Microbial Invasion Research Articles

The immune landscape in apical periodontitis: From mechanism to therapy.

Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.

Understanding dental pulp inflammation: from signaling to structure

The pulp is a unique tissue within each tooth that is susceptible to painful inflammation, known as pulpitis, triggered by microbial invasion from carious lesions or trauma that affect many individuals. The host response involves complex immunological processes for pathogen defense and dentin apposition at the site of infection. The interplay of signaling between the immune and non-immune cells via cytokines, chemokines, neuropeptides, proteases, and reactive nitrogen and oxygen species leads to tissue reactions and structural changes in the pulp that escalate beyond a certain threshold to irreversible tissue damage. If left untreated, the inflammation, which is initially localized, can progress to pulpal necrosis, requiring root canal treatment and adversely affecting the prognosis of the tooth. To preserve pulp vitality and dental health, a deeper understanding of the molecular and cellular mechanisms of pulpitis is imperative. In particular, elucidating the links between signaling pathways, clinical symptoms, and spatiotemporal spread is essential to develop novel therapeutic strategies and push the boundaries of vital pulp therapy.

Microbial interactions impact stress tolerance in a model oral community.

Microbial interactions are critical modulators of the emergence of microbial communities and their functions. However, how these interactions impact the fitness of microbes in established communities upon exposure to environmental stresses is poorly understood. Here, we utilized a two-species community consisting of Aggregatibacter actinomycetemcomitans and Streptococcus gordonii to examine the impact of synergistic and antagonistic interactions on microbial resilience to environmental fluctuations and susceptibility to microbial invasion. We focused on the S. gordonii-produced extracellular molecules, L-lactate and H2O2, which have been shown to mediate interactions between these two microbes. We discovered that seemingly beneficial functions, such as A. actinomycetemcomitans cross-feeding on S. gordonii-produced L-Lactate, can paradoxically exacerbate vulnerabilities, such as susceptibility to antibiotics. Moreover, our data highlight the context-dependent nature of microbial interactions, emphasizing that a seemingly potent antimicrobial, such as H2O2, can have both synergistic and antagonistic effects on a microbial community dependent on the environment.

Structural basis for the access and binding of resolvin D1 (RvD1) to formyl peptide receptor 2 (FPR2/ALX), a class A GPCR.

Inflammation is essential to the body's defense against tissue injury and microbial invasion. However, uncontrolled inflammation is highly detrimental and can result in chronic inflammatory diseases such as asthma, cancer, obesity, and diabetes. An increasing body of evidence suggests that specialized pro-resolving lipid mediators (SPMs), such as resolvins, are actively involved in critical cellular events that drive the resolution of inflammation and a return to homeostasis. An imbalance caused by insufficient SPMs can result in the unsuccessful resolution of inflammation. The D-series resolvins (metabolites of docosahexaenoic acid), such as resolvin D1 (RvD1) and resolvin D2 (RvD2), carry out their pro-resolving functions by directly binding to class A G protein-coupled receptors FPR2/ALXR and GPR32, and GPR18, respectively. We recently demonstrated that RvD1 and RvD2 preferentially partition and accumulate at the polar headgroup regions of the membrane. However, the mechanistic detail of how RvD1 gains access to the FPR2 binding site from a surrounding membrane environment remains unknown. In this study, we used classical MD and well-tempered metadynamics simulations to examine the structural basis for the access and binding of RvD1 to its target receptor from aqueous and membrane environments. The results offer valuable insights into the access path, potential binding pose, and key residue interactions essential for the access and binding of RvD1 to FPR2/ALXR and may help in identifying small molecule therapeutics as a possible treatment for inflammatory disorders.

