Multi-imaging platform for rhizosphere studies: Phosphorus and oxygen fluxes.

Rhizosphere is a soil volume of high spatio-temporal heterogeneity and intensive plant-soil-microbial interactions, for which visualization and process quantification is of highest scientific and applied relevance, but still very challenging. A novel methodology for quick assessment of two-dimensional distribution of available phosphorus (P) in rhizosphere was suggested, tested, and development up to the application platform. Available P was firstly trapped by an in-situ diffusive gradients in thin-films (DGT) sampler with precipitated zirconia as the binding gel, and subsequently, the loaded gel was analyzed with an optimized colorimetric imaging densitometry (CID). The imaging platform was established linking: i) DGT, ii) planar optode, and iii) soil zymography techniques to simultaneously determine available P, oxygen, and acid phosphatase in rhizosphere at sub-millimeter spatial scales. The DGT identified available P level in rice rhizosphere were spatially overlapping to the localized redox hotspots and phosphatase activity. The spatial relationship between available P and acid phosphatase activity was dependent on root development. The root radial oxygen loss (ROL) remained active during the experimental observations (2-3 days), while a flux of available P of 10 pg cm-2 s-1 was visualized within 2-3 mm of roots, confirming the correlative response of rice roots to oxygen secretion and P uptake. Summarizing, the established imaging platform is suitable to capture spatial heterogeneity and temporal dynamics of root activities, nutrient bioavailability, ROL and enzyme activities in rhizosphere.

Antibacterial Effects of Ramulus mori Oligosaccharides against Streptococcus mutans.

Ramulus mori has been widely used in traditional Chinese medicine because of its physiological activities, including antibacterial, anti-inflammatory, and antioxidant activities. Antimicrobial properties of Ramulus mori extract have been well described. However, no information is available regarding on Ramulus mori oligosaccharides (RMOS). The aim of this study was to investigate the effects of RMOS on the growth and virulence properties of the cariogenic bacterium Streptococcus mutans. The effects of RMOS on the biofilm structure and virulence gene expression of S. mutans were also evaluated, and the results were compared with the effects of commercial prebiotic galactooligosaccharides. RMOS were found to have an antibacterial effect against S. mutans, resulting in significant reductions in acid production, lactate dehydrogenase activity, adhesion, insoluble extracellular polysaccharide production, glucosyltransferase activity, and biofilm formation in a dose-dependent manner. Moreover, the biofilm structure was visibly damaged. A quantitative real-time PCR assay revealed downregulation of virulence gene-regulated acid production, polysaccharide production, adhesion, biofilm formation, and quorum sensing. These findings suggest that RMOS may be a promising natural product for the prevention of dental caries.

Essential nutrients and cerebral small vessel diseases: a two-sample Mendelian randomization study.

Background: Previous studies have suggested a potential association between nutrients and cerebral small vessel disease (CSVD), but this association has not been fully addressed. Object: We intended to clarify the causal associations between four categories of essential nutrients (amino acids, polyunsaturated fatty acids, minerals and vitamins) and two acute manifestations of CSVD (intracerebral hemorrhage and small vessel stroke) using two-sample Mendelian randomization (MR) analysis. Method: We obtained European-based large-scale genome-wide association studies (GWASs) related to CSVD (6,255 cases and 233,058 controls) and nutrient concentrations. Causality evaluation mainly included the results of the inverse variance-weighted (IVW) method. The simple median method, the weighted median method and the MR-Egger method were adopted for sensitivity analyses. Results: For ICH or SVS, increased levels of phenylalanine (OR = 1.188, p < 0.001) and dihomo-gamma-linolenic acid (DGLA) (OR = 1.153, p = 0.001) showed risk effects, while docosapentaenoic acid (DPA) (OR = 0.501, p < 0.001), zinc (OR = 0.919, p < 0.001), and arachidonic acid (OR = 0.966, p = 0.007) showed protective effects. For lobar hemorrhage or SVS, AA (OR = 0.978, p < 0.001), zinc (OR = 0.918, p < 0.001), and retinol (OR = 0.753, p < 0.001) showed risk effects; DPA (OR = 0.682, p = 0.022), gamma-linolenic acid (OR = 0.120, p = 0.033) and 25(OH)D (OR = 0.874, p = 0.040) showed protective effects. For nonlobar hemorrhage or SVS, DGLA (OR = 1.088, p < 0.001) and phenylalanine (OR = 1.175, p = 0.001) showed risk effects. Conclusion: Our study analyzed the effect of nutrients on CSVD risk from a genetic perspective, with implications for CSVD prevention through nutrient supplementation.

