Role of immune cell interactions in alcohol-associated liver diseases

Research on inflammatory response,liver injury,and immune regulation has demonstrated that the intricate interactions among immune cells constitute a critical regulatory network.Alcohol consumption alters the liver microenvironment,triggering inflammation and immune responses.Elucidating the inhibitory,cooperative,and synergistic effects among lymphocytes and myeloid cells may reveal the core mechanisms of alcohol-associated liver disease(ALD)pathogenesis and identify promising therapeutic targets.This review seeks to elucidate the intricate and multifaceted interactions among immune cells,encompassing both direct cellular interactions and the secretion of various effector molecules.It is essential to underscore that these interactions have broader and more complex roles in ALD than the activities of individual immune cell types.These interactions play a crucial role in mutually regulating one another,thereby preserving the homeostasis of the inflammatory and immune response in the liver environment.Targeting these immune cell interactions is anticipated to offer a novel approach to the prevention and treatment of ALD.

Cell-cell interactions and communication dynamics in lung fibrosis

Cell-cell interactions are essential components of coordinated cell function in lung homeostasis.Lung diseases involve altered cell-cell interactions and communication between different cell types,as well as between subsets of cells of the same type.The identification and understanding of intercellular signaling in lung fibrosis offer insights into the molecular mechanisms underlying these interactions and their implications in the development and progression of lung fibrosis.A comprehensive cell atlas of the human lung,established with the facilita-tion of single-cell RNA transcriptomic analysis,has enabled the inference of intercellular communications using ligand-receptor databases.In this review,we provide a comprehensive overview of the modified cell-cell commu-nications in lung fibrosis.We highlight the intricate interactions among the major cell types within the lung and their contributions to fibrogenesis.The insights presented in this review will contribute to a better understand-ing of the molecular mechanisms underlying lung fibrosis and may guide future research efforts in developing targeted therapies for this debilitating disease.

A cell transcriptomic profile p ovides insights into adipocytes of porcine mammary gland across development

Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes.Results Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages(d 90 of gestation, G90;d 0 after lactation, L0;d 20 after lactation, L20;2 d post natural involution, PI2;7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation(G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation(L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution(PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells to maintain the lactation potential of mammary glands for the next lactation cycle.Conclusion The molecular mechanisms of dedifferentiation, proliferation and redifferentiation of adipocytes and epithelial cells were revealed from late pregnancy to natural involution. This cell transcriptomic profile constitutes an essential reference for future studies in the development and remodeling of the mammary gland at different stages.

Advances in tumor-endothelial cells co-culture and interaction on microfluidics

The metastasis in which the cancer cells degrade the extracellular matrix （ECM） and invade to the sur- rounding and far tissues of the body is the leading cause of mortality in cancer patients, With a lot of advancement in the field, yet the biological cause of metastasis are poorly understood, The microfluidic system provides advanced technology to reconstruct a variety of in vivo-like environment for studying the interactions between tumor ceils （TCs） and endothelial ceils （ECs）. This review gives a brief account of both two-dimensional models and three-dimensional microfluidic systems for the analysis of TCs-ECs co- culture as well as their applications to anti-cancer drug screening, Furthermore, the advanced methods for analyzing cell-to-cell interactions at single-cell level were also discussed,

Virus/host cell interactions:From structure to medical implication

The first event in viral infection is the attachment of a virus to specific receptors on the host cell surface. This will trigger conformational changes of the viral surface protein. For

Bone biomaterials and interactions with stem cells

Bone biomaterials play a vital role in bone repair by providing the necessary substrate for cell adhesion, proliferation, and differentiation and by modulating cell activity and function. In past decades, extensive efforts have been devoted to developing bone biomaterials with a focus on the following issues： （1） developing ideal biomaterials with a combination of suitable biological and mechanical properties; （2） constructing a cell microenvironment with pores ranging in size from nanoscale to submicro- and microscale; and （3） inducing the oriented differentiation of stem cells for artificial-to-biological transformation. Here we present a comprehensive review of the state of the art of bone biomaterials and their interactions with stem cells. Typical bone biomaterials that have been developed, including bioactive ceramics, biodegradable polymers, and biodegradable metals, are reviewed, with an emphasis on their characteristics and applications. The necessary porous structure of bone biomaterials for the cell microenvironment is discussed, along with the corresponding fabrication methods. Additionally, the promising seed stem cells for bone repair are summarized, and their interaction mechanisms with bone biomaterials are discussed in detail. Special attention has been paid to the signaling pathways involved in the focal adhesion and osteogenic differentiation of stem cells on bone biomaterials. Finally, achievements regarding bone biomaterials are summarized, and future research directions are proposed.

