Current Molecular Evidence Research Articles

Insights into the phylogenetic relationships and species boundaries of the Myricaria squamosa complex (Tamaricaceae) based on the complete chloroplast genome

Myricaria plants are widely distributed in Eurasia and are helpful for windbreak and embankment protection. Current molecular evidence has led to controversy regarding species boundaries within the Myricaria genus and interspecific phylogenetic relationships between three specific species—M. bracteata, M. paniculata and M. squamosa—which have remained unresolved. This study treated these three unresolved taxa as a species complex, named the M. squamosa complex. The genome skimming approach was used to determine 35 complete plastome sequences and nuclear ribosomal DNA sequences for the said complex and other closely related species, followed by de novo assembly. Comparative analyses were conducted across Myricaria to identify the genome size, gene content, repeat type and number, SSR (simple sequence repeat) abundance, and codon usage bias of chloroplast genomes. Tree-based species delimitation results indicated that M. bracteata, M. paniculata and M. squamosa could not be distinguished and formed two monophyletic lineages (P1 and P2) that were clustered together. Compared to plastome-based species delimitation, the standard nuclear DNA barcode had the lowest species resolution, and the standard chloroplast DNA barcode and group-specific barcodes delimitated a maximum of four out of the five species. Plastid phylogenomics analyses indicated that the monophyletic M. squamosa complex is comprised of two evolutionarily significant units: one in the western Tarim Basin and the other in the eastern Qinghai-Tibet Plateau. This finding contradicts previous species discrimination and promotes the urgent need for taxonomic revision of the threatened genus Myricaria. Dense sampling and plastid genomes will be essential in this effort. The super-barcodes and specific barcode candidates outlined in this study will aid in further studies of evolutionary history.

The molecular and clinical role of Tensin 1/2/3 in cancer.

Tensin 1 was originally described as a focal adhesion adaptor protein, playing a role in extracellular matrix and cytoskeletal interactions. Three other Tensin proteins were subsequently discovered, and the family was grouped as Tensin. It is now recognized that these proteins interact with multiple cell signalling cascades that are implicated in tumorigenesis. To understand the role of Tensin 1-3 in neoplasia, current molecular evidence is categorized by the hallmarks of cancer model. Additionally, clinical data involving Tensin 1-3 are reviewed to investigate the correlation between cellular effects and clinical phenotype. Tensin proteins commonly interact with the tumour suppressor, DLC1. The ability of Tensin to promote tumour progression is directly correlated with DLC1 expression. Members of the Tensin family appear to have tumour subtype-dependent effects on oncogenesis; despite numerous data evidencing a tumour suppressor role for Tensin 2, association of Tensins 1-3 with an oncogenic role notably in colorectal carcinoma and pancreatic ductal adenocarcinoma is of potential clinical relevance. The complex interplay between these focal adhesion adaptor proteins and signalling pathways are discussed to provide an up to date review of their role in cancer biology.

Evaluating Current Molecular Techniques and Evidence in Assessing Microbiome in Placenta-Related Health and Disorders in Pregnancy

The microbiome is of great interest due to its potential influence on the occurrence and treatment of some human illnesses. It may be regarded as disruptions to the delicate equilibrium that humans ordinarily maintain with their microorganisms or the microbiota in their environment. The focus of this review is on the methodologies and current understanding of the functional microbiome in pregnancy outcomes. We present how novel techniques bring new insights to the contemporary field of maternal–fetal medicine with a critical analysis. The maternal microbiome in late pregnancy has been extensively studied, although data on maternal microbial changes during the first trimester are rare. Research has demonstrated that, in healthy pregnancies, the origin of the placental microbiota is oral (gut) rather than vaginal. Implantation, placental development, and maternal adaptation to pregnancy are complex processes in which fetal and maternal cells interact. Microbiome dysbiosis or microbial metabolites are rising as potential moderators of antenatal illnesses related to the placenta, such as fetal growth restriction, preeclampsia, and others, including gestational diabetes and preterm deliveries. However, because of the presence of antimicrobial components, it is likely that the bacteria identified in placental tissue are (fragments of) bacteria that have been destroyed by the placenta’s immune cells. Using genomic techniques (metagenomics, metatranscriptomics, and metaproteomics), it may be possible to predict some properties of a microorganism’s genome and the biochemical (epigenetic DNA modification) and physical components of the placenta as its environment. Despite the results described in this review, this subject needs further research on some major and crucial aspects. The phases of an in utero translocation of the maternal gut microbiota to the fetus should be explored. With a predictive knowledge of the impacts of the disturbance on microbial communities that influence human health and the environment, genomics may hold the answer to the development of novel therapies for the health of pregnant women.

