Stiffness and surface topology of silicone implants competitively mediate inflammatory responses of macrophages and foreign body response.

Adverse inflammatory responses, dominated by macrophages, that are induced by physical cues of silicone implants can heavily damage the life quality of patients via causing fibrosis and device failure. As stiffness and surface topology affect macrophages at the same time, the competition or partnership among physical cues against the regulation of macrophages is still ambiguous. Herein, a series of PDMS implants with different stiffness at ∼ MPa and surface topology at tens of micrometers were fabricated to investigate the relationship, the regulation rule, and the underlying mechanism of the two physical cues against the inflammatory responses of M1 macrophages.

Hyaluronidase-Responsive Bactericidal Cryogel for Promoting Healing of Infected Wounds: Inflammatory Attenuation, ROS Scavenging, and Immune Regulation.

Wounds infected with multidrug-resistant (MDR) bacteria are increasingly threatening public health and challenging clinical treatments because of intensive bacterial colonization, excessive inflammatory responses, and superabundant oxidative stress. To overcome this malignant burden and promote wound healing, a multifunctional cryogel (HA/TA2/KR2) composed of hyaluronic acid (HA), tannic acid (TA), and KR-12 peptides is designed. The cryogel exhibited excellent shape-memory properties, strong absorption performance, and hemostatic capacity.

Corrigendum to "BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia" [Heliyon 8(10) (October 2022) e11190].

[This corrects the article DOI: 10.1016/j.heliyon.

Hypoxic microenvironment promotes dermal fibroblast migration and proliferation via a BNIP3-autophagy pathway.

Upon injury, nearby cells, including fibroblasts at the wound edge, are often found in a hypoxic microenvironment. Nevertheless, the influence of hypoxia on skin fibroblasts is poorly understood. Using previously established mouse full-thickness wounds, we show that Bcl-2 and adenovirus E1B 19-kDa interacting protein 3 (BNIP3) expression was significantly elevated at the wound edge, and hypoxia treatment enhanced BNIP3 expression in fibroblasts.

BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia.

Chemotherapy and immunotherapy for pancreatic ductal adenocarcinoma (PDAC) have limited success for the intricated surrounding cancer microenvironment. Hypoxic microenvironment in PDAC causes the activation of multiple different molecules and signaling pathways compared with normoxia. We studied the roles of BNIP3 for the migration and proliferation of PDAC and Panc1 cells .

Multifunctional chitosan/gelatin@tannic acid cryogels decorated with reduced silver nanoparticles for wound healing.

Background: Most traditional wound dressings only partially meet the needs of wound healing because of their single function. Patients usually suffer from the increasing cost of treatment and pain resulting from the frequent changing of wound dressings. Herein, we have developed a mutifunctional cryogel to promote bacterial infected wound healing based on a biocompatible polysaccharide.

Impaired Retrograde Transport Due to Lack of TBC1D5 Contributes to the Trafficking Defect of Lysosomal Cathepsins in Ischemic/Hypoxic Cardiomyocytes.

Lysosomal dysfunction has been found in many pathological conditions, and methods to improve lysosomal function have been reported to be protective against infarcted hearts. However, the mechanisms underlying lysosomal dysfunction caused by ischemic injury are far less well-established. The retromer complex is implicated in the trafficking of cation-independent mannose 6-phosphate receptor (CI-MPR), which is an important protein tag for the proper transport of lysosomal contents and therefore is important for the maintenance of lysosomal function.

Microtubule associated protein 4 (MAP4) phosphorylation reduces cardiac microvascular density through NLRP3-related pyroptosis.

Phosphorylation of MAP4 (p-MAP4) causes cardiac remodeling, with the cardiac microvascular endothelium being considered a vital mediator of this process. In the current study, we investigated the mechanism underlying p-MAP4 influences on cardiac microvascular density. We firstly confirmed elevated MAP4 phosphorylation in the myocardium of MAP4 knock-in (KI) mice.