Bufei huoxue capsule alleviates bleomycin-induced pulmonary fibrosis in mice via TGF-ß1/Smad2/3 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Bufei huoxue (BFHX) is a Traditional Chinese Medicine formulation that consists of Astragalus Exscapus L, Paeonia Lactiflora Pall, and Psoralea Aphylla L. It can ameliorate collagen deposition and inhibit EMT. However, it remains unknown whether and how BFHX alleviates IPF. AIM OF THE STUDY: Our work aimed to explore the therapeutic efficacy of BFHX on IPF and dissect the mechanisms involved. MATERIALS AND METHODS: A mouse model of IPF was induced by bleomycin. BFHX was administered on the first day of modeling and maintained for 21 days. Pulmonary fibrosis and inflammation were evaluated by micro-CT, lung histopathology, pulmonary function assessment, and cytokines in BALF. In addition, we examined the signaling molecules involved in EMT and ECM by immunofluorescence, western Blot, EdU, and MMP (Δψm) assays. RESULTS: BFHX alleviated lung parenchyma fibrosis as evidenced by Hematoxylin-eosin (H&E), Masson's trichrome staining, and micro-CT, and it improved lung function. In addition, BFHX treatment not only decreased the levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), but also upregulated E-cadherin (E-Cad) and downregulated α-smooth muscle actin (α-SMA), collagen Ӏ (Col Ӏ), vimentin, and fibronectin (FN). Mechanistically, BFHX repressed TGF-ß1-driven Smad2/3 phosphorylation, which, in turn, suppressed EMT and transition of fibroblasts to myofibroblasts in vivo and in vitro. CONCLUSION: BFHX effectively reduces the occurrence of EMT and inhibits the production of ECM by inhibiting the TGF-ß1/Smad2/3 signaling pathway, which provides a potential novel therapeutic strategy for IPF.

Mechanism of lead adsorption by a Bacillus cereus strain with indole-3-acetic acid secretion and inorganic phosphorus dissolution functions.

BACKGROUND: Heavy metal pollution has become a major source of environmental pollution because of increasing industrialization. Microbial remediation is a promising approach to remediate lead-contaminated environments owing to its cost-effective, environment-friendly, ecologically sustainable, and highly efficient properties. In this study, the growth-promoting functions and lead-adsorption ability of Bacillus cereus SEM-15 were examined, and the functional mechanism of the strain was preliminarily identified using scanning electron microscopy, energy spectrum, infrared spectrum, and genome analyses, providing theoretical support for utilization of B. cereus SEM-15 in heavy metals remediation. RESULTS: B. cereus SEM-15 showed strong ability to dissolve inorganic phosphorus and secrete indole-3-acetic acid. The lead adsorption efficiency of the strain at lead ion concentration of 150 mg/L was more than 93%. Single factor analysis revealed the optimal conditions for heavy metal adsorption by B. cereus SEM-15 (adsorption time, initial lead ion concentration, pH, and inoculum amount were 10 min, 50-150 mg/L, 6-7, and 5 g/L, respectively) in nutrient-free environment, with the lead adsorption rate reaching 96.58%. Scanning electron microscopy of B. cereus SEM-15 cells before and after lead adsorption showed adherence of a large number of granular precipitates to the cell surface after lead adsorption. X-Ray photoelectron spectroscopy and Fourier transform infrared spectroscopy results indicated the characteristic peaks of Pb-O, Pb-O-R (R = functional group), and Pb-S bonds after lead adsorption, and a shift in the characteristic peaks of bonds and groups related to C, N, and O. Genome annotation results showed the presence of genes related to heavy metals tolerance and plant growth promotion in B. cereus SEM-15, providing a molecular basis for the strain's heavy metals tolerance and plant growth promotion functions. CONCLUSIONS: This study analyzed the lead adsorption characteristics of B. cereus SEM-15 and the associated influencing factors, and discussed the adsorption mechanism and related functional genes, providing a basis for clarifying the underlying molecular mechanism and offering a reference for further research on plant-microorganisms combined remediation of heavy metals polluted environments.