Temporal and spatial regulation of biomimetic vascularization in 3D-printed skeletal muscles

In the intricate skeletal muscle tissue,the symbiotic relationship between myotubes and their supporting vasculature is pivotal in delivering essential oxygen and nutrients.This study explored the complex interplay between skeletal muscle and endothelial cells in the vascularization ofmuscle tissue.By harnessing the capabilities of three-dimensional(3D)bioprinting and modeling,we developed a novel approach involving the co-construction of endothelial and muscle cells,followed by their subsequent differentiation.Our findings highlight the importance of the interaction dynamics between these two cell types.Notably,introducing endothelial cells during the advanced phases of muscle differentiation enhanced myotube assembly.Moreover,it stimulated the development of the vascular network,paving the way for the early stages of vascularized skeletal muscle development.The methodology proposed in this study indicates the potential for constructing large-scale,physiologically aligned skeletal muscle.Additionally,it highlights the need for exploring the delicate equilibrium and mutual interactions between muscle and endothelial cells.Based on the multicell-type interaction model,we can predict promising pathways for constructing even more intricate tissues or organs.

Advances in single-cell sequencing:insights from organ transplantation

Single-cell RNA sequencing(scRNA-seq)is a comprehensive technical tool to analyze intracellular and intercellular interaction data by whole transcriptional profile analysis.Here,we describe the application in biomedical research,focusing on the immune system during organ transplantation and rejection.Unlike conventional transcriptome analysis,this method provides a full map of multiple cell populations in one specific tissue and presents a dynamic and transient unbiased method to explore the progression of allograft dysfunction,starting from the stress response to final graft failure.This promising sequencing technology remarkably improves individualized organ rejection treatment by identifying decisive cellular subgroups and cell-specific interactions.

The origin and role of innate lymphoid cells in the lung

Innate lymphoid cells(ILCs),a newly identified member of the lymphoid population,play a critical role in the transition from innate to adaptive immunity in host defense.ILCs are important in mucosal barrier immunity,tissue homeostasis,and immune regulation throughout the body.Significant alterations in ILC responses in lung diseases have been observed and reported.Emerging evidence has shown that ILCs are importantly involved in the pathogenesis and development of a variety of lung diseases,i.e.,helminth infections,allergic airway inflammation,and airway hyper-responsiveness.However,as a tissue-resident cell population,the role of ILCs in the lung remains poorly characterized.In this review,we discuss the role of ILCs in lung diseases,the mechanisms underlying the ILCmediated regulation of immunity,and the therapeutic potential of modulating ILC responses.

Ink-structing the future of vascular tissue engineering:a review of the physiological bioink design

Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.

A Brief Review on Hydroxyapatite Nanoparticles Interactions with Biological Constituents

With the pursuit of new cancer therapies and more effective treatment to diseases in the last decades, nanotechnology has been an important ally for healthcare professionals and patients in critical clinical conditions. Nanomaterials offer an alternative way to deliver toxic chemotherapeutic drugs to specific biological tissues, specific cells or specific microbial beings, resulting in avoidance of strong side effects or resilience to effective drugs. Among these materials, stands out the hydroxyapatite nanoparticles, a ceramic class of calcium phosphates that present chemical and structural similarities with the mineral phase of the human skeleton’s bone matrix, resulting in important biological features, such as biocompatibility, osteoconductive, osteoinduction and osteoaffinity, which led to a lot of scientific researches to apply these nanoparticles for bone diseases diagnosis and therapeutics. Due to the hydroxyapatite biological activities and due to the possibility to promote chemical and physical modifications in these nanoparticles, they can interact with biological cells or microorganisms in different ways, resulting in multiple potentialities to be explored such as apoptosis induction to cancerous cells, osteogenesis promotion, cellular proliferation, angiogenesis and tissue recovery, in addition to promote cell adhesion and cell uptake. Furthermore, chemical and physical modifications, such as surface functionalization, dopant inclusions and radiolabeling process, allow scientists to track the particle activities in biological environments. In the last decades of scientific productions, the literature brings together important data on how hydroxyapatite nanoparticles interact with biological tissues and such data are crucial for the development of more effective therapeutic and diagnostic agents. In the present review, we intend to compile scholarly information to explore the biological relations of nanosized hydroxyapatite with the human cellular environment and the feasible modifications that may improve the theragnostic efficacy of these molecules.

