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Background: The pathogenetic mechanisms of ventilator-induced lung injury (VILI) still need to be elucidated. The mechanical forces during mechanical ventilation are continually sensed and transmitted by mechanosensitive ion channels (MSICs) in pulmonary endothelial, epithelial, and immune cells. In recent years, MSICs have been shown to be involved in VILI. Methods: A systematic search across PubMed, the Cochrane Library, Web of Science, and ScienceDirect was performed from inception to March 2024, and the review was conducted in accordance with PRISMA guidelines. The potential eligible studies were evaluated by two authors independently. Study characteristics, quality assessment, and potential mechanisms were analyzed. Results: We included 23 eligible studies, most of which were performed with murine animals in vivo. At the in vitro level, 52% and 48% of the experiments were conducted with human or animal cells, respectively. No clinical studies were found. The most reported MSICs include Piezo channels, transient receptor potential channels, potassium channels, and stretch-activated sodium channels. Piezo1 has been the most concerned channel in the recent five years. This study found that signal pathways, such as RhoA/ROCK1, could be enhanced by cyclic stretch-activated MSICs, which contribute to VILI through dysregulated inflammation and immune responses mediated by ion transport. The review indicates the emerging role of MSICs in the pathogenesis of VILI, especially as a signal-transmitting link between mechanical stretch and pathogenesis such as inflammation, disruption of cell junctions, and edema formation. Conclusions: Mechanical stretch stimulates MSICs to increase transcellular ion exchange and subsequently generates VILI through inflammation and other pathogeneses mediated by MSICs signal-transmitting pathways. These findings make it possible to identify potential therapeutic targets for the prevention of lung injury through further exploration and more studies. Systematic review registration: https://inplasy.com/inplasy-2024-10-0115/ , identifier INPLASY2024100115. [ABSTRACT FROM AUTHOR]

Patients with Alzheimer's disease and related dementia (ADRD) are faced with a formidable challenge of focal amyloid deposits and cerebral amyloid angiopathy (CAA). The treatment of amyloid deposits in ADRD by targeting only oxidative stress, inflammation and hyperlipidemia has not yielded significant positive clinical outcomes. The chronic high-fat diet (HFD), or gut dysbiosis, is one of the major contributors of ADRD in part by disrupted transport, epigenetic DNMT1 and the folate 1-carbon metabolism (FOCM) cycle, i.e., rhythmic methylation/de-methylation on DNA, an active part of epigenetic memory during genes turning off and on by the gene writer (DNMT1) and eraser (TET2/FTO) and the transsulfuration pathway by mitochondrial 3-mercaptopyruvate sulfur transferase (3MST)-producing H2S. The repeat CAG expansion and m6A disorder causes senescence and AD. We aim to target the paradigm-shift pathway of the gut–brain microbiome axis that selectively inhibits amyloid deposits and increases mitochondrial transsulfuration and H2S. We have observed an increase in DNMT1 and decreased FTO levels in the cortex of the brain of AD mice. Interestingly, we also observed that probiotic lactobacillus-producing post-biotic folate and lactone/ketone effectively prevented FOCM-associated gut dysbiosis and amyloid deposits. The s-adenosine-methionine (SAM) transporter (SLC25A) was increased by hyperhomocysteinemia (HHcy). Thus, we hypothesize that chronic gut dysbiosis induces SLC25A, the gene writer, and HHcy, and decreases the gene eraser, leading to a decrease in SLC7A and mitochondrial transsulfuration H2S production and bioenergetics. Lactobacillus engulfs lipids/cholesterol and a tri-directional post-biotic, folic acid (an antioxidant and inhibitor of beta amyloid deposits; reduces Hcy levels), and the lactate ketone body (fuel for mitochondria) producer increases SLC7A and H2S (an antioxidant, potent vasodilator and neurotransmitter gas) production and inhibits amyloid deposits. Therefore, it is important to discuss whether lactobacillus downregulates SLC25A and DNMT1 and upregulates TET2/FTO, inhibiting β-amyloid deposits by lowering homocysteine. It is also important to discuss whether lactobacillus upregulates SLC7A and inhibits β-amyloid deposits by increasing the mitochondrial transsulfuration of H2S production. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) can lead to short-term and long-term physical and cognitive impairments, which have significant impacts on patients, families, and society. Currently, treatment outcomes for this disease are often unsatisfactory, due at least in part to the fact that the molecular mechanisms underlying the development of TBI are largely unknown. Here, we observed significant upregulation of Piezo2, a key mechanosensitive ion channel protein, in the injured brain tissue of a mouse model of TBI induced by controlled cortical impact. Pharmacological inhibition and genetic knockdown of Piezo2 after TBI attenuated neuronal death, brain edema, brain tissue necrosis, and deficits in neural function and cognitive function. Mechanistically, the increase in Piezo2 expression contributed to TBI-induced neuronal death and subsequent production of TNF-α and IL-1β, likely through activation of the RhoA/ROCK1 pathways in the central nervous system. Our findings suggest that Piezo2 is a key player in and a potential therapeutic target for TBI. [ABSTRACT FROM AUTHOR]

Mechanosensitive ion channels, particularly Piezo channels, are widely expressed in various tissues. However, their role in immune cells remains underexplored. Therefore, this study aimed to investigate the functional role of Piezo1 in the human eosinophil cell line AML14.3D10. We detected Piezo1 mRNA expression, but not Piezo2 expression, in these cells, confirming the presence of the Piezo1 protein. Activation of Piezo1 with Yoda1, its specific agonist, resulted in a significant calcium influx, which was inhibited by the Piezo1-specific inhibitor Dooku1, as well as other nonspecific inhibitors (Ruthenium Red, Gd3+, and GsMTx-4). Further analysis revealed that Piezo1 activation modulated the expression and secretion of both pro-inflammatory and anti-inflammatory cytokines in AML14.3D10 cells. Notably, supernatants from Piezo1-activated AML14.3D10 cells enhanced capsaicin and ATP-induced calcium responses in the dorsal root ganglion neurons of mice. These findings elucidate the physiological role of Piezo1 in AML14.3D10 cells and suggest that factors secreted by these cells can modulate the activity of transient receptor potential 1 (TRPV1) and purinergic receptors, which are associated with pain and itch signaling. The results of this study significantly advance our understanding of the function of Piezo1 channels in the immune and sensory nervous systems. [ABSTRACT FROM AUTHOR]

In nephrotic syndrome, the podocyte filtration structures are damaged in a process called foot process effacement. This is mediated by the actin cytoskeleton; however, which actins are involved and how they interact with other filtration components, like the basement membrane, remains poorly understood. Here, we used the well-established Drosophila pericardial nephrocyte—the equivalent of podocytes in flies—knockdown models (RNAi) to study the interplay of the actin cytoskeleton (Act5C, Act57B, Act42A, and Act87E), alpha- and beta-integrin (basement membrane), and the slit diaphragm (Sns and Pyd). Knockdown of an actin gene led to variations of formation of actin stress fibers, the internalization of Sns, and a disrupted slit diaphragm cortical pattern. Notably, deficiency of Act5C, which resulted in complete absence of nephrocytes, could be partially mitigated by overexpressing Act42A or Act87E, suggesting at least partial functional redundancy. Integrin localized near the actin cytoskeleton as well as slit diaphragm components, but when the nephrocyte cytoskeleton or slit diaphragm was disrupted, this switched to colocalization, both at the surface and internalized in aggregates. Altogether, the data show that the interdependence of the slit diaphragm, actin cytoskeleton, and integrins is key to the structure and function of the Drosophila nephrocyte. [ABSTRACT FROM AUTHOR]

