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Abstract Darier disease (DD) is a rare severe acantholytic skin disease caused by mutations in the ATP2A2 gene that encodes for the sarco/endoplasmic reticulum calcium ATPase isoform 2 (SERCA2). SERCA2 maintains endoplasmic reticulum calcium homeostasis by pumping calcium into the ER, critical for regulating cellular calcium dynamics and cellular function. To date, there is no treatment that specifically targets the disease mechanisms in DD. Dantrolene sodium (Dl) is a ryanodine receptor antagonist that inhibits calcium release from ER to increase ER calcium levels and is currently used for non-dermatological indications. In this study, we first identified dysregulated genes and molecular pathways in DD patient skin, demonstrating downregulation of cell adhesion and calcium homeostasis pathways, as well as upregulation of ER stress and apoptosis. We then show in various in vitro models of DD and SERCA2 inhibition that Dl aided in the retention of ER calcium and promoted cell adhesion. In addition, Dl treatment reduced ER stress and suppressed apoptosis. Our findings suggest that Dl specifically targets pathogenic mechanisms of DD and may be a potential treatment.

Abstract Circulating leukocytes enter tissue either through endothelial junctions (paracellular) or via a pore through the body of endothelial cells (transcellular). We have previously shown that genetically replacing VE-cadherin with a VE-cadherin-α-catenin (VEC-αC) fusion construct—which binds constitutively to actin—obstructs junctions, and blocks leukocyte extravasation in lung, skin and postcapillary venules of cremaster muscle. However, neutrophil recruitment into the inflamed peritoneal cavity was unimpaired. Investigating reasons for this, here, we visualized neutrophil diapedesis by 3D intravital video microscopy in the cremaster muscle and omentum, the major site of neutrophil recruitment into the peritoneal cavity. We found that 80% of neutrophil-extravasation occurred through HEVs in the omentum, which was unimpaired by VEC-αC. In addition, in larger venules (60–85 µm) of both tissues, less than 15% of neutrophils extravasated transcellularly in WT mice. However, in VEC-α-C mice, transcellular diapedesis increased severalfold in the omentum, but not in the cremaster. In line with this, omental venules expressed higher levels of ICAM-1 and atypical chemokine receptor 1. Furthermore, only in the omentum, VEC-αC expression caused reduced elongation of venular endothelium in flow-direction, suggesting different biomechanical properties. Collectively, VEC-αC does not inhibit paracellular transmigration in all types of venules and can modulate the diapedesis route.

Abstract Exploring the mechanism of breast cancer metastasis and searching for new drug therapeutic targets are still the focuses of current research. RNA-binding proteins (RBPs) may affect breast cancer metastasis by regulating alternative splicing (AS) during epithelial-mesenchymal transition (EMT). We hypothesised that during EMT development in breast cancer cells, the expression level of RBPs and the gene AS pattern in the cell were significantly changed on a genome-wide scale. Using GEO database, this study identified differentially expressed RBPs and differential AS events at different stages of EMT in breast cancer cells. By establishing the correlation network of differential RBPs and differential AS events, we found that RBM47, PCBP3, FRG1, SRP72, RBMS3 and other RBPs may regulate the AS of ITGA6, ADGRE5, TNC, COL6A3 and other cell adhesion genes. By further analysing above EMT-related RBPs and AS in breast cancer tissues in TCGA, it was found that the expression levels of ADAT2, C2orf15, SRP72, PAICS, RBMS3, APOBEC3G, NOA1, ACO1 and the AS of TNC and COL6A3 were significantly correlated with the prognosis of breast cancer patients. The expression levels of all 8 RBPs were significantly different in breast cancer tissues without metastasis compared with normal breast tissues. Conclusively, eight RBPs such as RBMS3 and AS of TNC and COL6A3 could be used as predictors of breast cancer prognosis. These findings need to be further explored as possible targets for breast cancer treatment.

The most common type of liver cancer is hepatocellular carcinoma (HCC) causes a lower survival rate even after systemic treatment. Previous studies have shown evidence that various molecular and epigenetic mechanisms are involved in the transition of HCC from normal liver cells. Epigenetics plays an important role in maintaining genomic stability in normal liver cells. Apart from the mutation of genes, epigenetic factors are involved in HCC progression. miRNA tends to be a major epigenetic factor involved in regulating major cell cycle pathways. miRNA regulates the HCC progression by inhibiting the major apoptotic pathways and favors angiogenesis and tumor microenvironment. Apart from regulating major pathways, miRNA appears to regulate tight junction integrity. Tight junction proteins appear to be strong barrier proteins involved in cell adhesion and integrity. Disturbance in cell adhesion and integrity leads to the major dysregulation of cell cycle resulting in cancer progression. Moreover, dysregulation of tight junction integrity was observed in the pathogenesis of HCC. The regulation of tight junction proteins via miRNA were studied in various diseases. Here, we discussed the regulation of tight junction proteins via miRNA in HCC progression. This review may focus on the significance of miRNA in cellular function and its role in regulating tight junction proteins that impact in HCC progression which opens a new approach to develop a new diagnostic marker for an early detection of HCC and novel therapeutic approach against HCC.

Objective To deposit degradable amino-hybrid mesoporous silica (AHMS) in situ on the surface of titanium nanotube (TNT) and explore its protective effect on nanomorphology and osteogenesis. Methods TNT and TNT@AHMS were sequentially prepared via an anodizing method: the oil-water two-phase method (experimental group) and the acid-etched titanium method [control group (Ti)]. The parameters for synthesis were explored by changing the silicon source dosage ratio (3∶1, 1∶1, 1∶3); the surface morphology was observed by scanning electron microscope(SEM), hydrophilicity was detected by Water Contact Angle Tester, elemental composition was detected by X-ray photoelectron spectroscopy (XPS); nanoindentation test and ultrasonic oscillator were used to observe the morphological holding effect as mechanical strength of TNT@AHMS in vitro; simulated immersion experiments in vitro was used to observe the degradation behavior of the material. the MC3T3-E1 cell line was used to observe the effect of cell adhesion, proliferation and differentiation on the material; and an SD rat femoral implant model and micro-CT were used to verify the protective effect and osseointegration effect of AHMS on TNT morphology. Results The morphologies of TNT and TNT@AHMS were successfully prepared, and the silicon source ratio was 1:3. SEM showed that the titanium nanotubes were uniformly covered with AHMS coating, and the mesoporous pore size was about 4 nm. After AHMS was incorporated, the surface of the material was hydrophilic (12.78°), the presence of amino groups (NH2-) was detected, the material was completely degraded within 12 h in vitro, and the active morphology of the TNT was re-exposed with a cumulative silicon release of 10 ppm. Nanoindentation test showed that TNT@AHMS exhibited more ideal surface mechanical strength. SEM revealed that TNT maintains its own morphology under the protection of AHMS, and the TNT group suffered severe exfoliation. In addition, the early adhesion and proliferation rates, ALP activity, and bone volume fraction of cells on the TNT@AHMS surface 4 weeks after implantation were significantly higher than those in the TNT group. Conclusion By depositing AHMS on the surface of TNT, the nanotopography can be protected. It not only prevents the active base topography from exerting subsequent biological effects but also further endows the material with the ability to promote bone regeneration, laying a foundation for the future development of nanotopography-modified titanium implants.

Microfluidic devices serve as essential tools across diverse fields like medicine, biotechnology, and chemistry, enabling advancements in analytical techniques, point‐of‐care diagnostics, microfluidic cell cultures, and organ‐on‐chip models. While polymeric microfluidics are favoured for their cost‐effectiveness and ease of fabrication, their inherent hydrophobic properties necessitate surface functionalization, often post‐sealing. Here, we introduce a versatile apparatus for functionalizing sealed microfluidic devices using atmospheric plasma processing, with a focus on PDMS (polydimethylsiloxane) microfluidics. Through meticulous analysis of surface properties and capillary speed, before and after plasma treatment, along with a comparison between vacuum and atmospheric plasma functionalization methods, we demonstrate the efficacy of our approach. Subsequent experimentation within 3D PDMS microfluidic chambers, combining atmospheric pressure plasma treatment with collagen coating to facilitate mesenchymal stem cells (MSCs) growth over five days, reveals enhanced initial cell adhesion and proliferation, highlighting the potential of our method for improving cell‐based applications within microfluidic systems. [ABSTRACT FROM AUTHOR]