Complete Chloroplast Genomes of 14 Subspecies of D. glomerata: Phylogenetic and Comparative Genomic Analyses.

Orchardgrass (Dactylis glomerata L.) is a species in the Gramineae family that is highly important economically and valued for its role in ecology. However, the phylogeny and taxonomy of D. glomerata are still controversial based on current morphological and molecular evidence. The study of chloroplast (cp) genomes has developed into a powerful tool to develop molecular markers for related species and reveal the relationships between plant evolution and phylogenetics. In this study, we conducted comparative genomic analyses and phylogenetic inferences on 14 cp genomes of D. glomerata originating from the Mediterranean and Eurasia. The genome size ranged from 134,375 bp to 134,993 bp and exhibited synteny of gene organization and order. A total of 129–131 genes were identified, including 85–87 protein coding genes, 38 tRNA genes and 8 rRNA genes. The cp sequences were highly conserved, and key sequence variations were detected at the junctions of inverted repeats (IRs)/small single–copy (SSC) regions. Moreover, nine highly variable regions were identified among the subspecies based on a sequence divergence analysis. A total of 285 RNA editing sites were detected that were relevant to 52 genes, where rpoB exhibited the most abundant RNA editing sites. The phylogenetic analysis revealed that all Dactylis subspecies clustered into a monophyletic group and most branches provided a high support bootstrap. The main divergence time of D. glomerata was dated to the Miocene era, and this could have been due to changes in the climate. These findings will provide useful insights for further studies on phylogeny, the identification of subspecies and the development of hypotheses for the evolutionary history of the genus Dactylis and of the Gramineae family.

Phylum Nematoda: a classification, catalogue and index of valid genera, with a census of valid species.

A classification of the entire Phylum Nematoda is presented, based on current molecular, developmental and morphological evidence. The classification reflects the evolutionary relationships within the phylum, as well as significant areas of uncertainty, particularly related to the early evolution of nematodes. It includes 3 classes, 8 subclasses, 12 superorders, 32 orders, 53 suborders, 101 superfamilies, 276 families, 511 subfamilies, 3030 genera, and 28537 species. All valid species named from the time of publication of the previous classification and census (2010) to the end of 2019 are listed, along with the number of valid species in each genus. Taxonomic authorities are provided for taxon names of all ranks. The habitats where the species in each genus are found are listed, and an alphabetic index of genus names is provided. The systematics of nematodes is reviewed, along with a history of nematode classification; evolutionary affinities and origins of nematodes; and the current diagnosis of the group. Short overviews of the general biology, ecology, scientific and economic importance of the group are presented.

Update on the molecular landscape of thoracic aortic aneurysmal disease.

Thoracic aortic aneurysms and dissections (TAADs) are a major health problem in the Western population. This review summarises recent discoveries in the genetic landscape of TAAD disease, discusses current challenges in clinical practice, and describes the molecular road ahead in TAAD research. Disorders, in which aneurysmal disease is not observed in the thoracic aorta, are not discussed. Current gene discovery studies have pinpointed about 40 genes associated with TAAD risk, accounting for about 30% of the patients. Importantly, novel genes, and their subsequent functional characterisation, have expanded the knowledge on disease-related pathways providing crucial information on key elements in this disease, and it pinpoints new therapeutic targets. Moreover, current molecular evidence also suggests the existence of less monogenic nature of TAAD disease, in which the presentation of a diseased patient is most likely influenced by a multitude of genetic and environmental factors. Ongoing molecular genetic research continues to expand our understanding on the pathomechanisms underlying TAAD disease in order to improve molecular diagnosis, optimise risk stratification, advance therapeutic strategies and facilitate counselling of TAAD patients and their families.

Complete chloroplast genomes of Leptodermis scabrida complex: Comparative genomic analyses and phylogenetic relationships.

