Mammalian Tissues Research Articles

Bioselective and Radiopaque Zinc-Biopolymeric Complex-Based Porous Biomaterials Promote Mammalian Tissue Ingrowth In Vivo While Inhibiting Microbial Biofilm Gene Expression and Biofilm Formation.

Metal-organic complexes have shown astounding bioactive properties; however, they are rarely explored as biomaterials. Recent studies showed that carboxymethyl-chitosan (CMC) genipin-conjugated zinc biomimetic scaffolds have unique bioselective properties. The biomaterial was reported to be mammalian cell-friendly; at the same time, it was found to discourage microbial biofilm formation on its surface, which seemed to be a promising solution to addressing the problem of trauma-associated biofilm formation and development of antimicrobial resistance. However, the mechanically frail characteristics and zinc overload raise concerns and limit the potential of the said biomaterials. Hence, the present work is focused on improving the strength of the earlier scaffold formulations, testing its in vivo efficacy and reaffirming its action against biofilm-forming microbe Staphylococcus aureus. Scaling up of CMC proportion increased rigidity, and 8% CMC was found to be the ideal concentration for robust scaffold fabrication. Freeze-dried CMC scaffolds with or without genipin (GP) cross-linking were conjugated with zinc using 2 M zinc acetate solution. Characterization results indicated that the CMC-Zn scaffolds, without genipin, showed mechanical properties close to bone fillers, resist in vitro enzymatic degradation until 4 weeks, are porous in nature, and have radiopacity close to mandibular bones. Upon implantation in a subcutaneous pocket of Wistar rats, the scaffolds showed tissue in-growth with simultaneous degradation without any signs of toxicity past 28 days. Neither were there any signs of toxicity in any of the vital organs. Considering many superior properties among the other formulations, the CMC-Zn scaffolds were furthered for biofilm studies. CMC-Zn showed negligible S. aureus biofilm formation on its surface as revealed by an alamar blue-based study. RT-PCR analysis revealed that CMC-Zn downregulated the expression of pro-biofilm effector genes such as icaC and clfB. A protein docking study predicted the inhibitory mechanism of CMC-Zn. Although it binds strongly when alone, at high density, it may cause inactivation of the transmembrane upstream activators of the said genes, thereby preventing their dimerization and subsequent inactivation of the effector genes. In conclusion, zinc-conjugated carboxymethyl-chitosan scaffolds are mechanically robust, porous, yet biodegradable, harmless to the host in the long term, they are radiopaque and prevent biofilm gene expression in notorious microbes; hence, they could be a suitable candidate for bone filler applications.

Marine bryozoan colonization of terrestrial biomineralized tissues: Taphonomic insights and forensic implications

AbstractThe taphonomy and diagenesis of bone and teeth recovered from any environments provide crucial information for forensic sciences and investigations. This leads to the estimation of the postmortem interval (PMI) and the postmortem submersion interval (PMSI) of the organism/s. Aquatic taxa can induce macroscopic and microscopic alterations in biomineralized tissues (e.g., grooves) or can colonize them by attachment (e.g., Bryozoa). Bryozoa are tiny invertebrates that form colonies in freshwater and saltwater. They can survive for years as suspension feeders in all climates. Most marine Bryozoa species have a biomineralized exoskeleton that can be preserved after their death. This research analyzes eight fragments of archeological elephant ivory with a known PMSI of 314 years, which were inhabited by three distinct bryozoan colonies. The variations in the preservation of the bryozoan exoskeletons and the overgrowth of different marine taxa reveal that one colony (lichenoporid cyclostomatid) was alive at the time of the ivory collection from the submerged archeological site while the two other colonies (cheilostomatid) had previously died at different times. The primary objective of this observation is to contribute to the understanding of the taphonomy of terrestrial mammalian biomineralized tissues recovered in marine environments. Additionally, the study discusses the potential forensic implications of this association, such as the evidence of marine submersion and the PMSI. A secondary objective is to present the Bryozoa colonies within a distinctive depositional context, considering that many bryozoan species of the Western Australian coast remain undescribed. The complexity of the Bryozoa ecobiology is also highlighted, with the need of further research (e.g., minimum time for colonization). Finally, this study highlights the urgency of multidisciplinary collaboration to advance aquatic forensic capabilities.