Synergistic effect of lecithin and alginate, CMC, or PVP in stabilizing curcumin and its potential mechanism.

This work aims to advance the understanding of the synergistic mechanism of lecithin and polymers (alginate, CMC, and PVP) in stabilizing curcumin, with a major focus on understanding the nanocomplex formation process and the main binding energy between molecules. It is demonstrated that lecithin and polymers have a synergistic effect in increasing the thermal acid, light, and digestion stability of curcumin. The potential mechanism is that the hydrophobic parts of curcumin molecules are first anchored at the region of the hydrophobic cavity of lecithin by van der Waals, while the hydrophilic parts are outward and are further encapsulated by hydrophilic polymers by van der Waals and electrostatic interaction to form a protective shell. This study contributes to our understanding of the synergistic mechanism of lecithin, polymers, and hydrophobic compounds, which can promote the synergistic use of lecithin and polymers to prepare nanocomplexes as an important tool for delivering bioactive compounds.

Ferulic Acid Prevents Nonalcoholic Fatty Liver Disease by Promoting Fatty Acid Oxidation and Energy Expenditure in C57BL/6 Mice Fed a High-Fat Diet.

There is a consensus that ferulic acid (FA), the most prominent phenolic acid in whole grains, displays a protective effect in non-alcoholic fatty liver disease (NAFLD), though its underlying mechanism not fully elucidated. This study aimed to investigate the protective effect of FA on high-fat diet (HFD)-induced NAFLD in mice and its potential mechanism. C57BL/6 mice were divided into the control diet (CON) group, the HFD group, and the treatment (HFD+FA) group, fed with an HFD and FA (100 mg/kg/day) by oral gavage for 12 weeks. Hematoxylin and eosin (H&E) staining and Oil Red O staining were used to evaluate liver tissue pathological changes and lipid accumulation respectively. It was demonstrated that FA supplementation prevented HFD-induced NAFLD, which was evidenced by the decreased accumulation of lipid and hepatic steatosis in the HFD+FA group. Specifically, FA supplementation decreased hepatic triacylglycerol (TG) content by 33.5% (p < 0.01). Metabolic cage studies reveal that FA-treated mice have elevated energy expenditure by 11.5% during dark phases. Mechanistically, FA treatment increases the expression of rate-limiting enzymes of fatty acid oxidation and ketone body biosynthesis CPT1A, ACOX1 and HMGCS2, which are the peroxisome proliferator-activated receptors α (PPARα) targets in liver. In conclusion, FA could effectively prevent HFD-induced NAFLD possibly by activating PPARα to increase energy expenditure and decrease the accumulation of triacylglycerol in the liver.

D-chiro-Inositol facilitates adiponectin biosynthesis and activates the AMPKα/PPARs pathway to inhibit high-fat diet-induced obesity and liver lipid deposition.

D-chiro-Inositol (DCI) is a natural cyclohexanol isomer that widely exists in all living beings, which can effectively prevent glucose and lipid metabolism disorders in mammals. This study revealed the DCI elevated adiponectin levels to reduce obesity and hepatic lipid deposition in high-fat diet (HFD) fed mice. Twelve weeks of DCI supplementation (50 and 100 mg per kg body weight per day) lowered body weight and serum triglyceride, total cholesterol, insulin, and fasting glucose levels. Histopathology analysis revealed that DCI inhibited hepatic steatosis and adipocyte expansion. Remarkably, DCI significantly increased serum adiponectin levels and upgraded the expressions of adiponectin receptors (AdipoR1 and AdipoR2) in the liver. The results of western blot and qRT-PCR showed that DCI impeded the inhibitory effect of HFD on liver AMPKα and PPARs activities through activating AdipoRs and regulated downstream fatty acid metabolism. In addition, we analyzed the concentration difference of DCI in mouse liver and adipose tissue by the HRLC-MS/MS technology, indicating the preference of DCI in different tissues. Therefore, DCI relieved liver lipid deposition and hyperlipidemia potentially by promoting adiponectin synthesis in white adipose tissue and activating the AdipoR-AMPKα/PPARs pathway in the liver.