Background/Aims: Tactile perception relies on mechanoreceptors and nerve fibers, including c-fibers, Aβ-fibers and Aδ-fibers. Schwann cells (SCs) play a crucial role in supporting nerve fibers, with non-myelinating SCs enwrapping c-fibers and myelinating SCs ensheathing Aβ and Aδ fibers. Recent research has unveiled new functions for cutaneous sensory SCs, highlighting the involvement of nociceptive SCs in pain perception and Meissner corpuscle SCs in tactile sensation. Furthermore, Piezo2, previously associated with Merkel cell tactile sensitivity, has been identified in SCs. The goal of this study was to investigate the channels implicated in SC mechanosensitivity and the release process of neurotrophic factor secretion. Methods: Immortalized IFRS1 SCs and human primary SCs generated two distinct subtypes of SCs: undifferentiated and differentiated SCs. Quantitative PCR was employed to evaluate the expression of differentiation markers and mechanosensitive channels, including TRP channels (TRPV4, TRPM7 and TRPA1) and Piezo channels (Piezo1 and Piezo2). To validate the functionality of specific mechanosensitive channels, Ca2+ imaging and electronic cell sizing experiments were conducted under hypotonic conditions, and inhibitors and siRNAs were used. Protein expression was assessed by Western blotting and immunostaining. Additionally, secretome analysis was performed to evaluate the release of neurotrophic factors in response to hypotonic stimulation, with BDNF, a representative trophic factor, quantified using ELISA. Results: Induction of differentiation increased Piezo2 mRNA expression levels both in IFRS1 and in human primary SCs. Both cell types were responsive to hypotonic solutions, with differentiated SCs displaying a more pronounced response. Gd3+ and FM1-43 effectively inhibited hypotonicity-induced Ca2+ transients in differentiated SCs, implicating Piezo2 channels. Conversely, inhibitors of Piezo1 and TRPM7 (Dooku1 and NS8593, respectively) had no discernible impact. Moreover, Piezo2 in differentiated SCs appeared to participate in regulatory volume decreases (RVD) after cell swelling induced by hypotonic stimulation. A Piezo2 deficiency correlated with reduced RVD and prolonged cell swelling, leading to heightened release of the neurotrophic factor BDNF by upregulating the function of endogenously expressed Ca2+-permeable TRPV4. Conclusion: Our study unveils the mechanosensitivity of SCs and implicates Piezo2 channels in the release of neurotrophic factors from SCs. These results suggest that Piezo2 may contribute to RVD, thereby maintaining cellular homeostasis, and may also serve as a negative regulator of neurotrophic factor release. These findings underscore the need for further investigation into the role of Piezo2 in SC function and neurotrophic regulation. [ABSTRACT FROM AUTHOR]

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology for treatment of severe male infertility introduced into clinical practice in 1992. This review provides a brief history of the development of ICSI by acknowledging major developments in the field. The review addresses key developments in pre-clinical and early studies, how ICSI compares with in vitro fertilisation, long-term consequences, how the mechanistic approach to ICSI has changed in both manual and semi-automated approaches, and how sperm selection procedures are integrated into ICSI. From the beginnings using animal models in the 1960–1970s, the development of ICSI is a remarkable and transformative success story. Indeed, its broad use (70% of cycles globally) exceeds the need required for treating infertile males, and this remains a controversial issue. There remain questions around the long-term health impacts of ICSI. Furthermore, advances in automation of the ICSI procedure are occurring. An estimated 6 million children have been born from the ICSI procedure. With further automation of sperm selection technologies, coupled with automation of the injection procedure, it is likely that the proportion of children born from ICSI will further increase. Intracytoplasmic sperm injection, better known by its acronym 'ICSI', is a technique that enables the injection of a single sperm into an egg. Since first practiced in 1992 with human sperm and eggs, it has revolutionised the treatment of male infertility, and an estimated 6 million children have since been born. However, it is not without controversy, especially concerning the long-term health of children conceived through ICSI, as well as the recent push towards automation of sperm selection and injection. Image by M. Inge. This article belongs to the Collection Dedication to Jim Cummins. [ABSTRACT FROM AUTHOR]

BackgroundThe pathogenetic mechanisms of ventilator-induced lung injury (VILI) still need to be elucidated. The mechanical forces during mechanical ventilation are continually sensed and transmitted by mechanosensitive ion channels (MSICs) in pulmonary endothelial, epithelial, and immune cells. In recent years, MSICs have been shown to be involved in VILI.MethodsA systematic search across PubMed, the Cochrane Library, Web of Science, and ScienceDirect was performed from inception to March 2024, and the review was conducted in accordance with PRISMA guidelines. The potential eligible studies were evaluated by two authors independently. Study characteristics, quality assessment, and potential mechanisms were analyzed.ResultsWe included 23 eligible studies, most of which were performed with murine animals in vivo. At the in vitro level, 52% and 48% of the experiments were conducted with human or animal cells, respectively. No clinical studies were found. The most reported MSICs include Piezo channels, transient receptor potential channels, potassium channels, and stretch-activated sodium channels. Piezo1 has been the most concerned channel in the recent five years. This study found that signal pathways, such as RhoA/ROCK1, could be enhanced by cyclic stretch-activated MSICs, which contribute to VILI through dysregulated inflammation and immune responses mediated by ion transport. The review indicates the emerging role of MSICs in the pathogenesis of VILI, especially as a signal-transmitting link between mechanical stretch and pathogenesis such as inflammation, disruption of cell junctions, and edema formation.ConclusionsMechanical stretch stimulates MSICs to increase transcellular ion exchange and subsequently generates VILI through inflammation and other pathogeneses mediated by MSICs signal-transmitting pathways. These findings make it possible to identify potential therapeutic targets for the prevention of lung injury through further exploration and more studies.Systematic review registrationhttps://inplasy.com/inplasy-2024-10-0115/, identifier INPLASY2024100115.

Abstract Background The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm. Results In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, plays key roles in larval feeding behavior and, more importantly, is essential for eupyrene spermatogenesis and male fertility. CRISPR/Cas9-mediated loss of BmPiezo function decreases larval appetite and subsequent body size and weight. Immunofluorescence analyses reveal that BmPiezo is intensely localized in the inflatable point of eupyrene sperm bundle induced by peristaltic squeezing. BmPiezo is also enriched in the middle region of apyrene sperm bundle before peristaltic squeezing. Cytological analyses of dimorphic sperm reveal developmental arrest of eupyrene sperm bundles in BmPiezo mutants, while the apyrene spermatogenesis is not affected. RNA-seq analysis and q-RT-PCR analyses demonstrate that eupyrene spermatogenic arrest is associated with the dysregulation of the actin cytoskeleton. Moreover, we show that the deformed eupyrene sperm bundles fail to migrate from the testes, resulting in male infertility due to the absence of eupyrene sperm in the bursa copulatrix and spermatheca. Conclusions In conclusion, our studies thus uncover a new role for Piezo in regulating spermatogenesis and male fertility in insects.