Speckle-enabled in vivo demixing of neural activity in the mouse brain

Functional imaging of neuronal activity in awake animals, using a combination of fluorescent reporters of neuronal activity and various types of microscopy modalities, has become an indispensable tool in neuroscience. While various imaging modalities based on one-photon (1P) excitation and parallel (camera-based) acquisition have been successfully used for imaging more transparent samples, when imaging mammalian brain tissue, due to their scattering properties, two-photon (2P) microscopy systems are necessary. In 2P microscopy, the longer excitation wavelengths reduce the amount of scattering while the diffraction-limited 3D localization of excitation largely eliminates out-of-focus fluorescence. However, this comes at the cost of time-consuming serial scanning of the excitation spot and more complex and expensive instrumentation. Thus, functional 1P imaging modalities that can be used beyond the most transparent specimen are highly desirable. Here, we transform light scattering from an obstacle into a tool. We use speckles with their unique patterns and contrast, formed when fluorescence from individual neurons propagates through rodent cortical tissue, to encode neuronal activity. Spatiotemporal demixing of these patterns then enables functional recording of neuronal activity from a group of discriminable sources. For the first time, we provide an experimental, in vivo characterization of speckle generation, speckle imaging and speckle-assisted demixing of neuronal activity signals in the scattering mammalian brain tissue. We found that despite an initial fast speckle decorrelation, substantial correlation was maintained over minute-long timescales that contributed to our ability to demix temporal activity traces in the mouse brain in vivo. Informed by in vivo quantifications of speckle patterns from single and multiple neurons excited using 2P scanning excitation, we recorded and demixed activity from several sources excited using 1P oblique illumination. In our proof-of-principle experiments, we demonstrate in vivo speckle-assisted demixing of functional signals from groups of sources in a depth range of 220–320 µm in mouse cortex, limited by available speckle contrast. Our results serve as a basis for designing an in vivo functional speckle imaging modality and for maximizing the key resource in any such modality, the speckle contrast. We anticipate that our results will provide critical quantitative guidance to the community for designing techniques that overcome light scattering as a fundamental limitation in bioimaging.

Electrochemiluminescent evaluation of GLUT4 expression in rat adipocytes induced by Ganoderma lucidum polysaccharides

Glucose transporter 4 (GLUT4) directly facilitates cellular uptake of glucose and plays a crucial role in mammalian adipose tissue glucose metabolism. In this work, we constructed a cytosensor for sensitive electrochemiluminescence (ECL) detection of GLUT4 in rat adipocytes (RA cells). A carbon nanotube sponge (CNTSP) was selected to fabricate a permeable electrode to overcome the steric hindrance of cells on the electrode. The expression of GLUT4 after treatment with Ganoderma lucidum polysaccharide (GLP) was assessed by analyzing the luminescence emitted from cell-surface ECL probes. Our preliminary results suggest that GLP promote the expression of GLUT4, thereby enhancing the uptake of the fluorescent glucose 2-NBDG. Treatment with GLP affected GLUT4 expression in RA cells in a dose-dependent manner. Additionally, the ECL cytosensor contributes to the development of ECL imaging of receptors on the cell surface for clinical drug evaluation.

An unexpected path for Malat1 in neurons: trafficking out of the nucleus for translation.

The Malat1 (metastasis-associated lung adenocarcinoma transcript 1) long noncoding RNA is highly and broadly expressed in mammalian tissues, accumulating in the nucleus where it modulates expression and pre-mRNA processing of many protein-coding genes. In this issue of Genes & Development, Xiao and colleagues (doi:10.1101/gad.351557.124) report that a significant fraction of Malat1 transcripts in cultured mouse neurons are surprisingly exported from the nucleus. These transcripts are packaged with Staufen proteins in RNA granules and traffic down the lengths of neurites. They then can be released in a stimulus-dependent manner to be locally translated into a microprotein that alters neuronal gene expression patterns.