Study on the regulatory effect of leech peptide HE-D on macrophages in atherosclerosis by transcriptome sequencing.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of atherosclerotic cardiovascular disease is a serious threat to human health. Leeches are used in traditional Chinese medicine to treat cardiovascular diseases. HE-D is an active peptide extracted and isolated from leeches, which can inhibit the migration of RAW264.7 macrophages. AIM: This study shows the effects of HE-D on macrophages in atherosclerosis and the mechanism of inhibition on the migration of macrophages based on transcriptome sequencing (RNA-Seq). MATERIALS AND METHODS: The transwell method was used to detect the activity of HE-D in inhibiting the migration of macrophages. Macrophages were divided into control group, lipopolysaccharide group, and HE-D group. Samples were collected and RNA-Seq performed. The DEseq2 method detected significantly differentially expressed genes (DEGs), GO and KEGG Pathway databases were used to analyze the functions and pathway enrichment of DEGs. Finally, qRT-PCR and Western blotting were used to verify the genes screened by RNA-Seq analyses. RESULTS: Cell experiments showed that HE-D can inhibit the migration of RAW264.7 macrophages induced by LPS. DEseq2 analyses showed that there were 363 DEGs after HE-D administration in the result of RNA-Seq. The GO function of DEGs was significantly enriched in cell migration and inflammation, and the DEGs related to cell migration were significantly enriched in the NF-κB signaling pathway. qRT-PCR and Western blot analyses, showed that when compared with the LPS group, the related genes IKKα, IKKγ, TRAF6, TLR4, and TRAF5 in the NF-κB pathway were significantly down-regulated in the HE-D group. In addition, it was found that the inflammatory factors iNOS and TNF-α were significantly down-regulated, and Arg-1 and IL-10 were up-regulated. CONCLUSION: HE-D can inhibit the migration of macrophages by inhibiting IKKα and IKKγ in the NF-κB signaling pathway, and promote the transformation of macrophages from M1to M2 subtypes. Therefore, HE-D can potentially be used as a drug for the treatment of atherosclerosis.

The anticancer potential of the dietary polyphenol rutin: Current status, challenges, and perspectives.

Rutin is one of the most common dietary polyphenols found in vegetables, fruits, and other plants. It is metabolized by the mammalian gut microbiota and absorbed from the intestines, and becomes bioavailable in the form of conjugated metabolites. Rutin exhibits a plethora of bioactive properties, making it an extremely promising phytochemical. Numerous studies demonstrate that rutin can act as a chemotherapeutic and chemopreventive agent, and its anticancer effects can be mediated through the suppression of cell proliferation, the induction of apoptosis or autophagy, and the hindering of angiogenesis and metastasis. Rutin has been found to modulate multiple molecular targets involved in carcinogenesis, such as cell cycle mediators, cellular kinases, inflammatory cytokines, transcription factors, drug transporters, and reactive oxygen species. This review summarizes the natural sources of rutin, its bioavailability, and in particular its potential use as an anticancer agent, with highlighting its anticancer mechanisms as well as molecular targets. Additionally, this review updates the anticancer potential of its analogs, nanoformulations, and metabolites, and discusses relevant safety issues. Overall, rutin is a promising natural dietary compound with promising anticancer potential and can be widely used in functional foods, dietary supplements, and pharmaceuticals for the prevention and management of cancer.

Soybean lecithin-stabilized oil-in-water (O/W) emulsions increase the stability and in vitro bioaccessibility of bioactive nutrients.

This study was proposed to investigate the possibility of co-delivering essential oils and lipophilic nutrients via lecithin stabilized emulsions. Emulsions with different droplet sizes (62.5-105 nm), zeta potentials (-33.7 to -58.6 mV), and PdI values (0.155-0.275) were successfully prepared. Incorporation of curcumin into emulsions significantly improved its water solubility (1700-fold), thermal and photochemical stability. The droplet size of curcumin-loaded emulsions did not change over 30 days of storage at 4 °C. Gastrointestinal tract (GIT) digestion caused significant changes in the droplet size and interfacial properties of curcumin-loaded emulsions. The bioaccessibility of encapsulated curcumin was 4.79-10.6-fold higher than that of free molecule. This is mainly attributed to the different solubility of curcumin in essential oils, which also showed different bioaccessibility. The findings suggested that emulsions can be novel carriers for co-delivering essential oils and lipophilic nutrients with increased stability and bioaccessibility.

Oridonin Suppresses Human Gastric Cancer Growth in Vitro and in Vivo via Inhibition of VEGF, Integrin ß3, and PCNA.