Leptodermis scabrida complex is one of the important components of genus Leptodermis, which is mainly distributed in the Himalaya Mountains. It includes species of L. gracilis, L. hirsutiflora, L. hirsutiflora var. ciliata, L. kumaonensis, L. pilosa var. acanthoclada and L. scabrida. However, species boundaries and relationships within this complex are unclear based on current morphological and molecular evidence. We sequenced 13 complete chloroplast (cp) genomes representing seven taxa of the complex and two non-Leptodermis scabrida complex taxa. After de novo assembly and annotation, we performed comparative genomic analysis. All cp genomes showed highly conserved structures, and the genome sizes ranged from 154,369bp to 154,885bp and possessed the same GC content (37.5%). A total of 113 unique genes were identified in each cp sample, including 79 protein coding genes, 30 tRNAs, and four rRNAs. Repeat sequences and SSRs were detected, showing great similarity among all taxa in this complex. Six highly variable regions, including trnS-trnG, rps2-rpoC2, ndhF, rpl32-ccsA, ccsA-ndhD, and ndhA, were screened as potential molecular markers for phylogenetic reconstruction. Based on a total of 27 complete cp genome sequences, the consistent and robust phylogenetic relationships were firstly constructed and the same species within L. scabrida complex clustered into a group. The divergence time of Leptodermis from ancestral taxa occurred at the middle Eocene, which might be due to geological and climatic changes. The 13 complete cp genome sequences reported will provide new clues for phylogeny elucidation, species identification and evolutionary history speculation of Leptodermis, as well as in Rubiaceae.

Torquenema n. g., Wallabicola n. g., and Macropostrongyloides phascolomys n. sp.: New Genera and a New Species of Nematode (Strongylida: Phascolostrongylinae) Parasitic in Australian Macropodid and Vombatid Marsupials

Simple SummaryThis article describes two new genera of parasitic nematodes, Torquenema n. g. from the eastern grey kangaroo and Wallabicola n. g. from the swamp wallaby, and a new species, Macropostrongyloides phascolomys n. sp. from the caecum of the common wombat. The strongyloid nematodes belonging to the subfamily Phascolostrongylinae occur primarily in the large intestines of macropodid and vombatid marsupials. Current molecular evidence suggests that the two nematode species, Macropostrongyloides dissimilis and Paramacropostrongylus toraliformis, from macropodid marsupials are distant from their respective congeners. Furthermore, specimens of Macropostrongyloides lasiorhini from the large intestines of the southern hairy-nosed wombat (Lasiorhinus latifrons) and the common wombat (Vombatus ursinus) are genetically distinct. This study aimed to describe the new genera Torquenema n. g. (with T. toraliforme n. comb. as the type species) from the eastern grey kangaroo, Wallabicola n. g. (with W. dissimilis n. comb. as the type species) from the swamp wallaby and a new species Macropostrongyloides phascolomys n. sp. from the common wombat, using light and scanning electron microscopy.

Is Trichomonas vaginalis a Risk Factor for Prostate Cancer? A Systematic Review and Meta-analysis

Clinical studies have shown that patients exposed to the protozoan Trichomonas vaginalis (TV) may present an increased risk to develop prostate cancer (PCa). However, since data from other studies and meta-analyses did not provide so far univocal results this issue remains controversial. In this systematic review, we examined the current molecular, cellular and clinical evidence in favor or against a possible association between TV prostatitis and the incidence of PCa. Electronic database search, title/abstract screening and full-text reading yielded a total of 17 clinical articles and meta-analyses and 12 articles showing the results of preclinical investigations. Preclinical evidence points to the involvement of TV in proliferative disorders in prostate cells, involving an array of immune cell mediators. Five clinical case-control studies documented a significantly increased odds for PCa in patients with a positive TV serostatus, whereas seven other studies showed nonsignificant results. Our meta-analysis including 12 studies retrieved up to June 1, 2021, did not evidence a significant association between a positive TV serostatus and PCa of any grade (odds ratio [OR], 1.14; 95% confidence interval [CI]: 0.84–1.53). Moreover, we could not find a significant association between advanced/lethal PCa and TV exposure (OR, 1.18; 95% CI: 0.70–2.00). In conclusion, the association between a positive TV serostatus and PCa remains uncertain. Studies focused on a large sample of documented cases of symptomatic, clinical TV chronic prostatitis are warranted to make a conclusive statement in this regard.

Chromosome 14 deletions, rings, and epilepsy genes: A riddle wrapped in a mystery inside an enigma.