Objective Animal Studied Procedures Results Conclusions The application of canine amniotic membrane (cAM) for corneal reconstruction is widely used in the veterinary field. However, the information on biological properties and alternative forms of cAM for corneal wound healing is limited. This study aimed to investigate the proteomic profiles and corneal wound healing properties of cAM, cAM extract (cAME), and lyophilized cAM extract (cAMX).A total number of 14 cAMs were sterilely harvested from healthy full‐term puppies and randomly divided into three different forms: cAM (n = 14), cAME (n = 14), and cAMX (n = 14).Each form of cAMs was subjected to proteomic analysis using label‐free liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS), followed by bioinformatic analysis. The proteins were classified into properties by comparing them with the literature search on human amniotic membrane (hAM) properties and the effect on corneal wound healing when given topically.The analyses identified 8136 proteins in cAM, 8211 proteins in cAME, and 7093 proteins in cAMX. A total number of 100 proteins were matched with proteins in hAM properties and were classified into anti‐inflammatory, anti‐fibrotic, anti‐microbial, anti‐angiogenic, promotion of epithelialization, analgesic, and support cell adhesion and growth properties. Furthermore, proteins with corneal wound healing effects were identified in cAME and cAMX.cAM and its extracts contain numerous proteins, including proteins related to corneal wound healing properties. Additionally, cAME and cAMX showed proteins involved in corneal wound healing and their potential benefits for topical use in ophthalmology. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) tissue-engineered scaffolds mimic the physiological environment of cells by providing essential structural support, biochemical cues, and the mechanical strength needed for cell adhesion, proliferation, migration, and differentiation. Hydrogels like polyethylene glycol diacrylate (PEGDA) are commonly used biomaterials for cell culture due to their affordability, tunable stiffness, and ability to efficiently transport nutrients and gases. However, PEGDA lacks cell adhesion sites essential for cell proliferation and migration and has limited degradability. Methacrylated gelatin (GelMA) produced from denatured bovine collagen, crosslinks under ultraviolet light (UV) resulting in a degradable hydrogel with cell adhesion sites. Here, we synthesized GelMA with variable degree of methacrylation and crosslinked it with PEGDA to produce cell scaffolds with independently tunable mechanical and biochemical properties by varying the ratios of the two polymers. We determined polymer ratios that resulted in scaffolds with different mechanical properties but the same gelatin concentrations (providing cell adhesion and degradation sites) as well as different gelatin concentrations but the same mechanical properties. With the developed scaffold library, we further used a design of experiments approach to probe the parameter space and perform detailed analysis on chemical compositionscaffold properties as well as scaffold properties-cell behavior correlations. Our findings showed that hydrogel properties such as modulus, swelling, pore size, and permeability, strongly depended on total polymer concentration and not on theGelMA fraction. GelMA significantly influenced cell spreading, while addition of any amount of PEGDA delayed cell spreading significantly. We suggest that such analysis will broaden the utility of the GelMA/PEGDA hydrogels, presenting a versatile platform for mechanosensing research in 3D environments. [ABSTRACT FROM AUTHOR]

In this study, we conducted an in-depth exploration of Alzheimer's Disease (AD) by integrating state-of-the-art methodologies, including single-cell RNA sequencing (scRNA-seq), weighted gene co-expression network analysis (WGCNA), and a convolutional neural network (CNN) model. Focusing on the pivotal role of microglia in AD pathology, our analysis revealed 11 distinct microglial subclusters, with 4 exhibiting obviously alterations in AD and HC groups. The investigation of cell–cell communication networks unveiled intricate interactions between AD-related microglia and various cell types within the central nervous system (CNS). Integration of WGCNA and scRNA-seq facilitated the identification of critical genes associated with AD-related microglia, providing insights into their involvement in processes such as peptide chain elongation, synapse-related functions, and cell adhesion. The identification of 9 hub genes, including USP3, through the least absolute shrinkage and selection operator (LASSO) and COX regression analyses, presents potential therapeutic targets. Furthermore, the development of a CNN-based model showcases the application of deep learning in enhancing diagnostic accuracy for AD. Overall, our findings significantly contribute to unraveling the molecular intricacies of microglial responses in AD, offering promising avenues for targeted therapeutic interventions and improved diagnostic precision. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to patients with nosocomial infections, and infection is strongly associated with biofilm formation. Gallic acid (GA) is a natural bioactive compound found in traditional Chinese medicines that exerts potent antimicrobial activity. However, the anti-MRSA biofilm efficacy of GA remained to be determined. This study investigated the antimicrobial activities of GA against MRSA and the mechanisms involved. The results revealed the significant antibacterial and antibiofilm activities of GA. The minimal inhibitory concentration of GA against MRSA was 32 μg/mL and a growth curve assay confirmed the significant inhibitory effect of GA on planktonic MRSA. Crystal violet and XTT assays showed that 8 µg/mL GA effectively inhibited the formation of new biofilms and disrupted existing biofilms by reducing both biofilm biomass and metabolic activities. Alkaline phosphatase and β-galactosidase leakage assays and live/dead staining provided evidence that GA disrupted the integrity of bacterial cell walls and membranes within the biofilm. Scanning electron microscopy observations showed that GA significantly inhibited bacterial adhesion and aggregation, affecting the overall structure of the biofilm. Bacterial adhesion, polysaccharide intercellular adhesion (PIA) production and real-time quantitative PCR assay confirmed that GA inhibited bacterial adhesion, PIA synthesis, and the expression of icaAD and sarA. These results suggested that GA inhibited biofilm formation by inhibiting the expression of sarA, then downregulating the expression of icaA and icaD, thereby reducing the synthesis of PIA to attenuate the adhesion capacity of MRSA. GA is therefore a promising candidate for development as a pharmaceutical agent for the prevention and treatment of bacterial infections caused by MRSA. [ABSTRACT FROM AUTHOR]

Cell migration modes can vary, depending on a number of environmental and intracellular factors. The high motility of the pathogenic amoeba Entamoeba histolytica is a decisive factor in its ability to cross the human colonic barrier. We used quantitative live imaging techniques to study the migration of this parasite on fibronectin, a key tissue component. Entamoeba histolytica amoebae on fibronectin contain abundant podosome-like structures. By using a laminar flow chamber, we determined that the adhesion forces generated on fibronectin were twice those on non-coated glass. When migrating on fibronectin, elongated amoeboid cells converted into fan-shaped cells characterized by the presence of a dorsal column of F-actin and a broad cytoplasmic extension at the front. The fan shape depended on the Arp2/3 complex, and the amoebae moved laterally and more slowly. Intracellular measurements of physical variables related to fluid dynamics revealed that cytoplasmic pressure gradients were weaker within fan-shaped cells; hence, actomyosin motors might be less involved in driving the cell body forward. We also found that the Rho-associated coiled-coil containing protein kinase regulated podosome dynamics. We conclude that E. histolytica spontaneously changes its migration mode as a function of the substrate composition. This adaptive ability might favour E. histolytica's invasion of human colonic tissue. By combining microfluidic experiments, mechanical modelling, and image analysis, our work also introduces a computational pipeline for the study of cell migration. Author summary: Even though we know increasingly well how cells move in tissues, the question of whether parasites modify their migration as a function of the host tissue environment requires further investigation. Cell motility is triggered by environmental stimuli, and the migration mode depends on adhesion, activated enzymatic pathways, and changes in the actin cytoskeleton dynamics and thus cell morphology. The protozoan intestinal parasitic Entamoeba histolytica is the causative agent of amoebiasis (a major food- and water-borne disease) in humans. During invasion of the colon, E. histolytica degrades the mucus layer, adheres to and removes the epithelium, progresses along the fibronectin-rich basement membrane towards the crypts of Lieberkühn, and penetrates the mucosa. This invasive process raises the question of how the parasite moves in a varying intestinal environment. E. histolytica is known to display an amoeboid migration mode and binds fibronectin through podosome adhesion structures. We hypothesized that fibronectin triggers signalling pathways that influence the trophozoite's migration. We found that E. histolytica can migrate with a non-amoeboid mode on fibronectin-coated glass. Our finding suggests that for tissue invasion, E. histolytica's migration mode is modulated to suit the environment. [ABSTRACT FROM AUTHOR]

The adhesion of cells to the extracellular matrix engages cell surface receptors such as integrins, proteoglycans and other types of cell adhesion molecules such as CD44. To closely examine the determinants of cell adhesion, herein we describe the generation of high-density peptide arrays and test the growth of cells on these multifunctionalized surfaces. The peptide library used consists of over 11,000 different sequences, either random or derived from existing proteins. By applying this screen to SW620 mCherry colorectal cancer cells, we select for peptides with both maximum cell adhesion and maximum cell repulsion. All of these extreme properties are based on unique combinations of amino acids. Here, we identify peptides with maximum cell repulsion on secreted frizzled- and Dickkopf-related proteins. Peptides with strong cell repulsion are found at the poles of the TNF-alpha homotrimer. The formation of cellular patterns on alternating highly repulsive and adhesive peptides are examined. Our screen allows the identification of peptides suitable for biomedical and tissue engineering applications. A screen on high-density peptide arrays identified peptides with high cell-adhesion/ repulsion properties. Peptides with high repulsive properties as those found in TNF-alpha are particularly suitable for biomedical/bioengineering applications. [ABSTRACT FROM AUTHOR]