The diterpenoid oridonin is an extract from the herb Rabdosia rubescens, commonly used in Traditional Chinese medicine. Oridonin has putative inhibitory activity in many human cancers. This study continued investigations into the therapeutic potential of oridonin against gastric carcinoma, and the underlying mechanism. An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with BGC823 cells was used to examine the cytotoxicity and apoptosis associated with oridonin treatment. RT-PCR and immunocytochemistry results showed evaluated levels of vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), integrin ß3, and proliferating cell nuclear antigen (PCNA) in BGC823 cells, or BGC823 xenografts nude mice. The inhibitory effect of oridonin was determined in vivo using the xenograft model, comparing tumor weight and volume, and calculating the tumor inhibition rate. The oridonin treatment and control groups were compared for associations between microvessel density and tumor inhibition rate, VEGF mRNA, integrin ß3 mRNA, and PCNA protein. The IC50s of oridonin at 12 and 72 h were 17.08 ± 2.38 and 8.76 ± 0.90 µg/mL, respectively. VEGF protein levels dramatically decreased in a time- and dose-dependent manner with oridonin treatment. BGC823 xenograft growth was notably less in the oridonin treatment groups, responding in a dose-dependent manner. After 14 d of treatment, VEGF, integrin ß3, and PCNA levels were dramatically lower, and positively correlated with CD31 levels. Oridonin was associated with inhibition of BGC823 cell growth and tumor angiogenesis, in vitro and in vivo, in a dose-and-time dependent manner with lower levels of VEGF, integrin ß3, and PCNA. Oridonin is a potential candidate agent for chemotherapy of gastric carcinoma.

The CCDC43-ADRM1 axis regulated by YY1, promotes proliferation and metastasis of gastric cancer.

Previous studies have shown an association between coiled-coil domain-containing (CCDC) genes and different cancers. Our previous studies revealed that CCDC43 is highly expressed in colorectal cancer, but the expression and molecular mechanisms of CCDC43 in gastric cancer (GC) are yet to be determined. Here, we show that CCDC43 is overexpressed in gastric tissues. CCDC43 expression is closely related to tumor differentiation, lymph-node-metastasis, and prognosis of gastric cancer. Overexpression of CCDC43 promotes the proliferation, invasion, and metastasis of GC cells. CCDC43 may upregulate and stabilize ADRM1, resulting in the construction of the ubiquitin-mediated proteasome. In contrast, inhibition of ADRM1 could reverse the function of CCDC43 in GC both in vitro and in vivo. Our data demonstrate that transcription factor YY1 directly binds to CCDC43 and ADRM1 gene promoters, leading to over-expression of CCDC43 and ADRM1. Furthermore, in vitro experiments demonstrate that knock down of CCDC43 or ADRM1 attenuates the YY1-mediated malignant phenotypes. Finally, the association among YY1, CCDC43 and ADRM1 is validated in clinical samples. Our findings suggest that the CCDC43-ADRM1 axis regulated by YY1, promotes proliferation and metastasis of GC, and the axis may be a potential therapeutic target for GC.

Hovenia dulcis polysaccharides: Influence of multi-frequency ultrasonic extraction on structure, functional properties, and biological activities.

The directional effect of single-frequency ultrasonic was the cause of the low extraction yield of polysaccharide macromolecule. Thus, a possible solution was to use multi-frequency ultrasonic technology to improve the yield of polysaccharide. Single-frequency (SF), dual-frequency (DF), and three-frequency (TF) ultrasonic extraction were applied to extract polysaccharides of Hovenia dulcis (HDPs). A maximal polysaccharide extraction yield (9.02 ±â€¯0.29%) was gat using the dual-frequency ultrasonic with optimized DF conditions comprising 58.00 °C, 33.00 min, 28&40 kHz. The three HDPs were compared for their physicochemical, rheological, and functional properties, and their antioxidant activities. DF-HDPs contain higher uronic acid than SF-HDPs and TF-HDPs. Rheological tests indicated that the HDPs had excellent colloid properties and a promising potential to serve as a thickener, gelatinizer, and stabilizing agent in the food industry. Moreover, the DF-HDPs exhibited a notable oil holding capacity (3.92 ±â€¯0.04 g oil/g), foaming capacity (35.26 ±â€¯0.47%), and emulsion capacity (43.96 ±â€¯0.67%). Compared to the SF- and TF-HDPs, the DF-HDPs had superior antioxidant activities. In conclusion, a better extraction method (dual-frequency ultrasonic extraction) was achieved.