To investigate whether PIEZO–intracytoplasmic sperm injection (PIEZO-ICSI) increases the fertilization rate, decreases the degeneration rate, and increases the utilization rate per oocyte injected compared with conventional intracytoplasmic sperm injection (ICSI). Sibling oocyte split multicenter trial. Fertility clinics. Women with a diagnosis of infertility who used ICSI as their method of insemination and had ≥6 mature oocytes for injection. Participants had their mature oocyte cohort divided, where half were injected using conventional ICSI and the other half were injected using PIEZO-ICSI. For patients with an uneven oocyte number, the extra oocyte was injected using conventional ICSI. The injection technique used first was also randomized to ensure that there was no bias due to order of injection. The primary outcome measure was the fertilization rate after injection. A total of 108 patients underwent a sibling split use of conventional ICSI and PIEZO-ICSI. The fertilization rate was 71.6% in PIEZO-ICSI, which significantly increased compared with that in conventional ICSI 65.6%. In addition, the oocyte degeneration rate decreased in PIEZO-ICSI compared with that in conventional ICSI (6.3% vs. 12.1% respectively), and the blastocyst quality increased, as measured by the number of grade A and B quality blastocysts present on day 5 of development (33.3% vs. 27.5%). No significant differences in the aneuploidy or utilization rate, clinical pregnancy, or live birth outcome after single embryo transfer were noted between the two injection techniques. This trial supports the possibility that PIEZO-ICSI increases the fertilization rates, decreases the oocyte degeneration rates, and increases the blastocyst quality compared with conventional ICSI; however, it does not appear to influence the clinical pregnancy or live birth rate per transfer. Australian and New Zealand Clinical Trial Registry ACTRN12620000407998. [ABSTRACT FROM AUTHOR]

Background: The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm. Results: In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, plays key roles in larval feeding behavior and, more importantly, is essential for eupyrene spermatogenesis and male fertility. CRISPR/Cas9-mediated loss of BmPiezo function decreases larval appetite and subsequent body size and weight. Immunofluorescence analyses reveal that BmPiezo is intensely localized in the inflatable point of eupyrene sperm bundle induced by peristaltic squeezing. BmPiezo is also enriched in the middle region of apyrene sperm bundle before peristaltic squeezing. Cytological analyses of dimorphic sperm reveal developmental arrest of eupyrene sperm bundles in BmPiezo mutants, while the apyrene spermatogenesis is not affected. RNA-seq analysis and q-RT-PCR analyses demonstrate that eupyrene spermatogenic arrest is associated with the dysregulation of the actin cytoskeleton. Moreover, we show that the deformed eupyrene sperm bundles fail to migrate from the testes, resulting in male infertility due to the absence of eupyrene sperm in the bursa copulatrix and spermatheca. Conclusions: In conclusion, our studies thus uncover a new role for Piezo in regulating spermatogenesis and male fertility in insects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Heart failure is associated with a high rate of mortality and morbidity, and ventricular remodeling invariably precedes heart failure. Ventricular remodeling is fundamentally driven by mechanotransduction that is regulated by both the nervous system and the immune system. However, it remains unknown which key molecular factors govern the neuro/immune/cardio axis that underlies mechanotransduction during ventricular remodeling. Here, we investigated whether the mechanosensitive Piezo cation channel–mediated neurogenic inflammatory cascade underlies ventricular remodeling–related mechanotransduction. METHODS: By ligating the left coronary artery of rats to establish an in vivo model of chronic myocardial infarction (MI), lentivirus-mediated thoracic dorsal root ganglion (TDRG)–specific Piezo1 knockdown rats and adeno-associated virus–PHP.S—mediated TDRG neuron–specific Piezo1 knockout mice were used to investigate whether Piezo1 in the TDRG plays a functional role during ventricular remodeling. Subsequently, neutralizing antibody–mediated TDRG IL-6 (interleukin-6) inhibition rats and adeno-associated virus–PHP.S—mediated TDRG neuron–specific IL-6 knockdown mice were used to determine the mechanism underlying neurogenic inflammation. Primary TDRG neurons were used to evaluate Piezo1 function in vitro. RESULTS: Expression of Piezo1 and IL-6 was increased, and these factors were functionally activated in TDRG neurons at 4 weeks after MI. Both knockdown of TDRG-specific Piezo1 and deletion of TDRG neuron–specific Piezo1 lessened the severity of ventricular remodeling at 4 weeks after MI and decreased the level of IL-6 in the TDRG or heart. Furthermore, inhibition of TDRG IL-6 or knockdown of TDRG neuron–specific IL-6 also ameliorated ventricular remodeling and suppressed the IL-6 cascade in the heart, whereas the Piezo1 level in the TDRG was not affected. In addition, enhanced Piezo1 function, as reflected by abundant calcium influx induced by Yoda1 (a selective agonist of Piezo1), led to increased release of IL-6 from TDRG neurons in mice 4 weeks after MI. CONCLUSIONS: Our findings point to a critical role for Piezo1 in ventricular remodeling at 4 weeks after MI and reveal a neurogenic inflammatory cascade as a previously unknown facet of the neuronal immune signaling axis underlying mechanotransduction. [ABSTRACT FROM AUTHOR]

Alterations in intraocular and external pressure critically involve the pathogenesis of glaucoma, traumatic retinal injury (TRI), and other retinal disorders, and retinal neurons have been reported to express multiple mechanical-sensitive channels (MSCs) in recent decades. However, the role of MSCs in visual functions and pressure-related retinal conditions has been unclear. This review will focus on the variety and functional significance of the MSCs permeable to K+, Na+, and Ca2+, primarily including the big potassium channel (BK); the two-pore domain potassium channels TRAAK and TREK; Piezo; the epithelial sodium channel (ENaC); and the transient receptor potential channels vanilloid TRPV1, TRPV2, and TRPV4 in retinal photoreceptors, bipolar cells, horizontal cells, amacrine cells, and ganglion cells. Most MSCs do not directly mediate visual signals in vertebrate retinas. On the other hand, some studies have shown that MSCs can open in physiological conditions and regulate the activities of retinal neurons. While these data reasonably predict the crossing of visual and mechanical signals, how retinal light pathways deal with endogenous and exogenous mechanical stimulation is uncertain. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this research was to investigate the functions of Piezo channels in dentin defect, including mechanical signalling and odontoblast responses. Methods: Rat dentin-defect models were constructed, and spatiotemporal expression of Piezo proteins was detected in the pulpo-dentinal complex. Real-time polymerase chain reaction (rtPCR) was used to investigate the functional expression pattern of Piezo channels in odontoblasts. Moreover, RNA interference technology was employed to uncover the underlying mechanisms of the Piezo-driven inflammatory response and repair under fluid shear stress (FSS) conditions in vitro. Results: Piezo1 and Piezo2 were found to be widely expressed in the odontoblast layer and dental pulp in the rat dentin-defect model during the end stage of reparative dentin formation. The expression levels of the Piezo1 and Piezo2 genes in MDPC-23 cells were high in the initial stage under FSS loading and then decreased over time. Moreover, the expression trends of inflammatory, odontogenic, and mineralisation genes were generally contrary to those of Piezo1 and Piezo2 over time. After silencing of Piezo1/Piezo2, FSS stimulation resulted in significantly higher expression of inflammatory, odontogenesis, and mineralisation genes in MDPC-23 cells. Finally, the expression of genes involved in the integrin β1/ERK1 and Wnt5b/β-catenin signalling pathways was changed in response to RNA silencing of Piezo1 and Piezo2. Conclusions: Piezo1 and Piezo2 may be involved in regulating the expression of inflammatory and odontogenic genes in odontoblasts stimulated by FSS.

Abstract Background Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. Methods A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. Results We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. Conclusions Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.