Purpose: Cadherin-17 (CDH17) is a calcium-dependent cell adhesion protein that is overexpressed in several adenocarcinomas, including gastric, colorectal, and pancreatic adenocarcinoma. High levels of CDH17 have been linked to metastatic disease and poor prognoses in patients with these malignancies, fueling interest in the protein as a target for diagnostics and therapeutics. Herein, we report the synthesis, in vitro validation, and in vivo evaluation of a CDH17-targeted 89Zr-labeled immunoPET probe. Methods: The CDH17-targeting mAb D2101 was modified with an isothiocyanate-bearing derivative of desferrioxamine (DFO) to produce a chelator-bearing immunoconjugate — DFO-D2101 — and flow cytometry and surface plasmon resonance (SPR) were used to interrogate its antigen-binding properties. The immunoconjugate was then radiolabeled with zirconium-89 (t1/2 ~ 3.3 days), and the serum stability and immunoreactive fraction of [89Zr]Zr-DFO-D2101 were determined. Finally, [89Zr]Zr-DFO-D2101's performance was evaluated in a trio of murine models of pancreatic ductal adenocarcinoma (PDAC): subcutaneous, orthotopic, and patient-derived xenografts (PDX). PET images were acquired over the course of 5 days, and terminal biodistribution data were collected after the final imaging time point. Results: DFO-D2101 was produced with a degree of labeling of ~ 1.1 DFO/mAb. Flow cytometry with CDH17-expressing AsPC-1 cells demonstrated that the immunoconjugate binds to its target in a manner similar to its parent mAb, while SPR with recombinant CDH17 revealed that D2101 and DFO-D2101 exhibit nearly identical KD values: 8.2 × 10−9 and 6.7 × 10−9 M, respectively. [89Zr]Zr-DFO-D2101 was produced with a specific activity of 185 MBq/mg (5.0 mCi/mg), remained >80% stable in human serum over the course of 5 days, and boasted an immunoreactive fraction of >0.85. In all three murine models of PDAC, the radioimmunoconjugate yielded high contrast images, with high activity concentrations in tumor tissue and low uptake in non-target organs. Tumoral activity concentrations reached as high as >60 %ID/g in two of the cohorts bearing PDXs. Conclusion: Taken together, these data underscore that [89Zr]Zr-DFO-D2101 is a highly promising probe for the non-invasive visualization of CDH17 expression in PDAC. We contend that this radioimmunoconjugate could have a significant impact on the clinical management of patients with both PDAC and gastrointestinal adenocarcinoma, most likely as a theranostic imaging tool in support of CDH17-targeted therapies. [ABSTRACT FROM AUTHOR]

PTPRK is a receptor tyrosine phosphatase that is linked to the regulation of growth factor signalling and tumour suppression. It is stabilized at the plasma membrane by trans homophilic interactions upon cell–cell contact. PTPRK regulates cell–cell adhesion but is also reported to regulate numerous cancer-associated signalling pathways. However, the signalling mechanism of PTPRK remains to be determined. Here, we find that PTPRK regulates cell adhesion signalling, suppresses invasion and promotes collective, directed migration in colorectal cancer cells. In vivo, PTPRK supports recovery from inflammation-induced colitis. In addition, we confirm that PTPRK functions as a tumour suppressor in the mouse colon and in colorectal cancer xenografts. PTPRK regulates growth factor and adhesion signalling, and suppresses epithelial to mesenchymal transition (EMT). Contrary to the prevailing notion that PTPRK directly dephosphorylates EGFR, we find that PTPRK regulation of both EGFR and EMT is independent of its catalytic function. This suggests that additional adaptor and scaffold functions are important features of PTPRK signalling. [ABSTRACT FROM AUTHOR]

Focal adhesion kinase (FAK; encoded by PTK2) was discovered over 30 years ago as a cytoplasmic protein tyrosine kinase that is localized to cell adhesion sites, where it is activated by integrin receptor binding to extracellular matrix proteins. FAK is ubiquitously expressed and functions as a signaling scaffold for a variety of proteins at adhesions and in the cell cytoplasm, and with transcription factors in the nucleus. FAK expression and intrinsic activity are essential for mouse development, with molecular connections to cell motility, cell survival and gene expression. Notably, elevated FAK tyrosine phosphorylation is common in tumors, including pancreatic and ovarian cancers, where it is associated with decreased survival. Small molecule and orally available FAK inhibitors show on-target inhibition in tumor and stromal cells with effects on chemotherapy resistance, stromal fibrosis and tumor microenvironment immune function. Herein, we discuss recent insights regarding mechanisms of FAK activation and signaling, its roles as a cytoplasmic and nuclear scaffold, and the tumor-intrinsic and -extrinsic effects of FAK inhibitors. We also discuss results from ongoing and advanced clinical trials targeting FAK in low- and high-grade serous ovarian cancers, where FAK acts as a master regulator of drug resistance. Although FAK is not known to be mutationally activated, preventing FAK activity has revealed multiple tumor vulnerabilities that support expanding clinical combinatorial targeting possibilities. [ABSTRACT FROM AUTHOR]

Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase crucial for B cell development and function, acts downstream of the B cell receptor (BCR) in the BCR pathway. Other kinases involved downstream of the BCR besides BTK such as Syk, Lyn, PI3K, and Mitogen-activated protein (MAP) kinases also play roles in relaying signals from the BCR to provide pro-survival, activation, and proliferation cues. BTK signaling is implicated in various B-cell lymphomas such as mantle cell lymphoma, Waldenström Macroglobulinemia, follicular lymphoma, and diffuse large B cell lymphoma, leading to the development of transformative treatments like ibrutinib, the first-in-class covalent BTK inhibitor, and pirtobrutinib, the first-in-class noncovalent BTK inhibitor. However, kinase-deficient mutations C481F, C481Y, C481R, and L528W in the BTK gene confer resistance to both covalent and non-covalent BTK inhibitors, facilitating B cell survival and lymphomagenesis despite kinase inactivation. Further studies have revealed BTK's non-catalytic scaffolding function, mediating the assembly and activation of proteins including Toll-like receptor 9 (TLR9), vascular cell adhesion protein 1 (VCAM-1), hematopoietic cell kinase (HCK), and integrin-linked kinase (ILK). This non-enzymatic role promotes cell survival and proliferation independently of kinase activity. Understanding BTK's dual roles unveils opportunities for therapeutics targeting its scaffolding function, promising advancements in disrupting lymphomagenesis and refining B cell lymphoma treatments. [ABSTRACT FROM AUTHOR]

In this study, the novel 3D‐printed pressure chamber for encapsulated single‐cell stimulation (3D‐PRESS) platform is introduced for the mechanical stimulation of single stem cells in 3D microgels. The custom‐designed 3D‐PRESS, allows precise pressure application up to 400 kPa at the single‐cell level. Microfluidics is employed to encapsulate single mesenchymal stem cells within ionically cross‐linked alginate microgels with cell adhesion RGD peptides. Rigorous testing affirms the leak‐proof performance of the 3D‐PRESS device up to 400 kPa, which is fully biocompatible. 3D‐PRESS is implemented on mesenchymal stem cells for mechanotransduction studies, by specifically targeting intracellular calcium signaling and the nuclear translocation of a mechanically sensitive transcription factor. Applying 200 kPa pressure on individually encapsulated stem cells reveals heightened calcium signaling in 3D microgels compared to conventional 2D culture. Similarly, Yes‐associated protein (YAP) translocation into the nucleus occurs at 200 kPa in 3D microgels with cell‐binding RGD peptides unveiling the involvement of integrin‐mediated mechanotransduction in singly encapsulated stem cells in 3D microgels. Combining live‐cell imaging with precise mechanical control, the 3D‐PRESS platform emerges as a versatile tool for exploring cellular responses to pressure stimuli, applicable to various cell types, providing novel insights into single‐cell mechanobiology. [ABSTRACT FROM AUTHOR]

Zirconia is one of the most commonly used materials for abutments of dental implants, especially in the anterior region. Soft tissue integration to the zirconia abutment surface remains a challenge. Peri-implant soft tissue integration serves as a physiological barrier, attenuating pathogen penetration and preventing peri‑implant disease. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but the effects under inflammatory conditions are still unclear. In this study, we established two micro-nano structures on zirconia surfaces using a femtosecond laser, including microgrooves with widths of 30 µm (G3) and 60 µm (G6) and depths of 5 µm, and nanoparticles inside the microgrooves. Polished surfaces were used as controls. HGFs were seeded onto the three groups of zirconia specimens and stimulated with lipopolysaccharide. The HGFs on micro-nano-structured zirconia surfaces exhibited lower inflammatory responses and higher cell adhesion, proliferation, and migration under inflammatory conditions compared with the polished surfaces. Additionally, the G3 group exhibited lower inflammatory responses and higher cell adhesion and migration than the G6 group. The micro-nano-structured zirconia surface exhibited decreased neutrophil infiltration and increased M2-type macrophage polarization in vivo. To explore the molecular mechanism, RNA sequencing and gene silencing were utilized, which revealed two critical target genes regulated by the G3 group. Overall, we proposed an innovative micro-nano-structured zirconia surface that reduced the in vitro and in vivo inflammatory responses and promoted HGF adhesion, migration, and proliferation under inflammatory conditions, in which TRAFD1 and NLRC5 were the underlying key genes. Zirconia is one of the most commonly used materials for abutments, especially in the anterior region. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but few studies have investigated these effects under inflammatory conditions, and the mechanism remains unclear. In this study, we developed an innovative micro-nano-structured zirconia surface using a femtosecond laser, which reduces the in vitro and in vivo pro-inflammatory responses and promotes HGFs adhesion, migration, and proliferation under inflammatory conditions compared with the polished zirconia surface. The potential underlying mechanism was also investigated. This work has provided some theoretical basis for the micro-nano-structured zirconia surface in potentially reducing the inflammation and enhancing peri‑implant soft-tissue integration under inflammatory conditions. [Display omitted] [ABSTRACT FROM AUTHOR]