PARKIN is not required to sustain OXPHOS function in adult mammalian tissues

Loss-of-function variants in the PRKN gene encoding the ubiquitin E3 ligase PARKIN cause autosomal recessive early-onset Parkinson’s disease (PD). Extensive in vitro and in vivo studies have reported that PARKIN is involved in multiple pathways of mitochondrial quality control, including mitochondrial degradation and biogenesis. However, these findings are surrounded by substantial controversy due to conflicting experimental data. In addition, the existing PARKIN-deficient mouse models have failed to faithfully recapitulate PD phenotypes. Therefore, we have investigated the mitochondrial role of PARKIN during ageing and in response to stress by employing a series of conditional Parkin knockout mice. We report that PARKIN loss does not affect oxidative phosphorylation (OXPHOS) capacity and mitochondrial DNA (mtDNA) levels in the brain, heart, and skeletal muscle of aged mice. We also demonstrate that PARKIN deficiency does not exacerbate the brain defects and the pro-inflammatory phenotype observed in mice carrying high levels of mtDNA mutations. To rule out compensatory mechanisms activated during embryonic development of Parkin-deficient mice, we generated a mouse model where loss of PARKIN was induced in adult dopaminergic (DA) neurons. Surprisingly, also these mice did not show motor impairment or neurodegeneration, and no major transcriptional changes were found in isolated midbrain DA neurons. Finally, we report a patient with compound heterozygous PRKN pathogenic variants that lacks PARKIN and has developed PD. The PARKIN deficiency did not impair OXPHOS activities or induce mitochondrial pathology in skeletal muscle from the patient. Altogether, our results argue that PARKIN is dispensable for OXPHOS function in adult mammalian tissues.

Molecular Prevalence, Genetic Diversity, and Tissue Tropism of Bartonella Species in Small Mammals from Yunnan Province, China.

Bartonella is an intracellular parasitic zoonotic pathogen that can infect animals and cause a variety of human diseases. This study investigates Bartonella prevalence in small mammals in Yunnan Province, China, focusing on tissue tropism. A total of 333 small mammals were sampled from thirteen species, three orders, four families, and four genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified thirty, ten, and five strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in Episoriculus leucops (GS136). Analysis of the different tissues naturally infected by Bartonella species revealed varied copy numbers across different tissues, with the highest load in spleen tissue. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting the presence of extensive tissue tropism in Bartonella species naturally infecting small mammalian tissues.

The effect of baseline O2 conditions on the response of prostate cancer cells to hypoxia.

The transcriptional response to hypoxia is largely regulated by the hypoxia-inducible factors (HIFs), which induce the expression of genes involved in glycolysis, angiogenesis, proliferation, and migration. Virtually all cell culture-based hypoxia experiments have used near-atmospheric (18% O2) oxygen levels as baseline for comparison to hypoxia. However, this is hyperoxic compared to mammalian tissue microenvironments, where oxygen levels range from 2-9% O2 (physioxia). Thus, these experiments actually compare hyperoxia to hypoxia. To determine how the baseline O2 level affects the subsequent response to hypoxia, we cultured PC-3 prostate cancer cells in either 18% or 5% O2 for two weeks prior to exposing them to hypoxia (~1.1% pericellular O2) for 12-48 h. RNA-seq revealed that the transcriptional response to hypoxia was dependent on the baseline O2 level. Cells grown in 18% O2 prior to hypoxia exposure showed an enhanced induction of HIF targets, particularly genes involved in glucose metabolism, compared to cells grown in physioxia prior to hypoxia. Consistent with this, hypoxia significantly increased glucose consumption and metabolic activity only in cells previously cultured in 18% O2, but not in cells preadapted to 5% O2. Transcriptomic analyses also indicated effects on cell proliferation and motility, which were followed up by functional assays. While unaffected by hypoxia, both proliferation and migration rates were greater in cells cultured in 5% O2 versus 18% O2. We conclude that an inappropriately hyperoxic starting condition affects the transcriptional and metabolic responses of PC-3 cells to hypoxia, which may compromise experiments on cancer metabolism in vitro.

3-Methyl-phenanthrene (3-MP) disrupts the electrical and contractile activity of the heart of the polar fish, navaga cod (Eleginus nawaga)