Neutralizing antibodies in hepatitis C virus infection

Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodiesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.

Biocompatibility of marine magnetotactic ovoid strain MO-1 for in vivo application

Magnetotactic bacteria are capable of biosynthesizing magnetic nanoparticles,also called magnetosomes,and swimming along magnetic field lines.The abilities endow the whole cells of magnetotactic bacteria with such applications as targeted therapy and manipulation of microrobots.We have shown that the intact marine magnetotactic bacteria MO-1 kill efficiently antibiotic-resistant pathogen Staphylococcus aureus in vivo,but the biocompatibility of this marine bacterium is unknown.In this study,the strain MO-1 was chosen to analyze its biocompatibility and potential for biomedicine applications.Results showed that MO-1 cells could be guided at 37℃ under an external magnetic field and swim in the blood plasma and urine.They could keep active locomotivity within 40 min in the plasma and urine,although their velocity slowed down.When incubated with human cells,magnetotactic bacteria MO-1 had no obvious effects on cellular viability at low dose,while the cell toxicity increased with the augmentation of the quantity of the MO-1 cells added.In the in-vivo experiments,the median lethal dose of magnetotactic bacteria MO-1 in rats was determined to be 7.9×10^(10) bacteria/kg.These results provided the foundation for the biocompatibility and safety evaluations of magnetotactic bacteria MO-1 and suggested that they could be basically used in clinical targeted therapy.

Clinical implications of interleukins-31, 32, and 33 in gastric cancer

BACKGROUND Gastric cancer(GC) is one of the most common malignancies in China with a high morbidity and mortality.AIM To determine whether interleukin(IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients.METHODS Tissue array(n = 180) gastric specimens were utilised. IL-31, IL-32, and IL-33 expression in GC and non-GC tissues was detected immunohistochemically. The correlations between IL-31, IL-32, and IL-33 expression in GC and severity of clinicopathological parameters were evaluated. Survival curves were plotted using the Kaplan-Meier method/Cox regression. Circulating IL-31, IL-32, and IL-33 were detected by ELISA.RESULTS We found that the expression levels of IL-31, IL-32, and IL-33 were all lower in GC than in adjacent non-GC gastric tissues(P < 0.05). IL-33 in peripheral blood of GC patients was significantly lower than that of healthy individuals(1.50 ± 1.11 vs 9.61 ± 8.00 ng/m L, P <0.05). Decreased IL-31, IL-32, and IL-33 in GC were observed in younger patients(< 60 years), and IL-32 and IL-33 were lower in female patients(P < 0.05). Higher IL-32 correlated with a longer survival in two GC subgroups: T4 invasion depth and TNM I-II stage. Univariate/multivariate analysis revealed that IL-32 was an independent prognostic factor for GC in the T4 stage subgroup. Circulating IL-33 was significantly lower in GC patients at TNM stage IV than in healthy people(P < 0.05).CONCLUSION Our findings may provide new insights into the roles of IL-31, IL-32, and IL-33 in the carcinogenesis of GC and demonstrate their relative usefulness as prognostic markers for GC. The underlying mechanism of IL-31, IL-32, and IL-33 actions in GC should be further explored.

Chronic lung allograft dysfunction post-lung transplantation:The era of bronchiolitis obliterans syndrome and restrictive allograft syndrome

Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment.The consensus statement from the International Society for Heart and Lung Transplantation on CLAD in 2019 classified CLAD into two main phenotypes:Bronchiolitis obliterans syndrome and restrictive allograft syndrome.Along with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired.In this review,we summarize the new definition of CLAD and update and summarize the existing knowledge on the underlying mechanisms of bronchiolitis obliterans syndrome and restrictive allograft syndrome,which have been elucidated from clinicopathological observations and animal experiments worldwide.