Autophagy-Related LC3 Accumulation Interacted Directly With LIR Containing RIPK1 and RIPK3, Stimulating Necroptosis in Hypoxic Cardiomyocytes.

The exact relationships and detailed mechanisms between autophagy and necroptosis remain obscure. Here, we demonstrated the link between accumulated autophagosome and necroptosis by intervening with autophagic flux. We first confirmed that the LC3 interacting region (LIR) domain is present in the protein sequences of RIPK1 and RIPK3.

H(+)/Cl(‑) exchange transporter 7 promotes lysosomal acidification‑mediated autophagy in mouse cardiomyocytes.

Autophagy protects cardiomyocytes in various pathological and physiological conditions; however, the molecular mechanisms underlying its influence and the promotion of autophagic clearance are not completely understood. The present study aimed to explore the role of H(+)/Cl(‑) exchange transporter 7 (CLC‑7) in cardiomyocyte autophagy. In this study, rapamycin was used to induce autophagy in mouse cardiomyocytes, and the changes in CLC‑7 were investigated.

CD38 Causes Autophagic Flux Inhibition and Cardiac Dysfunction Through a Transcriptional Inhibition Pathway Under Hypoxia/Ischemia Conditions.

Induced autophagy is protective against myocardial hypoxia/ischemia (H/I) injury, but evidence regarding the extent of autophagic clearance under H/I and the molecular mechanisms that influence autophagic flux has scarcely been presented. Here, we report that CD38 knockout improved cardiac function and autophagic flux in mice and neonatal cardiomyocytes (CMs) under H/I conditions. Mechanistic studies demonstrated that overexpression of CD38 specifically downregulated the expression of Rab7 and its adaptor protein pleckstrin homology domain-containing protein family member 1 (PLEKHM1) through nicotinamide adenine dinucleotide (NAD)-dependent and non-NAD-dependent pathways, respectively.

TRPV1 activation mitigates hypoxic injury in mouse cardiomyocytes by inducing autophagy through the AMPK signaling pathway.

Autophagy is a highly conserved self-protection mechanism that plays a crucial role in cardiovascular diseases. Cardiomyocyte hypoxic injury promotes oxidative stress and pathological alterations in the heart, although the interplay between these effects remains elusive. The transient receptor potential vanilloid 1 (TRPV1) ion channel is a nonselective cation channel that is activated in response to a variety of exogenous and endogenous physical and chemical stimuli.

The Lysosomal Membrane Protein Lamp2 Alleviates Lysosomal Cell Death by Promoting Autophagic Flux in Ischemic Cardiomyocytes.

Lysosomal membrane permeabilization (LMP) has recently been recognized as an important cell death pathway in various cell types. However, studies regarding the correlation between LMP and cardiomyocyte death are scarce. Lysosomal membrane-associated protein 2 (Lamp2) is an important component of lysosomal membranes and is involved in both autophagy and LMP.

Microtubule-associated protein 4 phosphorylation regulates epidermal keratinocyte migration and proliferation.

Both cell migration and proliferation are indispensable parts of reepithelialization during skin wound healing, which is a complex process for which the underlying molecular mechanisms are largely unknown. Here, we identify a novel role for microtubule-associated protein 4 (MAP4), a cytosolic microtubule-binding protein that regulates microtubule dynamics through phosphorylation modification, as a critical regulator of epidermal wound repair. We showed that MAP4 phosphorylation was induced in skin wounds.

Myocardial Adipose Triglyceride Lipase Overexpression Protects against Burn-Induced Cardiac Lipid Accumulation and Injury.

Maladaptive cardiac metabolism is a common trigger of cardiac lipid accumulation and cardiac injury under serious burn challenge. Adipose triglyceride lipase (ATGL) is the key enzyme that catalyzes triglyceride hydrolysis; however, its alteration and impact on cardiac function following serious burn injury are still unknown. Here, we found that the cardiac fatty acid (FA) metabolism increased, accompanied by augmented FA accumulation and ATGL expression, after serious burn injury.