Preparation of injectable self-healing hydrogels using carboxymethyl chitosan and oxidized dextran with incorporating quercetin-loaded PF127 micelles for wound healing

Rapid achievement of the irregularly shaped post-wound closure is closely related to the effectiveness of clinical hydrogel-based wound dressings to inhibit microbial invasion and promote wound healing. Herein, an injectable and self-healing hydrogel with rapid gelation was engineered based on carboxymethyl chitosan (CMCS) and oxidized dextran (Odex). The hydrophobic drug, quercetin, with antioxidant and antibacterial effects, was loaded in the PF127 micelles with an encapsulation efficiency of 59.06 %, and then quercetin-loaded PF127 micelles were ingeniously incorporated into the hydrogels. The prepared composite hydrogels not only showed a stable and sustained release behavior of quercetin, but also possessed excellent antioxidant activities and antibacterial properties against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. Moreover, the composite hydrogels with microstructure (150–250 μm) also exhibited self-healing and injectable properties. In addition, the survival rates of NIH 3T3 cells when cultured with hydrogel extract were all over 80 %, illustrating the excellent biocompatibility of hydrogels. Therefore, our prepared multifunctional composite hydrogels showed a broad prospect as wound dressings for treating acute skin injuries.

Antibacterial and Healing Potential of Zn-Al LDHs/Cellulose Acetate Nanocomposite in Burns and Wounds: A Study on Earthworms as a Human Skin Model

AbstractProtection against microbial invasion has gained much attention to accelerate wound healing. Layered double hydroxides (LDHs) have antimicrobial properties due to their partial release of metallic ions. In this study, Zn-Al LDHs was chemically prepared and then supported on cellulose acetate (CA) in the form of nanocomposite. This novel Zn-Al LDHs/CA nanocomposite was in vitro characterized, and its antibacterial efficacy was determined using the agar well diffusion method. Moreover, healing capabilities of the nanocomposite were evaluated via topical application on wounds and burns induced in earthworms as a model of human skin like. The average crystallite sizes of Zn-Al LDHs and 50% Zn-Al/CA nanocomposite were 18.4 nm and 14.8 nm, respectively. TEM micrographs revealed that pure CA, pure Zn-Al LDHs, and 50% Zn-Al LDHs/CA nanocomposites had an average particle size of 27.7 ± 13.5, 296.2 ± 123, and 223.2 ± 83.4 nm, respectively. Pure Zn-Al LDHs showed antibacterial activity against different bacterial strains (Inhibition zone: 15 ± 2 to 20 ± 4 mm). However, when 50% Zn-Al LDHs was supported on CA, the inhibition zone was significantly higher (20 ± 3 to 26 ± 2 mm). Visual inspection, scanning electron microscopy and histological studies of earthworm skin revealed better morphology and shorter healing duration with Zn-Al LDHs/CA nanosystem (66 h for wounds and 144 h for burns) when compared with untreated control (> 400 h). In conclusion, these findings reveal that Zn-Al LDHs/CA nanocomposite is a promising promoter for wound and burn healing due to its biocompatibility and antibacterial activity.

Machine learning reveals the rules governing the efficacy of mesenchymal stromal cells in septic preclinical models

BackgroundMesenchymal Stromal Cells (MSCs) are the preferred candidates for therapeutics as they possess multi-directional differentiation potential, exhibit potent immunomodulatory activity, are anti-inflammatory, and can function like antimicrobials. These capabilities have therefore encouraged scientists to undertake numerous preclinical as well as a few clinical trials to access the translational potential of MSCs in disease therapeutics. In spite of these efforts, the efficacy of MSCs has not been consistent—as is reflected in the large variation in the values of outcome measures like survival rates. Survival rate is a resultant of complex cascading interactions that not only depends upon upstream experimental factors like dosage, time of infusion, type of transplant, etc.; but is also dictated, post-infusion, by intrinsic host specific attributes like inflammatory microniche including proinflammatory cytokines and alarmins released by the damaged host cells. These complex interdependencies make a researcher’s task of designing MSC transfusion experiments challenging.MethodsIn order to identify the rules and associated attributes that influence the final outcome (survival rates) of MSC transfusion experiments, we decided to apply machine learning techniques on manually curated data collected from available literature. As sepsis is a multi-faceted condition that involves highly dysregulated immune response, inflammatory environment and microbial invasion, sepsis can be an efficient model to verify the therapeutic effects of MSCs. We therefore decided to implement rule-based classification models on data obtained from studies involving interventions of MSCs in sepsis preclinical models.ResultsThe rules from the generated graph models indicated that survival rates, post-MSC-infusion, are influenced by factors like source, dosage, time of infusion, pre-Interleukin-6 (IL-6)/ Tumour Necrosis Factor- alpha (TNF-α levels, etc.ConclusionThis approach provides important information for optimization of MSCs based treatment strategies that may help the researchers design their experiments.