Simple Summary: PIEZO1 is a mechanically activated ion channel connected to many important cellular functions. While implicated to various degrees in different types of cancers, the clinical significance of PIEZO1 has not been explored in breast cancer. We conducted various bioinformatic analyses on PIEZO1 in breast cancer, using publicly available online datasets from The Cancer Genome Atlas and GSE3494. Our results show that PIEZO1 expression is higher in hormone-receptor (HR)-negative cohorts than HR-positive cohorts. We also found that high PIEZO1 expression is correlated with worse survival outcomes in HR-negative patients, suggesting that PIEZO1 could be utilized as a prognostic biomarker in HR-negative breast cancer. Further analysis suggests that these worse survival outcomes may be due to increased aggressive cancer pathways, including epithelial–mesenchymal transition and hypoxia, along with decreased CD8+ and CD4+ T cell infiltration in high-PIEZO1 HR-negative tumors. PIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in cancer; elevated levels of PIEZO1 have been correlated with increased migration in breast cancer cells, chemo-resistance and invasion in gastric cancer cells, and increased invasion of osteosarcoma cells. In addition, high PIEZO1 expression levels were correlated with a worse prognosis in glioma patients. On the other hand, studies in lung cancer have attributed high PIEZO1 levels to better patient outcomes. However, the clinical impact of PIEZO1 in breast cancer is not well characterized. Therefore, our goal was to determine the clinical relevance of PIEZO1 in breast cancer. An analysis of breast cancer data from The Cancer Genome Atlas (TCGA) was conducted to investigate PIEZO1 expression levels and correlation to survival, followed by validation in an independent dataset, GSE3494. We also performed gene set enrichment analysis (GSEA) and pathway enrichment analysis. We also analyzed the immune cell composition in breast tumors from TCGA through a CIBERSORT algorithm. Our results demonstrated that the PIEZO1 expression levels are higher in hormone-receptor (HR)-negative than in HR-positive cohorts. High PIEZO1 expression is correlated with a significant decrease in survival in HR-negative cohorts, especially in triple-negative breast cancer (TNBC), suggesting that PIEZO1 could be utilized as a prognostic biomarker in HR-negative breast cancer. GSEA showed that various signaling pathways associated with more invasive phenotypes and resistance to treatments, including epithelial–mesenchymal transition (EMT), hypoxia, and multiple signaling pathways, are enriched in high-PIEZO1 HR-negative tumors. Our results also demonstrated a decrease in CD8+ and CD4+ T cell infiltration in high-PIEZO1 HR-negative tumors. Further investigations are necessary to elucidate the mechanistic roles of PIEZO1 in HR-negative breast cancer. [ABSTRACT FROM AUTHOR]

The purpose of this review is to evaluate the role of cholesterol in regulating mechanosensitive ion channels. Ion channels discussed in this review are sensitive to two types of mechanical signals, fluid shear stress and/or membrane stretch. Cholesterol regulates the channels primarily in two ways: 1) indirectly through localizing the channels into cholesterol-rich membrane domains where they interact with accessory proteins and/or 2) direct binding of cholesterol to the channel at specified putative binding sites. Cholesterol may also regulate channel function via changes of the biophysical properties of the membrane bilayer. Changes in cholesterol affect both mechanosensitivity and basal channel function. We focus on four mechanosensitive ion channels in this review Piezo, Kir2, TRPV4, and VRAC channels. Piezo channels were shown to be regulated by auxiliary proteins that enhance channel function in high cholesterol domains. The direct binding mechanism was shown in Kir2.1 and TRPV4 where cholesterol inhibits channel function. Finally, cholesterol regulation of VRAC was attributed to changes in the physical properties of lipid bilayer. Additional studies should be performed to determine the physiological implications of these sterol effects in complex cellular environments. [ABSTRACT FROM AUTHOR]

Background: Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. Methods: A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. Results: We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. Conclusions: Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology. [ABSTRACT FROM AUTHOR]

This study introduces an experimental energy harvesting system based on ground-mounted piezoelectric ceramic transducers for low-power applications where human mobility is high. The voltage that only a PZT can produce is not at a level that can energize a system alone. Therefore, the total power to be obtained has been increased by connecting PZTs in series and parallel with the appropriate circuit topology that can maximize the harvested power. In the experimental study, 5 PZTs were placed on each short side of a 20 × 30 cm wooden floor, and energy was harvested from 10 PZTs in total with 10 voltage doublers. Individuals of four different weights stepped on the experimental setup for one minute at three different walking speeds and all results were obtained graphically. A 220 KΩ resistor is used as load. When the experimental setup was tested with an individual weighing 48 kg, a maximum power 23.42 μW (2.27 volts), 13.13 μW (1.70 volts) for 58 kg, 59.56 μW (3.62 volts) for 71 kg and 55.68 μW (3.50 volts) for 85 kg was harvested. Experimental results have shown that as the walking speed of the same individual increases, the average tension to be obtained increases, and the heavier individuals at the same walking speeds provide more energy harvest. [ABSTRACT FROM AUTHOR]

Membrane protein TMEM120A (also known as TACAN) was presumed to be both a mechanically activated molecule and a lipid-modifying enzyme. TMEM120A has been identified as a negative regulator of the essential excitatory mechanosensitive protein PIEZO2. However, the extent to which TMEM120A mediates PIEZO2's activity during physiological processes remains largely unknown. In this study, we used the Caenorhabditis elegans reproductive tract to explore the functional contribution of tmem-120 , the sole TMEM120A/B ortholog, and its genetic interaction with pezo-1 in vivo. tmem-120 was expressed throughout the C. elegans development, particularly in the germline, embryos, and spermatheca. A tmem-120 mutant with a full-length deletion (tmem-120 Δ) displayed deformed germline, maternal sterility, and a reduced brood size. In vivo live imaging revealed that pinched zygotes were frequently observed in the uterus of tmem-120 Δ mutant animals, suggesting damage during spermathecal contraction. We then employed the auxin-inducible degradation system to degrade TMEM-120 protein in all somatic tissues or the germline, both of which resulted in reduced brood sizes. These findings suggested that multiple inputs of tmem-120 from different tissues regulate reproduction. Lastly, the loss of tmem-120 alleviated the brood size reduction and defective sperm navigation behavior in the pezo-1 Δ mutant. Overall, our findings reveal a role for tmem-120 in regulating reproductive physiology in C. elegans , and suggest an epistatic interaction between pezo-1 and tmem-120 when governing proper reproduction. [ABSTRACT FROM AUTHOR]

This study is to develop structures with the ability to convert a compression force into radial extension or shear force, to increase power output through piezo shear mode. In this work, a piezoceramic-spring system was developed with two types of force-spreading spring configurations, the Belleville disc springs and the crinkle washer. A force loading profile is applied to a piezoceramic element and structure causing the force to be distributed in different directions when compared to a conventional helical spring damping system or compression. The performances of these novel structures were studied using Multiphysics simulation and experiments. This work shows that both the Belleville disc and crinkle washer produce improved energy output between 15 and 22% compared to compression alone, whilst the Belleville disc spring outperformed a crinkle washer in both simulations and experiments. The results show that converting compression to shear force in energy harvesting could be a potential approach to increase the energy efficiency and energy density.

Mechanosensitive ion channels, particularly Piezo channels, are widely expressed in various tissues. However, their role in immune cells remains underexplored. Therefore, this study aimed to investigate the functional role of Piezo1 in the human eosinophil cell line AML14.3D10. We detected Piezo1 mRNA expression, but not Piezo2 expression, in these cells, confirming the presence of the Piezo1 protein. Activation of Piezo1 with Yoda1, its specific agonist, resulted in a significant calcium influx, which was inhibited by the Piezo1-specific inhibitor Dooku1, as well as other nonspecific inhibitors (Ruthenium Red, Gd3+, and GsMTx-4). Further analysis revealed that Piezo1 activation modulated the expression and secretion of both pro-inflammatory and anti-inflammatory cytokines in AML14.3D10 cells. Notably, supernatants from Piezo1-activated AML14.3D10 cells enhanced capsaicin and ATP-induced calcium responses in the dorsal root ganglion neurons of mice. These findings elucidate the physiological role of Piezo1 in AML14.3D10 cells and suggest that factors secreted by these cells can modulate the activity of transient receptor potential 1 (TRPV1) and purinergic receptors, which are associated with pain and itch signaling. The results of this study significantly advance our understanding of the function of Piezo1 channels in the immune and sensory nervous systems.

