2 (IL-2) and interferon gamma (IFN-gamma) and the Th2 cytokines IL-4 and IL-10 upon stimulation with concanavalin A. Garlic oil enhanced the lymphocyte proliferation rate accompanied by an elevated production of all four cytokines when given at a dose of 100 mg/kg. At 200 mg/kg, the production of IL-4 and IL-10 was further enhanced but IFN-gamma production was suppressed. The ratio of IFN-gamma to IL-4 was enhanced by 50 mg/kg garlic oil but suppressed by 200 mg/kg garlic oil. In conclusion, supplemental garlic oil has a dual effect on Th1-Th2 cell balance: an enhanced T cell response towards the Th1 type at low doses and towards the Th2 type at high doses.
Fatty liver induced by alcohol abuse is a major worldwide health hazard leading to morbidity and mortality. Previous studies indicate antifatty liver properties of garlic. This study investigated the molecular mechanisms of garlic oil (GO) or diallyl disulfide (DADS) imparted hepatoprotection against alcohol induced fatty liver in C57BL/6 mice using microarray-based global gene expression analysis. Alcohol liquid diet resulted in severe fatty liver with increased levels of serum aspartate aminotransferease and alanine aminotransferease as well as triglycerides and decreased levels of liver glutathione and antioxidant enzymes. The major canonical pathways implicated by alcohol treatment are the metabolisms of xenobiotics by cytochrome P450, glutathione, and arachidonic acid. Treatment with DADS or GO normalized the serum aminotransferease levels and liver antioxidant enzymes and reduced the contents of triglycerides and cholesterol. The canonical pathways involved in the amelioration of liver include arachidonic acid metabolism, altered T cell and B cell signaling, tryptophan metabolism, antigen presentation pathway for DADS, metabolism of xenobiotics, mitotic roles of Polo-like kinase, fatty acid metabolism, LPS/IL-1 mediated inhibition of RXR function, and C21-steroid hormone metabolism for GO.
Skin cancer is a serious concern whose incidence is increasing at an alarming rate. Allyl sulfides-i.e., sulfur metabolites in garlic oil-have been demonstrated to have anticancer activity against several cancer types, although the mechanisms underlying these effects remain enigmatic. Our previous study showed that diallyl trisulfide (DATS) is more potent than mono- and disulfides against skin cancer. DATS inhibits cell growth of human melanoma A375 cells and basal cell carcinoma (BCC) cells by increasing the levels of intracellular reactive oxygen species (ROS) and DNA damage and by inducing G2/M arrest, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis, including the caspase-dependent and -independent pathways. This short review focuses on the molecular mechanisms of garlic-derived allyl sulfides on skin cancer prevention.
Garlic has been used throughout history for both culinary and medicinal purpose. Allicin is a major component of crushed garlic. Although it is sensitive to heat and light and easily metabolized into various compounds such as diallyl disulfide, diallyl trisulfide, and diallyl sulfide, allicin is still a major bioactive compound of crushed garlic. The mortality of hepatocellular carcinoma is quite high and ranks among the top 10 cancer-related deaths in Taiwan. Although numerous studies have shown the cancer-preventive properties of garlic and its components, there is no study on the effect of allicin on the growth of human liver cancer cells. In this study, we focused on allicin-induced autophagic cell death in human liver cancer Hep G2 cells. Our results indicated that allicin induced p53-mediated autophagy and inhibited the viability of human hepatocellular carcinoma cell lines. Using Western blotting, we observed that allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway, and the level of Bcl-2 and increased the expression of AMPK/TSC2 and Beclin-1 signaling pathways in Hep G2 cells. In addition, the colocalization of LC3-II with MitoTracker-Red (labeling mitochondria), resulting in allicin-induced degradation of mitochondria, could be observed by confocal laser microscopy. In conclusion, allicin of garlic shows great potential as a novel chemopreventive agent for the prevention of liver cancer.
To evaluate the potential and correlation between near-infrared fluorescence (NIRF) imaging using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles (HGC-Cy5.5) and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) imaging of collagen-induced arthritis (CIA).
Molecular imaging has undergone an explosive advancement in recent years, due to the tremendous research efforts made to understand and visualize biological processes. Molecular imaging by definition assesses cellular and molecular processes in living subjects, with the targets of following metabolic, genomic, and proteomic events. Furthermore, reporter gene imaging plays a central role in this field. Many different approaches have been used to visualize genetic events in living subjects, such as, optical, radionuclide, and magnetic resonance imaging. Compared with the other techniques, magnetic resonance (MR)-based reporter gene imaging has not occupied center stage, despite its superior three-dimensional depictions of anatomical details. In this article, the authors review the principles and applications of various types of MR reporter gene imaging technologies and discuss their advantages and disadvantages.
Diallyl trisulfide (DATS), an active component of garlic oil, has attracted much attention because of its anticancer effect on several types of cancers. However, the mechanism of DATS-induced apoptosis of basal cell carcinoma (BCC) is not fully understood. In the present study, we revealed that DATS-mediated dose-dependent induction of apoptosis in BCC cells was associated with intracellular reactive oxygen species accumulation and disrupted mitochondrial membrane potential. Western analysis demonstrated concordant expression of molecules involved in mitochondrial apoptosis, including DATS-associated increases in phospho-p53, proapoptotic Bax, and decreases in antiapoptotic Bcl-2 and Bcl-xl in BCC cells. Moreover, DATS induced the release of cytochrome c, apoptosis-inducing factor, and HtrA2/Omi into the cytoplasm, and activated factors downstream of caspase-dependent and caspase-independent apoptosis, including nuclear translocation of apoptotic-inducing factor and endonuclease G and the caspase cascade. These results were confirmed by pretreatment with the antioxidant N-acetyl-L-cysteine and the caspase inhibitor (z-VAD-fmk), the latter of which did not completely enhance the viability of DATS-treated BBC cells. Exposure to DATS additionally induced endogenous endoplasmic reticulum stress markers and intracellular Ca2? mobilization, upregulation of Bip/GRP78 and CHOP/GADD153, and activation of caspase-4. Our findings suggest that DATS exerts chemopreventive potential via ER stress and the mitochondrial pathway in BCC cells.
The purpose of this study was to evaluate the tunnel widening using a multi-planar reformation of MRI (Magnetic Resonance Imaging) in the orientation of the tunnel. The hypotheses of this study were as follows: (1) tunnel widening would be reduced with the above-mentioned technique, (2) the degree of tunnel widening would be different at the site of the tunnels, and (3) the time interval from surgery to MRI acquisition would affect the magnitude of tunnel widening.
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