Inhibitory Effect of Tea Saponin on Major Apple-Disease-Inducing Fungi.

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.

Effects of cellulose nanofibrils treatment on antioxidant properties and aroma of fresh-cut apples.

Horticultural products tend to deteriorate during postharvest storage and processing. In this study, cellulose nanofibers (CNFs) were prepared from wood to investigate the effects of CNF treatment on the storage quality, aroma composition, and antioxidant system of fresh-cut apple (Malus domestica) wedges. Compared with control treatment, CNF coating treatment significantly improved the appearance of apple wedges; reduced the decay rate of apple wedges; and delayed the decline in weight loss, firmness, and titratable acid during storage. Gas chromatography-mass spectrometry showed that CNF treatment could maintain the aroma components of apple wedges (stored for 4 days). Further investigations showed that CNF treatment increased the antioxidant system level and decreased reactive oxygen species content and membrane lipid peroxidation level of apple wedges. Overall, this study showed that CNF coating could effectively maintain the quality of fresh-cut apples during cold storage.

Selenium-sensitive histone deacetylase 2 is required for forkhead box O3A and regulates extracellular matrix metabolism in cartilage.

INTRODUCTION: Selenium (Se) as well as selenoproteins are vital for osteochondral system development. Se deficiency (SeD) has a definite impact on the expression and activity of histone deacetylases (HDACs). Abnormal expression of some HDACs affects cartilage development. This current study aims to explore the relationship between differentially expressed HDACs and cartilage development, especially extracellular matrix (ECM) homeostasis maintenance, under SeD conditions. MATERIALS AND METHODS: Dark Agouti rats and C28/I2 cell line under SeD states were used to detect the differently expressed HDAC by RT-qPCR, western blotting and IHC staining. Meanwhile, the biological roles of the above HDAC in cartilage development and homeostasis maintenance were confirmed by siRNA transfection, western blotting, RNA sequence and inhibitor treatment experiments. RESULTS: HDAC2 exhibited lower expression at protein level in both animals and chondrocytes during SeD condition. The results of cell-level experiments indicated that forkhead box O3A (FOXO3A), which was required to maintain metabolic homeostasis of cartilage matrix, was reduced by HDAC2 knockdown. Meanwhile, induced HDAC2 was positively associated with FOXO3A in rat SeD model. Meanwhile, knockdown of HDAC2 and FOXO3A led to an increase of intracellular ROS level, which activated NF-κB pathway. Se supplementary significantly inhibited the activation of NF-κB pathway with IL-1ß treatment. CONCLUSION: Our results suggested that low expression of HDAC2 under SeD condition increased ROS content by decreasing FOXO3A in chondrocytes, which led to the activation of NF-κB pathway and ECM homeostasis imbalance.

Consensus of Minimally Invasive and Multidisciplinary Comprehensive Treatment for Hepatocellular Carcinoma - 2020 Guangzhou Recommendations.

In China, the majority of patients with hepatocellular carcinoma (HCC) result from long-term infection of hepatitis B. Pathologically, HCC is characterized by rich blood supply, multicentric origins, early vascular invasion and intrahepatic metastasis. Therefore, HCC is not a local disease but a systemic disease at the beginning of its occurrence. For this reason, a comprehensive treatment strategy should be adopted in the management of HCC, including local treatments (such as surgical resection, radiofrequency ablation, microwave ablation, chemical ablation and cryoablation, etc.), organ-level treatments [such as transcatheter arterial infusion of chemotherapy and transcatheter arterial chemoembolization (TACE)], and systemic treatments (such as immunotherapy, antiviral therapy and molecular targeted therapy, etc.). This consensus sets forth the minimally-invasive and multidisciplinary comprehensive guideline of HCC, focusing on the following eight aspects (1) using hepaticarteriography, CT hepatic arteriography (CTHA), CT arterial portography (CTAP), lipiodol CT (Lp-CT), TACE-CT to find the intrahepatic lesion and make precise staging (2) TACE combined with ablation or ablation as the first choice of treatment for early stage or small HCC, while other therapies are considered only when ablation is not applicable (3) infiltrating HCC should be regarded as an independent subtype of HCC (4) minimally-invasive comprehensive treatment could be adopted in treating metastatic lymph nodes (5) multi-level subdivision of M-staging should be used for individualized treatment and predicting prognosis (6) HCC with severe hepatic decompensation is the only candidate criterion for liver transplantation (7) bio-immunotherapy, traditional Chinese medicine therapy, antiviral therapy, and psychosocial and psychopharmacological interventions should be advocated through the whole course of HCC treatment (8) implementation of multicenter randomized controlled trials of minimally-invasive therapy versus surgery for early and intermediate stage HCC is recommended.

