scholarly journals Functional Deficits in Mice Expressing Human Interleukin 8

2020 ◽  
Vol 70 (3) ◽  
pp. 205-215
Author(s):  
Julie Michelle Brent ◽  
Zuozhen Tian ◽  
Lutian Yao ◽  
Jian Huang ◽  
Dessislava Z Markova ◽  
...  

We showed previously that inflammatory mediators, including IL8, in intervertebral disc tissues from patients with discogenic back pain may play a key role in back pain. To investigate the molecular mechanism of IL8 signaling in back pain, we generated a mouse model that conditionally expresses human (h) IL8. We hypothesized that hIL8 levels affect mouse activity and function. Briefly, hIL8 cDNA was inserted into the pCALL2 plasmid, linearized, and injected into mouse embryos. Resulting pCALL2–hIL8 mice were then bred with GDF5–Cre mice to express the transgene in cartilage and intervertebral disc (IVD) tissues. Functional capacities including nest-making and other natural behaviors were measured. Both male and female mice expressing hIL8 showed lower nesting scores than did littermates that did not express hIL8 (n = 14 to 16 per group). At 28 wk of age, mice expressing hIL8 (n = 35) spent more time immobile and eating during each night than littermate controls (n = 33). Furthermore, hIL8-expressing mice traveled shorter distances and at a lower average speed than littermate controls. Thus, in an initial effort to investigate the relationship between this chemokine and mouse behavior, we have documented changes in normal activities in mice conditionally expressing hIL8.

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Hosni Cherif ◽  
Daniel G Bisson ◽  
Matthew Mannarino ◽  
Oded Rabau ◽  
Jean A Ouellet ◽  
...  

Cellular senescence is a contributor to intervertebral disc (IVD) degeneration and low back pain. Here, we found that RG-7112, a potent mouse double-minute two protein inhibitor, selectively kills senescent IVD cells through apoptosis. Gene expression pathway analysis was used to compare the functional networks of genes affected by RG-7112, a pure synthetic senolytic with o-Vanillin a natural and anti-inflammatory senolytic. Both affected a functional gene network related to cell death and survival. O-Vanillin also affected networks related to cell cycle progression as well as connective tissue development and function. Both senolytics effectively decreased the senescence-associated secretory phenotype (SASP) of IVD cells. Furthermore, bioavailability and efficacy were verified ex vivo in the physiological environment of degenerating intact human discs where a single dose improved disc matrix homeostasis. Matrix improvement correlated with a reduction in senescent cells and SASP, supporting a translational potential of targeting senescent cells as a therapeutic intervention.


Pain Medicine ◽  
2021 ◽  
Author(s):  
Adam M R Groh ◽  
Dale E Fournier ◽  
Michele C Battié ◽  
Cheryle A Séguin

Abstract Objective: Back pain is an elusive symptom complicated by a variety of possible causes, precipitating and maintaining factors, and consequences. Notably, the underlying pathology remains unknown in a significant number of cases. Changes to the intervertebral disc (IVD) have been associated with back pain, leading many to postulate that the IVD may be a direct source of pain, typically referred to as discogenic back pain. Yet, despite decades of research into the neuroanatomy of the IVD, there is a lack of consensus in the literature as to the distribution and function of neural elements within the tissue. The current scoping review provides a comprehensive systematic overview of studies that document the topography, morphology, and immunoreactivity of neural elements within the IVD in humans. <uMel>thod: Articles were retrieved from six separate databases in a three-step systematic search, and independently evaluated by two reviewers. <Resul>ults: Three categories of neural elements were described within the IVD: perivascular nerves, sensory nerves independent of blood vessels, and mechanoreceptors. Nerves were consistently localized within the outer layers of the annulus fibrosus. Neural ingrowth into the inner annulus fibrosus and nucleus pulposus was found to occur only in degenerative states and disease states. Conclusion: While the pattern of innervation within the IVD is clear, the specific topographic arrangement and function of neural elements in the context of back pain remains unclear.


Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).


2019 ◽  
Vol 2 (1) ◽  
pp. 10402-1-10402-11
Author(s):  
Midori Tanaka ◽  
Takahiko Horiuchi ◽  
Ken’ichi Otani

Abstract A planetarium imitates a starry sky with physical and technical limitations using a dome, projector, and light source. It is widely used for entertainment, and astronomy and physics educations. In our previous study, we investigated the evaluation for faithful reproduction of a star field in a planetarium by performing psychometric experiments with 20 observers for plural projection patterns with different reproduction factors (color, luminance, and size of projected stars). In this study, we investigate the relationship between faithfulness and preference of a star field in a planetarium through a psychometric experiment with 47 observers. The experimental procedure followed the previous study. The rating of faithfulness improved for the projection pattern with a smaller star size. For the preference evaluation, the projection pattern with low luminance significantly lowered the preference rating. The results of the experiment indicate that the preferable star reproduction was different between male and female observers, whereas the faithful star reproduction was not significantly different in the evaluations between male and female observers. The male observers sought a faithful star reproduction as the preferred reproduction. In contrast, the female observers did not feel the faithful star reproduction preferable, and evaluated the more brilliant star reproduction as the preferred reproduction. These results were not dependent on the experience in astronomical observations.


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