Although bioabsorbable polymers are promising implant materials, implanting hydrophobic polymers induces platelet adhesions and subsequent thrombus formation. We recently reported that a multiblock copolymer composed of poly(l‐lactide‐co‐glycolide) (PLGA) and poly(1,5‐dioxepan‐2‐one) (PDXO) exhibited antiplatelet adhesive behavior. In this study, the cell adhesion behaviors of PLGA and PDXO random multiblock copolymers (PLGA−PDXO RMBCs) were examined. All the RMBCs showed antiplatelet adhesion behavior, and the copolymers containing 40 or 51 mol% of the PDXO component showed good antiplatelet adhesive behavior. Good culture behavior was observed for HeLa cells, but human umbilical vein endothelial cells (HUVECs) proliferation was poor on PLGA−PDXO RMBC surfaces. The cell attachment inhibition studies revealed that both integrin‐dependent and integrin‐independent interactions worked for HeLa cell culture, whereas only integrin‐dependent interactions played an important role for HUVEC culture proliferation on copolymer surfaces. The findings of this study revealed the unique cell‐selective adhesion behavior of PDXO containing multiblock polymers—being nonadhesive to platelets and HUVECs, and adhesive to HeLa cells. [ABSTRACT FROM AUTHOR]

Scaffolds play a key role in cultured meat production by providing an optimal environment for efficient cell attachment, growth, and development. This study investigated the effects of gelatin coating on the adhesion, proliferation, and adipogenic differentiation of adipose tissue-derived stem cells (ADSCs) cultured on soy protein–agarose scaffolds. Gelatin-coated scaffolds were prepared using 0.5% and 1.0% (w/v) gelatin solutions. The microstructure, water absorption rate, mechanical strength, cytotoxicity, cell adhesion, proliferation, and differentiation capabilities of the scaffolds were analyzed. Field emission scanning electron microscopy revealed the porous microstructure of the scaffolds, which was suitable for cell growth. Gelatin-coated scaffolds exhibited a significantly higher water absorption rate than that of non-coated scaffolds, indicating increased hydrophilicity. In addition, gelatin coating increased the mechanical strength of the scaffolds. Gelatin coating did not show cytotoxicity but significantly enhanced cell adhesion and proliferation. The gene expression levels of peroxisome proliferator-activated receptor gamma, CCAT/enhancer-binding protein alpha, and fatty acid-binding protein 4 were upregulated, and lipid accumulation was increased by gelatin coating. These findings suggest that gelatin-coated scaffolds provide a supportive microenvironment for ADSC growth and differentiation, highlighting their potential as a strategy for the improvement of cultured meat production and adipose tissue engineering. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae (the gonococcus, Gc) causes the sexually transmitted infection gonorrhea. Gc is a prominent threat to human health by causing severe lifelong sequelae, including infertility and chronic pelvic pain, which is amplified by the emergence of "superbug" strains resistant to all current antibiotics. Gc is highly adapted to colonize human mucosal surfaces, where it survives despite initiating a robust inflammatory response and influx of polymorphonuclear leukocytes (PMNs, neutrophils) that typically clear bacteria. Here, dual-species RNA-sequencing was used to define Gc and PMN transcriptional profiles alone and after infection. Core host and bacterial responses were assessed for two strains of Gc and three human donors' PMNs. Comparative analysis of Gc transcripts revealed overlap between Gc responses to PMNs, iron, and hydrogen peroxide; 98 transcripts were differentially expressed across both Gc strains in response to PMN co-culture, including iron-responsive and oxidative stress response genes. We experimentally determined that the iron-dependent TbpB is suppressed by PMN co-culture, and iron-limited Gc have a survival advantage when cultured with PMNs. Analysis of PMN transcripts modulated by Gc infection revealed differential expression of genes driving cell adhesion, migration, inflammatory responses, and inflammation resolution pathways. Production of pro-inflammatory cytokines, including IL1B and IL8, the adhesion factor ICAM1, and prostaglandin PGE2 were induced in PMNs in response to Gc. Together, this study represents a comprehensive and experimentally validated dual-species transcriptomic analysis of two isolates of Gc and primary human PMNs that gives insight into how this bacterium survives innate immune onslaught to cause disease. Author summary: The bacterium Neisseria gonorrhoeae (Gc) is a public health threat with emerging resistance to antibiotics. Gc induces robust mucosal inflammatory responses with abundant influx of white blood cells called polymorphonuclear leukocytes (PMNs, neutrophils). While PMNs are highly antimicrobial, Gc survives amongst PMNs for reasons incompletely understood. Here we detail the transcriptional profiles of PMNs from multiple human donors and Gc strains, to investigate this host-pathogen interaction in a comprehensive, unbiased manner. The core transcriptome across Gc exposed to PMNs overlaps transcriptomes of Gc exposed to stresses imparted by immune pressure, specifically nutrient metal starvation. Additionally, core host pathways induced upon PMN exposure to Gc include surface and secreted factors that enable PMN migration and activation. This study uncovers critical features of the Gc-PMN interface to inform how Gc resists innate immune clearance. [ABSTRACT FROM AUTHOR]

Coronary artery bypass surgery can result in endothelial dysfunction due to ischemia/reperfusion (IR) injury. Previous studies have demonstrated that DuraGraft helps maintain endothelial integrity of saphenous vein grafts during ischemic conditions. In this study, we investigated the potential of DuraGraft to mitigate endothelial dysfunction in arterial grafts after IR injury using an aortic transplantation model. Lewis rats (n = 7–9/group) were divided in three groups. Aortic arches from the control group were prepared and rings were immediately placed in organ baths, while the aortic arches of IR and IR + DuraGraft rats were preserved in saline or DuraGraft, respectively, for 1 h before being transplanted heterotopically. After 1 h after reperfusion, the grafts were explanted, rings were prepared, and mounted in organ baths. Our results demonstrated that the maximum endothelium-dependent vasorelaxation to acetylcholine was significantly impaired in the IR group compared to the control group, but DuraGraft improved it (control: 89 ± 2%; IR: 24 ± 1%; IR + DuraGraft: 48 ± 1%, p < 0.05). Immunohistochemical analysis revealed decreased intercellular adhesion molecule-1, 4-hydroxy-2-nonenal, caspase-3 and caspase-8 expression, while endothelial cell adhesion molecule-1 immunoreactivity was increased in the IR + DuraGraft grafts compared to the IR-group. DuraGraft mitigates endothelial dysfunction following IR injury in a rat bypass model. Its protective effect may be attributed, at least in part, to its ability to reduce the inflammatory response, oxidative stress, and apoptosis. [ABSTRACT FROM AUTHOR]

Cellular therapy is considered a better option for the treatment of degenerative disorders. Different cell types are being used for tissue regeneration. Despite extensive research in this field, several issues remain to be addressed concerning cell transplantation. One of these issues is the survival and homing of administered cells in the injured tissue, which depends on the ability of these cells to adhere. To enhance cell adherence and survival, Rap1 GTPase was activated in mesenchymal stem cells (MSCs) as well as in cardiomyocytes (CMs) by using 8‐pCPT‐2′‐O‐Me‐cAMP, and the effect on gene expression dynamics was determined through quantitative reverse transcriptase‐polymerase chain reaction analysis. Pharmacological activation of MSCs and CMs resulted in the upregulation of connexin‐43 and cell adhesion genes, which increased the cell adhesion ability of MSCs and CMs, and increased the fusion of MSCs with neonatal CMs. Treating stem cells with a pharmacological agent that activates Rap1a before transplantation can enhance their fusion with CMs and increase cellular regeneration. Significance Statement: Pharmacological activation of mesenchymal stem cells (MSCs) and cardiomyocytes (CMs) resulted in upregulation of cell adhesion genes. This, in turn, increased the cell adhesion ability of MSCs and CMs and promoted the fusion of MSCs with neonatal CMs. Treatment of stem cells before transplantation with a pharmacological agent that leads to Rap1a activation can promote the fusion of MSCs with CMs, leading to increased cellular regeneration. [ABSTRACT FROM AUTHOR]

The endometrium is an important part of women's bodies for menstruation and pregnancy. Various proteins are widely expressed on the surface of endometrial cells, and glycosylation is an important post-translational modification of proteins. Glycosylation modification is closely related not only to endometrial receptivity but also to common diseases related to endometrial receptivity. Glycosylation can improve endometrial receptivity, promote embryo localization and trophoblast cell adhesion and invasion, and contribute to successful implantation. Two diseases related to endometrial receptivity include endometriosis and endometrial cancer. As a common benign disease in women, endometriosis is often accompanied by an increased menstrual volume, prolonged menstrual periods, progressive and aggravated dysmenorrhea, and may be accompanied by infertility. Protein glycosylation modification of the endometrial surface indicates the severity of the disease and may be an important pathogenesis of endometriosis. In cancer, glycosylation modifications on the surface of tumor cells can be a marker to distinguish the type and severity of endometrial cancer. This review highlights the role of protein glycosylation in embryo–maternal endometrial dialogue and explores its potential mechanisms in diseases related to endometrial receptivity, which could provide a new clinical approach for their diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Gadolinium is a component of the MRI contrast agent Dotarem. Although Dotarem is the least toxic among MRI contrasts used, gadolinium present in Dotarem accumulates for many years in various organs and tissues exerting toxic effects. We showed previously that gadolinium remains in macrophages for at least 7 days after exposure to Dotarem. However, very little is known about the effect of gadolinium retention on the immune cells such as macrophages. We studied the effect of 1-day and 7-day retention of gadolinium on various functions and molecular pathways of macrophages. Gadolinium retention for 7 days decreased macrophage adhesion and motility and dysregulated the expression of adhesion and fibrotic pathway-related proteins such as Notch1 and its ligand Jagged1, adhesion/migration-related proteins PAK1 and Shp1, immune response-related transcription factors Smad3 and TCF19, and chemokines CXCL10 and CXCL13, and dysregulated the mRNA expression of fibrosis-related genes involved in extracellular matrix (ECM) synthesis, such as Col6a1, Fibronectin, MMP9, and MMP12. It also completely (below a level of detection) shut down the transcription of anti-inflammatory M2 macrophage polarization marker the Arg-1. Such changes, if they occur in MRI patients, can be potentially detrimental to the patient's immune system and immune response-related processes. [ABSTRACT FROM AUTHOR]

