Bone Marrow Adipocyte: An Intimate Partner With Tumor Cells in Bone Metastasis

The high incidences of bone metastasis in patients with breast cancer, prostate cancer and lung cancer still remains a puzzling issue. The “seeds and soil” hypothesis suggested that bone marrow (soil) may provide a favorable “niche” for tumor cells (seed). When seeking for effective ways to prevent and treat tumor bone metastasis, most researchers focus on tumor cells (seed) but not the bone marrow microenvironment (soil). In reality, only a fraction of circulating tumor cells (CTCs) could survive and colonize in bone. Thus, the bone marrow microenvironment could ultimately determine the fate of tumor cells that have migrated to bone. Bone marrow adipocytes (BMAs) are abundant in the bone marrow microenvironment. Mounting evidence suggests that BMAs may play a dominant role in bone metastasis. BMAs could directly provide energy for tumor cells, enhance the tumor cell proliferation, and resistance to chemotherapy and radiotherapy. BMAs are also known for releasing some inflammatory factors and adipocytokines to promote or inhibit bone metastasis. In this review, we made a comprehensive summary for the interaction between BMAs and bone metastasis. More importantly, we discussed the potentially promising methods for the prevention and treatment of bone metastasis. Genetic disruption and pharmaceutical inhibition may be effective in inhibiting the formation and pro-tumor functions of BMAs

Fasting Hyperglycemia Increases In-Hospital Mortality Risk in Nondiabetic Female Patients with Acute Myocardial Infarction: A Retrospective Study

Previous studies had shown that elevated admission plasma glucose (APG) could increase mortality rate and serious complications of acute myocardial infarction (AMI), but whether fasting plasma glucose (FPG) had the same role remains controversial. In this retrospective study, 253 cases of AMI patients were divided into diabetic (n=87) and nondiabetic group (n=166). Our results showed that: compared with the nondiabetic patients, diabetic patients had higher APG, FPG, higher plasma triglyceride, higher rates of painless AMI (P<0.01), non-ST-segment elevation myocardial infarction (NSTEMI), and reinfraction (P<0.05). They also had lower high density lipoprotein cholesterol and rate of malignant arrhythmia, but in-hospital mortality rate did not differ significantly (P>0.05). While nondiabetic patients were subgrouped in terms of APG and FPG (cut points were 11.1 mmol/L and 7.0 mmol/L, resp.), the mortality rate had significant difference (P<0.01), whereas glucose level lost significance in diabetic group. Multivariate logistic regression analysis showed that FPG (OR: 2.014; 95% confidence interval: 1.296–3.131; p<0.01) but not APG was independent predictor of in-hospital mortality for nondiabetic patients. These results indicate that FPG can be an independent predictor for mortality in nondiabetic female patients with AMI

Partial sequencing of the bottle gourd genome reveals markers useful for phylogenetic analysis and breeding

<p>Abstract</p> <p>Background</p> <p>Bottle gourd [<it>Lagenaria siceraria </it>(Mol.) Standl.] is an important cucurbit crop worldwide. Archaeological research indicates that bottle gourd was domesticated more than 10,000 years ago, making it one of the earliest plants cultivated by man. In spite of its widespread importance and long history of cultivation almost nothing has been known about the genome of this species thus far.</p> <p>Results</p> <p>We report here the partial sequencing of bottle gourd genome using the 454 GS-FLX Titanium sequencing platform. A total of 150,253 sequence reads, which were assembled into 3,994 contigs and 82,522 singletons were generated. The total length of the non-redundant singletons/assemblies is 32 Mb, theoretically covering ~ 10% of the bottle gourd genome. Functional annotation of the sequences revealed a broad range of functional types, covering all the three top-level ontologies. Comparison of the gene sequences between bottle gourd and the model cucurbit cucumber (<it>Cucumis sativus</it>) revealed a 90% sequence similarity on average. Using the sequence information, 4395 microsatellite-containing sequences were identified and 400 SSR markers were developed, of which 94% amplified bands of anticipated sizes. Transferability of these markers to four other cucurbit species showed obvious decline with increasing phylogenetic distance. From analyzing polymorphisms of a subset of 14 SSR markers assayed on 44 representative China bottle gourd varieties/landraces, a principal coordinates (PCo) analysis output and a UPGMA-based dendrogram were constructed. Bottle gourd accessions tended to group by fruit shape rather than geographic origin, although in certain subclades the lines from the same or close origin did tend to cluster.</p> <p>Conclusions</p> <p>This work provides an initial basis for genome characterization, gene isolation and comparative genomics analysis in bottle gourd. The SSR markers developed would facilitate marker assisted breeding schemes for efficient introduction of desired traits.</p

