Prostaglandin E2/EP4 axis is upregulated in Spondyloarthritis and contributes to radiographic progression.

Ankylosing spondylitis (AS) is an inflammatory disease leading to spine ankylosis; however, the mechanisms behind new bone formation are still not fully understood. Single Nucleotide Polymorphisms (SNPs) in PTGER4, encoding for the receptor EP4 of prostaglandin E2 (PGE2), are associated with AS. Since the PGE2-EP4 axis participates in inflammation and bone metabolism, this work aims at investigating the influence of the prostaglandin-E2 axis on radiographic progression in AS. In 185 AS (97 progressors), baseline serum PGE2 predicted progression, and PTGER4 SNP rs6896969 was more frequent in progressors. Increased EP4/PTGER4 expression was observed in AS circulating immune cells, synovial tissue, and bone marrow. CD14highEP4 + cells frequency correlated with disease activity, and when monocytes were cocultured with mesenchymal stem cells, the PGE2/EP4 axis induced bone formation. In conclusion, the Prostaglandin E2 axis is involved in bone remodelling and may contribute to the radiographic progression in AS due to genetic and environmental upregulation.

miR-22-enriched breast cancer cells display repressed glycolytic metabolism, increased glycogen synthesis, and reduced survival in low glucose conditions.

BACKGROUND: Breast cancer (BC) is the second leading cause of cancer-related mortality among women. Beyond the established tumourigenic role of genetic mutations, metabolic reprogramming is another key cancer hallmark. Glucose metabolism in particular is known to be prominently altered in tumours, in order to support biomass accumulation and cancer cell survival. The tumor suppressor microRNA (miRNA) miR-22 has been previously associated with a plethora of BC phenotypes such as growth, invasion-metastasis, and regulation of metabolic phenotypes such as lipid and folate metabolism. In this study, we aimed to investigate the role of miR-22 in the regulation of glucose metabolism in BC cells. METHODS AND RESULTS: Here we examined how miR-22 affects glucose metabolism in the MCF-7 BC cells. We found that over-expression of miR-22 caused a reduced glycolytic rate in these cells. Moreover, the miRNA also rendered MCF-7 cells more sensitive to lower glucose levels. We next unbiasedly screened the transcript levels of 84 genes relevant to glucose metabolism using the Human Glucose RT2 Profiler PCR Array. Interestingly, the strongest effect identified by this screen was the upregulation of genes involved in glycogen synthesis and the repression of gene involved in glycogen catabolism. Examination of publicly available transcriptomic datasets confirmed the correlations between expression of miR-22 and these glycogen metabolism genes in BC cells. CONCLUSION: This study has generated evidence for a regulatory role of miR-22 in glucose and glycogen metabolism, expanding the involvement of this miRNA in BC metabolic reprogramming.

Detection of SARS-CoV-2-Specific Antibodies in Human Breast Milk and Their Neutralizing Capacity after COVID-19 Vaccination: A Systematic Review.

SARS-CoV-2 is the virus that causes the infectious disease known as Corona Virus Disease 2019 (COVID-19). The severe impact of the virus on humans is undeniable, which is why effective vaccines were highly anticipated. As of 12 January 2022, nine vaccines have obtained Emergency Use Listing by the World Health Organization (WHO), and four of these are approved or authorized by the Centers for Disease Control and Prevention (CDC) in the United States. The initial clinical trials studying COVID-19 vaccine efficacy excluded pregnant and lactating individuals, meaning that data on the effects of the vaccine on breast milk were lacking. Until today, none of the authorized vaccines have been approved for use in individuals under six months. During the first months of life, babies do not produce their own antibodies; therefore, antibodies contained in their mothers' breastmilk are a critical protective mechanism. Several studies have shown the presence of SARS-CoV-2 antibodies in the breast milk of women who have been vaccinated or had been naturally infected. However, whether these are protective is still unclear. Additionally, research on the BNT162b2 mRNA vaccine developed by Pfizer-BioNTech and the mRNA-1273 vaccine developed by Moderna suggests that these vaccines do not release significant amounts, if any, of mRNA into breast milk. Hence, there is no evidence that vaccination of the mother poses any risk to the breastfed infant, while the antibodies present in breast milk may offer protection against the virus. The primary objective of this systematic review is to summarize the current understanding of the presence of immunoglobulins in human milk that are elicited by SARS-CoV-2 vaccines and to evaluate their ability to neutralize the virus. Additionally, we aim to quantify the side effects experienced by lactating mothers who have been vaccinated, as well as the potential for adverse effects in their infants. This study is critical because it can help inform decision-making by examining the current understanding of antibody secretion in breastmilk. This is particularly important because, although the virus tends to be less severe in younger individuals, infants who contract the disease are at a higher risk of requiring hospitalization compared to older children.