Electrospinning technology has recently attracted increased attention in the biomedical field, and preparing various cellulose nanofibril membranes for periodontal tissue regeneration has unique advantages. However, the characteristics of using a single material tend to make it challenging to satisfy the requirements for a periodontal barrier film, and the production of composite fibrous membranes frequently impacts the quality of the final fiber membrane due to the influence of miscibility between different materials. In this study, nanofibrous membranes composed of polylactic acid (PLA) and polycaprolactone (PCL) fibers were fabricated using side-by-side electrospinning. Different concentrations of gelatin were added to the fiber membranes to improve their hydrophilic properties. The morphological structure of the different films as well as their composition, wettability and mechanical characteristics were examined. The results show that PCL/PLA dual-fibrous composite membranes with an appropriate amount of gelatin ensures sufficient mechanical strength while obtaining improved hydrophilic properties. The viability of L929 fibroblasts was evaluated using CCK-8 assays, and cell adhesion on the scaffolds was confirmed by scanning electron microscopy and by immunofluorescence assays. The results demonstrated that none of the fibrous membranes were toxic to cells and the addition of gelatin improved cell adhesion to those membranes. Based on our findings, adding 30% gelatin to the membrane may be the most appropriate content for periodontal tissue regeneration, considering the scaffold's mechanical qualities, hydrophilic properties and biocompatibility. In addition, the PCL-gelatin/PLA-gelatin dual-fibrous membranes prepared using side-by-side electrospinning technology have potential applications for tissue engineering. [ABSTRACT FROM AUTHOR]

Background: CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC; < 50 years old). Methods: After germline exome sequencing in 20 EOGC patients and replication of relevant findings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed β-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling. Results: Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C > T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identified in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization. Conclusions: Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are a population of innate immune cells that have cytotoxic functions and are involved in protecting the body from viruses and transformed cells. Placental development is largely determined by the interaction of decidual NK cells and trophoblast cells. During pregnancy, NK cells accumulate around trophoblast cells, while regulating trophoblast proliferation, migration and invasion through the secretion of cytokines and growth factors. The trophoblast, in turn, secretes chemokines and expresses ligands for NK cell adhesion receptors. Thus, functional regulation of trophoblast and NK cells is reciprocal. Despite intensive research, the role of NK cells and methods for correcting their functional activity in reproduction remain controversial. The aim of this study was to assess the effect of NK cell lysate protein fractions on the phenotype, migration and apoptosis of trophoblast cells in an in vitro model experiment, using a new methodological approach. Chromatographic separation yielded six fractions with different protein cargoes. It was found that CD105 (endoglin) expression on the surface of JEG-3 trophoblast cells after their cultivation in the presence of high- (< 250 kDa) or low-molecular-weight (< 45 kDa) fractions of NK-92 whole-cell lysate was reduced compared to spontaneous expression, with the relative count of trophoblast cells with a CD105+ phenotype being also lowered. In addition, one of the low-molecular-weight fractions decreased TRAIL-R2 receptor expression by trophoblast cells. The high-molecular-weight fractions did not enable trophoblast cells to migrate completely through a semi-permeable membrane, with the area occupied by the migrated cells not exceeding the baseline control area. Moreover, the high-molecular-weight fraction containing the TGFβ dimer increased p-SMAD2/3 level in trophoblast cells 1 h after co-culture, followed by a decrease in the level of this phosphorylated form after 2 or more hours, and also elevated procaspase-3 level one day after co-culture. The data obtained hypothetically reflect the possible behavior of chorion cells under the influence of collapsing NK cells in the event of their death under both normal and pathological conditions caused by viral and bacterial infections, as well as other stress factors leading to reproductive pathology. [ABSTRACT FROM AUTHOR]

Wnt signaling is essential for embryonic development, influencing processes such as axis formation, cell proliferation and differentiation, cell fate decisions, and axon guidance. It also plays a role in maintaining tissue homeostasis in adult organisms. The loss of normal cell polarity and adhesion caused by Wnt signaling activation is a fundamental step for tumor progression and metastasis. Activating the canonical Wnt pathway is a driving force in many human cancers, especially colorectal, hepatocellular, and mammary carcinomas. Wnt causes the stabilization and nuclear transport of newly synthesized transcriptional regulator β‐catenin. The generally accepted view is that the canonical effects of Wnt growth factors are caused by the transcription of β‐catenin target genes. Here, we review recent findings that indicate Wnt is a regulator of many other cellular physiological activities, such as macropinocytosis, endosome trafficking, protein stability, focal adhesions, and lysosomal activity. Some of these regulatory responses occur within minutes and do not require new protein synthesis, indicating that there is much more to Wnt beyond the well‐established transcriptional role of β‐catenin. The main conclusion that emerges from these studies is that in basal cell conditions, the activity of the key protein kinase GSK3, which is inhibited by Wnt pathway activation, normally represses the actin machinery that orchestrates macropinocytosis with implications in cancer. These contributions expand our understanding of the multifaceted roles of Wnt signaling in cellular processes, development, and cancer, providing insights into potential therapeutic targets and strategies. [ABSTRACT FROM AUTHOR]

The use of electrospun fibers as anti-inflammatory drug carriers is currently one of the most interesting approaches for the design of drug delivery systems. In recent years, biodegradable polymers blended with naturally derived ones have been extensively studied to fabricate bioinspired platforms capable of driving biological responses by releasing selected molecular/pharmaceutical signals. Here, sodium diclofenac (DicNa)-loaded electrospun fibers, consisting of polycaprolactone (PCL) or gelatin-functionalized PCL, were studied to evaluate fibroblasts' in vitro and in vivo response. In vitro studies demonstrated that cell adhesion of L929 cells (≈70%) was not affected by the presence of DicNa after 4 h. Moreover, the initial burst release of the drug from PD and PGD fibers, e.g., 80 and 48%, respectively, after 5 h—combined with its sustained release—did not produce any cytotoxic effect and did not negatively influence the biological activity of the cells. In particular, it was demonstrated that the addition of gelatin concurred to slow down the release mechanism, thus limiting the antiproliferative effect of DicNa, as confirmed by the significant increase in cell viability and collagen deposition after 7 days, with respect to PCL alone. In vivo studies in a rat subcutaneous model also confirmed the ability of DicNa-loaded fibers to moderate the inflammatory/foreign body response independently through the presence of gelatin that played a significant role in supporting the formation of small-caliber vessels after 10 days of implantation. All of these results suggest using bicomponent fibers loaded with DicNa as a valid therapeutic tool capable of supporting the wound healing process and limiting in vivo inflammation and rejection phenomena. [ABSTRACT FROM AUTHOR]

The incidence of cardiovascular diseases, such as high blood pressure, is increasing worldwide, owing to population aging and irregular lifestyle habits. Previous studies have reported the vasorelaxant effects of Prunus yedoensis bark methanol extract. However, various solvent extracts of P. yedoensis bark and their vascular relaxation mechanisms have not been sufficiently studied. We prepared extracts of P. yedoensis bark using various solvents (water, 30% ethanol, and 70% ethanol). P. yedoensis bark 30% ethanol extract (PYB-30E) decreased the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in human umbilical vein endothelial cells (HUVECs) activated with 200 ng/mL TNF-α. Additionally, PYB-30E showed vasodilatory effects on isolated rat aortic rings. This was confirmed to be the result of the activation of the NO/cGMP pathway, regulation of non-selective calcium-activated K+ channels, and calcium channel blockade. Additionally, PYB-30E significantly reduced systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR). Taken together, our results indicated that PYB-30E is a candidate functional material with preventive and therapeutic effects against hypertension. [ABSTRACT FROM AUTHOR]

