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Objectives The medical and health facilities are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study tested the preprocedural prophylactic mouthwash rinses to reduce the oral viral load. The findings from this study will help the practitioners to select the best mouthwash for the patients to mitigate the risk of transmission during aerosolizing. This study aimed to evaluate the effectiveness of four commonly used types of mouthwash in reducing intraoral viral load among hospitalized coronavirus disease 2019 patients. Materials and Methods This prospective cohort study was conducted with 116 patients referred to the Masih Daneshvari Hospital in Tehran, Hamadan University of Medical Sciences of Hamadan City, and Mashhad University of Medical Sciences. Patients were randomized into four groups with each group rinsed their mouth with 20 mL of 2% povidone-iodine, 1% hydrogen peroxide, normal saline as a control study group, or 0.12% chlorhexidine, respectively, for 20 seconds. The standard reverse transcription polymerase chain reaction method evaluated the virus load before and at 1 hour, 2 hours, and 4 hours after using the mentioned mouthwash. Results Our results revealed that chlorhexidine and H2O2 showed the highest efficiency in reducing SARS-Co-2 load in the oral cavity and nasopharyngeal region of patients; they increased the Ct values by 9 to 10 (before: 25.84 vs. after 32. 4, p Conclusion Our findings suggest that chlorhexidine and H2O2 could be used in dental clinics to reduce the risk of transmitting the SARS-CoV-2 virus from infected individuals to dentists before dental procedures.

This case report describes a patient with a chronic urinary tract infection whose long-term treatment for right eye redness, discharge, pain, and decreased vision ultimately led to hospitalization and Pseudomonas aeruginosa resistant to multiple antibiotics.

Tumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two major contributors to poor therapeutic responses during cancer intervention. Pyroptosis, a lytic and inflammatory programmed cell death pathway distinct from apoptosis, has subsequently sparked notable interest among cancer researchers for its potential to be clinically harnessed and to address these problems. Recent evidence indicates that pyroptosis induction in tumor cells leads to a robust inflammatory response and marked tumor regression. Underlying its antitumor effect, pyroptosis is mediated by pore-forming gasdermin proteins that facilitate immune cell activation and infiltration through their release of pro-inflammatory cytokines and immunogenic material following cell rupture. Considering its inflammatory nature, however, aberrant pyroptosis may also be implicated in the formation of a tumor supportive microenvironment, as evidenced by the upregulation of gasdermin proteins in certain cancers. In this review, the molecular pathways leading to pyroptosis are introduced, followed by an overview of the seemingly entangled links between pyroptosis and cancer. We describe what is known regarding the impact of pyroptosis on anticancer immunity and give insight into the potential of harnessing pyroptosis as a tool and applying it to novel or existing anticancer strategies.

Lake Malawi cichlid fishes exhibit extensive divergence in form and function built from a relatively small number of genetic changes. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. Genome regions near differentiated variants are enriched for craniofacial, neural and behavioral categories. Following leads from genome sequence, we used rock- vs. sand-species and their hybrids to (i) delineate the push–pull roles of BMP signaling and irx1b in the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results demonstrate how divergent genome sequences can predict differences in key evolutionary traits. We highlight the promise of evolutionary reverse genetics—the inference of phenotypic divergence from unbiased genome sequencing and then empirical validation in natural populations.

Periodontal diseases are very common affecting the soft and hard tissue support of the teeth. Periodontitis is the most severe form of periodontal diseases, which can lead to tooth loss affecting not only esthetic and self-esteem but also nutritional status and general heath of affected individuals. Mechanical debridement remains the mainstay of management of periodontitis, but other therapeutic options include local delivery of antimicrobial agents and guided tissue regeneration. Importantly, advances in tissue regeneration technologies coupled with our increasing understanding of stem cell biology have raised the prospect for regeneration of the periodontal complex. Among the variety of stem cells, induced pluripotent stem cells are gaining increased attention given their potential application for personalized healthcare. Thus, we will initially review prevalence and pathogenesis of periodontitis along with current treatment options and their limitations. Thereafter, and in the context of development of the dental complex, we will describe the potential of induced pluripotent stem cells, and emerging technologies, for periodontal regeneration.