Alterations in Circulating miRNA Levels after Infection with SARS-CoV-2 Could Contribute to the Development of Cardiovascular Diseases: What We Know So Far.

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses significant complications for cardiovascular disease (CVD) patients. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and influence several physiological and pathological processes, including CVD. This critical review aims to expand upon the current literature concerning miRNA deregulation during the SARS-CoV-2 infection, focusing on cardio-specific miRNAs and their association with various CVDs, including cardiac remodeling, arrhythmias, and atherosclerosis after SARS-CoV-2 infection. Despite the scarcity of research in this area, our findings suggest that changes in the expression levels of particular COVID-19-related miRNAs, including miR-146a, miR-27/miR-27a-5p, miR-451, miR-486-5p, miR-21, miR-155, and miR-133a, may be linked to CVDs. While our analysis did not conclusively determine the impact of SARS-CoV-2 infection on the profile and/or expression levels of cardiac-specific miRNAs, we proposed a potential mechanism by which the miRNAs mentioned above may contribute to the development of these two pathologies. Further research on the relationship between SARS-CoV-2, CVDs, and microRNAs will significantly enhance our understanding of this connection and may lead to the use of these miRNAs as biomarkers or therapeutic targets for both pathologies.

SARS-CoV-2 and HIV-1: So Different yet so Alike. Immune Response at the Cellular and Molecular Level.

In the past half century, humanity has experienced two devastating pandemics; the HIV-1 pandemic and the recent pandemic caused by SARS-CoV-2. Both emerged as zoonotic pathogens. Interestingly, SARS-CoV-2 has rapidly migrated all over the world in less than two years, much as HIV-1 did almost 40 years ago. Despite these two RNA viruses being different in their mode of transmission as well as the symptoms they generate, recent evidence suggests that they cause similar immune responses. In this mini review, we compare the molecular basis for CD4+ T cell lymphopenia and other effects on the immune system induced by SARS-CoV-2 and HIV-1 infections. We considered features of the host immune response that are shared with HIV-1 and could account for the lymphopenia and other immune effects observed in COVID-19. The information provided herein, may cast the virus-induced lymphopenia and cytokine storm associated with the acute SARS-CoV-2 infection and pathogenesis in a different light for further research on host immune responses. It can also provide opportunities for the identification of novel therapeutic targets for COVID-19. Furthermore, we provide some basic information to enable a comparative framework for considering the overlapping sets of immune responses caused by HIV-1 and SARS-CoV-2.

Detection and characterisation of novel alternative splicing variants of the mitochondrial folate enzyme MTHFD2.

Through the process of alternative splicing, proteins with distinct biological functions and localisations are generated from a single gene. The mitochondrial folate metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) has been receiving attention in recent years as one of the most frequently upregulated metabolic enzymes across multiple tumour types. We hypothesized that alternative splicing of MTHFD2 could be a mechanism that generates novel isoforms of this enzyme, with potentially distinct and important biological functions. Multiple alternatively spliced MTHFD2 transcripts were first characterized in the UCSC and Ensemble genome browser. Subsequently, investigating the transcriptomic data for the Genotype-Tissue Expression (GTeX) project it was found that beyond the canonical MTHFD2 transcript, alternative transcripts lacking the second exon of MTHFD2 are also common. The presence of MTHFD2 transcripts lacking the second exon was confirmed by RT-PCR in normal and cancer cells. Translation of MTHFD2 transcripts lacking this second exon are predicted to generate a truncated protein lacking the first 102 N-terminal amino acids of the full-length protein, including the mitochondrial transport sequence. Hence, the truncated MTHFD2 protein could be an isoform with distinct localisation and functions. However, we were not able to confirm the generation of a stable truncated MTHFD2 protein in eukaryotic cells. This study characterizes for the first time alternative spliced transcripts of the enzyme MTHFD2, although further work is required to investigate their biological significance.