Selenium-oxidizing Agrobacterium sp. T3F4 steadily colonizes in soil promoting selenium uptake by pak choi (Brassica campestris).

Selenium (Se) deficiency in soil is linked to its low content in edible crops, resulting in adverse impacts on the health of 15% of the global population. The crop mainly absorbs oxidized selenate and selenite from soil, then converts them into organic Se. However, the role of Se-oxidizing bacteria in soil Se oxidation, Se bioavailability and Se absorption into plants remains unclear. The strain Agrobacterium sp. T3F4, isolated from seleniferous soil, was able to oxidize elemental Se into selenite under pure culture conditions. The green fluorescent protein (gfp)-gene-marked strain (T3F4-GFP) and elemental Se or selenite (5 mg·kg-1) were added to pak choi (Brassica campestris ssp. chinensis) pot cultures. Observation of the fluorescence and viable counting indicated that GFP-expressing bacterial cells steadily colonized the soil in the pots and the leaves of the pak choi, reaching up to 6.6 × 106 and 2.0 × 105 CFU g-1 at 21 days post cultivation, respectively. Moreover, the total Se content (mostly organic Se) was significantly increased in the pak choi under T3F4 inoculated pot culture, with elemental Se(0) being oxidized into Se(IV), and soil Se(IV) being dissolved before being absorbed by the crop. After strain T3F4 was inoculated, no significant differences in microbial diversity were observed in the soils and roots, whereas the abundance of Rhizobium spp. was significantly increased. To our knowledge, this is the first time that Se-oxidizing Agrobacterium sp. T3F4 has been found to steadily colonize soil and plant tissues, and that its addition to soil increases the absorption of Se in plants. This study provides a potential strategy for Se biofortification.

T-2 Toxin Induces Epiphyseal Plate Lesions via Decreased SECISBP2-Mediated Selenoprotein Expression in DA Rats, Exacerbated by Selenium Deficiency.

OBJECTIVE: Both selenium (Se) deficiency and mycotoxin T2 lead to epiphyseal plate lesions, similar to Kashin-Beck disease (KBD). However, regulation of selenoproteins synthesis mediated by SECISBP2, in response to these 2 environmental factors, remained unclear. The present study proposed to explore the mechanism behind the cartilage degradation resulting from Se deficiency and mycotoxin T2 exposure. DESIGN: Deep chondrocyte necrosis and epiphyseal plate lesions were replicated in Dark Agouti (DA) rats by feeding them T2 toxin/Se deficiency artificial synthetic diet for 2 months. RESULTS: Se deficiency led to decreased expression of COL2α1, while T2 treatment reduced the heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) expression, both of which affected the cartilage extracellular matrix metabolism in the rat models. The expression of Col2α1, Acan, Hs6st2, Secisbp2, Gpx1, and Gpx4 were all significantly decreased in cartilage tissues from DA rats, fed a Se-deficient diet or exposed to T2 toxin, contrary to Adamts4, whose expression was increased in both conditions. In addition, T2 treatment led to the decreased expression of SBP2, GPX1, GPX4, and total GPXs activity in C28/I2 cells. CONCLUSION: DA rats exposed to T2 toxin and/or Se-deficient conditions serve as the perfect model of KBD. The 2 environmental risk factors of KBD, which serve as a "double whammy," can intensify the extracellular matrix metabolic imbalance and the antioxidant activity of chondrocytes, leading to articular cartilage degradation and epiphyseal plate abnormalities similar to those observed in KBD.

Chinese expert consensus on radioactive 125I seeds interstitial implantation brachytherapy for pancreatic cancer.