A Review of the Literature: Amniotic Fluid "Sludge"-Clinical Significance and Perinatal Outcomes.

Introduction: This paper seeks to report and emphasize the most important aspects from the scientific literature about the diagnostic accuracy of the amniotic fluid "sludge" (AFS), its characterization, its treatment, and its association with premature birth. AFS is defined as a floating freely hyperechogenic material within the amniotic cavity in the proximity of the internal os. Materials and Methods: We conducted a search on Pubmed and Google Scholar for relevant articles on the subject of amniotic fluid "sludge" published until January 2024. Searches were focused on articles about diagnosis, treatment, maternal and neonatal outcomes, risk of preterm birth, and case reports. The full-text reading stage resulted in the inclusion of 51 studies. Results: AFS is independently associated with chorioamnionitis, preterm delivery, short cervix, increased risk of neonatal morbidity, and cervical insufficiency. This hyperechogenic free-floating material is linked with preterm birth before 32 weeks of gestation, especially when it is associated with short cervical length. Discussion: Present studies identify some controversial benefits of antibiotics in reducing the incidence of preterm birth in women with AFS. Nevertheless, in this review, we can conclude that the presence of AFS in pregnancy is a marker for the microbial invasion of the amniotic cavity, as it is associated with preterm birth. Further studies on a larger group of patients are necessary to clarify and exactly define the terms of managing these cases.

Host long noncoding RNAs in bacterial infections.

Bacterial infections remain a significant global health concern, necessitating a comprehensive understanding of the intricate host-pathogen interactions that play a critical role in the outcome of infectious diseases. Recent investigations have revealed that noncoding RNAs (ncRNAs) are key regulators of these complex interactions. Among them, long noncoding RNAs (lncRNAs) have gained significant attention because of their diverse regulatory roles in gene expression, cellular processes and the production of cytokines and chemokines in response to bacterial infections. The host utilizes lncRNAs as a defense mechanism to limit microbial pathogen invasion and replication. On the other hand, some host lncRNAs contribute to the establishment and maintenance of bacterial pathogen reservoirs within the host by promoting bacterial pathogen survival, replication, and dissemination. However, our understanding of host lncRNAs in the context of bacterial infections remains limited. This review focuses on the impact of host lncRNAs in shaping host-pathogen interactions, shedding light on their multifaceted functions in both host defense and bacterial survival, and paving the way for future research aimed at harnessing their regulatory potential for clinical applications.

Flourishing in Darkness: Protist Communities of Water Sites in Shulgan-Tash Cave (Southern Urals, Russia)

Karst caves, formed by the erosion of soluble carbonate rocks, provide unique ecosystems characterized by stable temperatures and high humidity. These conditions support diverse microbial communities, including wall microbial fouling, aquatic biofilms, and planktonic communities. This study discloses the taxonomic diversity of protists in aquatic biotopes of Shulgan-Tash Cave, a culturally significant site and popular tourist destination, by 18S rRNA gene metabarcoding. Our findings reveal the rich protist communities in the cave’s aquatic biotopes, with the highest diversity observed in Blue Lake at the cave entrance. In contrast, Distant Lake in the depth of the cave was inhabited by specific communities of plankton, mats, and pool fingers, which exhibited lower richness and evenness, and were adapted to extreme conditions (cold, darkness, and limited nutrients). High-rank taxa including Opisthokonta, Stramenopiles, and Rhizaria dominated all biotopes, aligning with observations from other subterranean environments. Specific communities of biotopes inside the cave featured distinct dominant taxa: amoeboid stramenopile (Synchromophyceae) and flagellates (Choanoflagellatea and Sandona) in mats; flagellates (Choanoflagellatea, Bicoecaceae, Ancyromonadida) and amoeboid protists (Filasterea) in pool fingers; flagellates (Ochromonadales, Glissomonadida, Synchromophyceae), fungi-like protists (Peronosporomycetes), and fungi (Ustilaginomycotina) in plankton. The specificity of the communities was supported by LEfSe analysis, which revealed enriched or differentially abundant protist taxa in each type of biotope. The predominance of Choanoflagellatea in the communities of cave mats and pool fingers, as well as the predominance of Synchromophyceae in the cave mats, appears to be a unique feature of Shulgan-Tash Cave. The cold-tolerant yeast Malassezia recorded in other caves was present in both plankton and biofilm communities, suggesting its resilience to low temperatures. However, no potentially harmful fungi were detected, positioning this research as a baseline for future monitoring. Our results emphasize the need for ongoing surveillance and conservation efforts to protect the fragile ecosystems of Shulgan-Tash Cave from human-induced disturbances and microbial invasions.

