Background
Angiogenesis is a critical biological process essential for solid cancer growth and metastasis. It has been shown that microRNAs (miRNAs) play a vital role in a variety of biological ...processes in cancers. However, whether miR-130b is involved in prostate cancer angiogenesis remains ill-defined.
Methods
We performed the miRNA microarray to analyze miRNA expression in human prostate cancer specimens. In vitro gain-of-function assays and loss-of-function assays were conducted to explore the potential functions of miR-130b in human prostate cancer cells. Correlation analysis and dual-luciferase reporter assay were performed to validate whether tumor necrosis factor-α (TNF-α) was a direct target of miR-130b. The Matrigel plug and tumor vascular imaging assays were performed to confirm the anti-angiogenic activity of miR-130b in nude mice.
Results
We found that miR-130b was one of the miRNAs being most significantly downregulated. Subsequently, we found that miR-130b expression was markedly downregulated in human prostate cancer cell lines. Down-regulation of miR-130b in prostate cancer cells significantly promoted the proliferation, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs), while ectopic expression of miR-130b blocked prostate cancer angiogenesis in vitro and in vivo. Mechanistic analyses indicated that tumor necrosis factor-α (TNF-α) was regulated by miR-130b directly. MiR-130b attenuated nuclear factor-κB (NF-κB) signaling and its downstream gene vascular endothelial growth factor-A (VEGFA) by directly inhibiting TNF-α expression. Additionally, subsequent investigations identified that the ectopic level of VEGFA markedly abrogated the anti-angiogenic effect induced by miR-130b. Interestingly, VEGFA could in turn decrease the expression of miR-130b, thus forming a negative feedback loop that drives the angiogenesis of prostate cancer.
Conclusion
These findings show that miR-130b/TNF-α/NF-κB/VEGFA feedback loop is significantly correlated with angiogenesis in prostate cancer and miR-130b could be regarded as potential therapeutic target for prostate cancer anti-angiogenesis treatment.
The idea of "one airway, one disease" has been gaining importance in the last decade. In the upper and lower airways, allergic mechanisms interact with each other. In the initial stage of respiratory ...allergic inflammation, allergens contact the respiratory epithelium, which produces chemokines and inflammatory factors, which cause allergic reactions by binding to the corresponding receptors and chemotactic various inflammatory cells to reach the epithelium and tissues. It also drives inflammatory cells to activate and produce more inflammatory factors, thus producing a cascade amplification effect. Inflammatory cell aggregation and activation are very complex and interact with each other in a lattice structure. By blocking the action of various chemokines, inflammatory cell aggregation is reduced, and ultimately the symptoms of respiratory allergy are alleviated. Chemokines can serve as cues for coordinated recruitment of immune cells into and out of tissues, as well as directing the spatial organization of immune cells within tissues and cellular interactions. Chemokines are critical in directing immune cell migration and thus have an important role in the direction of respiratory allergy: however, chemokines are also involved in the production and recruitment of immune cells that contribute to respiratory allergy. In this article, linking the upper and lower respiratory tracts. We review the role of the chemokine system in the respiratory immune response and discuss how respiratory disease modulates overall chemokines to shape the type and outcome of the immune response to the treatment of respiratory allergic disease so that we can further deepen our knowledge of chemokines in the direction of respiratory allergy. In the future, we can do drug research and development based on this network structure and explore new research directions.
Esophageal squamous cell carcinoma (ESCC), the major histologic subtype of esophageal cancer, is a devastating disease characterized by distinctly high incidences and mortality rates. However, there ...remains limited understanding of molecular events leading to development and progression of the disease, which are of paramount importance to defining biomarkers for diagnosis, prognosis, and personalized treatment. By high-throughout transcriptome sequence profiling of nontumor and ESCC clinical samples, we identified a subset of significantly differentially expressed genes involved in integrin signaling. The Rab25 gene implicated in endocytic recycling of integrins was the only gene in this group significantly downregulated, and its downregulation was confirmed as a frequent event in a second larger cohort of ESCC tumor specimens by quantitative real-time PCR and immunohistochemical analyses. Reduced expression of Rab25 correlated with decreased overall survival and was also documented in ESCC cell lines compared with pooled normal tissues. Demethylation treatment and bisulfite genomic sequencing analyses revealed that downregulation of Rab25 expression in both ESCC cell lines and clinical samples was associated with promoter hypermethylation. Functional studies using lentiviral-based overexpression and suppression systems lent direct support of Rab25 to function as an important tumor suppressor with both anti-invasive and -angiogenic abilities, through a deregulated FAK-Raf-MEK1/2-ERK signaling pathway. Further characterization of Rab25 may provide a prognostic biomarker for ESCC outcome prediction and a novel therapeutic target in ESCC treatment.