Pancreatic cancer, also known as exocrine pancreatic carcinoma or pancreatic ductal adenocarcinoma, is one of the most challenging tumor entities worldwide, which is characterized as a highly aggressive disease with dismal overall prognosis. Treatment options for patients with locally advanced pancreatic cancer include surgery, chemotherapy, and radiotherapy. In many cases, surgical resection is not possible due to the advanced stage at diagnosis and poor responses to current treatments, therefore, treatment alternatives have to be performed. However, brachytherapy through radioactive 125I seeds (RIS) implantation into pancreatic cancer has been first applied in unresectable carcinoma and made accuracy curative effects. Therapeutic procedures of RIS implantation for pancreatic carcinoma were not identical in domestic medical centers, making it hard to achieve homogeneity and affecting the efficacy seriously at last. To maximize the benefits of RIS for patients with pancreatic cancer, Chinese Medical Doctor Association of Radioactive Seed Implantation Technology Expert Committee and Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association, Radioactive Seed Therapy Branch organized and helped establish China expert consensus on RIS implantation for the treatment of pancreatic cancer, to provide a reference for clinical practices.

Selenium-sensitive miRNA-181a-5p targeting SBP2 regulates selenoproteins expression in cartilage.

Selenium (Se) deficiency brings about defects in the biosynthesis of several selenoproteins and has been associated with aberrant chondrogenesis. Selenocysteine (Sec) Insertion Sequence (SECIS) and SECIS binding protein 2 (SBP2) interaction is a very critical node for the metabolic balance between Se and selenoproteins. The Gpx1, Gpx4 and SelS have different binding affinities with SBP2 in cells. According to our results, both miR-181a-5p and SBP2 appeared to be selenium-sensitive and regulated the expression of selenoproteins in C28/I2 cells under Se sufficient environment. However, they showed significantly opposite expression trend in Se deficiency rats cartilage and SeD C28/I2 cells. The SBP2 is a direct target gene of miR-181a-5p in C28/I2 cells as determined by reporter gene and off-target experiments. And the miR-181a-5p could regulate SBP2 and the selenoproteins in C28/I2 cells. Depending upon the Se supply levels, C28/I2 cells were divided into three groups, that is normal Se, SeD and SeS, which underwent through a 7-day Se deprivation process, then SBP2 was knocked-down and overexpressed in all the groups. Moreover, the selected selenoproteins were down-regulated in second-generation low Se diet rat cartilage. The selenoproteins expression was decreased by Se deficiency which depended on the Selenium-sensitive miR-181a-5p to participate and regulate SBP2 at post-transcriptional level. It involves a series of antioxidant and ECM (extracellular matrix) genes, to overcome the ROS-related stress for the protection of essential physiological functions and to maintain the balance between anabolism and catabolism of the cartilage.

DRm217 attenuates myocardial ischemia-reperfusion injury via stabilizing plasma membrane Na+-K+-ATPase, inhibiting Na+-K+-ATPase/ROS pathway and activating PI3K/Akt and ERK1/2.

Na+-K+-ATPase has close relationship with myocardial ischemia/reperfusion (IR) injury. Activation of Na+-K+-ATPase with its DR region specific antibody produces cardioprotective effect. In this study, we aimed to explore whether DRm217, a proved DR region specific antibody, could protect myocardial cells against IR injury and uncover the mechanisms under it. By employing H9c2 myocardial cell and SD rat, we found that DRm217 protected cardiac cells against IR-induced cell injury and apoptosis. DRm217 produced protective effect via stabilizing Na+-K+-ATPase membrane expression and inhibiting Na+-K+-ATPase/Src/NADPH oxidase dependent ROS accumulation. PI3K/Akt and ERK1/2 participated in DRm217-induced cardiomyocyte survival, but not in DRm217-related ROS reduction. Therefore, DRm217 can be used as a potential cardioprotective adjuvant in myocardial IR therapy and interference of Na+-K+-ATPase/ROS pathway will be a promising modality for clinical myocardial IR therapy.

Exendin-4 relieves the inhibitory effects of high glucose on the proliferation and osteoblastic differentiation of periodontal ligament stem cells.