Aquaporin‐3 (AQP3) is a membrane channel with dual aquaglyceroporin/peroxiporin activity, facilitating the diffusion of water, glycerol and H2O2 across cell membranes. AQP3 shows aberrant expression in melanoma and its role in cell adhesion, migration and proliferation is well described. Gold compounds were shown to modulate AQP3 activity with reduced associated toxicity, making them promising molecules for cancer therapy. In this study, we validated the phenotype resulting from AQP3‐silencing of two melanoma cell lines, MNT‐1 and A375, which resulted in decreased H2O2 permeability. Subsequently, the AQP3 inhibitory effect of a new series of organogold compounds derived from Auphen, a potent AQP3 inhibitor, was first evaluated in red blood cells (RBCs) that highly express AQP3, and then in HEK‐293T cells with AQP3 overexpression to ascertain the compounds' specificity. The first screening in RBCs unveiled two organogold compounds as promising blockers of AQP3 permeability. Moderate reduction of glycerol permeability but drastic inhibition of H2O2 permeability was detected for some of the gold derivatives in both AQP3‐overexpressing cells and human melanoma cell lines. Additionally, all compounds were effective in impairing cell adhesion, proliferation and migration, although in a cell type‐dependent manner. In conclusion, our data show that AQP3 peroxiporin activity is crucial for melanoma progression and highlight organogold compounds as promising AQP3 inhibitors with implications in melanoma cell adhesion, proliferation and migration, unveiling their potential as anticancer drugs against AQP3‐overexpressing tumours. Key points: AQP3 affects cellular redox balance.Gold compounds inhibit AQP3 permeability in melanoma cells.AQP3 is involved in cell adhesion, proliferation and migration of melanoma.Blockage of AQP3 peroxiporin activity impairs melanoma cell migration.Gold compounds are potential anticancer drug leads for AQP3‐overexpressing cancers. [ABSTRACT FROM AUTHOR]

Fluorescent nanoparticles known as quantum dots (QDs) have unique properties that make them useful in biomedicine. Specifically, CdSe/ZnS QDs, while good at fluorescing, show toxicity. Due to this, safer alternatives have been developed. This study uses a tetrazolium dye (XTT) viability assay, reactive oxygen species (ROS) fluorescent imaging, and apoptosis to investigate the effect of QD alternatives InP/ZnS, CuInS2/ZnS, and nitrogen-doped carbon dots (NCDs) in liver cells. The liver is a possible destination for the accumulation of QDs, making it an appropriate model for testing. A cancerous liver cell line known as HepG2 and an immortalized liver cell line known as THLE-2 were used. At a nanomolar range of 10–150, HepG2 cells demonstrated no reduced cell viability after 24 h. The XTT viability assay demonstrated that CdSe/ZnS and CuInS2/ZnS show reduced cell viability in THLE-2 cells with concentrations between 50 and 150 nM. Furthermore, CdSe/ZnS- and CuInS2/ZnS-treated THLE-2 cells generated ROS as early as 6 h after treatment and elevated apoptosis after 24 h. To further corroborate our results, apoptosis assays revealed an increased percentage of cells in the early stages of apoptosis for CdSe/ZnS-treated (52%) and CuInS2/ZnS-treated (38%) THLE-2. RNA transcriptomics revealed heavy downregulation of cell adhesion pathways such as wnt, cadherin, and integrin in all QDs except NCDs. In conclusion, NCDs show the least toxicity toward these two liver cell lines. While demonstrating less toxicity than CdSe/ZnS, the metallic QDs (InP/ZnS and CuInS2/ZnS) still demonstrate potential concerns in liver cells. This study serves to explore the toxicity of QD alternatives and better understand their cellular interactions. [ABSTRACT FROM AUTHOR]

Cryogels represent a valid strategy as scaffolds for tissue engineering. In order to adequately support adhesion and proliferation of anchorage-dependent cells, different polymers need to be combined within the same scaffold trying to mimic the complex features of a natural extracellular matrix (ECM). For this reason, in this work, gelatin (Gel) and chondroitin sulfate (CS), both functionalized with methacrylic groups to produce CSMA and GelMA derivatives, were selected to prepare cryogel networks. Both homopolymer and heteropolymer cryogels were produced, via radical crosslinking reactions carried out at −12 °C for 2 h. All the scaffolds were characterized for their mechanical, swelling and morphological properties, before and after autoclave sterilization. Moreover, they were evaluated for their biocompatibility and ability to support the adhesion of human gingival fibroblasts and tenocytes. GelMA-based homopolymer networks better withstood the autoclave sterilization process, compared to CSMA cryogels. Indeed, GelMA cryogels showed a decrease in stiffness of approximately 30%, whereas CSMA cryogels of approximately 80%. When GelMA and CSMA were blended in the same network, an intermediate outcome was observed. However, the hybrid scaffolds showed a general worsening of the biological performance. Indeed, despite their ability to withstand autoclave sterilization with limited modification of the mechanical and morphological properties, the hybrid cryogels exhibited poor cell adhesion and high LDH leakage. Therefore, not only do network components need to be properly selected, but also their combination and ability to withstand effective sterilization process should be carefully evaluated for the development of efficient scaffolds designed for tissue engineering purposes. [ABSTRACT FROM AUTHOR]

Cell adhesion is a dynamic process that plays a fundamental role in cell proliferation, maintenance, differentiation, and migration. Basal cell adhesion molecule (BCAM), also known as Lutheran (Lu), belongs to the immunoglobulin superfamily of cell adhesion molecules. Lu/BCAM, which is widely expressed in red blood cells, endothelial cells, smooth muscle cells and epithelial cells across various tissues, playing a crucial role in many cellular processes, including cell adhesion, cell motility and cell migration. Moreover, Lu/BCAM, dysregulated in many diseases, such as blood diseases and various types of cancer, may act as a biomarker and target for the treatment of these diseases. This review explores the significance of Lu/BCAM in cell adhesion and its potential as a novel target for treating hematological diseases and tumors. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA), or bile duct cancer, is the second most common liver malignancy, with an increasing incidence in Western countries. The lack of effective treatments associated with the absence of early symptoms highlights the need to search for new therapeutic targets for CCA. Sulfatides (STs), a type of sulfoglycosphingolipids, have been found in the biliary tract, with increased levels in CCA and other types of cancer. STs are involved in protein trafficking and cell adhesion as part of the lipid rafts of the plasma membrane. We aimed to study the role of STs in CCA by the genetic targeting of GAL3ST1, an enzyme involved in ST synthesis. We used the CRISPR-Cas9 system to generate GAL3ST1-deficient TFK1 cells. GAL3ST1 KO cells showed lower proliferation and clonogenic activity and reduced glycolytic activity compared to TFK1 cells. Polarized TFK1 GAL3ST1 KO cells displayed increased transepithelial resistance and reduced permeability compared to TFK1 wt cells. The loss of GAL3ST1 showed a negative effect on growth in 30 out of 34 biliary tract cancer cell lines from the DepMap database. GAL3ST1 deficiency partially restored epithelial identity and barrier function and reduced proliferative activity in CCA cells. Sulfatide synthesis may provide a novel therapeutic target for CCA. [ABSTRACT FROM AUTHOR]

Space travel presents multiple risks to astronauts such as launch, radiation, spacewalks or extravehicular activities, and microgravity. The lungs are composed of a combination of air, blood, and tissue, making it a complex organ system with interactions between the external and internal environment. Gravity strongly influences the structure of the lung which results in heterogeneity of ventilation and perfusion that becomes uniform in microgravity as shown during parabolic flights, Spacelab, and Skylab experiments. While changes in lung volumes occur in microgravity, efficient gas exchange remains and the lungs perform as they would on Earth; however, little is known about the cellular response to microgravity. In addition to spaceflight and real microgravity, devices, such as clinostats and random positioning machines, are used to simulate microgravity to study cellular responses on the ground. Differential expression of cell adhesion and extracellular matrix molecules has been found in real and simulated microgravity. Immune dysregulation is a known consequence of space travel that includes changes in immune cell morphology, function, and number, which increases susceptibility to infections. However, the majority of in vitro studies do not have a specific respiratory focus. These studies are needed to fully understand the impact of microgravity on the function of the respiratory system in different conditions. [ABSTRACT FROM AUTHOR]

Electrospun nanofiber scaffolds mimic the structure of the natural extracellular matrix, making them promising for application in tissue engineering. Based on this, the biopolymers poly(ε-caprolactone) (PCL) and gelatin, with good mechanical and biological properties, respectively, were electrospun with acetic acid as the only solvent, without the crosslinking process in order to reduce the cytotoxic effects of commonly used solvents. This study evaluated the influence of scaffold thicknesses on the physicochemical properties. Scaffolds with 4 different thicknesses were produced by increasing the electrospinning time (A = 1 h, B = 1.5 h, C = 2 h and D = 3 h). Thicker scaffolds (B, C and D, 0.142 ± 0.029 to 0.306 ± 0.053 nm) were manipulated easily, presented higher mechanical strength (from 156.21 to 178.53%) and smaller diameter fibers (approximately 300.0 nm). On the other hand, the longer the processing time, the less uniform the fibers and more melting regions between fibers, which may hinder the use of the scaffold and should be considered. Only the thickest scaffold (D) showed higher wettability (contact angle 31.1° ± 3°). Intermediate thickness scaffolds showed less beads and fiber irregularities. Cell adhesion was good due to gelatin, though cell proliferation remained constant for the thicker scaffold indicating that longer processing time may not be advantageous for cell application. Results showed that intermediate thickness scaffolds of PCL/gelatin (0.142 ± 0.029 to 0.195 ± 0.034 nm) assure good physicochemical properties to be applied for different cell types. [ABSTRACT FROM AUTHOR]