Application of transcriptomic and microRNA profiling in the evaluation of potential liver carcinogens.

Hepatocarcinogens are agents that increase the incidence of liver cancer in exposed animals or humans. It is now established that carcinogenic exposures have a widespread impact on the transcriptome, inducing both adaptive and adverse changes in the activities of genes and pathways. Chemical hepatocarcinogens have also been shown to affect expression of microRNA (miRNA), the evolutionarily conserved noncoding RNA that regulates gene expression posttranscriptionally. Considerable effort has been invested into examining the involvement of mRNA in chemical hepatocarcinogenesis and their potential usage for the classification and prediction of new chemical entities. For miRNA, there has been an increasing number of studies reported over the past decade, although not to the same degree as for transcriptomic studies. Current data suggest that it is unlikely that any gene or miRNA signature associated with short-term carcinogen exposure can replace the rodent bioassay. In this review, we discuss the application of transcriptomic and miRNA profiles to increase mechanistic understanding of chemical carcinogens and to aid in their classification.

Transforming a cookbook undergraduate microbiology laboratory to inquiry based using a semester-long PBL case study.

Microbial physiology is a basic course taught throughout biomedical science disciplines. Students study the structure, growth, and metabolism of microorganisms and often find it difficult to learn the information, usually because they fail to see the wider applications. The current microbiology laboratory series describes how to transform a "cookbook" undergraduate laboratory to an inquiry-based one by incorporating problem-based learning. The students use a food poisoning case study that develops over a series of seven experiments and take on the role of the microbiology technician who is responsible for coming up with the answer and submitting a report to a clinician. The case provides coherence to the sessions, and the students are given the opportunity to learn about, and practice, common techniques they would encounter in a clinical microbiology laboratory. Those include the aseptic method, cultivation of bacteria, quantification of bacteria in culture, isolation of pure culture, morphological observation by light microscopy, Gram staining, the use of selective and differential media, and the effectiveness of a variety of antimicrobials and antibiotics. This laboratory series has been designed so that it can be implemented in any setting, using simple materials and inexpensive, nonspecialized equipment. The experiments are carried out in small groups, and a facilitator may tutor up to two groups of 10 students at a time. The current method has been successfully implemented for the past 2 yr, and the students demonstrated greater motivation in learning and understanding.

Unraveling the signaling pathways promoting fibrosis in Dupuytren's disease reveals TNF as a therapeutic target.

Dupuytren's disease is a very common progressive fibrosis of the palm leading to flexion deformities of the digits that impair hand function. The cell responsible for development of the disease is the myofibroblast. There is currently no treatment for early disease or for preventing recurrence following surgical excision of affected tissue in advanced disease. Therefore, we sought to unravel the signaling pathways leading to the development of myofibroblasts in Dupuytren's disease. We characterized the cells present in Dupuytren's tissue and found significant numbers of immune cells, including classically activated macrophages. High levels of proinflammatory cytokines were also detected in tissue from Dupuytren's patients. We compared the effects of these cytokines on contraction and profibrotic signaling pathways in fibroblasts from the palmar and nonpalmar dermis of Dupuytren's patients and palmar fibroblasts from non-Dupuytren's patients. Exogenous addition of TNF, but not other cytokines, including IL-6 and IL-1ß, promoted differentiation into specifically of palmar dermal fibroblasts from Dupuytren's patients in to myofibroblasts. We also demonstrated that TNF acts via the Wnt signaling pathway to drive contraction and profibrotic signaling in these cells. Finally, we examined the effects of targeted cytokine inhibition. Neutralizing antibodies to TNF inhibited the contractile activity of myofibroblasts derived from Dupuytren's patients, reduced their expression of α-smooth muscle actin, and mediated disassembly of the contractile apparatus. Therefore, we showed that localized inflammation in Dupuytren's disease contributes to the development and progression of this fibroproliferative disorder and identified TNF as a therapeutic target to down-regulate myofibroblast differentiation and activity.

Calreticulin mutations in myeloproliferative neoplasms and new methodology for their detection and monitoring.