Lake Malawi cichlid fishes exhibit extensive divergence in form and function among closely related species separated by a relatively small number of genetic changes. During the past million years, hundreds of species have diversified along an ecological axis in rock vs. sand habitats. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants in which genes differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. The majority of divergent coding variants are missense and/or loss of function. Regions near differentiated variants are enriched for craniofacial, neural and behavioral functional categories. To follow up experimentally, we used rock- vs. sand-species and their hybrids to (i) clarify the push-pull roles of BMP signaling andirx1bin the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results suggest compelling ties between early brain development and adult behavior and highlight the promise of evolutionary reverse genetics – the identification of functional variants from genome sequencing in natural populations.

Tray tooth bleaching involves the use of carbamide peroxide in a custom-fitted tray to bleach teeth. One of the most difficult stains to bleach is tetracycline. This paper will present several different patient situations of tetracycline-stained teeth being bleached and will discuss the benefits and limitations of bleaching tetracycline-stained teeth. By providing the patient with realistic potential outcomes of bleaching, as well as the preservation of tooth structure and cost-benefit ratio of bleaching compared to veneers or crowns, the chance for a successful acceptance of the outcome is better, even if the outcome is less than ideal. Bleaching before prosthodontic treatment can also provide a better outcome for subsequent veneers or crowns if that is possible, but sensitivity may preclude bleaching.

(1) Background: The aim of this study was to test whether matrix-bound zoledronate (zol) molecules enhanced the oral biofilm colonization of a mineralized matrix, rendering the alveolar bone more susceptible to medication-related osteonecrosis of the jaw (MRONJ) following invasive dental procedures. (2) Methods: We tested the effect of matrix-bound zol on the growth and attachment of Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn) and Actinomyces israelii (Ai), and whether the nitrogen-containing component of zol contributed to such effect. The role of oral bacteria in the induction of osteonecrosis was then tested using an extra-oral bone defect model. (3) Results: The attachment of biofilm to hydroxyapatite discs increased when the discs were pre-treated with zol. Bacterial proliferation was not affected. Matrix-bound zol was more potent than non-nitrogen-containing etidronate in enhancing the colonization. Stimulation was dampened by pre-treating the bacteria with histidine. The delivery of oral biofilm to a tibial defect caused osteonecrosis in zol-treated rats. (4) Conclusions: We conclude that matrix-bound zol enhances the oral biofilm colonization of hydroxyapatite. This enhancement depended on the presence of the nitrogen-containing group. The oral biofilm rendered the extra-oral bone susceptible to medication-related osteonecrosis, suggesting that it has an important role in the induction of MRONJ.

Significance Nearly one-third of adults over the age of 65 have lost all their teeth. We set out to understand tooth renewal in animals that have replacement and regeneration capabilities. Using cichlid fishes and mouse models, we discovered plasticity between tooth and taste bud progenitor cell derivatives, mediated by BMP. Our results suggest that oral organs have surprising regenerative capabilities and can be manipulated to express characteristics of different tissue types., In Lake Malawi cichlids, each tooth is replaced in one-for-one fashion every ∼20 to 50 d, and taste buds (TBs) are continuously renewed as in mammals. These structures are colocalized in the fish mouth and throat, from the point of initiation through adulthood. Here, we found that replacement teeth (RT) share a continuous band of epithelium with adjacent TBs and that both organs coexpress stem cell factors in subsets of label-retaining cells. We used RNA-seq to characterize transcriptomes of RT germs and TB-bearing oral epithelium. Analysis revealed differential usage of developmental pathways in RT compared to TB oral epithelia, as well as a repertoire of genome paralogues expressed complimentarily in each organ. Notably, BMP ligands were expressed in RT but excluded from TBs. Morphant fishes bathed in a BMP chemical antagonist exhibited RT with abrogated shh expression in the inner dental epithelium (IDE) and ectopic expression of calb2 (a TB marker) in these very cells. In the mouse, teeth are located on the jaw margin while TBs and other oral papillae are located on the tongue. Previous study reported that tongue intermolar eminence (IE) oral papillae of Follistatin (a BMP antagonist) mouse mutants exhibited dysmorphic invagination. We used these mutants to demonstrate altered transcriptomes and ectopic expression of dental markers in tongue IE. Our results suggest that vertebrate oral epithelium retains inherent plasticity to form tooth and taste-like cell types, mediated by BMP specification of progenitor cells. These findings indicate underappreciated epithelial cell populations with promising potential in bioengineering and dental therapeutics.