Characterization of ultrasonic-assisted antifungal film loaded with fermented walnut meal on Rosa roxburghii Tratt during near-freezing temperature storage.

Fermented walnut meal (FW) has antifungal activity against Penicillium victoriae, a fungus responsible for Rosa roxbughii Tratt spoilage. This study characterized and applied ultrasonic-assisted antifungal film loaded with FW to preserve R. roxbughii Tratt during near-freezing temperature (NFT). Results showed that O2 and CO2 transmission rates decreased by 80.02% and 29.05%, respectively, and antimicrobial properties were improved with ultrasound at 560W for 5min and 1% FW. Fourier transform infrared spectroscopy and X-ray diffraction results revealed ultrasound improved hydrogen bonds and inductive effect via ─NH, ─OH, and C═O bonds. The addition of FW led to the formation of CMCS-GL-FW polymer via C═O bond. Thermogravimetric analysis and transmission electron microscope results demonstrated thermal degradation process was decomposed by ultrasound, and the internal structure of P. victoriae was accelerated by the addition of FW. Compared to the U-CMCS/GL group, the vitamin C content, peroxidase, and catalase activities of U-CMCS/GL/FW were enhanced by 4.24%, 8.52%, and 14.3% during NFT (-0.8 to -0.4°C), respectively. Particularly, the fungal count of the U-CMCS/GL/FW group did not exceed 105 CFU g-1 at the end of storage, and the relative abundance of P. victoriae decreased to 0.007%. Our findings provide an effective route for agricultural waste as natural antifungal compounds in the active packaging industry. PRACTICAL APPLICATION: In this study, the barrier and antimicrobial properties of film were successfully improved by ultrasonic treatment and loaded fermented walnut meal. The ultrasonic-assisted antifungal film loaded with fermented walnut meal effectively delayed the degradation of nutrients and reduced microbial invasion of Rosa roxburghii Tratt. These results provide a theoretical basis for the application of agricultural waste in the food packaging industry.

Intratumoral Microbiome in Head and Neck Paragangliomas.

Head and neck paragangliomas (HNPGLs) are rare neoplasms arising from paraganglia of the parasympathetic nervous system. HNPGLs are characterized by high vascularity and are located in proximity to major vessels and nerves, which may be potential sources of microbial invasion in these tumors. There have been no studies in the literature on the microbiota in HNPGLs. Investigation of the microbiome associated with paragangliomas is important for understanding tumor pathogenesis. In this study, we investigated the microbiome composition in two sets of HNPGLs. First, 29 fresh frozen (FF) tissues were subjected to 16S rRNA gene sequencing; concurrently, a panel of candidate laboratory-derived contaminants was investigated. Second, we analyzed microbial reads from whole transcriptome sequencing data obtained for 82 formalin-fixed paraffin-embedded (FFPE) HNPGLs. The bacterial diversity in FF tumors was found to be significantly lower than that observed in FFPE HNPGLs. Based on 16S rRNA gene sequencing, only seven bacterial families were identified as potential tumor inhabitants: Bryobacteraceae, Enterococcaceae, Neisseriaceae, Legionellaceae, Vibrionaceae, Obscuribacteraceae, and Mycobacteriaceae. However, RNA-Seq demonstrated higher sensitivity for identifying microbiome composition and revealed abundant bacterial families that partially correlated with those previously described in pheochromocytomas and extra-adrenal paragangliomas. No viruses were found in HNPGLs. In summary, our findings indicated the presence of a microbiome in HNPGLs, comprising a number of bacterial families that overlap with those observed in pheochromocytomas/paragangliomas and glioblastomas.

