Pyroptosis is a kind of pro-inflammatory cell death. Compared with autophagy and apoptosis, pyroptosis has unique characteristics in morphology and mechanism. Specifically, pyroptosis is a kind of cell lysis mediated by the Gasdermin family, releases inflammatory cytokines IL-1β and IL-18. There are three different forms of mechanism, which are caspase-1-mediated, caspase-4/5/11-mediated and caspase-3-mediated. A large number of studies have proved that pyroptosis is closely related to cardiovascular disease. This paper reviewed the recent progress in the related research on pyroptosis and myocardial infarction, ischemia-reperfusion, atherosclerosis, diabetic cardiomyopathy, arrhythmia, heart failure hypertension and Kawasaki disease. Therefore, we believe that pyroptosis may be a new therapeutic target in the cardiovascular field.

Avian feathers have robust growth and regeneration capability. To evaluate the contribution of signaling molecules and pathways in these processes, we profiled gene expression in the feather follicle using an absolute quantification approach. We identified hundreds of genes that mark specific components of the feather follicle: the dermal papillae (DP) which controls feather regeneration and axis formation, the pulp mesenchyme (Pp) which is derived from DP cells and nourishes the feather follicle, and the ramogenic zone epithelium (Erz) where a feather starts to branch. The feather DP is enriched in BMP/TGF-β signaling molecules and inhibitors for Wnt signaling including Dkk2/Frzb. Wnt ligands are mainly expressed in the feather epithelium and pulp. We find that while Wnt signaling is required for the maintenance of DP marker gene expression and feather regeneration, excessive Wnt signaling delays regeneration and reduces pulp formation. Manipulating Dkk2/Frzb expression by lentiviral-mediated overexpression, shRNA-knockdown, or by antibody neutralization resulted in dual feather axes formation. Our results suggest that the Wnt signaling in the proximal feather follicle is fine-tuned to accommodate feather regeneration and axis formation.

The ciliary body (CB) of the mammalian eye is responsible for secreting aqueous humor to maintain intraocular pressure, which is elevated in the eyes of glaucoma patients. It contains a folded two-layered epithelial structure comprising the nonpigmented inner ciliary epithelium (ICE), the pigmented outer ciliary epithelium (OCE), and the underlying stroma. Although the CB has an important function in the eye, its morphogenesis remains poorly studied. In this study, we show that conditional inactivation of the Jagged 1 (Jag1)-Notch2 signaling pathway in the developing CB abolishes its morphogenesis. Notch2 is expressed in the OCE of the CB, whereas Jag1 is expressed in the ICE. Conditional inactivation of Jag1 in the ICE or Notch2 in the OCE disrupts CB morphogenesis, but neither affects the specification of the CB region. Notch2 signaling in the OCE is required for promoting cell proliferation and maintaining bone morphogenetic protein (BMP) signaling, both of which have been suggested to be important for CB morphogenesis. Although Notch and BMP signaling pathways are known to crosstalk via the interaction between their downstream transcriptional factors, this study suggests that Notch2 maintains BMP signaling in the OCE possibly by repressing expression of secreted BMP inhibitors. Based on our findings, we propose that Jag1-Notch2 signaling controls CB morphogenesis at least in part by regulating cell proliferation and BMP signaling.T he mammalian eye is composed of the anterior segment, the posterior retina and the vitreous. The anterior segment consists of cornea, lens, and ciliary body (CB), whereas the posterior retina contains six types of retinal neurons and Müller glial cells, which are organized into three distinct cell layers. The light passes through the cornea and is then focused by the lens and detected by photoreceptors in the retina. Both the aqueous humor anteriorly and the vitreous humor posteriorly function together to sustain intraocular pressure (IOP) in the eye and thereby maintain its shape. Pressure regulation is particularly important because abnormally high IOP is a major risk factor for glaucoma (1). In the eye, the CB is responsible for producing aqueous humor (2). Although high IOP is often attributed to the blockage of the drainage system for the vitreous, known as the trabecular meshwork, abnormal CB function might also contribute to high IOP formation because of excess aqueous humor production. Finally, contraction of the muscles in the CB controls lens accommodation for near versus far vision. Despite its important biological functions and potential medical significance, the formation and development of the CB remain poorly studied.The CB contains two layers of apically adhered epithelial sheets, the pigmented outer ciliary epithelium (OCE) and the nonpigmented inner ciliary epithelium (ICE), and the underlying stroma (2). It forms at the periphery of the developing optic cup and first segregates from the retina and then from the iris. One previous study suggested that blood vesse...