Macrophages are critical in mediating immune and inflammatory responses, while monocyte-to-macrophage differentiation is one of the main macrophage resources that involves various matrix proteins. Matrix remodeling associated 7 (MXRA7) was recently discovered to affect a variety of physiological and pathological processes related to matrix biology. In the present study, we investigated the role of MXRA7 in monocyte-to-macrophage differentiation in vitro. We found that knockdown of MXRA7 inhibited the proliferation of THP-1 human monocytic cells. Knockdown of MXRA7 increased the adhesion ability of THP-1 cells through upregulation the expression of adhesion molecules VCAM-1 and ICAM1. Knockdown of MXRA7 alone could promoted the differentiation of THP-1 cells to macrophages. Furthermore, the MXRA7-knockdown THP-1 cells produced a more significant upregulation pattern with M1-type cytokines (TNF-α, IL-1β and IL-6) than with those M2-type molecules (TGF-β1 and IL-1RA) upon PMA stimulation, indicating that knockdown of MXRA7 facilitated THP-1 cells differentiation toward M1 macrophages. RNA sequencing analysis revealed the potential biological roles of MXRA7 in cell adhesion, macrophage and monocyte differentiation. Moreover, MXRA7 knockdown promoted the expression of NF-κB p52/p100, while PMA stimulation could increase the expression of NF-κB p52/p100 and activating MAPK signaling pathways in MXRA7 knockdown cells. In conclusion, MXRA7 affected the differentiation of THP-1 cells toward macrophages possibly through NF-κB signaling pathways. • MXRA7 was involved in the process of THP-1 differentiation into macrophages. • Knockdown of MXRA7 promoted the differentiation of THP-1 cells toward M1 macrophages upon PMA stimulation. • MXRA7 affected the differentiation of THP-1 cells to macrophages possibly through NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease that threaten human life with serious incidence and high mortality. High heterogeneity of tumor microenvironment (TME) was reported in multiple studies. However, the factor of controlling the tumor migration progression between eary and late-stage LUAD is still not fully understood. In this study, we conducted a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data of LUAD obtained from the GEO database. The identification of cell clusters revealed significant expansion of epithelial cells in late-stage patients. Interpretation of the cell-cell communication results between early-stage and late-stage patient samples indicated that early tumor cells may interact with epithelial cells through the TGF-β pathway to promote tumor progression. The cell cycle analysis demonstrated a significant increase in the number of cells in the G2 and M phases in late-stage lung cancer. Further analysis using Non-negative Matrix Factorization (NMF) revealed early-stage cell-specific gene features involved in cell adhesion-related biological processes. Among these, the Tensin (TNS) gene family, particularly TNS1, showed high expression in epithelial cells and fibroblasts of early-stage samples, specifically associated with cell adhesion. Survival analysis using TCGA database for LUAD demonstrated that patients with high expression of TNS1 exhibited significantly higher overall survival rates compared to those with low expression. Immunofluorescence experiments have demonstrated co-expression of TNS1 with fibroblast and tumor cell markers (α-SMA and EPCAM). Immunohistochemistry experiments further validated the significantly higher expression levels of TNS1 in early-stage LUAD tissues compared to late-stage lung cancer tissues (P<0.05). Pathway experiments have shown that early-stage tumor patients with high expression of TNS1 exhibit stronger phosphorylation levels of Akt and mTOR, indicating a more potent activation of the Akt/mTOR signaling pathway. In conclusion, the results of this study demonstrate that TNS1 is an adhesive molecule in the immune microenvironment of early-stage tumor cells, and it may serve as a novel prognostic marker for lug cancer. • Single-cell RNA sequencing results showed that light on the highly heterogeneous nature of the TME in LUAD. • Our study provides more evidence for the heterogeneity of LUAD's TME. • We present compelling evidence for the role of the Tensin (TNS) gene family, particularly TNS1, in early-stage LUAD. [ABSTRACT FROM AUTHOR]

In situ injectable hydrogels are effectively employed to fill irregular cavitary bone defects with initiating bone growth in targeted areas. Herein, an injectable composited hydrogel composed of collagen and alginate cross-linked in situ using different concentrations of calcium sulfate (0.15, 0.3 and 0.6%, wt./v) was synthesized. Recently, CaSO4 is frequently supported as a bone graft material for bone regeneration, owing to its biocompatibility and osteoconductive properties. Moreover, hydroxyapatite (Hap) after salinization-step by (3-Aminopropyl) triethoxysilane (APTES) was incorporated for further enhancing the osteoconductive property of injected hydrogels. All fabricated hydrogels were characterized by SEM, FTIR and XRD analyses. While physiochemical characteristics of hydrogels were assessed through swelling index, hydrolytic degradability and thermal stability measurements. In vitro bio-assessments, e.g., antimicrobial activity, cytotoxicity and cell adhesion tests using osteoblast-like cells (MG-63) were investigated. Results showed that addition of Hap offered better control of gelation time and formed uniform hydrogels, additionally improved significantly thermal stability, which leads to hindering of swelling index, prolonging hydrolytic degradability rates and significantly enhanced the antimicrobial activity of hydrogel; compared to hydrogel free-Hap. Hap-loaded Col–Alg–CaSO4 hydrogel with the highest concentration of CaSO4 recorded an enrichment of cell viability among all hydrogel samples. Notably, In vitro cell adhesion test showed that MG-63 cells adhered adequately with all hydrogels. The results support the approach of using an injectable Hap-loaded Col/Alg hydrogel cross-linked with CaSO4 as an alter and novel technique to enhance bone tissue regeneration, host–implant integration, quick/simple technique and easier for clinical handling. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of brain biomimetic electrical stimulation combined with Ginkgo biloba injection on hearing threshold gain and cochlear function in the treatment of sudden deafness. Methods: A total of 140 cases of patients with sudden deafness admitted to our hospital from October 2020 to October 2023 were selected and divided into observation group and matched group, with 70 cases each. The matched group patients received treatment with Ginaton injection, while the observation group received treatment with brain biomimetic electrical stimulation combined with Ginaton injection. Compare the clinical efficacy, cochlear function and hearing threshold gain before and Post-treatment between two groups of patients, as well as changes in anti endothelial cell antibody (AECA), soluble vascular intercellular adhesion factor-1 (sVCAM-1), endothelin (ET) related blood biomarker levels, and hemorheological indicators. Results: The total effective rate of the observation group was higher than that of the matched group(P<0.05); Pretherapy, there was no difference in the pure tone air conduction hearing threshold and decibels of hearing loss between the two groups of patients(P>0.05). Post-treatment, the pure tone air conduction hearing threshold and decibels of hearing loss decreased in both groups, with the observation group being lower than the matched group. At the same time, the gain value of the observation group's hearing threshold was higher than that of the matched group(P<0.05); Pretherapy, there was no difference in the levels of AECA, sVCAM-1, and ET between the two groups of patients(P>0.05). Post-treatment, both groups decreased, with the observation group being lower than the matched group(P<0.05); There was no difference in plasma viscosity and whole blood viscosity between the two groups(P>0.05), which decreased Post-treatment, and the observation group was lower than the matched group(P<0.05). Conclusion: Brain biomimetic electrical stimulation combined with Ginaton injection can enhance the therapeutic effect of sudden deafness, improve cochlear function, increase hearing threshold, and reduce the expression levels of blood markers AECA, sVCAM-1, and ET related to sudden deafness, reducing blood hypercoagulability. It is worth promoting in clinical practice. [ABSTRACT FROM AUTHOR]

Necrosis in solid tumors is commonly associated with poor prognostic but how these lesions expand remains unclear. Studies have found that neutrophils associate with and contribute to necrosis development in glioblastoma by inducing tumor cell ferroptosis through transferring myeloperoxidase-containing granules. However, the mechanism of neutrophilic granule transfer remains elusive. We performed an unbiased small molecule screen and found that statins inhibit neutrophil-induced tumor cell death by blocking the neutrophilic granule transfer. Further, we identified a novel process wherein neutrophils are engulfed by tumor cells before releasing myeloperoxidase-containing contents into tumor cells. This neutrophil engulfment is initiated by integrin-mediated adhesion, and further mediated by LC3-associated phagocytosis (LAP), which can be blocked by inhibiting the Vps34-UVRAG-RUBCN-containing PI3K complex. Myeloperoxidase inhibition or Vps34 depletion resulted in reduced necrosis formation and prolonged mouse survival in an orthotopic glioblastoma mouse model. Thus, our study unveils a critical role for LAP-mediated neutrophil internalization in facilitating the transfer of neutrophilic granules, which in turn triggers tumor cell death and necrosis expansion. Targeting this process holds promise for improving glioblastoma prognosis. Synopsis: Neutrophils induce ferroptosis in glioblastoma, thus promoting necrosis during early tumor progression but the underlying mechanisms remain unclear. Here, neutrophil engulfment by tumor cells is uncovered as a critical step facilitating the transfer of neutrophilic granules and tumor cell ferroptosis. Statins inhibit neutrophil-induced tumor cell death by blocking neutrophilic granule transfer. Integrin-mediated cell adhesion is required for tumor cell killing by neutrophils. Neutrophils are engulfed by tumor cells before releasing myeloperoxidase-containing contents into tumor cells. LC3-associated phagocytosis is responsible for neutrophil internalization by tumor cells. Myeloperoxidase inhibition or Vps34 depletion reduces necrosis in glioblastomas and prolongs survival of tumor-bearing mice. Neutrophil engulfment by tumor cells facilitates transfer of neutrophilic granules and ferroptosis in brain cancer. [ABSTRACT FROM AUTHOR]