Research Objective
Coordinated Specialty Care (CSC) is an evidence‐based intervention for individuals experiencing first‐episode psychosis. A team of clinicians and nonclinical specialists deliver ...CSC based on the principles of shared decision making and aimed at maximizing recovery. Mental Health Block Grant (MHBG) “set‐aside” funding earmarked by Congress in 2014 (and doubled in 2015) boosted implementation of CSC in the U.S. Currently, CSC teams around the country utilize idiosyncratic and patchwork approaches to funding. This study aims to identify prominent models of CSC financing, alignments or misalignments of such models with sustained implementation, and CSC provider perspectives on ideal payment approaches.
Study Design
Qualitative study based on semi‐structured interviews with informants from CSC provider organizations. A multi‐disciplinary team transcribed and analyzed digitally recorded interviews using the modified grounded theory method, iteratively developed a coding book, coded interview data, and identified recurring themes.
Population Studied
Purposeful sampling of CSC program directors or team leaders using a national, far‐reaching email listserv was supplemented by snowball sampling via recommendation of interview participants. Findings are based on analysis of interview data of 15 CSC programs in 12 states.
Principal Findings
A dominant model for CSC financing combined insurance billing (for billable services) and the MHBG funding (for nonbillable costs). CSC provider organizations viewed fee‐for‐service insurance billing as inadequate and seriously misaligned with CSC in the following ways: 1. Commercial insurance and Medicaid (to a less extent) typically do not cover services provided by nonclinician professionals (eg, supported employment and education specialists), services provided in the community, case management, or team operation and community outreach activities; 2. For covered services, the regular insurance billing rate is inadequate for the high intensity, low caseload of CSC; 3. Services provided prior to client enrollment (eg, to engage client and family) are often not covered; and 4. Insurance billing consumes substantial staff time and resources. CSC teams, regardless of their current financing approaches, almost universally endorsed a bundled/case rate payment as an ideal way of paying for CSC, with two major supporting rationales: 1. A bundled payment arrangement shifts the focus from “productivity” (in terms of billable encounters) to holistic problem‐solving and innovation with the explicit goal of improving patient engagement, outcomes, and experience; and 2. With a bundled payment, insured clients will not pick and choose which components of CSC to receive (eg, based on insurance coverage or out‐of‐pocket costs), thus preserving fidelity and provider autonomy in CSC service provision.
Conclusions
Heavy reliance on fee‐for‐service insurance billing is unsustainable and misaligned with the goals of CSC. CSC provider organizations expressed high consensus in support of a bundled payment.
Implications for Policy or Practice
To scale up and sustain population deployment of CSC, public and private payers should consider bundled payment approaches. Because of the diversity in CSC programs, populations, and existing funding mechanisms and rules, payer‐provider collaboration will be essential in designing the payment model. Data are needed to support the business case of covering CSC with a bundled rate, especially in terms of cost savings as a result of CSC.
Primary Funding Source
The Robert Wood Johnson Foundation.
The residency program director (PD) position is a valued leadership appointment in academic medicine. PDs are responsible for the success of their program and its residents. The objective of this ...study is to provide a cross-sectional analysis of baseline demographics and academic backgrounds of current neurosurgery program directors.
Data was compiled on neurosurgery PDs and their residency programs, as of the end of May 2021, using publicly available resources including Doximity, FREIDA, and Healthgrades. The Mann-Whitney and Fisher exact tests were used for statistical analysis.
Of 113 PDs identified, 91.15% are male (P < 0.01). The majority of PDs (88.5%) received their medical degrees from U.S. medical schools. The average age of current PDs is 54 years, and the average age at appointment was 48 years. Compared to their male counterparts, female PDs are more likely to be younger at appointment (41 vs. 48 years; P = 0.001) and while holding the same position (45 vs. 55 years; P = 0.001). As a result, female PDs experience less time to appointment after residency (8.6 years vs. 14.7 years, P = 0.013). There are no significant differences regarding the gender of the PD and university affiliation, current appointment, completion of a fellowship, and resident gender ratios.
The position of neurosurgery residency PD is dominated by fellowship-trained men in their late 40s to 50s. The gender ratio of neurosurgery residents is consistent with the underrepresentation of women in this position. With increasing female representation in neurosurgery, more women may assume this leadership position and begin to hasten the gender balance.
Iron oxide nanoparticles with extremely low dimensions have recently been explored as positive (T
) contrast agent for magnetic resonance imaging (MRI). However, their small sizes lead to fast renal ...clearance and limit their use in elongated in vivo tracking or therapy monitoring. In this paper, we present a state of art approach to forming nanoclusters by crosslinking ultrasmall iron oxide nanoparticles with bovine serum albumin. This novel design not only maintains the T
performance of the ultrasmall nanoparticles, but also significantly increases their blood circulation times from 15 minutes to over two hours. Our breast tumor model study also exhibited enhanced contrast at tumor sites for more than 24 hours. The ability of maintaining the T
performance of the ultrasmall nanoparticles is significant, because previous studies have shown complete T
loss or signal decrease upon polymer encapsulation. This design also shows great potential in encapsulating model drug molecules, which will greatly benefit the field of imaging-guided drug delivery.