The diagnosis of the BCR-ABL-negative myeloproliferative neoplasms (MPN), namely polycythemia vera, essential thombocythemia and primary myelofibrosis has relied significantly on the detection of known causative mutations in the JAK2 or MPL genes, which account for the majority of MPN patients. However, around 30 % of patients with MPN, primarily essential thombocythemia and primary myelofibrosis, lack mutations in these two genes making it difficult to reach a confident diagnosis in these cases. The recent discovery of frameshift mutations in CALR in approximately 70 % of MPN patients lacking the JAK2 and MPL mutations offers a reliable diagnostic marker for the latter group. A review of the current literature, plus unpublished data from our laboratory, shows that 55 different CALR insertion/deletion mutations have been identified so far in MPN patients. Among these 55 variants reported to date, a 52-base pair deletion and a 5-base pair insertion are by far the most prominent representing 50 and 35 %, respectively, of all cases with CALR mutations. In this paper, we describe a high-resolution melting (HRM) analysis and a Taqman® Real-Time PCR (RQ-PCR) assay and we propose a new clinical laboratory diagnostic algorithm for CALR mutation analysis. According to this algorithm, samples can go through front-line screening with HMR or fragment analysis, followed by the newly developed RQ-PCR to both discriminate and quantify the two most common mutations in CALR gene.

Cells of the immune system orchestrate changes in bone cell function.

There is a complex interplay between the cells of the immune system and bone. Immune cells, such as T and NK cells, are able to enhance osteoclast formation via the production of RANKL. Yet there is increasing evidence to show that during the resolution of inflammation or as a consequence of increased osteoclastogenesis there is an anabolic response via the formation of more osteoblasts. Furthermore, osteoblasts themselves are involved in the control of immune cell function, thus promoting the resolution of inflammation. Hence, the concept of "coupling"-how bone formation is linked to resorption-needs to be more inclusive rather than restricting our focus to osteoblast-osteoclast interactions as in a whole organism these cells are never in isolation. This review will investigate the role of immune cells in normal bone homeostasis and in inflammatory diseases where the balance between resorption and formation is lost.

Short-Chained Linear Scorpion Peptides: A Pool for Novel Antimicrobials.

Scorpion venom peptides are generally classified into two main groups: the disulfide bridged peptides (DBPs), which usually target membrane-associated ion channels, and the non-disulfide bridged peptides (NDBPs), a smaller group with multifunctional properties. In the past decade, these peptides have gained interest because most of them display functions that include antimicrobial, anticancer, haemolytic, and anti-inflammatory activities. Our current study focuses on the short (9-19 amino acids) antimicrobial linear scorpion peptides. Most of these peptides display a net positive charge of 1 or 2, an isoelectric point at pH 9-10, a broad range of hydrophobicity, and a Grand Average of Hydropathy (GRAVY) Value ranging between -0.05 and 1.7. These features allow these peptides to be attracted toward the negatively charged phospholipid head groups of the lipid membranes of target cells, a force driven by electrostatic interactions. This review outlines the antimicrobial potential of short-chained linear scorpion venom peptides. Additionally, short linear scorpion peptides are in general more attractive for large-scale synthesis from a manufacturing point of view. The structural and functional diversity of these peptides represents a good starting point for the development of new peptide-based therapeutics.

Special Issue: The Impact of Early Life Nutrition on Gut Maturation and Later Life Gut Health.

Nutrition during early life plays a crucial role in determining a child's long-term health [...].

Targeting Lactate Dehydrogenase-B as a Strategy to Fight Cancer: Identification of Potential Inhibitors by In Silico Analysis and In Vitro Screening.

Lactate dehydrogenase (LDH) is an enzyme that catalyzes the reversible conversion of lactate to pyruvate while reducing NAD+ to NADH (or oxidizing NADH to NAD+). Due to its central role in the Warburg effect, LDH-A isoform has been considered a promising target for treating several types of cancer. However, research on inhibitors targeting LDH-B isoform is still limited, despite the enzyme's implication in the development of specific cancer types such as breast and lung cancer. This study aimed to identify small-molecule compounds that specifically inhibit LDH-B. Our in silico analysis identified eight commercially available compounds that may affect LDH-B activity. The best five candidates, namely tucatinib, capmatinib, moxidectin, rifampicin, and acetyldigoxin, were evaluated further in vitro. Our results revealed that two compounds, viz., tucatinib and capmatinib, currently used for treating breast and lung cancer, respectively, could also act as inhibitors of LDH-B. Both compounds inhibited LDH-B activity through an uncompetitive mechanism, as observed in in vitro experiments. Molecular dynamics studies further support these findings. Together, our results suggest that two known drugs currently being used to treat specific cancer types may have a dual effect and target more than one enzyme that facilitates the development of these types of cancers. Furthermore, the results of this study could be used as a new starting point for identifying more potent and specific LDH-B inhibitors.