Does Digital Agricultural Technology Extension Service Enhance Sustainable Food Production? Evidence from Maize Farmers in China

This research aims to investigate the average and heterogeneous impacts of digital agricultural technology extension service use on eco-efficiency among 1302 maize-producing farmers from a major maize-producing area in Northeast China in 2022. The slack-based measure model with undesirable outputs is applied to calculate the eco-efficiency of maize production. To obtain an unbiased estimation of the average effect, the self-selection problem generated by observable and unobservable factors is solved by the endogenous switching regression model. Quantile regression is utilized to analyze the heterogeneous effect. Notably, the mediated effects model is utilized to examine the potential mechanism between them. Our findings indicate that digital agricultural technology extension service use can increase maize production’s eco-efficiency. Digital agricultural technology extension service users would have reduced the eco-efficiency of the service by 0.148 (21.11%) if they had not used it. Digital agricultural technology extension service nonusers would have improved the eco-efficiency of the service by 0.214 (35.20%) if they had used it. The robustness check reconfirms the results. Moreover, digital agricultural technology extension service use is more helpful for maize farmers who have lower eco-efficiency than those who have higher eco-efficiency. Digital agricultural technology extension service use can improve the eco-efficiency of maize production through the application of organic fertilizers, green pesticides, and biodegradable agricultural films. There are policy implications of these findings: there is an argument for using the publicity of the digital agricultural technology extension service to encourage farmers to use sustainable inputs; additionally, it might be worthwhile to implement a categorized promotion strategy based on the different real-world situations

Interferon-Gamma-Mediated Osteoimmunology

Osteoimmunology is the interdiscipline that focuses on the relationship between the skeletal and immune systems. They are interconnected by shared signal pathways and cytokines. Interferon-gamma (IFN-γ) plays important roles in immune responses and bone metabolism. IFN-γ enhances macrophage activation and antigen presentation. It regulates antiviral and antibacterial immunity as well as signal transduction. IFN-γ can promote osteoblast differentiation and inhibit bone marrow adipocyte formation. IFN-γ plays dual role in osteoclasts depending on its stage. Furthermore, IFN-γ is an important pathogenetic factor in some immune-mediated bone diseases including rheumatoid arthritis, postmenopausal osteoporosis, and acquired immunodeficiency syndrome. This review will discuss the contradictory findings of IFN-γ in osteoimmunology and its clinical application potential

Fasting Hyperglycemia Increases In-Hospital Mortality Risk in Nondiabetic Female Patients with Acute Myocardial Infarction: A Retrospective Study

Previous studies had shown that elevated admission plasma glucose (APG) could increase mortality rate and serious complications of acute myocardial infarction (AMI), but whether fasting plasma glucose (FPG) had the same role remains controversial. In this retrospective study, 253 cases of AMI patients were divided into diabetic (n=87) and nondiabetic group (n=166). Our results showed that: compared with the nondiabetic patients, diabetic patients had higher APG, FPG, higher plasma triglyceride, higher rates of painless AMI (P<0.01), non-ST-segment elevation myocardial infarction (NSTEMI), and reinfraction (P<0.05). They also had lower high density lipoprotein cholesterol and rate of malignant arrhythmia, but in-hospital mortality rate did not differ significantly (P>0.05). While nondiabetic patients were subgrouped in terms of APG and FPG (cut points were 11.1 mmol/L and 7.0 mmol/L, resp.), the mortality rate had significant difference (P<0.01), whereas glucose level lost significance in diabetic group. Multivariate logistic regression analysis showed that FPG (OR: 2.014; 95% confidence interval: 1.296–3.131; p<0.01) but not APG was independent predictor of in-hospital mortality for nondiabetic patients. These results indicate that FPG can be an independent predictor for mortality in nondiabetic female patients with AMI