Liver cancer is a malignant cancer with great harmfulness. Fenofibrate is a peroxisome proliferation activated receptor (PPARα) agonist widely used in the treatment of dyslipidemia. Previous studies ...have shown that fenofibrate may promote cell proliferation, but the underlying mechanism has not been fully characterized. The aim of this study was to investigate the role of PPARα agonist fenofibrate in cell proliferation of SMMC-7721 cells compared with that of THLE-2 cells. SMMC-7721 and THLE-2 cells were treated with different concentrations of fenofibrate. Cell proliferation was analyzed by MTT, using flow cytometry for cell cycle analysis, and CyclinD1, Cyclin-dependent kinases2 (CDK2) and Proliferating Cell Nuclear Antigen (PCNA) were analyzed by Western blotting. RT-qPCR method was used to assess CDK2, CyclinD1 and PCNA mRNA levels. The results showed that 10−9–10−4 mol/L fenofibrate could induce cell growth and 10−4, 10−5, 10−6 mol/L fenofibrate could reduce the number of G0/G1 phase cells and increased in the number of cells in S and G2/M phase of cell cycle in SMMC-7721 cells. Furthermore, fenofibrate could significantly increase the expression of cell cycle related protein (CyclinD1, CDK2)and cell proliferation related proteins (PCNA). The use of PPARα inhibitor MT886 inhibited cell cycle progression and promote tumor cell apoptosis. But fenofibrate had no obvious effect on THLE-2 cells. These results revealed the effect of fenofibrate on the cell cycle of liver cancer cells, and provided a reasonable explanation for studying how fenofibrate promotes cell proliferation.
Summary
The effect of human parathyroid hormone 1-34 (PTH) and zoledronic acid (ZA) alone or in combination on bone healing in osteoporotic settings was tested using implants inserted in tibiae of ...ovariectomized (OVX) rats. Combination therapy promoted bone healing more than each treatment alone 12 weeks after implant insertion.
Introduction
PTH and ZA have been demonstrated to be effective on implant fixation. However, reports about the combined use of PTH and ZA for promotion of bone healing around implant in osteoporotic settings are still limited. This study aims to investigate effects of PTH+ZA on implant stabilization in OVX rats.
Methods
Twelve weeks after bilateral ovariectomy, OVX rats randomly received implants without or with ZA (by immersion in 1 mg/ml ZA solution for 24 h). Subsequently, half of the animals from each group also received subcutaneous injections of PTH (60 μg/kg, three times a week) for 12 weeks. Thus, there were four groups: control, PTH, ZA, and PTH+ZA.
Results
All treatments promoted bone healing around implant compared to control, but PTH+ZA treatment showed significantly stronger effects than PTH or ZA alone in histological, micro-CT, and biomechanical tests.
Conclusion
The results indicated the additive effects of PTH and ZA on implant fixation in OVX rats; it was suggested that the anabolic effect of PTH was potent and not blunted by ZA during bone healing around implant when used concurrently.
Hypoxia-inducible factor (HIF) is considered an important transcription factor due to its roles in glycolysis, angiogenesis, cell differentiation, apoptosis, and other cellular pathways. It takes the ...role in various physiological and pathological states, such as solid tumors, vascular injury, and atherosclerotic lesion progression. In recent studies, HIF is found as a master regulator of body inflammation and immunity, not only in hypoxia but also in normoxia. Nasal inflammation has a close relationship with anoxia. But the role of HIF in nasal inflammation is still unclear.
We searched the Pubmed using the key words: "Hypoxia-inducible factor" and "nasal" or "Hypoxia-inducible factor", and reviewed the related articles.
HIF is composed of HIF-α and HIF-β subunits. HIF-a is an adjusting relational subunit, which is divided into three subtypes: HIF-1a, HIF-2a, and HIF-3a. HIF-1a is the key component and best understood. HIF-1a can be activated under hypoxic conditions or by various cytokines and growth factors. HIF-1α accumulation is critical for sustaining human allergic effector cell survival and function. The level of HIF-1a is increased in the patients with allergic rhinitis and become a new therapeutic target. HIF-1a also plays an important role in the pathogenesis of CRS and polyp formation. Some research found that the expression of HIF-1α was increased in CRS with polyps.
HIF-1a takes an important role in allergic rhinitis and chronic sinusitis. It will be a key therapeutic target of these diseases in the future.
PDF