BACKGROUND: With the impaired regenerative potential in patients with diabetes mellitus (DM), Periodontal ligament stem cells (PDLSCs) are regarded as an attractive source of stem cells for periodontal cytotherapy. Recent studies have shown that Exendin-4 (Ex-4) exerts cell-protective effects and bone remodeling ability on many types of cells. The aim of this study was to investigate whether Ex-4 alleviates the inhibition of high glucose on the proliferation and osteogenic differentiation of PDLSCs. METHODS: PDLSCs were incubated in medium supplemented with 5.5 mM d-glucose (NG), 30 mM d-glucose (HG), NG plus Ex-4, and HG plus different concentration (1, 10, 20, 100 nM) of Ex-4 respectively. Cell proliferation was detected by CCK-8 assay and cell cycle analysis. Osteogenesis was assessed by Alizarin Red S staining and evaluation of the mRNA expression of Runx2, ALP and Osx at day 7, 14 and 21. Intracellular level of reactive oxygen species (ROS) was detected using 5-(and-6)-chloromethyl-2',7'-dichlorodihydro-fluorescein diacetate (CMH2DCF-DA). RESULTS: The proliferation ability, mineralized nodules forming capacity and the mRNA expression of Runx2, ALP and Osx of PDLSCs in HG group were decreased, the ROS level was increased compared to NG group. With the treatment of Ex-4, the HG-inhibited proliferation ability and osteogenic differentiation ability of PDLSCs were significantly reversed, the HG-increased ROS level could be down-regulated. Moreover, Ex-4 enhanced the osteogenic differentiation of normal PDLSCs. CONCLUSIONS: Ex-4 alleviates the inhibitory effect of HG on the proliferation and osteoblastic differentiation of PDLSCs, and has a significant enhance in the osteoblastic differentiation of normal PDLSCs, giving new insights into the possible therapeutic method of diabetic periodontitis.

Feasibility and Efficacy of Microwave Ablation Combined with Iodine-125 Seed Implantation in Local Control of Recurrent Retroperitoneal Liposarcomas: Initial Clinical Experience.

INTRODUCTION: The objective of the present study was to evaluate the feasibility, safety, and short-term efficacy of microwave ablation (MWA) combined with iodine-125 (125I) seed implantation in recurrent retroperitoneal liposarcomas (rRPLs). MATERIALS AND METHODS: From September 2012 to March 2015, 11 patients were enrolled in this prospective study. Eleven tumors (median, 9 cm; range, 5.5-12.5 cm) were treated with computerized tomography-guided MWA for 11 sessions and 125I seed implantation for 18 sessions. 125I seed implantation was performed 4 weeks after MWA. RESULTS: There were no procedure-related deaths. Post-MWA pain (grade ≥2) was the most common complication (6 of 11 patients, 54.5%), and fever (grade ≥2) was observed in two patients. Reversible nerve injury, defined as transient limb paresthesia or leg weakness, was observed in one patient. There were fewer complications associated with the 125I seed implantation procedure compared with the MWA procedure. All 11 patients who underwent the MWA procedure achieved a partial response (PR), according to the modified Response Evaluation Criteria in Solid Tumors, 1 month post-ablation; after 125I seed implantation was performed, a complete response was observed in three, five, and six target tumors in 3, 6, and 12 months, respectively. CONCLUSION: In selected patients with rRPLs, MWA combined with 125I seed implantation is feasible and safe with favorable local control efficacy. IMPLICATIONS FOR PRACTICE: This study evaluated the feasibility, safety, and short-term efficacy of microwave ablation (MWA) combined with iodine-125 (125I) seed implantation in recurrent retroperitoneal liposarcomas (rRPLs). Results suggest that a single session of MWA may be not sufficient in large-volume rRPLs and that as a supplement treatment, 125I seed implantation is safe and easy accessible. MWA combined with 125I seed has excellent local control effectiveness, and long-term efficacy and survival benefit still need to be more comprehensively evaluated.

Abnormality of epiphyseal plate induced by selenium deficiency diet in two generation DA rats.

This study aimed to observe the effects of Se deficiency on epiphyseal plates of two generation DA rats fed with artificial total synthetic low Se diet. All F0 and F1 DA rats were fed with synthetic low Se diet (SeD group) and low Se diet supplied with Se (SeS group). The levels of selenium and enzyme activities of GPx were detected in plasma of the rats. General growth of bone and articular cartilage was measured macroscopically and microscopically. The epiphyseal plate of femur heads or tibia were obtained to histological and immunohistochemical examinations. The cartilage from left knee joints and femur heads was used to detect the gene expression of collagens, ADAMTSs and several selenoproteins by RT-qPCR. Two generation SeD rats showed Se insufficiency status. The thicknesses of the femur and tibial epiphyseal plates in both F0 and F1 SeD rats were significantly less than that of SeS rats. In F1 generation, SeD rats showed much fewer proliferative chondrocyte layers than SeS ones. Importantly, two generation SeD rats both showed significantly more serious pathological changes of epiphyseal plates. In two generation rats, gene expressions of COL II, GPx1 and GPx4 were significantly down-regulated in SeD rats than SeS ones; meanwhile ADAMTS-4 showed an up-regulated expression in cartilage. Dietary Se deficiency can apparently cause epiphyseal plate lesion and decrease cartilage type II collagen production and GPx1 activity in two generation DA rats fed with the artificial total synthesis low Se diet.