Remoras (echeneid fish) reversibly attach and detach to marine hosts, almost instantaneously, to “hitchhike” and feed. The adhesion mechanisms that they use are remarkably insensitive to substrate topology and quite different from the latching and suction cup-based systems associated with other species at similar length scales. Remora adhesion is also anisotropic; drag forces induced by the swimming host increase adhesive strength, while rapid detachment occurs when the remora reverses this shear load. In this work, an investigation of the adhesive system’s functional morphology and tissue properties was carried out initially through dissection and x-ray microtomographic analyses. Resulting finite element models of these components have provided new insights into the adaptive, hierarchical nature of the mechanisms and a path toward a wide range of engineering applications.

In many aquatic vertebrates, including bony and cartilaginous fishes, teeth and taste buds co-localize on jaw elements. In these animals, taste buds are renewed continuously throughout life, whereas teeth undergo cycled whole organ replacement by various means. Recently, studies of cichlid fishes have yielded new insights into the development and regeneration of these dental and sensory oral organs. Tooth and taste bud densities co-vary positively across species with different feeding strategies, controlled by common regions of the genome and integrated molecular signals. Developing teeth and taste buds share a bipotent epithelium during early patterning stages, from which dental and taste fields are specified. Moreover, these organs share a common epithelial ribbon that supports label-retaining cells during later stages of regeneration. During both patterning and regeneration stages, dental organs can be converted to taste bud fate by manipulation of BMP signaling. These observations highlight a surprising long-term plasticity between dental and sensory organ types. Here, we review these findings and discuss the implications of developmental plasticity that spans the continuum of craniofacial organ patterning and regeneration.

Teeth and taste buds are iteratively patterned structures that line the oro-pharynx of vertebrates. Biologists do not fully understand how teeth and taste buds develop from undifferentiated epithelium or how variation in organ density is regulated. These organs are typically studied independently because of their separate anatomical location in mammals: teeth on the jaw margin and taste buds on the tongue. However, in many aquatic animals like bony fishes, teeth and taste buds are colocalized one next to the other. Using genetic mapping in cichlid fishes, we identified shared loci controlling a positive correlation between tooth and taste bud densities. Genome intervals contained candidate genes expressed in tooth and taste bud fields. sfrp5 and bmper, notable for roles in Wingless (Wnt) and bone morphogenetic protein (BMP) signaling, were differentially expressed across cichlid species with divergent tooth and taste bud density, and were expressed in the development of both organs in mice. Synexpression analysis and chemical manipulation of Wnt, BMP, and Hedgehog (Hh) pathways suggest that a common cichlid oral lamina is competent to form teeth or taste buds. Wnt signaling couples tooth and taste bud density and BMP and Hh mediate distinct organ identity. Synthesizing data from fish and mouse, we suggest that the Wnt-BMP-Hh regulatory hierarchy that configures teeth and taste buds on mammalian jaws and tongues may be an evolutionary remnant inherited from ancestors wherein these organs were copatterned from common epithelium.

CC-BY-NC-SA; International audience; Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Vertebrate dentitions originated in the posterior pharynx of jawless fishes more than half a billion years ago. As gnathostomes (jawed vertebrates) evolved, teeth developed on oral jaws and helped to establish the dominance of this lineage on land and in the sea. The advent of oral jaws was facilitated, in part, by absence of hox gene expression in the first, most anterior, pharyngeal arch. Much later in evolutionary time, teleost fishes evolved a novel toothed jaw in the pharynx, the location of the first vertebrate teeth. To examine the evolutionary modularity of dentitions, we asked whether oral and pharyngeal teeth develop using common or independent gene regulatory pathways. First, we showed that tooth number is correlated on oral and pharyngeal jaws across species of cichlid fishes from Lake Malawi (East Africa), suggestive of common regulatory mechanisms for tooth initiation. Surprisingly, we found that cichlid pharyngeal dentitions develop in a region of dense hox gene expression. Thus, regulation of tooth number is conserved, despite distinct developmental environments of oral and pharyngeal jaws; pharyngeal jaws occupy hox-positive, endodermal sites, and oral jaws develop in hox-negative regions with ectodermal cell contributions. Next, we studied the expression of a dental gene network for tooth initiation, most genes of which are similarly deployed across the two disparate jaw sites. This collection of genes includes members of the ectodysplasin pathway, eda and edar, expressed identically during the patterning of oral and pharyngeal teeth. Taken together, these data suggest that pharyngeal teeth of jawless vertebrates utilized an ancient gene network before the origin of oral jaws, oral teeth, and ectodermal appendages. The first vertebrate dentition likely appeared in a hox-positive, endodermal environment and expressed a genetic program including ectodysplasin pathway genes. This ancient regulatory circuit was co-opted and modified for teeth in oral jaws of the first jawed vertebrate, and subsequently deployed as jaws enveloped teeth on novel pharyngeal jaws. Our data highlight an amazing modularity of jaws and teeth as they coevolved during the history of vertebrates. We exploit this diversity to infer a core dental gene network, common to the first tooth and all of its descendants., Author Summary During evolution, teeth originated deep in the pharynx of ancient and extinct jawless fishes. Later, with the evolution of bony fish, teeth appeared in the mouth, as in most current vertebrates, although some living fishes retain teeth in the posterior pharynx. We integrate comparative morphology, paleontology, and molecular biology to infer the genetic control of the first dentition. We identify Hox genes as important components of an ancient dental gene-regulatory circuit and pinpoint subsequent modifications to this gene network that accompanied the evolution of toothed oral jaws. Furthermore, we highlight a set of genes conserved in the construction of all teeth, regardless of location and lineage. This core dental gene network is evolutionarily essential: nature appears never to have made a dentition without it., A common gene regulatory circuit controls the development of all dentitions, from the original teeth in the throats of jawless fishes half a billion years ago, to the incisors and molars of modern vertebrates.