MiR-155 enhances apoptosis of macrophage through suppressing PI3K-AKT activation in Pseudomonas aeruginosa keratitis

Keratitis induced by Pseudomonas aeruginosa (P. aeruginosa) is an acute and serious corneal inflammation. As a family of gene regulators, miRNAs play a crucial role in modulating host response after microbial invasion. However, their functions in P. aeruginosa keratitis remain largely unclear. In the present study, we demonstrated that miR-155 expression was significantly increased in macrophages and corneal tissue after P. aeruginosa infection. In vivo studies demonstrated that mice with miR-155 knockdown displayed more resistance to P. aeruginosa keratitis, with a lower bacterial burden. In addition, in vitro and in vivo studies indicated that miR-155 enhanced apoptosis of macrophages after P. aeruginosa infection, and resulted in a susceptible phenotype of P. aeruginosa keratitis. Moreover, miR-155 induced apoptosis through reducing activation of PI3K-Akt signaling pathway. Our data provided evidence of miR-155 mediated apoptosis of macrophage in P. aeruginosa keratitis, which may be an underlying target for the therapy of P. aeruginosa keratitis and other infectious diseases.

Identification, molecular profiling and immune functions of cystatin M in silver pomfret (Pampus argenteus)

Cystatins play an important role in various physiological and pathological processes of organisms, including regulating protein metabolism, antigen processing, inflammatory response, nutritional disorders, and controlling enzyme activity. However, research on immunity functions of fish cystatin M is limited. In this study, Pampus argenteus cystatin M (Pacystatin M) was identified and analyzed. Its amino acid sequence was highly conserved in teleosts, and included the conserved cystatin cysteine protease inhibitor motifs. Pacystatin M was highly expressed in the gill, spleen, and intestine, whereas the expression levels of liver and kidney were lower. Furthermore, Nocardia seriolae infection up-regulated the expression of Pacystatin M in the kidney, spleen and liver, with particularly significant expression observed in the liver on day 15 post-infection. Functional analysis indicated that the recombinant Pacystatin M showed increasing inhibitory activity against papain within a certain concentration range, suggesting that the inhibition was likely competitive. Additionally, Pacystatin M demonstrated the ability to inhibit bacterial growth and high thermal stability. These results suggested that Pacystatin M might be involved in the immune response to microbial invasion and provided new reference addressing disease issues in the large-scale farming of silver pomfret.

Microbial challenges and solutions in root canal therapy

Root canal therapy (RCT) faces significant challenges due to microbial invasion and biofilm formation within the root canal system. The intricate anatomy of root canals, including isthmuses, lateral canals, and apical deltas, provides a conducive environment for pathogenic microorganisms, complicating effective disinfection. Key pathogens such as Enterococcus faecalis and Candida albicans are highly resilient, capable of forming biofilms that protect them from antimicrobial agents and host defences. Current antimicrobial strategies in endodontics combine mechanical instrumentation with chemical disinfection. Mechanical debridement, though essential, often falls short of thoroughly cleaning the complex root canal anatomy. Sodium hypochlorite (NaOCl), the gold standard irrigant, exhibits broad-spectrum antimicrobial properties but struggles to penetrate biofilms and dentinal tubules fully. Adjunctive solutions like chlorhexidine (CHX) and ethylenediaminetetraacetic acid (EDTA) enhance the antimicrobial efficacy of NaOCl by providing prolonged action and removing the smear layer, respectively. Intracanal medicaments, such as calcium hydroxide (Ca(OH)2), are utilized to maintain antimicrobial activity between treatment sessions. Despite its high pH and effectiveness against a wide range of bacteria, Ca(OH)2 shows limited efficacy against biofilm-forming bacteria like Enterococcus faecalis. Innovations in irrigation techniques, such as passive ultrasonic irrigation (PUI) and laser-activated irrigation (LAI), have improved the delivery and activation of irrigants, enhancing their ability to disrupt biofilms and penetrate the root canal system. Nanoparticle-based irrigants and medicaments represent a promising advancement in endodontic disinfection. Their small size and large surface area allow for better penetration and interaction with bacterial cells, significantly reducing bacterial load in the root canal system. Combining traditional and advanced antimicrobial strategies is essential for overcoming the limitations of current methods and improving the success rates of endodontic therapy. Understanding the mechanisms of microbial invasion and biofilm formation, along with integrating emerging technologies, can lead to more effective disinfection protocols. This approach aims to enhance treatment outcomes and ultimately ensure the longevity of endodontically treated teeth.