Alkylated polycyclic aromatic hydrocarbons are abundant in crude oil and are enriched during petroleum refinement but knowledge of their cardiotoxicity remains limited. Polycyclic aromatic hydrocarbons (PAHs) are considered the main hazardous components in crude oil and the tricyclic PAH phenanthrene has been singled out for its direct effects on cardiac tissue in mammals and fish. Here we test the impact of the monomethylated phenanthrene, 3-methylphenanthrene (3-MP), on the contractile and electrical function of the atrium and ventricle of a polar fish, the navaga cod (Eleginus nawaga). Using patch-clamp electrophysiology in atrial and ventricular cardiomyocytes we show that 3-MP is a potent inhibitor of the delayed rectifier current IKr (IC50 = 0.25 μM) and prolongs ventricular action potential duration. Unlike the parent compound phenanthrene, 3-MP did not reduce the amplitude of the L-type Ca2+ current (ICa) but it accelerated current inactivation thus reducing charge transfer across the myocyte membrane and compromising pressure development of the whole heart. 3-MP was a potent inhibitor (IC50 = 4.7 μM) of the sodium current (INa), slowing the upstroke of the action potential in isolated cells, slowing conduction velocity across the atrium measured with optical mapping, and increasing atrio-ventricular delay in a working whole heart preparation. Together, these findings reveal the strong cardiotoxic potential of this phenanthrene derivative on the fish heart. As 3-MP and other alkylated phenanthrenes comprise a large fraction of the PAHs in crude oil mixtures, these findings are worrisome for Arctic species facing increasing incidence of spills and leaks from the petroleum industry. 3-MP is also a major component of polluted air but is not routinely measured. This is also of concern if the hearts of humans and other terrestrial animals respond to this PAH in a similar manner to fish.

Screening Resorufin Pentyl Ether Analogs for Enhanced Antimicrobial Activity Against Francisella tularensis and Neisseria gonorrhoeae.

Antibiotic resistance is an urgent public health threat. The CDC estimates there are approximately 2.8 million new cases of antibiotic-resistant infections annually resulting in 35,000 deaths and billions of dollars in health care costs. The development of new drugs is imperative to combat this crisis and prevent the loss of additional lives from once “curable” diseases. Resazomycins, a novel family of antibiotics, have bactericidal activity against Francisella tularensis and Neisseria gonorrhoeae.  One resazomycin, resorufin pentyl ether (RPE), significantly reduces vaginal colonization by N. gonorrhoeae in a mouse model of infection.  Repeated administration of RPE, however, fails to clear the infection, in contrast to a single dose of ceftriaxone, an antibiotic commonly used to treat gonorrhea, which clears the infection within 24 hours. Further characterization of resazomycins revealed the efficacy of these compounds is limited by interaction with serum albumin and reduced oxygen concentrations found within mammalian tissues.  Therefore, we hypothesize that novel resazurin analogs that maintain antimicrobial activity in the presence of serum albumin and low oxygen will have improved therapeutic efficacy in vivo.  Resazurin has been chemically modified to generate ether and deoxygenated compound derivatives.  Six ether derivatives and two deoxygenated analogs exhibited robust antimicrobial activity against F. tularensis and N. gonorrhoeae.  In the presence of serum albumin, however, reduced efficacy was observed in the six ether analogs yet activity was maintained in the deoxygenated analogs.  We plan to screen the efficacy of additional ether and deoxygenated analogs against F. tularensis and N. gonorrhoeae.

Correction: Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors.

Correction: Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors.

Common occurrence of hotspots of single strand DNA breaks at transcriptional start sites

BackgroundWe recently developed two high-resolution methods for genome-wide mapping of two prominent types of DNA damage, single-strand DNA breaks (SSBs) and abasic (AP) sites and found highly complex and non-random patterns of these lesions in mammalian genomes. One salient feature of SSB and AP sites was the existence of single-nucleotide hotspots for both lesions.ResultsIn this work, we show that SSB hotspots are enriched in the immediate vicinity of transcriptional start sites (TSSs) in multiple normal mammalian tissues, however the magnitude of enrichment varies significantly with tissue type and appears to be limited to a subset of genes. SSB hotspots around TSSs are enriched on the template strand and associate with higher expression of the corresponding genes. Interestingly, SSB hotspots appear to be at least in part generated by the base-excision repair (BER) pathway from the AP sites.ConclusionsOur results highlight complex relationship between DNA damage and regulation of gene expression and suggest an exciting possibility that SSBs at TSSs might function as sensors of DNA damage to activate genes important for DNA damage response.

Fluorescent Protein-Based Sensors for Detecting Essential Metal Ions across the Tree of Life.