Nanochemoprevention with therapeutic benefits: An updated review focused on epigallocatechin gallate delivery.

Epigallocatechin gallate (EGCG) is a natural phenolic compound found in many plants, especially in green tea, which is a popular and restorative beverage with many claimed health benefits such as antioxidant, anti-cancer, anti-microbial, anti-diabetic, and anti-obesity activities. Despite its great curative potential, the poor bioavailability of EGCG restricts its clinical applcation. However, nanoformulations of EGCG are emerging as new alternatives to traditional formulations. This review focuses on the nanochemopreventive applications of various EGCG nanoparticles such as lipid-based, polymer-based, carbohydrate-based, protein-based, and metal-based nanoparticles. EGCG hybridized with these nanocarriers is capable of achieving advanced functions such as targeted release, active targeting, and enhanced penetration, ultimately increasing the bioavailability of EGCG. In addition, this review also summarizes the challenges for the use of EGCG in therapeutic applications, and suggests future directions for progress.

Phylogenetic Analysis of the Complete rRNA Gene Sequence of Nosema sp. SE Isolated from the Beet Armyworm Spodoptera exigua.

The microsporidium Nosema sp. SE is a pathogen that infects the beet armyworm Spodoptera exigua. The complete sequence of its 4,302-base pair (bp) ribosomal ribonucleic acid (rRNA) gene region was obtained by polymerase chain reaction amplification and sequencing. The rRNA organization of Nosema sp. SE was 5'-large subunit (LSU) rRNA-internal transcribed spacer-small subunit (SSU) rRNA-intergenic spacer-5S-3', which corresponded to the pattern of Nosema bombycis. Phylogenetic analysis based on LSU rRNA and SSU rRNA both indicated that the parasite had a close relationship with other true Nosema species, confirming that Nosema sp. SE belongs to true Nosema group of the genus Nosema.

Quality Formation Mechanism of Stiff Silkworm, Bombyx batryticatus Using UPLC-Q-TOF-MS-Based Metabolomics.

Bombyx batryticatus is a well-known animal in traditional Chinese medicine. The aim of the research was to reveal the quality formation mechanism of B. batryticatus and to screen out the characteristic component used for the quality control. The anticonvulsant effects of B. batryticatus with a stiff time of one, five, and nine days (D1, D5 and D9, respectively) and healthy silkworm of the same developmental stage (SW) were determined by animal experiment. The dynamic changes in chemical composition were analyzed using UPLC-Q-TOF-MS-based metabolomics. D5 and D9 B. batryticatus exhibited significant anticonvulsant effects (p < 0.05 and p < 0.01, respectively). Accordingly, principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA) indicated that the chemical composition of D5 and D9 B. batryticatus changed significantly. The different metabolites mainly consisted of primary metabolites such as lipids and amino acids and secondary metabolites such as flavonoids, beauvericin, and glycolipids. Interestingly, the relative abundance of quercetin-7-O-ß-d-4-O-methylglucoside, the characteristic component of B. batryticatus, increased with stiff time and was promised to be used as an index component of quality control. The results expand our understanding of the quality formation mechanism of B. batryticatus. In addition, it highlights the potential of UPLC-Q-TOF-MS-based metabolomics for the quality control purpose of TCMs.

Effect of adjuvant radioactive iodine therapy on survival in rare oxyphilic subtype of thyroid cancer (Hürthle cell carcinoma).