Combination of individualized local control and target-specific agent to improve unresectable liver cancer managements: a matched case-control study.

Management of late-stage hepatocellular carcinoma is difficult. A direct comparison of clinical data is needed in order to demonstrate the survival benefits of different therapies. We directly compared various therapies in a retrospective matched case-control study. A total of 79 patients with unresectable tumors greater than 10 cm in size were included in the study between 2008 and 2012. Thirty-five patients were treated with transarterial chemoembolization for local control, 20 were treated with sorafenib systemic chemotherapy, and 24 received combination treatment. The total follow-up time after initial therapy was 4.5 years. Survival time after treatment was significantly longer in the combination therapy group (P < 0.0001). The median survival times for combination, local control, and systemic chemotherapy were 15 (12-21), 10 (9-13), and 3.5 (2.5-9.0) months (95 % confidence interval), respectively. The hazard ratios for local control and systemic chemotherapy were 1.985 and 5.102, respectively, with combination treatment as the reference. There was no observed difference in combination therapy from the side effects of the individual therapies. In conclusion, the limited availability of therapeutic options for late-stage liver cancer necessitates reliance on multidisciplinary personalized medicine approaches with target-specific medications to increase survival time. Combining individualized local control therapy and drugs that target specific disease markers provides more benefits to patients.

Refractory malignant fibrous histiocytoma: CT-guided treatment with a multidisciplinary, minimally invasive approach.

The purpose of this study is to evaluate the effectiveness and safety of a computed tomography (CT)-guided, multidisciplinary, minimally invasive approach to the treatment of patients with large, refractory malignant fibrous histiocytoma. This approach includes microwave ablation and absolute alcohol therapy combined with 125I seed implantation. Seven patients (5 males and 2 females, 26-78 years old, mean 49.7 years old) with large, refractory malignant fibrous histiocytoma participated in this study. The tumors had an average maximum diameter of 14.1 cm (10.0-19.0 cm). Follow-up was conducted for an average of 35.7 months to determine the local control rate, overall survival rate, and clinical complications. Follow-up times ranged from 2 to 45 months. Pain was significantly relieved in patients treated with multidisciplinary, minimally invasive approach. Complete response was achieved in 5 patients (71.4%), partial response in the other 2 patients (28.6%). The response rate of this treatment was 100%. The median survival time was 35.7 months. All patients were alive in 2 years after the treatment. Five patients were still alive after 3 years. The 3 year survival rate was 71.4%. The long-term complications included hyperpigmentation at the operative sites (n = 5) and insensible feeling at the ablation sites (n = 3).This CT-guided multidisciplinary, minimally invasive approach is an effective, safe, and feasible means of treating large, refractory malignant fibrous histiocytoma with minimal damage and few complications, but large-scale randomized clinical trials are necessary to confirm this assessment.

The inhibitory effects of extracellular ATP on the growth of nasopharyngeal carcinoma cells via P2Y2 receptor and osteopontin.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignant tumor observed in the populations of southern China and Southeast Asia. However, little is known about the effects of purinergic signal on the behavior of NPC cells. This study analyzed the effects of ATP on the growth and migration of NPC cells, and further investigated the potential mechanisms during the effects. METHODS: Cell viability was estimated by MTT assay. Transwell assay was utilized to assess the motility of NPC cells. Cell cycle and apoptosis were detected by flow cytometry analysis. Changes in OPN, P2Y2 and p65 expression were assessed by western blotting analysis or immunofluorescence. The effects of ATP and P2Y2 on promoter activity of OPN were analyzed by luciferase activity assay. The binding of p65 to the promoter region of OPN was examined by ChIP assay. RESULTS: An MTT assay indicated that ATP inhibited the proliferation of NPC cells in time- and dose-dependent manners, and a Transwell assay showed that extracellular ATP inhibited the motility of NPC cells. We further investigated the potential mechanisms involved in the inhibitory effect of extracellular ATP on the growth of NPC cells and found that extracellular ATP could reduce Bcl-2 and p-AKT levels while elevating Bax and cleaved caspase-3 levels in NPC cells. Decreased levels of p65 and osteopontin were also detected in the ATP-treated NPC cells. We demonstrated that extracellular ATP inhibited the growth of NPC cells via p65 and osteopontin and verified that P2Y2 overexpression elevated the inhibitory effect of extracellular ATP on the proliferation of NPC cells. Moreover, a dual luciferase reporter assay showed that the level of osteopontin transcription was inhibited by extracellular ATP and P2Y2. ATP decreased the binding of p65 to potential sites in the OPN promoter region in NPC cells. CONCLUSION: This study indicated that extracellular ATP inhibited the growth of NPC cells via P2Y2, p65 and OPN. ATP could be a promising agent serving as an adjuvant in the treatment of NPC.