New DNA probe for studying cell membrane interactions

Subject Code:B05 With the support by the National Natural Science Foundation of China and the US National Institutes of Health,a team led by Dr.Tan Weihong(谭蔚泓)at Hunan University and the University of Florida reported a new DNA probe for studying cell membrane interactions,which was recently published

Matrix metalloproteinase-sensitive poly(ethylene glycol)/peptide hydrogels as an interactive platform conducive to cell proliferation during 3D cell culture

The response of extracellular matrix(ECM) to dynamic cell signals is of great significance for the regulation of cell behavior. In the present study, we prepared a type of matrix metalloproteinase(MMP)-sensitive degradable hydrogels(MSDHs) via the catalyst-free o-phthalaldehyde(OPA)/amine cross-linking reaction between o-phthalaldehyde-grafted four-arm poly(ethylene glycol)(4aPEG-OPA) and an MMP-sensitive degradable peptide. The gelation rates and storage moduli of MSDHs and the MMP-insensitive hydrogels(MIHs) based on an MMP-insensitive scramble peptide were comparable and dependent on the concentrations of precursor polymers. MSDHs were degradable while MIHs were stable in the presence of proteinase in vitro.The degradation of MSDHs was obviously faster than that of MIHs after subcutaneous injection into rats. In addition, both types of poly(ethylene glycol)/peptide hydrogels displayed excellent cytocompatibility in vitro, and showed good histocompatibility in vivo in the subcutaneous layer of rats. Furthermore, the proliferation of several MMP-expressing cell lines including MDA-MB-231 cells within MSDHs was obviously faster than that in MIHs, indicating the influence of metabolism-mediated scaffold degradation on the cell proliferation. This study provides a new biocompatible and biodegradable 3 D cell culture interactive platform for regulation of cell behavior.

Experimental measurements and CFD modelling of hydroxyapatite scaffolds in perfusion bioreactors for bone regeneration

In the field of bone tissue engineering,particular interest is devoted to the development of 3D cultures to study bone cell proliferation under conditions similar to in vivo ones,e.g.by artificially producing mechanical stresses promoting a biological response(mechanotransduction).Of particular relevance in this context are the effects generated by the flow shear stress,which governs the nutrients delivery rate to the growing cells and which can be controlled in perfusion reactors.However,the introduction of 3D scaffolds complicates the direct measurement of the generated shear stress on the adhered cells inside the matrix,thus jeopardizing the potential of using multi-dimensional matrices.In this study,an anisotropic hydroxyapatite-based set of scaffolds is considered as a 3D biomimetic support for bone cells deposition and growth.Measurements of sample-specific flow resistance are carried out using a perfusion system,accompanied by a visual characterization of the material structure.From the obtained results,a subset of three samples is reproduced using 3D-Computational Fluid Dynamics(CFD)techniques and the models are validated by virtually replicating the flow resistance measurement.Once a good agreement is found,the analysis of flow-induced shear stress on the inner B-HA structure is carried out based on simulation results.Finally,a statistical analysis leads to a simplified expression to correlate the flow resistance with the entity and extensions of wall shear stress inside the scaffold.The study applies CFD to overcome the limitations of experiments,allowing for an advancement in multi-dimensional cell cultures by elucidating the flow conditions in 3D reactors.

Mimicking the physical cues of the ECM in angiogenic biomaterials

A functional microvascular system is imperative to build and maintain healthy tissue.Impaired microvasculature results in ischemia,thereby limiting the tissue’s intrinsic regeneration capacity.Therefore,the ability to regenerate microvascular networks is key to the development of effective cardiovascular therapies.To stimulate the formation of new microvasculature,researchers have focused on fabricating materials that mimic the angiogenic properties of the native extracellular matrix(ECM).Here,we will review biomaterials that seek to imitate the physical cues that are natively provided by the ECM to encourage the formation of microvasculature in engineered constructs and ischemic tissue in the body.

Immunomodulatory nanodiamond aggregate-based platform for the treatment of rheumatoid arthritis

We previously demonstrated that octadecylamine-functionalized nanodiamond(ND-ODA)and dexamethasone(Dex)-adsorbed ND-ODA(ND-ODA–Dex)promoted anti-inflammatory and proregenerative behavior in human macrophages in vitro.In this study,we performed a pilot study to investigate if these immunomodulatory effects translate when used as a treatment for rheumatoid arthritis in mice.Following local injection in limbs of mice with collagen type II-induced arthritis,microcomputed tomography showed that mice treated with a low dose of ND-ODA and ND-ODA–Dex did not experience bone loss to the levels observed in non-treated arthritic controls.A low dose of ND-ODA and ND-ODA–Dex also reduced macrophage infiltration and expression of proinflammatory mediators iNOS and tumor necrosis factor-a compared to the arthritic control,while a high dose of ND-ODA increased expression of these markers.Overall,these results suggest that ND-ODA may be useful as an inherently immunomodulatory platform,and support the need for an in-depth study,especially with respect to the effects of dose.