The purpose of this review is to evaluate the role of cholesterol in regulating mechanosensitive ion channels. Ion channels discussed in this review are sensitive to two types of mechanical signals, fluid shear stress and/or membrane stretch. Cholesterol regulates the channels primarily in two ways: 1) indirectly through localizing the channels into cholesterol-rich membrane domains where they interact with accessory proteins and/or 2) direct binding of cholesterol to the channel at specified putative binding sites. Cholesterol may also regulate channel function via changes of the biophysical properties of the membrane bilayer. Changes in cholesterol affect both mechanosensitivity and basal channel function. We focus on four mechanosensitive ion channels in this review Piezo, Kir2, TRPV4, and VRAC channels. Piezo channels were shown to be regulated by auxiliary proteins that enhance channel function in high cholesterol domains. The direct binding mechanism was shown in Kir2.1 and TRPV4 where cholesterol inhibits channel function. Finally, cholesterol regulation of VRAC was attributed to changes in the physical properties of lipid bilayer. Additional studies should be performed to determine the physiological implications of these sterol effects in complex cellular environments.

SOx emissions are primarily caused by compounds containing sulfur in petroleum and fuels, which lead to severe air pollution. For this reason, it is necessary to develop a fast and simple desulfurization method in order to comply with ever-increasing environmental regulations. The newly discovered piezo-catalyst nanocomposite CexOy/SrO can convert mechanical energy directly into chemical energy, thereby enabling mechanically oxidative sulfur desulfurization. 320 W of bath sonication were used to polarize and activate the prepared piezo-catalyst nanocomposite CexOy/SrO for sulfur removal from thiophene and dibenzothiophene as model fuels and kerosene as a real fuel. Using uniform and spherical CeO2/SrO nanocomposites resulted in the highest desulfurization rates of 95.4 %, 97.3 %, and 59.7 %, respectively, for thiophene and dibenzothiophene. This study examined the effect of several parameters, such as sulfur concentration, pH of fuel, dosage of CexOy/SrO nanocomposite, power and time of ultrasonic, and shaking time, on the piezo-desulfurization of thiophene (TP) and dibenzothiophene (DBTP). To identify the major active species in piezo desulfurization, radical trapping experiments were conducted. This study investigated the possibility of reusing the catalyst, and the piezo-desulfurization activity that was demonstrated in the removal of TP and DBTP after 11 cycles as well as the ability of the catalyst to remove real fuel even after 14 cycles was promising. As the kinetic results show, the reaction follows the second order with K = 0.0050. Also, thermodynamic results showed the oxidation of sulfide to sulfoxide and sulfoxide is endothermic. Activation energy for second order rate constant is (3.824 Kj/mole). 0.0236 mol-1. Sec−1 was calculated for Arrhenius Constant.

Studies have probed nanoplastic toxicity on environmental organisms, but the regulatory role of animal PIEZO-type mechanosensitive ion channel component (PIEZO) remains unclear. Herein, we identified the sole PIEZO in Caenorhabditis elegans (C. elegans), utilizing amino acid homology analysis and Trans-Membrane prediction using Hidden Markov Models (TMHMM). In C. elegans, RNAi knockdown of pezo-1 had no impact on lifespan, body length, lethality, locomotion behaviors, or oxidative response (P > 0.05). However, exposure to 15 μg/L nanopolystyrene in the pezo-1 RNAi group resulted in severe locomotion changes: head trashes (P

Introduction: Diabetic distal symmetric polyneuropathy (DDSP) is the most prevalent form of diabetic peripheral neuropathy, and 25% of patients develop pain in their toes. DDSP is associated with increased cutaneous microvessel density (MVD), reduced skin blood flow, endothelial dysfunction, and impaired fluid filtration with vasodilation. The Piezo family of mechanosensitive channels is known to be involved in the control of vascular caliber by converting mechanical force into intracellular signals. Furthermore, Piezo2 is particularly involved in peripheral pain mechanisms of DDSP patients. To date, very little is known about the number, structure, and PIEZO expression in cutaneous blood vessels (BVs) of individuals with DDSP and their relation with pain and time span of diabetes. Methods and results: We studied microvessels using endothelial markers (CD34 and CD31) and smooth cell marker (a-SMA) by indirect immunohistochemical assay in sections of the glabrous skin of the toes from patients and controls. MVD was assessed through CD34 and CD31 immunoreaction. MVD determined by CD34 is higher in short-term DDSP patients (less than 15 years of evolution), regardless of pain. However, long-term DDSP patients only had increased BV density in the painful group for CD31. BVs of patients with DDSP showed structural disorganization and loss of shape. The BVs affected by painful DDSP underwent the most dramatic structural changes, showing rupture, leakage, and abundance of material that occluded the BV lumen. Moreover, BVs of DDSP patients displayed a Piezo1 slight immunoreaction, whereas painful DDSP patients showed an increase in Piezo2 immunoreaction. Discussion: These results suggest that alterations in the number, structure, and immunohistochemical profile of specific BVs can explain the vascular impairment associated with painful DDSP, as well as the temporal span of diabetes. Finally, this study points out a possible correlation between increased vascular Piezo2 immunostaining and pain and decreased vascular Piezo1 immunostaining and the development of vasodilation deficiency. [ABSTRACT FROM AUTHOR]

In the gastrointestinal tract, serotonin (5-hydroxytryptamine, 5-HT) is an important monoamine that regulates intestinal dynamics. QGP-1 cells are human-derived enterochromaffin cells that secrete 5-HT and functionally express Piezo ion channels associated with cellular mechanosensation. Piezo ion channels can be blocked by Grammostola spatulata mechanotoxin 4 (GsMTx4), a spider venom peptide that inhibits cationic mechanosensitive channels. The primary aim of this study was to explore the effects of GsMTx4 on 5-HT secretion in QGP-1 cells in vitro. We investigated the transcript and protein levels of the Piezo1/2 ion channel, tryptophan hydroxylase 1 (TPH1), and mitogen-activated protein kinase signaling pathways. In addition, we observed that GsMTx4 affected mouse intestinal motility in vivo. Furthermore, GsMTx4 blocked the response of QGP-1 cells to ultrasound, a mechanical stimulus.The prolonged presence of GsMTx4 increased the 5-HT levels in the QGP-1 cell culture system, whereas Piezo1/2 expression decreased, and TPH1 expression increased. This effect was accompanied by the increased phosphorylation of the p38 protein. GsMTx4 increased the entire intestinal passage time of carmine without altering intestinal inflammation. Taken together, inhibition of Piezo1/2 can mediate an increase in 5-HT, which is associated with TPH1, a key enzyme for 5-HT synthesis. It is also accompanied by the activation of the p38 signaling pathway. Inhibitors of Piezo1/2 can modulate 5-HT secretion and influence intestinal motility. [ABSTRACT FROM AUTHOR]