Author Correction: Involvement of autophagy in hypoxia-BNIP3 signaling to promote epidermal keratinocyte migration.

Following publication of the original article, it has come to our attention that the Materials and Methods section of the paper was missing. This is because this section was accidentally omitted from the final version of the manuscript when it was submitted to production. Both the PDF and HTML versions of the article have been updated with the missing section and references.

Involvement of autophagy in hypoxia-BNIP3 signaling to promote epidermal keratinocyte migration.

BNIP3 is an atypical BH3-only member of the Bcl-2 family with pro-death, pro-autophagic, and cytoprotective functions, depending on the type of stress and cellular context. Recently, we demonstrated that BNIP3 stimulates the migration of epidermal keratinocytes under hypoxia. In the present study found that autophagy and BNIP3 expression were concomitantly elevated in the migrating epidermis during wound healing in a hypoxia-dependent manner.

High Glucose Suppresses Keratinocyte Migration Through the Inhibition of p38 MAPK/Autophagy Pathway.

Wound healing is delayed frequently in patients with diabetes. Proper keratinocyte migration is an essential step during re-epithelialization. Impaired keratinocyte migration is a critical underlying factor responsible for the deficiency of diabetic wound healing, which is mainly attributed to the hyperglycemic state.

Autophagy is required for the directed motility of keratinocytes driven by electric fields.

Endogenous wound electric fields (EFs), an important and fundamental occurrence of wound healing, profoundly influence the directed migration of keratinocytes. Although numerous studies have unveiled the signals responsible for EF-biased direction, the mechanisms by which EFs promote keratinocyte motility remains to be elucidated. In our study, EFs enhanced the directed migratory speed of keratinocytes by inducing autophagic activity, thereby facilitating skin barrier restoration.

Microtubule associated protein 4 phosphorylation leads to pathological cardiac remodeling in mice.

Background: Cardiac remodeling is a pathophysiological process that involves various changes in heart, including cardiac hypertrophy and fibrosis. Cardiac remodeling following pathological stimuli is common trigger leading to cardiac maladaptation and onset of heart failure, and their pathogenesis remains unclear.

Methods: Heart specimens of tetralogy of Fallot (TOF) patients, myocardial infarction (MI) and transverse aortic constriction (TAC) mouse models were collected to determine changes of microtubule associated protein 4 (MAP4) phosphorylation.

FG-4592 Accelerates Cutaneous Wound Healing by Epidermal Stem Cell Activation via HIF-1α Stabilization.

Background/aims: Regional hypoxia promptly develops after trauma because of microvascular injury and increased oxygen consumption. This acute hypoxia plays a positive role in early skin wound healing. One of the mechanisms underlying the beneficial effects of acute hypoxia on wound healing may be increased hypoxia-inducible factor-1 (HIF-1α) expression.

Electric field-induced suppression of PTEN drives epithelial-to-mesenchymal transition via mTORC1 activation.

Background: Naturally occurring electric fields (EFs) are an intrinsic property of wounds. Endogenous EFs in skin wounds play critical roles in the dynamic and well-ordered biological process of wound healing. The epithelial-to-mesenchymal transition (EMT) allows keratinocytes to transition from sedentary cells to motile cells, facilitating wound healing.

BNIP3 promotes the motility and migration of keratinocyte under hypoxia.

The migration of keratinocytes from wound margins plays a critical role in the re-epithelialization of skin wounds. Hypoxia occurs immediately after injury and acts as an early stimulus to initiate the healing processes. Although our previous studies have revealed that hypoxia promotes keratinocyte migration, the precise mechanisms involved remain unclear.

Extracellular pH regulates autophagy via the AMPK-ULK1 pathway in rat cardiomyocytes.

Various pathological conditions contribute to pH fluctuations and affect the functions of vital organs such as the heart. In this study, we show that in rat cardiomyocytes, acidic extracellular pH (pHe) inhibits autophagy, whereas alkaline pHe stimulates it. We also find that adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Unc-51-like kinase 1 (ULK1) are very sensitive to pHe changes.