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Mechanical stimuli have profound effects on the cellular architecture and functions. Over the past two decades, considerable progress has been made in unraveling the molecular machineries that confer cells the ability to sense and transduce mechanical input into biochemical signals. This has resulted in the identification of several force-sensing proteins or mechanically activated ion channels distributed throughout most cell types, whereby the plasma membrane, cytoskeleton, and the nucleus have garnered much attention. Although organelles from the endomembrane system make up significant portion of cell volume and play pivotal roles in the spatiotemporal distribution of signaling molecules, they have received surprisingly little attention in mechanobiology. In this mini-review, we summarize results that document participation of the endomembrane system in sensing and responding to mechanical cues.

Based on the aortic pressure waveform, a specially designed computational fluid dynamic (CFD) method was proposed to determine coronary angiography-derived diastolic pressure ratio (caDPR) without using invasive pressure wire. The aim of the study is to retrospectively assess diagnostic performance of the caDPR in the catheterization laboratory, based on a previous multicenter trial for online assessment of coronary angiography-derived FFR (caFFR).

Patients with diagnosis of stable or unstable angina pectoris were enrolled in six centers. Wire-derived FFR was measured in coronary arteries with 30-90% diameter stenosis. Offline caDPR was assessed in blinded fashion against wire-derived FFR at an independent core laboratory. Selleck PF-07220060 A total of 330 patients who met the inclusion/exclusion criteria were enrolled from June 26 to December 18, 2018. Offline computed caDPR and wire-derived FFR were compared in 328 interrogated vessels. The caDPR with a cutoff value of 0.89 shows diagnostic accuracy of 87.7%, sensitivity of 89.5%, specificity of 86.8%, and AUC of 0.940 against the wire-derived FFR with a cutoff value of 0.80.

Using wired-based FFR as the standard reference, there is good diagnostic performance of the novel-CFD-design caDPR. Hence, caDPR could enhance the hemodynamic assessment of coronary lesions.

Using wired-based FFR as the standard reference, there is good diagnostic performance of the novel-CFD-design caDPR. Hence, caDPR could enhance the hemodynamic assessment of coronary lesions.Bone is a mechanosensitive tissue for which mechanical stimuli are crucial in maintaining its structure and function. Bone cells react to their biomechanical environment by activating molecular signaling pathways, which regulate their proliferation, differentiation, and matrix production. Bone implants influence the mechanical conditions in the adjacent bone tissue. Optimizing their mechanical properties can support bone regeneration. Furthermore, external biomechanical stimulation can be applied to improve implant osseointegration and accelerate bone regeneration. One promising anabolic therapy is vertical whole-body low-magnitude high-frequency vibration (LMHFV). This form of vibration is currently extensively investigated to serve as an easy-to-apply, cost-effective, and efficient treatment for bone disorders and regeneration. This review aims to provide an overview of LMHFV effects on bone cells in vitro and on implant integration and bone fracture healing in vivo. In particular, we review the current knowledge on cellular signaling pathways which are influenced by LMHFV within bone tissue. Most of the in vitro experiments showed that LMHFV is able to enhance mesenchymal stem cell (MSC) and osteoblast proliferation. Furthermore, osteogenic differentiation of MSCs and osteoblasts was shown to be accelerated by LMHFV, whereas osteoclastogenic differentiation was inhibited. Furthermore, LMHFV increased bone regeneration during osteoporotic fracture healing and osseointegration of orthopedic implants. Important mechanosensitive pathways mediating the effects of LMHFV might be the Wnt/beta-catenin signaling pathway, the estrogen receptor (ER) signaling pathway, and cytoskeletal remodeling.Photodynamic therapy (PDT) is already (Food and Drug Administration) FDA approved and used in the clinic for oncological treatment of pancreatic, lung, esophagus, bile duct, and of course several cancers of skin. It is an important tool in the oncological array of treatments, but for it exist several shortcomings, the most prominent of which is the shallow depth penetration of light within tissues. One-way researchers have attempted to circumvent this is through the creation of self-exciting "auto-PDT" nanoplatforms, which do not require the presence of an external light source to drive the PDT process. Instead, these platforms are driven either through oxidative chemical excitation in the form of chemiluminescence or radiological excitation from beta-emitting isotopes in the form of Cherenkov luminescence. In both, electronic excitations are generated and then transferred to the photosensitizer (PS) via Resonance Energy Transfer (RET) or Cherenkov Radiation Energy Transfer (CRET). Self-driven PDT has many cofferent parts of the complex "auto-PDT" system.Osteoporosis is a chronic disease requiring long-term, sometimes lifelong, management. With the aging population, the prevalence of osteoporosis is increasing, and with it so is the risk of hip fracture and subsequent poor quality of life and higher mortality. Current therapies for osteoporosis have various significant side effects limiting patient compliance and use. Recent evidence has demonstrated the significant role of exosomes in osteoporosis both in vivo and in vitro. In this review, we summarize the pathogenesis of senile osteoporosis, highlight the properties and advantages of exosomes, and explore the recent literature on the use of exosomes in osteogenesis regulation. This is a very helpful review as several exosomes-based therapeutics have recently entered clinical trials for non-skeletal applications, such as pancreatic cancer, renal transplantation, and therefore it is urgent for bone researchers to explore whether exosomes can become the next class of orthobiologics for the treatment of osteoporosis.

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