Objective: Subdural osteoma (SO) is a rarely reported benign tumor, and there is no report of SO manifested with epileptic seizures. We aim to further the understanding of SO-related epilepsy. Methods: Here, we report a meaningful case of epilepsy secondary to SO. A systematic review of the literature about SO using the electronic database PubMed and Web of science up to December 2022 was conducted. Results: A 15-year-old girl presented with epileptic seizures for 8 years. Magnetic resonance imaging revealed an irregular lesion with heterogeneous signal in the right frontal convexity. Right frontal craniotomy was performed to remove the lesion. The pathological diagnosis was SO. Histological analysis revealed that the mechanosensitive ion channels Piezo 1/2 were upregulated in the brain tissue compressed by the osteoma, compared with the levels in the osteoma-free region. Seizure freedom was obtained during the 6-month follow-up after the surgery. We identified 24 cases of SO in 23 articles. With our case, a total of 25 cases with 32 SOs was included. Of 25 cases, 24 are adults, and 1 is a child. Seizure has been reported only in our case. Frontal osteoma was found in 76% of the patients. Symptoms were cured in 56% of the patients after surgery. Conclusion: Surgery is a safe and effective approach to the treatment of symptomatic osteoma. Mechanical compression on cerebral cortex may be a predisposing factor of the epileptogenesis caused by the SO. [ABSTRACT FROM AUTHOR]

Introduction: Mild traumatic brain injury (mTBI) caused by repetitive low-intensity blast overpressure (relBOP) in military personnel exposed to breaching and heavy weapons is often unrecognized and is understudied. Exposure to relBOP poses the risk of developing abnormal behavioral and psychological changes such as altered cognitive function, anxiety, and depression, all of which can severely compromise the quality of the life of the affected individual. Due to the structural and anatomical heterogeneity of the brain, understanding the potentially varied effects of relBOP in different regions of the brain could lend insights into the risks from exposures. Methods: In this study, using a rodent model of relBOP and western blotting for protein expression we showed the differential expression of various neuropathological proteins like TDP-43, tight junction proteins (claudin-5, occludin, and glial fibrillary acidic protein (GFAP)) and a mechanosensitive protein (piezo-2) in different regions of the brain at different intensities and frequency of blast. Results: Our key results include (i) significant increase in claudin-5 after 1x blast of 6.5 psi in all three regions and no definitive pattern with higher number of blasts, (ii) significant increase in piezo-2 at 1x followed by significant decrease after multiple blasts in the cortex, (iii) significant increase in piezo-2 with increasing number of blasts in frontal cortex and mixed pattern of expression in hippocampus and (iv) mixed pattern of TDP-3 and GFAP expression in all the regions of brain. Discussion: These results suggest that there are not definitive patterns of changes in these marker proteins with increase in intensity and/or frequency of blast exposure in any particular region; the changes in expression of these proteins are different among the regions. We also found that the orientation of blast exposure (e.g. front vs. side exposure) affects the altered expression of these proteins. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic distal symmetric polyneuropathy (DDSP) is the most prevalent form of diabetic peripheral neuropathy, and 25% of patients develop pain in their toes. DDSP is associated with increased cutaneous microvessel density (MVD), reduced skin blood flow, endothelial dysfunction, and impaired fluid filtration with vasodilation. The Piezo family of mechanosensitive channels is known to be involved in the control of vascular caliber by converting mechanical force into intracellular signals. Furthermore, Piezo2 is particularly involved in peripheral pain mechanisms of DDSP patients. To date, very little is known about the number, structure, and PIEZO expression in cutaneous blood vessels (BVs) of individuals with DDSP and their relation with pain and time span of diabetes.Methods and results: We studied microvessels using endothelial markers (CD34 and CD31) and smooth cell marker (α-SMA) by indirect immunohistochemical assay in sections of the glabrous skin of the toes from patients and controls. MVD was assessed through CD34 and CD31 immunoreaction. MVD determined by CD34 is higher in short-term DDSP patients (less than 15 years of evolution), regardless of pain. However, long-term DDSP patients only had increased BV density in the painful group for CD31. BVs of patients with DDSP showed structural disorganization and loss of shape. The BVs affected by painful DDSP underwent the most dramatic structural changes, showing rupture, leakage, and abundance of material that occluded the BV lumen. Moreover, BVs of DDSP patients displayed a Piezo1 slight immunoreaction, whereas painful DDSP patients showed an increase in Piezo2 immunoreaction.Discussion: These results suggest that alterations in the number, structure, and immunohistochemical profile of specific BVs can explain the vascular impairment associated with painful DDSP, as well as the temporal span of diabetes. Finally, this study points out a possible correlation between increased vascular Piezo2 immunostaining and pain and decreased vascular Piezo1 immunostaining and the development of vasodilation deficiency.

IntroductionMild traumatic brain injury (mTBI) caused by repetitive low-intensity blast overpressure (relBOP) in military personnel exposed to breaching and heavy weapons is often unrecognized and is understudied. Exposure to relBOP poses the risk of developing abnormal behavioral and psychological changes such as altered cognitive function, anxiety, and depression, all of which can severely compromise the quality of the life of the affected individual. Due to the structural and anatomical heterogeneity of the brain, understanding the potentially varied effects of relBOP in different regions of the brain could lend insights into the risks from exposures.MethodsIn this study, using a rodent model of relBOP and western blotting for protein expression we showed the differential expression of various neuropathological proteins like TDP-43, tight junction proteins (claudin-5, occludin, and glial fibrillary acidic protein (GFAP)) and a mechanosensitive protein (piezo-2) in different regions of the brain at different intensities and frequency of blast.ResultsOur key results include (i) significant increase in claudin-5 after 1x blast of 6.5 psi in all three regions and no definitive pattern with higher number of blasts, (ii) significant increase in piezo-2 at 1x followed by significant decrease after multiple blasts in the cortex, (iii) significant increase in piezo-2 with increasing number of blasts in frontal cortex and mixed pattern of expression in hippocampus and (iv) mixed pattern of TDP-3 and GFAP expression in all the regions of brain.DiscussionThese results suggest that there are not definitive patterns of changes in these marker proteins with increase in intensity and/or frequency of blast exposure in any particular region; the changes in expression of these proteins are different among the regions. We also found that the orientation of blast exposure (e.g. front vs. side exposure) affects the altered expression of these proteins.

Real-time condition monitoring of various types of machinery using sensor technology has gained significant importance in recent years. However, relying on batteries to power these sensors proves to be sub-optimal, as it necessitates regular charging or replacement. To address this, harvesting waste energy from ambient sources emerges as a more efficient alternative. Everyday applications like vehicle wheels, fans, and turbines present ambient sources of waste rotational energy. In this study, we propose a novel rotational energy harvester design that converts rotational energy into linear energy. This linear energy impacts a piezoelectric disk, generating an electric potential. Through simulations, the expected electric potential at varying frequencies was evaluated. Subsequently, experimental tests were conducted by connecting the harvester to a rectifier for AC-to-DC signal conversion and an oscilloscope for voltage measurement. A DC motor replicated the rotational motion at the frequencies from the simulation, and the power output was measured. Using the power transfer theorem, simulation and experimental power outputs were calculated, resulting in values of 188, 513, and 1293 μW and 88.89, 336, and 923 μW, respectively. These results reveal that the designed harvester is competitive with those of existing rotational energy harvester designs, demonstrating the promising potential of this novel harvester. [ABSTRACT FROM AUTHOR]

Mechanosensitive ion channels comprise a broad group of proteins that sense mechanical extracellular and intracellular changes, translating them into cation influx to adapt and respond to these physical cues. All cells in the organism are mechanosensitive, and these physical cues have proven to have an important role in regulating proliferation, cell fate and differentiation, migration and cellular stress, among other processes. Indeed, the mechanical properties of the extracellular matrix in cancer change drastically due to high cell proliferation and modification of extracellular protein secretion, suggesting an important contribution to tumor cell regulation. In this review, we describe the physiological significance of mechanosensitive ion channels, emphasizing their role in cancer and immunity, and providing compelling proof of the importance of continuing to explore their potential as new therapeutic targets in cancer research. [ABSTRACT FROM AUTHOR]