Background Periodic patterning of iterative structures is a fundamental process during embryonic organization and development. Studies have shown how gene networks are employed to pattern butterfly eyespots, fly bristles and vertebrate epithelial appendages such as teeth, feathers, hair and mammary glands. Despite knowledge of how these features are organized, little is known about how diversity in periodic patterning is generated in nature. We address this problem through the molecular analysis of oral jaw dental diversity in Lake Malawi cichlids, where closely related species exhibit from 1 to 20 rows of teeth, with total teeth counts ranging from around 10 to 700. Results We investigate the expression of conserved gene networks (involving bmp2, bmp4, eda, edar, fgf8, pax9, pitx2, runx2, shh and wnt7b) known to pattern iterative structures and teeth in other vertebrates. We show that spatiotemporal variation in expression pattern reflects adult morphological diversity among three closely related Malawi cichlid species. Combinatorial epithelial expression of pitx2 and shh appears to govern the competence both of initial tooth sites and future tooth rows. Epithelial wnt7b and mesenchymal eda are expressed in the inter-germ and inter-row regions, and likely regulate the spacing of these shh-positive units. Finally, we used chemical knockdown to demonstrate the fundamental role of hedgehog signalling and initial placode formation in the organization of the periodically patterned cichlid dental programme. Conclusion Coordinated patterns of gene expression differ among Malawi species and prefigure the future-ordered distribution of functional teeth of specific size and spacing. This variation in gene expression among species occurs early in the developmental programme for dental patterning. These data show how a complex multi-rowed vertebrate dentition is organized and how developmental tinkering of conserved gene networks during iterative pattern formation can impact upon the evolution of trophic novelty.

Background Lake Malawi cichlids represent one of a growing number of vertebrate models used to uncover the genetic and developmental basis of trait diversity. Rapid evolutionary radiation has resulted in species that share similar genomes but differ markedly in phenotypes including brains and behavior, nuptial coloration and the craniofacial skeleton. Research has begun to identify the genes, as well as the molecular and developmental pathways that underlie trait divergence. Results We assemble a compendium of gene expression for Lake Malawi cichlids, across pharyngula (the phylotypic stage) and larval stages of development, encompassing hundreds of gene transcripts. We chart patterns of expression in Bone morphogenetic protein (BMP), Fibroblast growth factor (FGF), Hedgehog (Hh), Notch and Wingless (Wnt) signaling pathways, as well as genes involved in neurogenesis, calcium and endocrine signaling, stem cell biology, and numerous homeobox (Hox) factors—in three planes using whole-mount in situ hybridization. Because of low sequence divergence across the Malawi cichlid assemblage, the probes we employ are broadly applicable in hundreds of species. We tabulate gene expression across general tissue domains, and highlight examples of unexpected expression patterns. Conclusions On the heels of recently published genomes, this compendium of developmental gene expression in Lake Malawi cichlids provides a valuable resource for those interested in the relationship between evolution and development.