Self-Assembled BODIPY Derivative with A-D-A Structure as Organic Nanoparticles for Photodynamic/Photothermal Cancer Therapy

Organic nanomaterials have attracted considerable attention in the area of photodynamic and photothermal therapy, owing to their outstanding biocompatibility, potential biodegradability, well-defined chemical structure, and easy functionalization. However, it is still a challenge to develop a single organic molecule that obtains both photothermal and photodynamic effects. In this contribution, we synthesized a new boron-dipyrromethene (BODIPY)-based derivative (DPBDP) with an acceptor–donor–acceptor (A-D-A) structure by coupling 3,6-di(2-thienyl)-2,5-dihydropyrrolo [3,4-c] pyrrole-1,4-dione (DPP) and BODIPY. To enhance the hydrophilicity of the BODIPY derivative, the polyethylene glycol (PEG) chains were introduced to the meso- position of BODIPY core. The amphiphilic DPBDP was then self-assembled into related nanoparticles (DPBDP NPs) with improved hydrophilicity and enhanced absorbance in the NIR region. DPBDP NPs could simultaneously generate the singlet oxygen (1O2) and heat under the irradiation of a single laser (690 nm). The 1O2 quantum yield and photothermal conversion efficiency (PCE) of DPBDP NPs were calculated to be 14.2% and 26.1%, respectively. The biocompatibility and phototherapeutic effect of DPBDP NPs were evaluated through cell counting kit-8 (CCK-8) assay. Under irradiation of 690 nm laser (1.0 W/cm2), the half maximal inhibitory concentration (IC50) of DPBDP NPs was calculated to be 16.47 µg/mL. Thus, the as-prepared DPBDP NPs could be acted as excellent candidates for synergistic photodynamic/photothermal therapy

Epstein-Barr Virus Promotes Inflammatory Cytokine Production in Human Gingival Fibroblasts

Background: Periodontitis is one of the most common chronic oral inflammatory diseases. Over the past decade, herpes viruses, particularly Epstein-Barr virus (EBV), have been considered promising pathogenic candidates for periodontitis. However, the specific mechanism by which EBV contributes to the development of periodontitis is still unknown. This study aimed to explore the mechanism of EBV underlying the inflammatory response in human gingival fibroblasts (HGFs). Materials and methods: HGFs were stimulated with different concentrations of EBV (104, 105, 106, 107, and 108 DNA copies/mL) for 0, 8, 24, or 48 hours. The mRNA levels of interleukin (IL)-1β, tumour necrosis factor-α (TNF-α), IL-8, monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor 9 (TLR9) were measured using quantitative real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assays (ELISAs) were performed for determining the mRNA and protein levels of IL-1β, TNF-α, IL-8, and MCP-1. Real-time PCR and ELISA were performed to determine the protein levels of IL-1β, TNF-α, IL-8, and MCP-1. Activation of the TLR9/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) pathway was evaluated using western blotting. Results: The expressions of IL-1β, TNF-α, IL-8, and MCP-1 were significantly upregulated in HGFs under EBV stimulation in a concentration- and time-dependent manner. EBV promoted TLR9 and MyD88 expression and induced NF-κB transcription. On the contrary, the upregulation of these factors and the activation of NF-κB pathway were drastically inhibited by TLR9 antagonists. Conclusions: Our findings demonstrate that EBV promotes the production of inflammatory cytokines IL-1β and TNF-α and chemokines IL-8 and MCP-1 in HGFs through the TLR9/MyD88/NF-κB pathway