Does Bidens pilosa L. Affect Carbon and Nitrogen Contents, Enzymatic Activities, and Bacterial Communities in Soil Treated with Different Forms of Nitrogen Deposition?

The deposition of nitrogen in soil may be influenced by the presence of different nitrogen components, which may affect the accessibility of soil nitrogen and invasive plant-soil microbe interactions. This, in turn, may alter the success of invasive plants. This study aimed to clarify the influences of the invasive plant Bidens pilosa L. on the physicochemical properties, carbon and nitrogen contents, enzymatic activities, and bacterial communities in soil in comparison to the native plant Pterocypsela laciniata (Houtt.) Shih treated with simulated nitrogen deposition at 5 g nitrogen m-2 yr-1 in four forms (nitrate, ammonium, urea, and mixed nitrogen). Monocultural B. pilosa resulted in a notable increase in soil pH but a substantial decrease in the moisture, electrical conductivity, ammonium content, and the activities of polyphenol oxidase, β-xylosidase, FDA hydrolase, and sucrase in soil in comparison to the control. Co-cultivating B. pilosa and P. laciniata resulted in a notable increase in total soil organic carbon content in comparison to the control. Monocultural B. pilosa resulted in a notable decrease in soil bacterial alpha diversity in comparison to monocultural P. laciniata. Soil FDA hydrolase activity and soil bacterial alpha diversity, especially the indices of Shannon's diversity, Simpson's dominance, and Pielou's evenness, exhibited a notable decline under co-cultivated B. pilosa and P. laciniata treated with nitrate in comparison to those treated with ammonium, urea, and mixed nitrogen.

Characterization of Inflammation/Immune-, Acute Phase-, Extracellular Matrix-, Adhesion-, and Serine Protease-Related Proteins in the Amniotic Fluid of Women With Early Preterm Prelabor Rupture of Membranes.

To determine whether altered concentrations of various inflammation/immune-, acute phase-, extracellular matrix-, adhesion-, and serine protease-related proteins in the amniotic fluid (AF) are independently associated with microbial invasion of the amniotic cavity and/or intra-amniotic inflammation (MIAC/IAI), imminent spontaneous preterm delivery (SPTD; ≤7 days), and major neonatal morbidity/mortality (NMM) in women with early preterm prelabor rupture of membranes (PPROM). This was a retrospective cohort study involving 111 singleton pregnant women with PPROM (24-31 weeks) undergoing amniocentesis to diagnose MIAC/IAI. The following proteins were measured in stored AF samples by enzyme-linked immunosorbent assay (ELISA): APRIL, DKK-3, Gal-3BP, IGFBP-2, IL-8, VDBP, lumican, MMP-2, MMP-8, SPARC, TGFBI, TGF-β1, E-selectin, ICAM-5, P-selectin, haptoglobin, hepcidin, SAA1, kallistatin, and uPA. Multivariate logistic regression analyses revealed that (i) elevated APRIL, IL-8, MMP-8, and TGFBI levels in the AF, reduced lumican and SPARC levels in the AF, and high percentages of samples above the lower limit of quantification for AF TGF-β1 and uPA were significantly associated with MIAC/IAI; (ii) elevated AF levels of IL-8 and MMP-8 were significantly associated with SPTD within 7 days; and (iii) elevated AF IL-6 levels were significantly associated with increased risk for major NMM, when adjusted for baseline covariates. ECM (lumican, SPRAC, TGFBI, and TGF-β1)- and serine protease (uPA)-associated proteins in the AF are involved in the regulation of the host response to infection/inflammation in the amniotic cavity, whereas AF inflammation (IL-8, MMP-8, and IL-6)-associated mediators are implicated in the development of preterm parturition and major NMM in early PPROM.

Artificial mucus layer formed in response to ROS for the oral treatment of inflammatory bowel disease.