The ring 14 syndrome is a rare condition caused by the rearrangement of one chromosome 14 into a ring-like structure. The formation of the ring requires two breakpoints and loss of material from the short and long arms of the chromosome. Like many other chromosome syndromes, it is characterized by multiple congenital anomalies and developmental delays. Typical of the condition are retinal anomalies and drug-resistant epilepsy. These latter manifestations are not found in individuals who are carriers of comparable 14q deletions without formation of a ring (linear deletions). To find an explanation for this apparent discrepancy and gain insight into the mechanisms leading to seizures, we reviewed and compared literature cases of both ring and linear deletion syndrome with respect to both their clinical manifestations and the role and function of potentially epileptogenic genes. Knowledge of the epilepsy-related genes in chromosome 14 is an important premise for the search of new and effective drugs to combat seizures. Current clinical and molecular evidence is not sufficient to explain the known discrepancies between ring and linear deletions.

Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms

Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms

Pre-eclamptic Fetal Programming Alters Neuroinflammatory and Cardiovascular Consequences of Endotoxemia in Sex-Specific Manners.

Pre-eclampsia (PE)-induced fetal programming predisposes offspring to health hazards in adult life. Here, we tested the hypothesis that pre-eclamptic fetal programming elicits sexually dimorphic inflammatory and cardiovascular complications to endotoxemia in adult rat offspring. PE was induced by oral administration of L-NAME (50 mg/kg per day for seven consecutive days) starting from day 14 of conception. Cardiovascular studies were performed in conscious adult male and female offspring preinstrumented with femoral indwelling catheters. Compared with non-PE male counterparts, intravenous administration of lipopolysaccharide (LPS, 5 mg/kg) to PE male offspring caused significantly greater 1) falls in blood pressure, 2) increases in heart rate, 3) rises in arterial dP/dtmax, a correlate of left ventricular contractility, and 4) decreases in time- and frequency-domain indices of heart rate variability (HRV). By contrast, the hypotensive and tachycardic actions of LPS in female offspring were independent of the pre-eclamptic state and no clear changes in HRV or dP/dtmax were noted. Measurement of arterial baroreflex activity by vasoactive method revealed no sex specificity in baroreflex dysfunction induced by LPS. Immunohistochemical studies showed increased protein expression of toll-like receptor 4 in heart as well as in brainstem neuronal pools of the nucleus of solitary tract and rostral ventrolateral medulla in endotoxic PE male, but not female, offspring. Enhanced myocardial, but not neuronal, expression of monocyte chemoattractant protein-1 was also demonstrated in LPS-treated male offspring. Together, pre-eclamptic fetal programming aggravates endotoxic manifestations of hypotension and autonomic dysfunction in male offspring via exacerbating myocardial and neuromedullary inflammatory pathways. SIGNIFICANCE STATEMENT: Current molecular and neuroanatomical evidence highlights a key role for pre-eclamptic fetal programming in offspring predisposition to health hazards induced by endotoxemia in adult life. Pre-eclampsia accentuates endotoxic manifestations of hypotension, tachycardia, and cardiac autonomic dysfunction in male offspring via exacerbating myocardial and central inflammatory pathways. The absence of such detrimental effects in female littermates suggests sexual dimorphism in the interaction of pre-eclamptic fetal programming with endotoxemia.

Physical exercise: bulking up neurogenesis in human adults

Whether neurogenesis occurs in the adult human brain has been a long-debated topic fueled by conflicting data both for and against neurogenesis in the mature brain. Recent reports from two independent teams may have indubitably proven that adult, hippocampal neurogenesis persists throughout the human lifespan. Llorens-Martín et al. found that thousands of immature, neurogenesis related, doublecortin-positive (DCX+) labelled neurons can be detected in the human dentate gyrus (DG) up to the eighth decade of life. While the presence of these DCX+ neurons decrease with age, they are significantly decrease in patient with Alzheimer’s disease. Another group have also found mammalian embryonic Hopx+ precursors to persist beyond the early development stage as quiescent Hopx+ radial glial-like neural progenitors during early postnatal period, then as Hopx+ adult dentate neural progenitors. Together, the findings from these two groups suggest that unlike the previously thought, neurogenesis and neuroplasticity can occur well into adulthood in some capacity, at least in the hippocampus. These recent findings that neurogenesis can occur beyond development have brought into questions whether physical exercise can be shown to promote neurogenesis and brain health, as it has been shown to promote the function of other organ systems. Some data has already shown physical exercise to induce adult hippocampal neurogenesis (AHN) as demonstrated by restoration of cognitive functions, improvement of synaptic plasticity, and enhancement of angiogenesis. A large-scale meta-analysis has also demonstrated that 45–60 min of moderate-intensity physical exercise to dramatically improve cognitive functions in human subjects over the age of 50. Given these convergent developments in our understanding of neurogenesis and exercise induced improvement in cognitive function, we speculate that hippocampal neurogenesis can be promoted by physical exercise and discuss the current molecular evidence supporting the likely molecular pathways involved.