In light of external bias potential separating charge carriers on the photocatalyst surface, piezo materials' built-in electric field plays a comparable role in enhancing photocatalyst performance. The synergistic effect provided by combining piezo materials assures the future of photocatalysis in practical applications. This paper discusses the principles and mechanisms of piezo-photocatalysis and various materials and structures used for piezo-photocatalytic processes. In piezo-photocatalyst composites, the built-in electric field introduced by the piezo component provides bias potential and extracts photocatalytically generated charge carriers for their subsequent reaction to form reactive oxygen species, which crucially affects the catalytic performance. In the composites, the shape and structure of substrate materials particularly matter. The potential of this technology in other applications, such as energy generation and environmental remediation, are discussed. To shed light on the practical application and future direction of the technique, this review gives opinions on moving the technique forward in terms of material development, process optimization, pilot-scale studies, comprehensive assessment of the technology, and regulatory frameworks to advance practical applications, and by analyzing its principles, applications, and challenges, we hope to inspire further research and development in this field and promote the adoption of piezo-photocatalysis as a viable treatment method for treating emerging pollutants in wastewater. [ABSTRACT FROM AUTHOR]

Cells sense and respond to mechanical stimuli by converting those stimuli into biological signals, a process known as mechanotransduction. Mechanotransduction is essential in diverse cellular functions, including tissue development, touch sensitivity, pain, and neuronal pathfinding. In the search for key players of mechanotransduction, several families of ion channels were identified as being mechanosensitive and were demonstrated to be activated directly by mechanical forces in both the membrane bilayer and the cytoskeleton. More recently, Piezo ion channels were discovered as a bona fide mechanosensitive ion channel, and its characterization led to a cascade of research that revealed the diverse functions of Piezo proteins and, in particular, their involvement in neuronal repair. [ABSTRACT FROM AUTHOR]

Teeth are subject to a variety of mechanical forces and vectors. The periodontal ligament (PDL), fibrous tissue that connects the cementum of the tooth to the bony socket, plays a decisive role in transmitting force to alveolar bone via Sharpey fibers, transforming and converting these forces into biological signals. This interaction effects significant osteoblastic and osteoclastic responses via autocrine proliferative and paracrine responses. Recent discoveries of receptors for temperature and touch by the Nobel laureates David Julius and Ardem Patapoutian, respectively have a profound impact on orthodontics. Transient receptor vanilloid channel 1 (TRPV1), initially described as a receptor for temperature, has been proposed to participate in the sensing of force. TRPV4, another ion channel receptor, perceives tensile forces as well as thermal and chemical stimuli. Piezo1 and 2, the classic receptors for touch, in addition to the aforementioned receptors, have similarly been described on PDL‐derived cells. In this text, we review the role of the temperature‐sensitive ion channels and mechanosensitive ion channels on their biological function and influence in orthodontic treatment. [ABSTRACT FROM AUTHOR]

Hematopoietic stem and progenitor cells maintain blood cell homeostasis by integrating various cues provided by specialized microenvironments or niches. Biomechanical forces are emerging as key regulators of hematopoiesis. Here, we report that mechanical stimuli provided by blood flow in the vascular niche control Drosophila hematopoiesis. In vascular niche cells, the mechanosensitive channel Piezo transduces mechanical forces through intracellular calcium upregulation, leading to Notch activation and repression of FGF ligand transcription, known to regulate hematopoietic progenitor maintenance. Our results provide insight into how the vascular niche integrates mechanical stimuli to regulate hematopoiesis. [ABSTRACT FROM AUTHOR]

The urinary bladder requires adequate concentrations of extracellular adenosine 5′-triphosphate (ATP) and other purines at receptor sites to function properly. Sequential dephosphorylation of ATP to ADP, AMP and adenosine (ADO) by membrane-bound and soluble ectonucleotidases (s-ENTDs) is essential for achieving suitable extracellular levels of purine mediators. S-ENTDs, in particular, are released in the bladder suburothelium/lamina propria (LP) in a mechanosensitive manner. Using 1,N6-etheno-ATP (eATP) as substrate and sensitive HPLC-FLD methodology, we evaluated the degradation of eATP to eADP, eAMP and eADO in solutions that were in contact with the LP of ex vivo mouse detrusor-free bladders during filling prior to substrate addition. The inhibition of neural activity with tetrodotoxin and ω-conotoxin GVIA, of PIEZO channels with GsMTx4 and D-GsMTx4 and of the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1) with PACAP6-38 all increased the distention-induced but not spontaneous release of s-ENTDs in LP. It is conceivable, therefore, that the activation of these mechanisms in response to distention restricts the further release of s-ENTDs and prevents excessive hydrolysis of ATP. Together, these data suggest that afferent neurons, PIEZO channels, PAC1 receptors and s-ENTDs form a system that operates a highly regulated homeostatic mechanism to maintain proper extracellular purine concentrations in the LP and ensure normal bladder excitability during bladder filling. [ABSTRACT FROM AUTHOR]

Abstract Mechanosensitive Piezo ion channels were first reported in 2010 in a mouse neuroblastoma cell line, opening up a new field for studying the composition and function of eukaryotic mechanically activated channels. During the past decade, Piezo ion channels were identified in many species, such as bacteria, Drosophila, and mammals. In mammals, basic life activities, such as the sense of touch, proprioception, hearing, vascular development, and blood pressure regulation, depend on the activation of Piezo ion channels. Cumulative evidence suggests that Piezo ion channels play a major role in lung vascular development and function and diseases like pneumonia, pulmonary hypertension, apnea, and other lung-related diseases. In this review, we focused on studies that reported specific functions of Piezos in tissues and emphasized the physiological and pathological effects of their absence or functional mutations on the respiratory system.

Members of both the Piezo and transmembrane channel-like (TMC) families are bona fide mammalian mechanotransducers. In a recent study, Zhang, Shao et al. discovered that TMC7, a non-mechanosensitive TMC, inhibits Piezo2-dependent mechanosensation, with implications for the importance of cellular context for Piezo2 channels in normal and pathological responses to mechanical pain. [ABSTRACT FROM AUTHOR]

The extracellular milieu is a rich source of different stimuli and stressors. Some of them depend on the chemical–physical features of the matrix, while others may come from the 'outer' environment, as in the case of mechanical loading applied on the bones. In addition to these forces, a plethora of chemical signals drives cell physiology and fate, possibly leading to dysfunctions when the homeostasis is disrupted. This variety of stimuli triggers different responses among the tissues: bones represent a particular milieu in which a fragile balance between mechanical and metabolic demands should be tuned and maintained by the concerted activity of cell biomolecules located at the interface between external and internal environments. Plasma membrane ion channels can be viewed as multifunctional protein machines that act as rapid and selective dual-nature hubs, sensors, and transducers. Here we focus on some multisensory ion channels (belonging to Piezo, TRP, ASIC/EnaC, P2XR, Connexin, and Pannexin families) actually or potentially playing a significant role in bone adaptation to three main stressors, mechanical forces, oxidative stress, and acidosis, through their effects on bone cells including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. Ion channel-mediated bone remodeling occurs in physiological processes, aging, and human diseases such as osteoporosis, cancer, and traumatic events. [ABSTRACT FROM AUTHOR]