Survival of Vaccine-Induced Human Milk SARS-CoV-2 IgG, IgA and SIgA Immunoglobulins across Simulated Human Infant Gastrointestinal Digestion.

Breastfeeding can be a vital way of acquiring passive immunity via the transfer of antibodies from the mother to the breastfeeding infant. Recent evidence points to the fact that human milk contains immunoglobulins (Ig) against the SARS-CoV-2 virus, either after natural infection or vaccination, but whether these antibodies can resist enzymatic degradation during digestion in the infant gastrointestinal (GI) tract or indeed protect the consumers remains inconclusive. Herein, we evaluated the levels of IgG, IgA, and secretory IgA (SIgA) antibodies against the spike protein of SARS-CoV-2 in 43 lactating mothers who received at least two doses of either an mRNA-based vaccine (Pfizer/BioNTech, Moderna; n = 34) or an adenovirus-based vaccine (AstraZeneca; n = 9). We also accessed the potential persistence of SARS-CoV-2 IgA, IgG, and secretory IgA (SIgA) antibodies from vaccinated women in the GI tract of the infants by means of a static in vitro digestion protocol. Our data depict that, although slightly reduced, the IgA antibodies produced after vaccination resist both the gastric and intestinal phases of infant digestion, whereas the IgGs are more prone to degradation in both phases of digestion. Additionally, SIgA antibodies were found to greatly resist the gastric phase of digestion albeit showing some reduction during the intestinal phase. The evaluation of the vaccine induced Ig profile of breastmilk, and the extent to which these antibodies can resist digestion in the infant GI tract provide important information about the potential protective role of this form of passive immunity that could help decision making during the COVID-19 pandemic and beyond.

Seroprevalence of immunoglobulin G antibodies against SARS-CoV-2 in Cyprus.

Monitoring the levels of IgG antibodies against the SARS-CoV-2 is important during the coronavirus disease 2019 (COVID-19) pandemic, to plan an adequate and evidence-based public health response. After this study we report that the plasma levels of IgG antibodies against SARS-CoV-2 spike protein were higher in individuals with evidence of prior infection who received at least one dose of either an mRNA-based vaccine (Comirnaty BNT162b2/Pfizer-BioNTech or Spikevax mRNA-1273/Moderna) or an adenoviral-based vaccine (Vaxzervia ChAdOx1 nCoV-19 /Oxford-Astra Zeneca) (n = 39) compared to i) unvaccinated individuals with evidence of prior infection with SARS-CoV-2 (n = 109) and ii) individuals without evidence of prior infection with SARS-CoV-2 who received one or two doses of one of the aforementioned vaccines (n = 342). Our analysis also revealed that regardless of the vaccine technology (mRNA-based and adenoviral vector-based) two doses achieved high anti- SARS-CoV-2 IgG responses. Our results indicate that vaccine-induced responses lead to higher levels of IgG antibodies compared to those produced following infection with the virus. Additionally, in agreement with previous studies, our results suggest that among individuals previously infected with SARS-CoV-2, even a single dose of a vaccine is adequate to elicit high levels of antibody response.

Elucidation of binding sites of dual antagonists in the human chemokine receptors CCR2 and CCR5.