Engineering tissue-specific blood vessels.

Vascular diversity among organs has recently become widely recognized. Several studies using mouse and human fetal tissues revealed distinct characteristics of organ‐specific vasculature in molecular and functional levels. Thorough understanding of vascular heterogeneities in human adult tissues is significant for developing novel strategies for targeted drug delivery and tissue regeneration. Recent advancements in microfabrication techniques, biomaterials, and differentiation protocols allowed for incorporation of microvasculature into engineered organs. Such vascularized organ models represent physiologically relevant platforms that may offer innovative tools for dissecting the effects of the organ microenvironment on vascular development and expand our present knowledge on organ‐specific human vasculature. In this article, we provide an overview of the current structural and molecular evidence on microvascular diversity, bioengineering methods used to recapitulate the microenvironmental cues, and recent vascularized three‐dimensional organ models from the perspective of tissue‐specific vasculature.

Climatic niche comparison across a cryptic species complex.

According to current molecular evidence, the Chionaspis pinifoliae heterophyllae species complex has been recognized as 10 cryptic species. In this study, we construct potential distribution maps for seven cryptic species based on climatic variables. This was done to assess the main environmental factors that have contributed to the distribution map and test the degree of niche overlap across the seven cryptic species. We used MaxEnt to build the climatic niche models under climatic variables. For these models, the similarities and differences of the niches across the cryptic species were estimated. By comparing the potential distribution model of each cryptic species, our results suggested parapatric, sympatric and allopatry populations for this cryptic species complex. Our results showed high variability in niche overlap, and more often niche conservatism than niche divergence. The current species delimitation of the Chionaspis pinifoliae heterophyllae complex by molecular information and the hypothesis that the niche overlap in the sympatric population is higher than that of the allopatry population were supported based on the findings. This study will provide baseline data and a distribution range to facilitate the further control of these insects and formulate quarantine measures.

Metformin and Breast Cancer: Molecular Targets

Metformin has been the first-line drug for the treatment of type II diabetes mellitus for decades, being presently the most widely prescribed antihyperglycemic drug. Retrospective studies associate the use of metformin with a reduction in cancer incidence and cancer-related death. However, despite extensive research about the molecular effects of metformin in cancer cells, its mode of action remains controversial. The major molecular targets of metformin include complex I of the mitochondrial electron transport chain, adenosine monophosphate (AMP)-activated protein kinase (AMPK), and mechanistic target of rapamycin complex 1 (mTORC1), but AMPK-independent effects of metformin have also been described. Breast cancer is one of the leading causes of cancer-related morbidity and mortality among women worldwide. Several studies have reinforced a link between breast cancer risk and diabetes. Moreover, metformin significantly reduces breast cancer risk, compared to patients who are not using metformin and is independent of diabetes status. In this review, we summarize the current molecular evidence to elucidate metformin's mode of action against breast cancer cells.

Emerging paradigms in the treatment of liver metastases in colorectal cancer.

Efforts to combat colorectal cancer have benefited from improved screening and surveillance, which facilitates early detection. The survival rate associated with diagnosis at stage I is approximately 90%. However, progress in improving survival in metastatic colorectal cancer (mCRC) has been minimal. This review focuses on mCRC with special emphasis on the molecular aspects of liver metastases, which is one of the most frequently involved organ site. Better molecular evidence is required to guide the decisions for surgical and other interventions used in the clinical management of mCRC. Results from different treatment modalities have exposed significant gaps in the existing paradigms of the mCRC management. Indeed there is a critical need to better understand molecular events and pathways that lead to colorectal cancer liver metastasis. Such a focused approach may help identify biomarkers and drug targets that can be useful in the clinical applications. With this focus, we provide an account of the molecular pathways involved in the spread of CRC to the liver. Specifically, the molecular changes at the DNA and RNA levels that are associated with liver metastases are discussed. Similarly, we describe relevant microRNAs that are identified as regulators of gene expression and can also serve as biomarkers. Conventionally applied biomarkers are not yet specific and sensitive enough to be relied in routine clinical decision making. Hence search for novel biomarkers is critically needed especially if these can be utilized using liquid biopsies. This review provides a comprehensive analysis of current molecular evidence along with potential future directions that could reshape the diagnostic and management paradigms and thus mitigate the devastating impact of colorectal cancer metastasis to the liver.