Purpose: Limited research has been published comparing PIEZO-ICSI with conventional ICSI. While positive effects have been documented in improving fertilization and degeneration, the outcomes in patients with previous poor results from conventional ICSI remain unclear. It is hypothesized that these patients may benefit the most from this form of insemination. Methods: This retrospective paired within-patient cohort study investigated patients (n=72) undertaking PIEZO-ICSI after a previous conventional ICSI cycle resulted in poor outcomes (including low fertilization (<50%), high degeneration (>15%), and/or poor embryo development and utilization). Patients required at least five oocytes collected in both cycles and a period of less than 2 years between the cycles. The outcomes of both cycles were compared in respect to fertilization, degeneration, embryo utilization, and pregnancy rates. Further analyses were applied to patients <38 and ≥38 years of age, with <50% or ≥50% fertilization with conventional ICSI and with <20% or ≥20% utilization with conventional ICSI. Results: PIEZO-ICSI resulted in significantly higher fertilization (61.9% vs 45.3%, P<0.0001) and lower degeneration (7.7% vs 18.2%, P=0.0001) when compared to the conventional ICSI cycles. The greatest benefit was seen in patients who had less than 50% fertilization or <20% utilization in their conventional ICSI cycle, with improvements in fertilization and degeneration rates resulting in a significantly higher number of embryos utilized (frozen or transferred) per cycle. Conclusions: PIEZO-ICSI improved fertilization, degeneration, and utilization rates in patients with previous poor outcomes from conventional ICSI. The number of embryos available for use per cycle was also increased. Further significant improvements were achieved in patients who exhibited poor fertilization (<50%) or low utilization (<20%) from conventional ICSI. [ABSTRACT FROM AUTHOR]

Itch is a common sensation which is amenable to disabling patients' life under pathological and chronic conditions. Shared assertion easily limits itch to chemical itch, without considering mechanical itch and alloknesis, its pathological counterpart. However, in recent years, our understanding of the mechanical itch pathway, particularly in the central nervous system, has been enhanced. In addition, Merkel complexes, conventionally considered as tactile end organs only responsible for light touch perception due to Piezo2 expressed by both Merkel cells and SA1 Aβ‐fibres ‐ low threshold mechanical receptors (LTMRs) ‐, have recently been identified as modulators of mechanical itch. However, the tactile end organs responsible for initiating mechanical itch remain unexplored. The consensus is that some LTMRs, either SA1 Aβ‐ or A∂‐ and C‐, are cutaneous initiators of mechanical itch, even though they are not self‐sufficient to finely detect and encode light mechanical stimuli into sensory perceptions, which depend on the entire hosting tactile end organ. Consequently, to enlighten our understanding of mechanical itch initiation, this article discusses the opportunity to consider Merkel complexes as potential tactile end organs responsible for initiating mechanical itch, under both healthy and pathological conditions. Their unsuspected modulatory abilities indeed show that they are tuned to detect and encode light mechanical stimuli leading to mechanical itch, especially as they host not only SA1 Aβ‐LTMRs but also A∂‐ and C‐fibres. [ABSTRACT FROM AUTHOR]

Piezo1 and 2 are evolutionarily conserved mechanosensory cation channels known to function on the cell surface by responding to external pressure and transducing a mechanically activated Ca2+ current. Here we show that both Piezo1 and 2 also exhibit concentrated intracellular localization at centrosomes. Both Piezo1 and 2 loss-of-function and Piezo1 activation by the small molecule Yoda1 result in supernumerary centrosomes, premature centriole disengagement, multi-polar spindles, and mitotic delay. By using a GFP, Calmodulin and M13 Protein fusion (GCaMP) Ca2+-sensitive reporter, we show that perturbations in Piezo modulate Ca2+ flux at centrosomes. Moreover, the inhibition of Polo-like-kinase 1 eliminates Yoda1-induced centriole disengagement. Because previous studies have implicated force generation by microtubules as essential for maintaining centrosomal integrity, we propose that mechanotransduction by Piezo maintains pericentrosomal Ca2+ within a defined range, possibly through sensing cell intrinsic forces from microtubules. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate accurately the effect of the meiotic spindle imaging of human oocytes on their fertilization and embryo development by using the Piezo-ICSI. Methods: We retrospectively assessed 529 oocytes with the first polar body retrieved from 124 infertile couples (147 cycles) who attended our clinic between May 2016 and December 2018. Of these, 489 oocytes (92.4%) with visible meiotic spindle comprised the Spindle (+) group and 40 oocytes (7.6%) not observed meiotic spindle comprised the Spindle (−) group. The meiotic spindle was imaged using polarized light microscopy. The rates of fertilization, high-quality day-3 embryo, day-5 blastocyst, and high-quality day-5 blastocyst were evaluated in both groups. Results: The fertilization rates of Spindle (+) and Spindle (−) were 92.0% (450/489) and 70.0% (28/40), respectively; high-quality day-3 embryo rates were 62.9% (283/450) and 35.7% (10/28); day-5 blastocyst rates were 53.7% (205/382) and 32.1% (9/28); high-quality day-5 blastocyst rates were 29.8% (114/382) and 3.6% (1/28). Fertilization, high-quality day-3 embryo, day-5 blastocyst, and high-quality day-5 blastocyst rates were significantly higher in the Spindle (+) group than in the Spindle (−) group. Conclusion: Spindle imaging (i.e., oocytes with a visible meiotic spindle or with not observed meiotic spindle) influences the outcome of Piezo-ICSI in human oocytes, including fertilization and embryo development. To our knowledge, this study is the first to evaluate the effect of meiotic spindle imaging on fertilization or embryo development among oocytes after Piezo-ICSI. The meiotic spindle imaging could be the indicator for the quality management of medical doctors and embryologists.

The PIEZO protein family was first described in animals where these mechanosensitive calcium channels perform numerous essential functions, including the perception of light touch, shear, and compressive forces. PIEZO homologs are present in most eukaryotic lineages and recently we reported that two PIEZO homologs from moss Physcomitrium patens localize to the vacuolar membrane and modulate its morphology in tip-growing caulonemal cells. Here we show that predicted structures of both PpPIEZO1 and PpPIEZO2 are very similar to that of mouse Piezo2. Furthermore, we show that both moss PIEZO genes are ubiquitously expressed in moss vegetative tissues and that they are not required for normal vacuolar pH or intracellular osmotic potential. These results suggest that moss PIEZO proteins are widely expressed mechanosensory calcium channels that serve a signaling rather than maintenance role in vacuoles.

Piezo1 is the stretch activated Ca2+ channel in red blood cells that mediates homeostatic volume control. Here, we study the organization of Piezo1 in red blood cells using a combination of super-resolution microscopy techniques and electron microscopy. Piezo1 adopts a non-uniform distribution on the red blood cell surface, with a bias toward the biconcave ‘dimple’. Trajectories of diffusing Piezo1 molecules, which exhibit confined Brownian diffusion on short timescales and hopping on long timescales, also reflect a bias toward the dimple. This bias can be explained by ‘curvature coupling’ between the intrinsic curvature of the Piezo dome and the curvature of the red blood cell membrane. Piezo1 does not form clusters with itself, nor does it colocalize with F-actin, Spectrin, or the Gardos channel. Thus, Piezo1 exhibits the properties of a force-through-membrane sensor of curvature and lateral tension in the red blood cell.

Piezo1 is a stretch-gated ion channel required for mechanosensation in many organ systems. Recent findings point to a new role for Piezo1 in the gut, suggesting that it is a sensor of microbial single-stranded RNA (ssRNA) rather than mechanical force. If true, this would redefine the scope of Piezo biology. Here, we sought to replicate the central finding that fecal ssRNA is a natural agonist of Piezo1. While we observe that fecal extracts and ssRNA can stimulate calcium influx in certain cell lines, this response is independent of Piezo1. Additionally, sterilized dietary extracts devoid of gut biome RNA show similar cell line-specific stimulatory activity to fecal extracts. Together, our data highlight potential confounds inherent to gut-derived extracts, exclude Piezo1 as a receptor for ssRNA in the gut, and support a dedicated role for Piezo channels in mechanosensing.