Genetically encoded fluorescent metal ion sensors are powerful tools for elucidating metal dynamics in living systems. Over the last 25 years since the first examples of genetically encoded fluorescent protein-based calcium indicators, this toolbox of probes has expanded to include other essential and non-essential metal ions. Collectively, these tools have illuminated fundamental aspects of metal homeostasis and trafficking that are crucial to fields ranging from neurobiology to human nutrition. Despite these advances, much of the application of metal ion sensors remains limited to mammalian cells and tissues and a limited number of essential metals. Applications beyond mammalian systems and in vivo applications in living organisms have primarily used genetically encoded calcium ion sensors. The aim of this Perspective is to provide, with the support of historical and recent literature, an updated and critical view of the design and use of fluorescent protein-based sensors for detecting essential metal ions in various organisms. We highlight the historical progress and achievements with calcium sensors and discuss more recent advances and opportunities for the detection of other essential metal ions. We also discuss outstanding challenges in the field and directions for future studies, including detecting a wider variety of metal ions, developing and implementing a broader spectral range of sensors for multiplexing experiments, and applying sensors to a wider range of single- and multi-species biological systems.

Epigenetics in Cancer Therapy

Epigenetics regulates parts of the genetic information accessible to cellular machinery, thus contributing to cellular diversity. Disruption of epigenetic harmonisation can lead to dysregulation of signaling pathways and contribute to diseases like cancer. Epigenetic processes are crucial in coordinating the normal growth and preservation of gene activity unique to mammal tissues. Epigenetic studies in current cancer research are vital for early detection through biomarker identification, understanding tumor heterogeneity, predicting treatment responses, and uncovering resistance mechanisms. This knowledge informs targeted therapies, enhances personalized medicine, and improves overall outcomes in cancer patients. This review comprehensively explores epigenetic processes in healthy cells, emphasizing histone modification-lysine acetylation and DNA methylation. The intricate mechanisms governing genetic expression and their dysregulation in cancer progression are also reviewed. Examining prevalent cancer types, this review stresses the pivotal role of epigenetics in understanding and potentially targeting these processes for therapeutic interventions.

The first report of the presence of collagen X in mammalian dentinal matrix

Collagen X is an extracellular matrix protein, usually found in the hypertrophic cartilage destined to be mineralized. It is intimately associated with the mineralization process of the mammalian hard tissues, and particularly, regulating the compartmentalization of matrix components. Despite the fact that the dentine of the tooth is highly mineralized, there are no previous reports to indicate the presence of collagen X in this connective tissue. Here we report, for the first time, its presence in mammalian dentine based on micromorphological and immunohistochemical data. We hypothesize that the collagen X in dentine may in the long term arrest the progression of the mineralization front towards the soft tissue components of the pulp that are not destined to be mineralized.

On the Possible Effect of Phytic Acid (Myo-Inositol Hexaphosphoric Acid, IP6) on Cytochromes P450 and Systems of Xenobiotic Metabolism in Different Hepatic Models.

As compounds of natural origin enter human body, it is necessary to investigate their possible interactions with the metabolism of drugs and xenobiotics in general, namely with the cytochrome P450 (CYP) system. Phytic acid (myo-inositol hexaphosphoric acid, IP6) is mainly present in plants but is also an endogenous compound present in mammalian cells and tissues. It has been shown to exhibit protective effect in many pathological conditions. For this paper, its interaction with CYPs was studied using human liver microsomes, primary human hepatocytes, the HepG2 cell line, and molecular docking. Docking experiments and absorption spectra demonstrated the weak ability of IP6 to interact in the heme active site of CYP1A. Molecular docking suggested that IP6 preferentially binds to the protein surface, whereas binding to the active site of CYP1A2 was found to be less probable. Subsequently, we investigated the ability of IP6 to modulate the metabolism of xenobiotics for both the mRNA expression and enzymatic activity of CYP1A enzymes. Our findings revealed that IP6 can slightly modulate the mRNA levels and enzyme activity of CYP1A. However, thanks to the relatively weak interactions of IP6 with CYPs, the chances of the mechanisms of clinically important drug-drug interactions involving IP6 are low.