Paenibacillus selenii sp. nov., isolated from selenium mineral soil.

Strain W126(T), a Gram-reaction-positive, spore-forming, rod-shaped, facultatively anaerobic bacterium, motile by means of peritrichous flagella, was isolated from selenium mineral soil in Hubei province of China. 16S rRNA gene sequence analysis demonstrated that this isolate belonged to the genus Paenibacillus, with 97.9 % sequence similarity to Paenibacillus anaericanus MH21(T), while compared with the other species of the genus Paenibacillus, the 16S rRNA gene sequence similarities were less than 96.0%. DNA-DNA hybridization between strain W126(T) and Paenibacillus anaericanus DSM 15890(T) was 24%. The major isoprenoid menaquinone was menaquinone-7. Anteiso-C(15 : 0) was the major fatty acid. The DNA G+C content was 42.3 mol%. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unknown aminophospholipids and an unknown lipid. Strain W126(T) contained A1γ-meso-diaminopimelic acid in the cell-wall peptidoglycan. The phenotypic, chemotaxonomic and genotypic data indicate that strain W126(T) represents a novel species of the genus Paenibacillus, for which the name Paenibacillus selenii sp. nov. is proposed. The type strain is W126(T) ( = KCTC 33420(T) = CCTCC AB 2014003(T)).

Ginsenoside Rg1 of Panax ginseng stimulates the proliferation, odontogenic/osteogenic differentiation and gene expression profiles of human dental pulp stem cells.

Ginsenoside Rg1 is one of the major active components of Panax ginseng C. A. Mey. Human dental pulp stem cells (hDPSCs) play an important role in the dentin formation, reparation and tooth tissue engineering. This study investigated the effects of ginsenoside Rg1 on the proliferation, odontogenic differentiation of hDPSCs and revealed the underlying molecular mechanisms. [³H]-thymidine incorporation assay and cell cycle analysis were applied to investigate the proliferation of hDPSCs after the treatment of ginsenoside Rg1. Immunocytochemistry analysis and fluorescent quantitative reverse transcriptase-polymerase chain reaction (FQ-PCR) were performed to evaluate the odontogenic differentiation of hDPSCs. Gene and protein expressions of bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor 2 (FGF2) were detected by FQ-PCR and enzyme-linked immunosorbent assay. The Roche Nimblegen Whole Human Genome Expression profile microarray was used to detected representative gene expression profiles of hDPSCs by ginsenoside Rg1. The results indicated that ginsenoside Rg1 significantly increased hDPSCs proliferation (p<0.05). Gene expressions of DSPP, ALP, OCN, BMP-2, FGF2 and protein expressions of BMP-2 and FGF2 were increased compared with the untreated group (p<0.05). Gene expression profile analysis revealed that 2059 differentially expressed genes were detected by ginsenoside Rg1. Ginsenoside Rg1 promoted the proliferation and differentiation of hDPSCs through alteration of gene expression profiles.

Refractory nasopharyngeal carcinoma: positron emission tomography combined with computed tomography-guided 125I seed implantation therapy after repeated traditional radiochemotherapy.