The interaction between the integrin and collagen is important in cell adhesion and signaling. Collagen, as the main component of extracellular matrix, is a base material for tissue engineering constructs. In tissue engineering, the collagen structure and molecule state may be altered to varying degrees in the process of processing and utilizing, thereby affecting its biological properties. In this work, the impact of changes in collagen structure and molecular state on the binding properties of collagen to integrin α2β1 and integrin specific cell adhesion were explored. The results showed that the molecular structure of collagen is destroyed under the influence of heating, freeze-grinding and irradiation, the triple helix integrity is reduced and molecular breaking degree is increased. The binding ability of collagen to integrin α2β1 is increased with the increase of triple helix integrity and decays exponentially with the increase of molecular breaking degree. The collagen molecular state can also influences the binding ability of collagen to cellular receptor. The collagen fibrils binding to integrin α2β1 and HT1080 cells is stronger than to collagen monomolecule. Meanwhile, the hybrid fibril exhibits a different cellular receptor binding performance from corresponding single species collagen fibril. These findings provide ideas for the design and development of new collagen-based biomaterials and tissue engineering research. [ABSTRACT FROM AUTHOR]

Glycosylation is the most common form of post‐translational modification in the brain. Aberrant glycosylation has been observed in cerebrospinal fluid and brain tissue of Alzheimer's disease (AD) cases, including dysregulation of terminal sialic acid (SA) modifications. While alterations in sialylation have been identified in AD, the localization of SA modifications on cellular or aggregate‐associated glycans is largely unknown because of limited spatial resolution of commonly utilized methods. The present study aims to overcome these limitations with novel combinations of histologic techniques to characterize the sialylation landscape of O‐ and N‐linked glycans in autopsy‐confirmed AD post‐mortem brain tissue. Sialylated glycans facilitate important cellular functions including cell‐to‐cell interaction, cell migration, cell adhesion, immune regulation, and membrane excitability. Previous studies have not investigated both N‐ and O‐linked sialylated glycans in neurodegeneration. In this study, the location and distribution of sialylated glycans were evaluated in three brain regions (frontal cortex, hippocampus, and cerebellum) from 10 AD cases using quantitative digital pathology techniques. Notably, we found significantly greater N‐sialylation of the Aβ plaque microenvironment compared with O‐sialylation. Plaque‐associated microglia displayed the most intense N‐sialylation proximal to plaque pathology. Further analyses revealed distinct differences in the levels of N‐ and O‐sialylation between cored and diffuse Aβ plaque morphologies. Interestingly, phosphorylated tau pathology led to a slight increase in N‐sialylation and no influence of O‐sialylation in these AD brains. Confirming our previous observations in mice with novel histologic approach, these findings support microglia sialylation appears to have a relationship with AD protein aggregates while providing potential targets for therapeutic strategies. [ABSTRACT FROM AUTHOR]

With the rising prevalence of end-stage kidney disease, the use of expanded criteria donor allografts, seen as essential for meeting organ demand, still proves challenging due to their higher risk of graft loss, delayed function, and rejection. Machine perfusion, a technique in preserving allografts, offers improved allograft outcomes compared to static cold storage while allowing for the noninvasive measurement of kidney injury biomarkers in the perfusate solution. This offers an objective method to assess graft function at various preservation stages. We conducted a narrative review of the databases PubMed and Scopus, including studies written in the English language and published after 2010. In this narrative review, we identified biomarkers, like 4-hydroxyproline, taurine, and glutathione transferase, as predictive markers of delayed graft function. Additionally, biomarkers, like extracellular histone h3, vascular cell adhesion protein, and matrix metalloprotease protein, have shown correlation with decreased graft function, although their predictive ability remains inconclusive. The review outlines various suggestions for potential areas of research focus to enhance future expanded criteria donor allograft utilization. However, limitations exist, including the absence of a singular reliable biomarker and the challenges of validating biomarker effectiveness across diverse outcomes. [ABSTRACT FROM AUTHOR]

Tuning cell adhesion geometry can affect cytoskeleton organization and the distribution of cytoskeleton forces, which play critical roles in controlling cell functions. To elucidate the geometrical relationship with cytoskeleton force distribution, it is necessary to control cell morphology. In this study, a series of dextral vortex micropatterns were prepared to precisely control cell morphology for investigating the influence of the curvature degree of adhesion curves on intracellular force distribution and stem cell differentiation at a sub-cellular level. Peripherial actin filaments of micropatterned cells were assembled along the adhesion curves and showed different orientations, filament thicknesses and densities. Focal adhesion and cytoskeleton force distribution were dependent on the curvature degree. Intracellular force distribution was also regulated by adhesion curves. The cytoskeleton and force distribution affected the osteogenic differentiation of mesenchymal stem cells through a YAP/TAZ-mediated mechanotransduction process. Thus, regulation of cell adhesion curvature, especially at cytoskeletal filament level, is critical for cell function manipulation. In this study, a series of dextral micro-vortexes were prepared and used for the culture of human mesenchymal stem cells (hMSCs) to precisely control adhesive curvatures (0°, 30°, 60°, and 90°). The single MSCs on the micropatterns had the same size and shape but showed distinct focal adhesion (FA) and cytoskeleton orientations. Cellular nanomechanics were observed to be correlated with the curvature degrees, subsequently influencing nuclear morphological features. As a consequence, the localization of the mechanotransduction sensor and activator-YAP/TAZ was affected, influencing osteogenic differentiation. The results revealed the pivotal role of adhesive curvatures in the manipulation of stem cell differentiation via the machanotransduction process, which has rarely been investigated. [Display omitted] [ABSTRACT FROM AUTHOR]

The clinical success of implanted biomaterials such as dental implants is largely determined by the molecular signaling that occurs at the tissue-implant interface. The modification of surface topography is a widely-employed strategy for optimizing tissue integration with dental implants. However, little is known regarding the direct, cellular-level effects of substratum topography on platelet signaling and adhesion, despite these cells being the first to encounter the implant surface during surgical placement. Here we compared platelet adhesion and secretion on four (4) different titanium surfaces, notably, the modifications applied to commercially available dental implants: smooth (S) titanium; acid-etched (AE), sandblasted (SB) and a combined acid-etching/sandblasting procedure (SLA). Platelets were isolated from human blood, washed, and seeded on to the 4 test surfaces; platelet adhesion was quantified by microscopy. In addition, the secretion of critical molecules stored in platelet granules (platelet factor 4, PF4; soluble P-selectin, sCD62P; transforming growth factor-beta1, TGF-β1; platelet-derived growth factor-AB, PDGF-AB) was measured by enzyme-linked immunosorbent assay (ELISA) analysis of the supernatants. There was greater platelet adhesion to the rougher AE and SB surfaces, however, the concentration of the secreted growth factors was comparable on all surfaces. We conclude that while surface topography can be engineered to modulate initial platelet adhesion, granule secretion is likely regulated as a separate and independent process. [Display omitted] [ABSTRACT FROM AUTHOR]

The key factor that enables pathogenic bacteria to establish successful infections lies largely in their ability to escape the host's immune response and adhere to host surfaces. Vitronectin (Vn) is a multidomain glycoprotein ubiquitously present in blood and the extracellular matrix of several tissues, where it plays important roles as a regulator of membrane attack complex (MAC) formation and as a mediator of cell adhesion. Vn has emerged as an intriguing target for several microorganisms. Vn binding by bacterial receptors confers protection from lysis resulting from MAC deposition. Furthermore, through its Arg-Gly-Asp (RGD) motif, Vn can bind several host cell integrins. Therefore, Vn recruited to the bacterial cell functions as a molecular bridge between bacteria and host surfaces, where it triggers several host signaling events that could promote bacterial internalization. Each bacterium uses different receptors that recognize specific Vn domains. In this review, we update the current knowledge of Vn receptors of major bacterial pathogens, emphasizing the role they may play in the host upon Vn binding. Focusing on the structural properties of bacterial proteins, we provide details on the residues involved in their interaction with Vn. Furthermore, we discuss the possible involvement of Vn adsorption on biomaterials in promoting bacterial adhesion on abiotic surfaces and infection. [ABSTRACT FROM AUTHOR]

Objective: The current review is designed to elaborate and reveal the underlying mechanism of sericin and its conjugates of drug delivery during wounds and wound-related issues. Significance: Wound healing is a combination of different humoral, molecular, and cellular mechanisms. Various natural products exhibit potential in wound healing but among them, sericin, catches much attention of researchers due to its bio-functional properties such as being biodegradable, biocompatible, anti-oxidant, anti-bacterial, photo-protector, anti-inflammatory and moisturizing agent. Methods and Results: Sericin triggers the activity of anti-inflammatory cytokines which decrease cell adhesion and promote epithelial cell formation. Moreover, sericin enhances the anti-oxidant enzymes in the wounded area which scavenge the toxic consequences of reactive species (ROS). Conclusions: This article highlights the mechanisms of how topical administration of sericin formulations along with 4-hexylresorcinol,\Chitosan\Ag@MOF-GO, polyvinyl alcohol (PVA), platelet lysate and UV photo cross-linked hydrogel sericin methacrylate which recruits a large number of cytokines on wounded area that stimulate fibroblasts and keratinocyte production as well as collagen deposition that led to early wound contraction. It also reviews the different sericin-based nanoparticles that play a significant role in rapid wound healing. [ABSTRACT FROM AUTHOR]