Effects of Coptis extract combined with chemotherapeutic agents on ROS production, multidrug resistance, and cell growth in A549 human lung cancer cells

Background: Non–small cell lung cancer is associated with high expression of multidrug resistance (MDR) proteins and low production of reactive oxygen species (ROS). Coptis extract (COP), a Chinese medicinal herb, and its major constituent, berberine (BER), have anticancer properties. This study aims to investigate the effects of COP and BER combined with chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX), on cell proliferation, ROS production, and MDR in A549 human non-small cell lung cancer cells. Methods: A549 cells were treated with different doses of COP and BER, combined with 5-FU, CPT, and TAX. Cell viability was measured by an XTT (2,3-bis-(2-methoxy-4- nitro-5-sulfophenyl)-2 H-tetrazolium-5-carboxanilide) assay. Intracellular ROS levels were determined by measuring the oxidative conversion of cell permeable 2′,7′-dichlorofluorescein diacetate to fluorescent dichlorofluorescein. MDR of A549 cells was assessed by rhodamine 123 retention assay. Results: Both COP and BER significantly inhibited A549 cell growth in a dose-dependent manner. Combinations of COP or BER with chemotherapeutic agents (5-FU, CPT, and TAX) exhibited a stronger inhibitory effect on A549 cell growth. In addition, COP and BER increased ROS production and reduced MDR in A549 cells. Conclusion: As potential adjuvants to chemotherapy for non–small cell lung cancer, COP and BER increase ROS production, reduce MDR, and enhance the inhibitory effects of chemotherapeutic agents on A549 cell growth

The association between S100A13 and HMGA1 in the modulation of thyroid cancer proliferation and invasion

Additional file 5: Figure S3. Lentivirus-mediated S100A13 knockdown was utilized to detect the effect on migration capability with scratch-wound assays in TPC1 cell

Omega-3 Polyunsaturated Fatty Acids Protect Neural Progenitor Cells against Oxidative Injury

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), derived mainly from fish oil, play important roles in brain development and neuroplasticity. Here, we reported that application of ω-3 PUFAs significantly protected mouse neural progenitor cells (NPCs) against H2O2-induced oxidative injury. We also isolated NPCs from transgenic mice expressing the Caenorhabditis elegans fat-1 gene. The fat-1 gene, which is absent in mammals, can add a double bond into an unsaturated fatty acid hydrocarbon chain and convert ω-6 to ω-3 fatty acids. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that a marked decrease in apoptotic cells was found in fat-1 NPCs after oxidative injury with H2O2 as compared with wild-type NPCs. Quantitative RT-PCR and Western blot analysis demonstrated a much higher expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor for antioxidant genes, in fat-1 NPCs. The results of the study provide evidence that ω-3 PUFAs resist oxidative injury to NPCs

Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice

Recent studies have shown that a tumor-supportive microenvironment is characterized by high levels of pro-inflammatory and pro-angiogenic eicosanoids derived from omega-6 (n−6) arachidonic acid (AA). Although the metabolic pathways (COX, LOX, and P450) that generate these n−6 AA eicosanoids have been targeted, the role of endogenous AA production in tumorigenesis remains unexplored. Delta-6 desaturase (D6D) is the rate-limiting enzyme responsible for the synthesis of n−6 AA and increased D6D activity can lead to enhanced n−6 AA production. Here, we show that D6D activity is upregulated during melanoma and lung tumor growth and that suppressing D6D activity, either by RNAi knockdown or a specific D6D inhibitor, dramatically reduces tumor growth. Accordingly, the content of AA and AA-derived tumor-promoting metabolites is significantly decreased. Angiogenesis and inflammatory status are also reduced. These results identify D6D as a key factor for tumor growth and as a potential target for cancer therapy and prevention

Label-Free Biomedical Imaging with High Sensitivity by Stimulated Raman Scattering Microscopy

Label-free chemical contrast is highly desirable in biomedical imaging. Spontaneous Raman microscopy provides specific vibrational signatures of chemical bonds, but is often hindered by low sensitivity. Here we report a three-dimensional multiphoton vibrational imaging technique based on stimulated Raman scattering (SRS). The sensitivity of SRS imaging is significantly greater than that of spontaneous Raman microscopy, which is achieved by implementing high-frequency (megahertz) phase-sensitive detection. SRS microscopy has a major advantage over previous coherent Raman techniques in that it offers background-free and readily interpretable chemical contrast. We show a variety of biomedical applications, such as differentiating distributions of omega-3 fatty acids and saturated lipids in living cells, imaging of brain and skin tissues based on intrinsic lipid contrast, and monitoring drug delivery through the epidermis.Chemistry and Chemical Biolog

A visualized dynamic prediction model for survival of patients with geriatric thyroid cancer: A population-based study