Purpose To assess the relationship among corneal stiffness, thickness, and biomechanical parameters in keratoconus. Setting The EENT Hospital of Fudan University, Shanghai, China. Design Comparative study. Methods In this cross-sectional prospective study, 75 keratoconic eyes of 44 patients were recruited. Eyes were divided three groups according to the steepest K-readings (Kmax): mild (31 eyes; 42.1–54.5D); moderate (27 eyes, 55.0–61.6D); and severe (17 eyes, 65.2–94.5D). Thirty-one healthy subjects were recruited as the control group. All patients underwent Corvis ST, Pentacam and ORA examinations at the same time. Stiffness parameter A1 (SP-A1) and other dynamic parameters were assessed using the Corvis ST. Kmax and thinnest corneal thickness (TCT) was obtained using the Pentacam. Corneal resistance factor (CRF) and corneal hysteresis (CH) were measured using the ORA. Analysis of correlation was applied to investigate the association between variables. Results There was a decrease in SP-A1 in different stages of keratoconus compared with controls ( P ≤ 0.001): with increasing severity, the value of SP-A1 became smaller ( P < 0.05). A statistically significant linear relationship was noted between SP-A1 and TCT in each subgroup of keratoconus ( P ≤ 0.001). In all three groups, SP-A1 was found to be positively correlated with first applanation time ( P < 0.01), while negatively correlated with deformation amplitude ( P < 0.05). Analysis of SP-A1 with regard to CRF and CH indicated statistically positive correlation in keratoconus ( P < 0.05). Conclusion Significant decreases in corneal stiffness were noted in kerotoconic eyes compared with normal eyes. The stiffness parameter could be a valuable clinical tool enables biomechanically track progression with keratoconus. Synopsis Our study found that corneal thinning and biomechanical decreasing synchronize with one another throughout the progression of the keratoconus, and SP-A1 could be a potential biomarker evaluating disease progression.

Purpose To investigate two-year outcomes of Visian Implantable Collamer Lens with a central hole (ICL V4c) implantation for correcting high myopia. Methods Sixty-one eyes of 32 patients went through ICL V4c implantation. Safety, efficacy, predictability, and intraocular pressure were evaluated 2 years postoperatively. Anterior chamber volume (ACV), anterior chamber depth (ACD), anterior chamber angle width (ACAW), and vault were measured using a Scheimpflug tomography imaging system. Results At 2 years, the spherical equivalent refraction decreased from preoperative −14.62 ± 4.29 D to −0.90 ± 0.95 D, with 79% of the eyes within ±0.50 D and 98% within ±1.00 D of the intended correction. The efficacy index was 1.03 ± 0.23, and the safety index was 1.24 ± 0.26. Corrected distance visual acuity (CDVA) remained unchanged in 23% of the eyes, 75% gained one or more lines of CDVA, and 2% lost one line. The ACV, ACD, and ACAW, respectively, decreased from 193.28 ± 29.15 mm3, 3.15 ± 0.23 mm, and 36.51 ± 6.54 degree to 112.48 ± 17.01 mm3, 2.99 ± 0.23 mm, and 22.54 ± 5.27 degree (p=0.0008, 0.008, and  0.0003, resp.). Intraocular pressure was 15.39 ± 2.88 mmHg before surgery and was 15.86 ± 4.11 mmHg at 2 years (p=0.11). Conclusion Implantation of ICL V4c is a safe, effective, and predictable procedure for correcting high myopia. Reduction of anterior chamber space after surgery did not induce intraocular pressure increase during the 2-year follow-up.

Chemotherapeutic agents induce complex tissue responses in vivo and damage normal organ functions. Here we use the feather follicle to investigate details of this damage response. We show that cyclophosphamide treatment, which causes chemotherapy-induced alopecia in mice and man, induces distinct defects in feather formation: feather branching is transiently and reversibly disrupted, thus leaving a morphological record of the impact of chemotherapeutic agents, whereas the rachis (feather axis) remains unperturbed. Similar defects are observed in feathers treated with 5-fluorouracil or taxol but not with doxorubicin or arabinofuranosyl cytidine (Ara-C). Selective blockade of cell proliferation was seen in the feather branching area, along with a downregulation of sonic hedgehog (Shh) transcription, but not in the equally proliferative rachis. Local delivery of the Shh inhibitor, cyclopamine, or Shh silencing both recapitulated this effect. In mouse hair follicles, those chemotherapeutic agents that disrupted feather formation also downregulated Shh gene expression and induced hair loss, whereas doxorubicin or Ara-C did not. Our results reveal a mechanism through which chemotherapeutic agents damage rapidly proliferating epithelial tissue, namely via the cell population-specific, Shh-dependent inhibition of proliferation. This mechanism may be targeted by future strategies to manage chemotherapy-induced tissue damage.

Anemia is a complication of chronic kidney disease (CKD), primarily due to insufficient secretion of erythropoietin (EPO) by the kidney. Erythropoiesis-stimulating agents (ESAs) are used to treat anemia associated with chronic kidney disease. A poor response to ESAs has been associated with inflammation. Inflammation can affect erythrocytes and its production in many ways, but mainly through the inflammatory cytokine IL-6 to stimulate the synthesis of hepcidin in the liver. Hepcidin causes iron insufficiency, which causes erythrocytes to fail to mature normally. In addition, inhibition of bone marrow erythroid precursor cells by inflammatory cytokines such as IL-1 and TNF-α also affects bone marrow hematopoiesis. These cytokines are also important factors leading to EPO resistance. Roxadustat is a new drug for the treatment of renal anemia. In addition to promoting the production of EPO, clinical trials have shown that it can significantly reduce hepcidin and can potentially be used for the treatment of inflammation-induced anemia in CKD.

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