Histone MacroH2A1: A Chromatin Point of Intersection between Fasting, Senescence and Cellular Regeneration.

Histone variants confer chromatin unique properties. They have specific genomic distribution, regulated by specific deposition and removal machineries. Histone variants, mostly of canonical histones H2A, H2B and H3, have important roles in early embryonic development, in lineage commitment of stem cells, in the converse process of somatic cell reprogramming to pluripotency and, in some cases, in the modulation of animal aging and life span. MacroH2A1 is a variant of histone H2A, present in two alternatively exon-spliced isoforms macroH2A1.1 and macroH2A1.2, regulating cell plasticity and proliferation, during pluripotency and tumorigenesis. Furthermore, macroH2A1 participates in the formation of senescence-associated heterochromatic foci (SAHF) in senescent cells, and multiple lines of evidence in genetically modified mice suggest that macroH2A1 integrates nutritional cues from the extracellular environment to transcriptional programs. Here, we review current molecular evidence based on next generation sequencing data, cell assays and in vivo models supporting different mechanisms that could mediate the function of macroH2A1 in health span and life span. We will further discuss context-dependent and isoform-specific functions. The aim of this review is to provide guidance to assess histone variant macroH2A1 potential as a therapeutic intervention point.

Transcriptional networks in rodent models support a role for gut-brain communication in neurogenic hypertension: a review of the evidence

Hypertension (HTN) is the most prevalent condition observed in primary health care. Hypertension shows complex etiology, and neuroinflammation, overactive sympathetic drive, and the microbiome are each associated with the disease. To obtain mechanistic perspective into neurogenic HTN, we first constructed a framework for transcriptional regulators of the disease using the Comparative Toxicogenomics Database. This approach yielded a core group of 178 transcripts that are prevalent in studies of HTN, including leptin and neuropeptide Y. We then conducted a meta-analysis for transcriptome data generated in brain tissue from HTN studies. Eight expression studies were reanalyzed, in which transcriptomics was conducted in hypertensive animal models [spontaneously hypertensive rats (SHR) and high blood pressure (BPH/2J) Schlager mice] (140 microarrays). Most strikingly, a gut-brain connection was a dominant theme in both rodent models of HTN. The transcriptomic data in the rat CNS converged on processes that included gastrointestinal motility and appetite, among others. In the mouse model, pathways converged on gastrointestinal transit. Thus, our data provide a powerful review of current molecular evidence of the interplay between gut and brain in HTN. Analyses of meta-genome data also suggested that transcriptome networks related to natriuresis, thermoregulation, reproduction (lactation and pregnancy), and vasoconstriction were associated to HTN, supporting physiological observations in independent studies by others. Lastly, we present novel transcriptome networks that may contribute to a neurogenic origin of HTN. Using this framework, new therapeutic targets can be proposed and investigated in treatment strategies.

Challenging a Misnomer? The Role of Inflammatory Pathways in Inflammatory Breast Cancer.

Inflammatory breast cancer is a rare, yet highly aggressive form of breast cancer, which accounts for less than 5% of all locally advanced presentations. The clinical presentation of inflammatory breast cancer often differs significantly from that of noninflammatory breast cancer; however, immunohistochemistry reveals few, if any, distinguishing features. The more aggressive triple-negative and HER2-positive breast cancer subtypes are overrepresented in inflammatory breast cancer compared with noninflammatory breast cancer, with a poorer prognosis in response to conventional therapies. Despite its name, there remains some controversy regarding the role of inflammation in inflammatory breast cancer. This review summarises the current molecular evidence suggesting that inflammatory signaling pathways are upregulated in this disease, including NF-κB activation and excessive IL-6 production among others, which may provide an avenue for novel therapeutics. The role of the tumor microenvironment, through tumor-associated macrophages, infiltrating lymphocytes, and cancer stem cells is also discussed, suggesting that these tumor extrinsic factors may help account for the differences in behavior between inflammatory breast cancer and noninflammatory breast cancer. While there are various novel treatment strategies already underway in clinical trials, the need for further development of preclinical models of this rare but aggressive disease is paramount.