OBJECTIVE: To evaluate the feasibility of positron emission tomography combined with computed tomography (PET-CT)-guided (125)I seed implantation in the treatment of patients with refractory nasopharyngeal carcinoma after repeated traditional radiochemotherapy. STUDY DESIGN: Case series with chart review. SETTING: University medical center. SUBJECTS AND METHODS: A total of 26 patients (18 men, 8 women; mean age, 51.3 ± 10.8 years; totaling 53 lesions with an average diameter of 2.86 ± 1.61 cm) were treated by PET-CT-guided (125)I seed implantation. All of the patients received a PET-CT scan 2 months after the treatment. Follow-up was conducted for ~2 to 43 months (median, 28.2 months) to observe the local control rate, overall survival rate, and clinical complications. RESULTS: The local control rates of refractory nasopharyngeal carcinoma after repeated traditional radiochemotherapy after 3, 6, 12, 24, and 36 months were 90.6% (48/53), 79.3% (42/53), 71.7% (38/53), 62.3% (33/53), and 56.6% (30/53), respectively. The overall 1-, 2-, and 3-year survival rates were 87.2%, 71.3%, and 56.5%, respectively, with a median survival time of 28.2 months. Of all patients, 19.2% (5/26) died of local recurrence and 15.4% (4/26) died of metastases. One patient died of hypertensive cerebral hemorrhage, and another patient died from cachexia and infection. The long-term complications included hyperpigmentation at operative sites (n = 5), insensible feeling on the lateral cheek (n = 2), dryness of the oral cavity (n = 1), and headache (n = 1). CONCLUSION: PET-CT-guided (125)I seed implantation is an acceptable and feasible method for treating refractory nasopharyngeal carcinoma with minimal damage and few complications.

Recurrent gliomas: comparison of computed tomography (CT)-guided 125I seed implantation therapy and traditional radiochemotherapy.

BACKGROUND: Primary brain tumors have always been associated with high morbidity and mortality. Glioma is the most common type of malignant brain tumors,with a high probability of recurrence after surgical excision and with poor prognosis.The purpose of this study was to compare the therapeutic efficacy of computed tomography (CT)-guided interstitial (125)I seed implantation with traditional radiochemotherapy for treatment of recurrent gliomas. RESULTS: The response rate at 1, 3, 6 and 12 months after (125)I seed implantation was 68.6, 74.3, 77.1 and 62.8% respectively, which was significantly higher than the group treated with the conventional chemoradiation protocol (p < 0.05). Patients exposed to (125)I seed implantation had a median survival of 29.0 months, whereas the median survival of those treated with traditional radiochemotherapy was 19.0 months. The difference observed between the two groups was significant. There were no severe complications or mortality associated with either treatment, except for one case of intracerebral hemorrhage around the tumor area in the (125)I seed implants group. METHODS: From November 2002 to May 2010, 73 consecutive patients with recurrent gliomas were treated with CT-guided (125)I seed implantation (35 cases) or traditional radiochemotherapy (38 cases). Patients were followed up after treatment and the therapeutic effect was evaluated by comparing the response and survival rates of the two groups. In particular, patients treated with (125)I seed implantation were monitored for adverse side effects. CONCLUSIONS: CT-guided (125)I seed implantation is safe and well-tolerated and more importantly, shows superior efficacy compared with conventional radiochemotherapy. This suggests that CT-guided (125)I seed implantation could be an alternative approach for recurrent gliomas.

An imageable retinoid acid derivative to detect human cancer xenografts and study therapeutic dosing to reduce its toxicity.

Developing agents with 'seek, treat and see' capability is critical for personalized molecular medicine. Those agents will specifically target the disease markers for diagnosis and apply the biologically effective dose for treatment. Retinoids regulate a multitude of biological processes. In addition, retinoic acid can reverse premalignancy, significantly decrease second primary tumors and provide a treatment benefit in head and neck, lung, esophagus, colon and bladder cancer. These data suggest that cancer cells can take up retinoids. Therefore, retinoids are potential tumor-imaging agents. We developed near-infrared (NIR)-labeled retinoid agents to detect human cancers, visualize drug redistribution within the body, determine the optimal biological dose and reduce systemic toxicity. Our data demonstrate that the retinoid agent, but not the free dye, binds to the human tumor cells and is internalized, where it permits the imaging of human cancer xenografts. The high dose of retinoid agent is significantly associated with systemic toxicity. In summary, synthetic NIR-labeled retinoid agents can be used to detect multiple human cancer xenografts as the agent is internalized by cancer cells. The binding of the agent to the tumor xenografts is dependent on the redistribution of the agent. Therapeutic agents labeled with reporters will interrogate tumor-drug interactions and permit analysis of biodistribution, pharmacokinetics and pharmacodynamics in real time. At the same time, we can apply the biologically effective dose for therapy, instead of the traditional maximum tolerated dose, to reduce systemic toxicity.