Abstract 6792: Investigating differential expression of Palladin isoform 3 in 2D and 3D pancreatic cancer cell cultures

Abstract Palladin (PALLD) is an actin-binding protein widely expressed in mammalian tissues that modulates cytoskeletal dynamics. Palladin is linked to the progression of breast, pancreatic, and renal cancers. There are at least 9 known isoforms of PALLD but isoforms 3 (iso3) and 4 (iso4) appear most significant in cancer cells and associated fibroblasts. Our goal is to understand iso3 in pancreatic cancer (PC) cell lines grown in various culture environments to shed light on the intricate interplay between culture conditions and gene regulation. Cell models were developed as 3D spheroids from hanging drops after optimizing culture conditions by utilizing a combination of inexpensive methylcellulose (MC) and rat tail collagen viscosity ranges across cell seeding densities. The quality of the developed spheroids was assessed using multiple parameters, like diameter, integrity, and circularity to determine ideal spheroid characteristics. Spheroids that formed at a lower MC viscosity range (350-550 mPa·s) led to peripheral loose cells and a higher viscosity range (7,000-10,000 mPa·s) resulted in elongated shapes. Moderate viscosity ranges (1,000-1,800 mPa·s and 3,500-5,600 mPa·s) consistently produced circular and compact spheroids. Optimal incubation times varied from 72 to 96 hr depending on the cell line. Invasion dynamics within collagen-MC gels revealed that PANC-1 had significantly higher invasion potential compared to BxPC-3 and a control cell line C2C12. RT-qPCR results show that PALLD iso3 was particularly overexpressed in the 3D culture environment of PANC-1, suggesting that elevated PALLD isoform 3 expression may be a characteristic of 3D culture, particularly in invasive PC types. Taken together, the study validates the importance of extracellular viscosity for influencing spheroid characteristics toward generating reproducible 3D spheroids. The investigation also highlights PALLD iso3 as a potentially valuable biomarker for aggressive forms of pancreatic cancer. Citation Format: Sonali Biswas, Jason A. Bush. Investigating differential expression of Palladin isoform 3 in 2D and 3D pancreatic cancer cell cultures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6792.

The Effect of Heparin and Other Exogenous Glycosaminoglycans (GAGs) in Reducing IL-1β-Induced Pro-Inflammatory Cytokine IL-8 and IL-6 mRNA Expression and the Potential Role for Reducing Inflammation.

Glycosaminoglycans (GAGs) are long linear polysaccharides found in every mammalian tissue. Previously thought only to be involved in cellular structure or hydration, GAGs are now known to be involved in cell signaling and protein modulation in cellular adhesion, growth, proliferation, and anti-coagulation. In this study, we showed that GAGs have an inhibitory effect on the IL-1β-stimulated mRNA expression of IL-6 and IL-8. Exogenous heparin (p < 0.0001), heparan (p < 0.0001), chondroitin (p < 0.049), dermatan (p < 0.0027), and hyaluronan (p < 0.0005) significantly reduced the IL-1β-induced IL-8 mRNA expression in HeLa cells. Exogenous heparin (p < 0.0001), heparan (p < 0.0001), and dermatan (p < 0.0027) also significantly reduced IL-1β-induced IL-6 mRNA expression in HeLa cells, but exogenous chondroitin and hyaluronan had no significant effect. The exogenous GAGs may reduce the transcription of these inflammatory cytokines through binding to TILRR, a co-receptor of IL-1R1, and block/reduce the interactions of TILRR with IL-1R1.

Bottlenecks in the Investigation of Retinal Sterol Homeostasis.

Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intratissue, intercellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis.

Roles of telocytes dominated cell–cell communication in fibroproliferative acute respiratory distress syndrome

AbstractTelocytes (TCs) are a new type of interstitial cell identified in multiple tissues of mammals, including the human lung, and mediate homocellular or heterocellular cell‐cell communication. Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure and combined with direct and indirect lung injury, which is induced by pneumonia, sepsis, burns, etc. Pulmonary fibrosis is a progressive lung disease that occurs due to increased fibrosis of lung tissue in response to chronic injury of the epithelium and gets more and more attention as a well‐recognized sequela of ARDS or mechanical ventilation. However, the existing intervention measures could not prevent the progression of pulmonary fibrosis. Although the protective effect of TCs in acute lung injury had been demonstrated in both cellular and animal models in previous studies by our or other researchers, the roles of TCs mediated cell‐cell communication in fibroproliferative ARDS is unclear. This review is aimed at integrating our understanding of TC‐mediated cell–cell communication in lung diseases with pulmonary fibrosis after ARDS.