Design of dual antagonists for the chemokine receptors CCR2 and CCR5 will be greatly facilitated by knowledge of the structural differences of their binding sites. Thus, we computationally predicted the binding site of the dual CCR2/CCR5 antagonist N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzohepten-8-yl] carbonyl]amino]benzyl]tetrahydro-2H-pyran-4-aminium (TAK-779), and a CCR2-specific antagonist N-(carbamoylmethyl)-3-trifluoromethyl benzamido-parachlorobenzyl 3-aminopyrrolidine (Teijin compound 1) in an ensemble of predicted structures of human CCR2 and CCR5. Based on our predictions of the protein-ligand interactions, we examined the activity of the antagonists for cells expressing thirteen mutants of CCR2 and five mutants of CCR5. The results show that residues Trp98(2.60) and Thr292(7.40) contribute significantly to the efficacy of both TAK-779 and Teijin compound 1, whereas His121(3.33) and Ile263(6.55) contribute significantly only to the antagonistic effect of Teijin compound 1 at CCR2. Mutation of residues Trp86(2.60) and Tyr108(3.32) adversely affected the efficacy of TAK-779 in antagonizing CCR5-mediated chemotaxis. Y49A(1.39) and E291A(7.39) mutants of CCR2 showed a complete loss of CCL2 binding and chemotaxis, despite robust cell surface expression, suggesting that these residues are critical in maintaining the correct receptor architecture. Modeling studies support the hypothesis that the residues Tyr49(1.39), Trp98(2.60), Tyr120(3.32), and Glu291(7.39) of CCR2 form a tight network of aromatic cluster and polar contacts between transmembrane helices 1, 2, 3, and 7.

Combined effect of glutamine at position 70 of HLA-DRB1 and alanine at position 57 of HLA-DQB1 in type 1 diabetes: An epitope analysis.

The contribution of specific HLA Class II alleles in type 1 diabetes is determined by polymorphic amino acid epitopes that direct antigen binding therefore, along with conventional allele frequency analysis, epitope analysis can provide important insights into disease susceptibility. We analyzed the highly heterogeneous Cypriot population for the HLA class II loci of T1DM patients and controls and we report for the first time their allele frequencies. Within our patient cohort we identified a subgroup that did not carry the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04:xx-DQA1*03:01-DQB1*03:02 risk haplotypes but a novel recombinant one, DRB1*04:XX-DQA1*03:01-DQB1*02:01 designated DR4-DQ2.3. Through epitope analysis we identified established susceptibility (DQB1 A57, DRB1 H13) and resistance (DQB1 D57) residues as well as other novel susceptibility residues DRB1 Q70, DQB1 L26 and resistance residues DRB1 D70, R70 and DQB1 Y47. Prevalence of susceptibility epitopes was higher in patients and was not exclusively a result of linkage disequilibrium. Residues DRB1 Q70, DQB1 L26 and A57 and a 10 amino acid epitope of DQA1 were the most significant in discriminating risk alleles. An extended haplotype containing these epitopes was carried by 92% of our patient cohort. Sharing of susceptibility epitopes could also explain the absence of risk haplotypes in patients. Finally, many significantly associated epitopes were non-pocket residues suggesting that critical immune functions may exist spanning further from the binding pockets.

MicroRNA responses to environmental liver carcinogens: Biological and clinical significance.

A large number of biological, chemical, and dietary factors have been implicated in the development of liver cancer. These involve complex and protracted interactions between genetic, epigenetic, and environmental factors. The survival rate for patients diagnosed with late-stage liver cancer is currently low due to the aggressive nature of the disease and resistance to therapy. An increasing body of evidence has offered support for the crucial role of non-coding microRNA (miRNA) in directing hepatic responses to environmental risk factors for liver cancer. In this review we focus on miRNA responses to environmental liver cancer risk factors and their potential biological and clinical significance.

Isometric contraction of Dupuytren's myofibroblasts is inhibited by blocking intercellular junctions.

Myofibroblasts (MFs) are responsible for both physiological wound and scar contraction. However, it is not known whether these cells act individually to contract the surrounding matrix or whether they behave in a coordinated manner. Therefore, we studied intercellular junctions of primary human MFs derived from patients with Dupuytren's disease, a fibrotic disorder of the dermis and subdermal tissues of the palm. The cells were maintained in anchored three-dimensional collagen lattices to closely mimic conditions in vivo. We found that selective blockade of adherens, mechanosensitive, or gap junctions effectively inhibited contraction of the collagen matrices and downregulated the MF phenotype. Our data indicate that MFs in part function as a coordinated cellular syncytium, and disruption of intercellular communication may provide a therapeutic target in diseases characterized by an overabundance of these contractile cells.