PURPOSE: Radioactive iodine (RAI) is widely used for adjuvant therapy after thyroidectomy, while its value for thyroid cancer has been controversial recently. The primary objectives of this study were to clarify the influence of Radioactive iodine (RAI) on the survival in rare oxyphilic subtype of thyroid cancer (Hürthle cell carcinoma, HCC). METHODS: Patients diagnosed with oxyphilic thyroid carcinoma from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results Program database. The Kaplan-Meier method was used to compare overall survival (OS) and cancer-specific survival (CSS) among patients who had adjuvant RAI use or not. Univariate and multivariate Cox proportional hazard models were performed for survival analysis, and subsequently visualized by nomogram. RESULTS: In all, 2,799 patients were identified, of which 1529 patients had adjuvant RAI use while 1,270 patients had not. Based on multivariate Cox analysis, the RAI therapy confers an improved OS for HCC patients (HR = 0.57, 95% CI [0.44-0.72], P < 0.001), whereas it has no significant benefit in the survival analysis regarding CSS (HR = 0.79, 95% CI [[0.47-1.34], P = 0.382). In a subgroup analysis, the same survival benefit of RAI treatment on OS, but not CSS was observed among patients stratified by AJCC stage and tumor extension. Nevertheless, patients with regional lymph node metastasis benefited from RAI therapy both in OS and CSS (P < 0.001, respectively). Furthermore, nomograms used for predicting long term survival of HCC patients exhibited a better prediction power for OS compared with traditional tumor, nodal and metastatic (TNM) stage made by American Joint Committee on Cancer (AJCC) (C-index = 0.833 of the nomogram model vs. 0.696 of the AJCC system). CONCLUSIONS: This study suggests that RAI therapy is significantly associated with improved OS in patients with Hürthle cell carcinoma. However, there was no association between treatment with radioiodine and CSS, possibly due to small number of deaths that were related to HCC.

Yi-qi-yang-yin-tian-sui-fang enhances cisplatin-induced tumor eradication and inhibits interleukin-7 reduction in non-small cell lung cancer.

Traditional Chinese Medicine (TCM) has been recognized to be conducive to enhancing the efficiency and reducing the side effects in the whole course of cancer treatment. The mechanisms of TCM/chemotherapy combination involved with interleukin-7 (IL-7) potentially enhance immune responses against tumor. In the present study, we emphasized on a herbal formulation Yi-qi-yang-yin-tian-sui-fang or TCM for short, and investigated its roles in chemotherapy in non-small cell lung cancer (NSCLC). The mice bared with tumor were treated with cisplatin (DDP) and simultaneously administrated with/without low, medium and high doses of TCMs (effective content: 0.5, 2.0 and 8.0 g/per mice) via oral gavage. The results indicated that combination of TCM further elevated the therapy efficiency of DDP in a dose-dependent manner. The growth of tumor cells was estimated by Ki-67 stain and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay. The addition of TCM to the DDP treatment could significantly decrease the expression of Ki-67 and promote the apoptosis of tumor cells. In addition, the serum IL-7 level was down-regulated by DDP but restored by the treatment of TCM. The expression of IL-7 and its receptor IL-7R in tumor tissues was also recovered by TCM. Furthermore, the side effect from bone marrow suppression (myelosuppression) induced by DDP were assessed. TCM could abrogate DDP-induced apoptosis of bone marrow and also remarkably induced the expressions of IL-7 and hematopoietic growth factors including G-CSF, GM-CSF, SCF, and SDF-1 in bone marrow. These data indicated that this TCM combined with DDP showed superior anti-tumor effects with reduced myelosuppression via up-regulating IL-7.

The regulation of skeletal muscle fiber-type composition by betaine is associated with NFATc1/MyoD.

Increasing evidence indicates that muscular dysfunction or alterations in skeletal muscle fiber-type composition not only are involved in muscle metabolism and function but also can limit functional capacity. Therefore, understanding the mechanisms regulating key events during skeletal myogenesis is necessary. Betaine is a naturally occurring component of commonly eaten foods. Here, we showed that 10 mM betaine supplementation in vitro significantly repressed myoblast proliferation and enhanced myoblast differentiation. This effect can be mediated by regulation of miR-29b-3p. Further analysis showed that betaine supplementation in vitro regulated skeletal muscle fiber-type composition through the induction of NFATc1 and the negative regulation of MyoD expression. Furthermore, mice fed with 10 mM betaine in water for 133 days showed no impairment in overall health. Consistently, betaine supplementation increased muscle mass, promoted muscle formation, and modulated the ratio of fiber types in skeletal muscle in vivo. These findings shed light on the diverse biological functions of betaine and indicate that betaine supplementation may lead to new therapies for diseases such as muscular dystrophy or other diseases related to muscle dysfunction. KEY MESSAGES: Betaine supplementation inhibits proliferation and promotes differentiation of C2C12 myoblasts. Betaine supplementation regulates fast to slow muscle fiber-type conversion and is associated with NFATc1/MyoD. Betaine supplementation enhances skeletal myogenesis in vivo. Betaine supplementation does not impair health of mice.