ObjectiveThyroid cancer (TC) is a common malignancy with a poor prognosis with aging. However, no accurate predictive survival model exists for patients with geriatric TC.We aimed to establish prediction models of prognosis in elderly TC.MethodsWe retrospectively reviewed the clinicopathology characteristics of patients with geriatric TC in the Surveillance, Epidemiology, and End Results database (SEER) from 2004 to 2018. The risk predictors used to build the nomograms were derived from the Cox proportional risk regression. These nomograms were used to predict 1-, 3-, and 5-year overall survival and cancer-specific survival in elderly patients with TC. The accuracy and discriminability of the new model were evaluated by the consistency index (C-index) and calibration curve. The clinical applicability value of the model was assessed using the decision curve analysis.ResultsWe used the SEER database to include 16475 patients with geriatric TC diagnosed from 2004 to 2018. The patients from 2004 to 2015 were randomly sorted out on a scale of 7:3. They were classified into a training group (n = 8623) and a validation group (n = 3669). Patients with TC diagnosed in 2016–2018 were classified into external validation groups (n = 4183). The overall survival nomogram consisted of 10 variables (age, gender, marital status, histologic type, grade, TNM stage, surgery status, and tumor size). A cancer-specific survival nomogram consisted of eight factors (age, tumor size, grade, histologic type, surgery, and TNM stage). The C-index values for the training, validation, and external validation groups were 0.775 (95% confidence interval [CI] 0.785–0.765), 0.776 (95% CI 0.792–0.760), and 0.895(95% CI 0.873–0.917), respectively. The overall survival was consistent with a nomogram based on the calibration curve. Besides, the decision curve analysis showed excellent clinical application value of the nomogram. Additionally, we found that surgery could improve the prognosis of patients with geriatric at high-risk (P < 0.001) but not those at low-risk (P = 0.069).ConclusionThis was the first study to construct predictive survival nomograms for patients with geriatric TC. The well-established nomograms and the actual results could guide follow-up management strategies

Comparison of the ocular surface microbiota between thyroid-associated ophthalmopathy patients and healthy subjects

PurposeThyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disease. In this study, high-throughput sequencing was used to investigate the diversity and composition of the ocular microbiota in patients with TAO.MethodsPatients with TAO did not receive treatment for the disease and did not have exposed keratitis. Patients with TAO (TAO group) and healthy individuals (control group) were compared. All samples were swabbed at the conjunctival vault of the lower eyelid. The V3 to V4 region of the 16S rDNA was amplified using polymerase chain reaction and sequenced on the Illumina HiSeq 2500 Sequencing Platform. Statistical analysis was performed to analyze the differences between the groups and the correlation between ocular surface microbiota and the disease. The ocular surface microbiota of patients and healthy individuals were cultured.ResultsThe ocular surface microbiota structure of TAO patients changed significantly. The average relative abundance of Bacillus and Brevundimonas increased significantly in the TAO group. Corynebacterium had a significantly decreased relative abundance (P<0.05). Paracoccus, Haemophilus, Lactobacillus, and Bifidobacterium were positively correlated with the severity of clinical manifestations or disease activity (P<0.05). Bacillus cereus and other opportunistic pathogens were obtained by culture from TAO patients.ConclusionsThis study found that the composition of ocular microbiota in patients with TAO was significantly different from that in healthy individuals. The ocular surface opportunistic pathogens, such as Bacillus, Brevundimonas, Paracoccus, and Haemophilus in TAO patients, increase the potential risk of ocular surface infection. The findings of this study provide a new avenue of research into the mechanism of ocular surface in TAO patients

Promising Clinical Outcome With Long Term Follow-Up After Body Gamma Knife Stereotactic Radiosurgery for Patients With Early Stage Non-small Cell Lung Cancer

Introduction: Stereotactic ablative radiosurgery (SRS) or stereotactic ablative body radiotherapy (SABR) is the standard treatment for patients with inoperable early stage non-small cell lung cancer (NSCLC), the body gamma knife SRS (ɤ-SRS) is a special SABR technology developed in China. This study prospectively assessed the clinical outcome, toxicity and cost following body ɤ-SRS for early stage NSCLC.Methods: From 2007 to 2010, a total of 29 patients with early stage NSCLC were prospectively enrolled in this study. The prescription dose for Planning Target Volume (PTV), Clinical Target Volume (CTV), and Gross Target Volume (GTV) were 50, 60, and 70 gray (Gy) in 10 fractions. Isodose curves of 50, 60, and 70% covered at least 100% of PTV, 90% of CTV, and 80% of GTV, respectively. The body ɤ-SRS was delivered 5 days per week and completed in 2 weeks.Results: Median follow-up time was 62.0 (range 11.1-140.3) months. 1-, 3-, 5-year OS rates were 93.1%, 72.0%, 60.3%; PFS rates were 86.2, 64.2 and 48.8%; and LR, RR, and DM rates were 10.9%, 21.4%, 29.0%. The median cost of the body ɤ-SRS during treatment was 4,838 (range 4,615–4,923) dollars and the median cost through 5 years was 36,960 (range 9920-56,824) dollars.Conclusion: With existing clinical data, the body ɤ-SRS is an effective treatment option for patients with medically inoperable early stage NSCLC or patients who do not prefer operation, as they may benefit from the minimized toxicity. Due to excellent cost effectiveness, the availability of the body ɤ-SRS will expand, especially in developing nations, and underdeveloped countries

Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy

The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively), muscle isotonic and tetanic force (by 29% and 18%, respectively), CSA of the soleus muscle (by 36%), and soleus muscle fibers (by 45%). Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs) ratio as compared with C57BL/6 wild-type mice (56%, p < 0.001). Fat-1 mice had lower soleus muscle dry mass loss (by 10%) and preserved absolute isotonic force (by 17%) and CSA of the soleus muscle (by 28%) after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70%) and MuRF-1 content decreased (by 50%) in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition