Compression enhances invasive phenotype and matrix degradation of breast Cancer cells via Piezo1 activation

Background Uncontrolled growth in solid breast cancer generates mechanical compression that may drive the cancer cells into a more invasive phenotype, but little is known about how such compression affects the key events and corresponding regulatory mechanisms associated with invasion of breast cancer cells including cellular behaviors and matrix degradation. Results Here we show that compression enhanced invasion and matrix degradation of breast cancer cells. We also identified Piezo1 as the putative mechanosensitive cellular component that transmitted compression to not only enhance the invasive phenotype, but also induce calcium influx and downstream Src signaling. Furthermore, we demonstrated that Piezo1 was mainly localized in caveolae, and both Piezo1 expression and compression-enhanced invasive phenotype of the breast cancer cells were reduced when caveolar integrity was compromised by either knocking down caveolin1 expression or depleting cholesterol content. Conclusions Taken together, our data indicate that mechanical compression activates Piezo1 channels to mediate enhanced breast cancer cell invasion, which involves both cellular events and matrix degradation. This may be a critical mechanotransduction pathway during breast cancer metastasis, and thus potentially a novel therapeutic target for the disease.

Creep Modelling of Rootstock during Holding in Watermelon Grafting

The fragile structure of a rootstock predisposes the stem to mechanical damage during grafting. Thus, it is necessary to take into account the rootstock’s rheological properties under mechanical compression when designing a clamping mechanism. This study focused on cucurbit, a typical rootstock for watermelon grafting. Firstly, we adopted a four-element Burgers model to analyze viscoelastic behavior and deformation characteristics of the rootstock, then conducted creep tests to obtain the parameters of the viscoelastic model. Next, we developed a model for the rootstock during holding based on viscoelastic parameters, loading force and contact time. Moreover, we evaluated the effect of various loading forces and test velocities on creep deformation to reveal the least damage on the rootstock. Results showed that the influence of loading force on the creep deformation was greater than test velocity. Finally, the holding test indicated that the clamping mechanism with silicone rubber can effectively prevent the damage to the stem. Specifically, the loading force should be controlled below 4 N to reduce the associated damage. Taken together, our findings provide a theoretical basis for analyzing the holding damage mechanism during watermelon grafting.

Lamina cribrosa vessel and collagen beam networks are distinct

Our goal was to analyze the spatial interrelation between vascular and collagen networks in the lamina cribrosa (LC). Specifically, we quantified the percentages of collagen beams with/without vessels and of vessels inside/outside of collagen beams. To do this, the vasculature of six normal monkey eyes was labelled by perfusion post-mortem. After enucleation, coronal cryosections through the LC were imaged using fluorescence and polarized light microscopy to visualize the blood vessels and collagen beams, respectively. The images were registered to form 3D volumes. Beams and vessels were segmented, and their spatial interrelationship was quantified in 3D. We found that 22% of the beams contained a vessel (range 14% to 32%), and 21% of vessels were outside beams (13% to 36%). Stated differently, 78% of beams did not contain a vessel (68% to 86%), and 79% of vessels were inside a beam (64% to 87%). Individual monkeys differed significantly in the fraction of vessels outside beams (p<0.01 by linear mixed effect analysis), but not in the fraction of beams with vessels (p>0.05). There were no significant differences between contralateral eyes in the percent of beams with vessels and of vessels outside beams (p>0.05). Our results show that the vascular and collagenous networks of the LC in monkey are clearly distinct, and the historical notions that each LC beam contains a vessel and all vessels are within beams are inaccurate. We postulate that vessels outside beams may be relatively more vulnerable to mechanical compression by elevated IOP than are vessels shielded inside of beams.

Transient complete heart block: a case report of a rare complication of tricuspid valve infective endocarditis

Background Right-sided tricuspid valve (TV) endocarditis can be difficult to identify and may be under-recognized in the absence of traditional risk factors. While generally identified with aortic valve pathology, infective endocarditis that extends beyond the leaflets of the TV have been reported to cause conduction disease. Case summary We present the case of a 63-year-old patient who presented with haemodynamically unstable complete heart block requiring temporary venous pacemaker support. Despite the absence of traditional risk factors or significant valvular disease on transthoracic echocardiogram, she was found to be persistently bacteraemic and subsequent transoesophageal echocardiogram identified large vegetation on the septal leaflet of the TV. Conduction disease was noted to reverse with antibiotic therapy and resolution of bacteraemia. Discussion Although rare, right-sided endocarditis involving the triangle of Koch may present with conduction disease due to local inflammation and mechanical compression. Conduction disease associated with right-sided disease appears to be readily reversible with medical therapy and temporary device support may be appropriate in the acute setting.