The artificial mucus layer, such as hydrogels, used to repair the damaged intestinal barrier, is a promising treatment for inflammatory bowel disease (IBD). However, the currently reported hydrogel-based artificial barriers are administered via rectal injection, causing unnecessary discomfort to patients. Herein, we report an oral hydrogel precursor solution based on thiol-modified hyaluronic acid (HASH). Owing to the reactive oxygen species (ROS)-responsive gelling behavior, our precursor solution formed an artificial mucus coating over the inflamed regions of the intestines, blocking microbial invasion and reducing abnormally activated immune responses. Notably, HASH also modulated the gut microbiota, including increasing the diversity and enhancing the abundance of short-chain fatty acid-associated bacteria, which play a key role in gut homeostasis. We believe that the ROS-responsive artificial mucus layer is a promising strategy for the oral treatment of IBD.

The Influence of Dental Status and Blood Parameters Characterizing Endogenous Intoxication on the Timing of Childbirth.

Background and Objectives: Epidemiological and microbiological-immunological studies have led to the conclusion that periodontal disease may be a risk factor for preterm birth. The aim of this study was to investigate and identify the relationship of some hematological cellular biomarkers characterizing the chronic oral focus of infection with pregnancy outcomes and their impact on those outcomes. Materials and Methods: Clinical and laboratory tests were conducted on 100 pregnant women, grouped by full-term or preterm births, with the assessment of the following markers: DMF, CPI and PIRI, PHP, microbiological examination of periodontal pockets and amniotic fluid, WBS count, WBCSI, LGI, and NMR. A statistical analysis was carried out with SPSS Statistics version 19.0. Results: Women with preterm labor had higher-grade caries (CSL > 0.3), while women with full-term childbirth had moderate caries (CSL < 0.3). A satisfactory level of oral hygiene efficiency was found in 50% (group 1) and 38.1% (group 2) of the expectant mothers. The periodontal status by the PIRI showed tissue lesions in 20.7% (group 1) and 92.9% (group 2) of the women. The WBCSI was 2.27 ± 0.82 and 2.15 ± 0.68, the NMR was 9.29 ± 5.119 and 11.62 ± 7.78, and the LGI was 3.54 ± 1.1 and 3.73 ± 0.81 in groups 1 and 2, respectively. Comparative analysis of bacterial contamination of the amniotic fluid revealed the predominance of Fusobacterium nucleatum (64.3%), Tannerella forsythia (57.1%), Prevotella intermedia (50%), Porphyromonas gingivalis (57.1%), Staphylococcus aureus (45.2%), and Candida albicans (50%) in women with premature birth. Conclusions: In women with preterm birth, the values of the indices characterizing a chronic oral focus of infection evoke more significant correlations with the timing of delivery, which indicates the significant role of an oral focus of infection. The presence of microbial invasion of amniotic fluid may indicate the role of periodontopathogenic bacteria in pregnant women diagnosed with a risk of preterm birth.

Staphylococcus aureus wraps around Candida albicans and synergistically escapes from Neutrophil extracellular traps.

NETs, a unique neutrophil immune mechanism, are vital in defending against microbial invasions. Understanding the mechanisms of co-infection by Candida albicans and Staphylococcus aureus, which often leads to higher mortality and poorer prognosis, is crucial for studying infection progression. In our study, we established a mouse model of subcutaneous infection to characterize the inflammation induced by co-infection. By purifying and extracting NETs to interact with microorganisms, we delve into the differences in their interactions with various microbial species. Additionally, we investigated the differences in NETs production by neutrophils in response to single or mixed microorganisms through the interaction between neutrophils and these microorganisms. Furthermore, we analyzed the gene expression differences during co-infection using transcriptomics. In vivo, C. albicans infections tend to aggregate, while S. aureus infections are more diffuse. In cases of co-infection, S. aureus adheres to and wraps C. albicans. NETs exhibit strong killing capability against C. albicans but weaker efficacy against S. aureus. When NETs interact with mixed microorganisms, they preferentially target and kill the outer layer of S. aureus. In the early stages, neutrophils primarily rely on phagocytosis to kill S. aureus, but as the bacteria accumulate, they stimulate neutrophils to produce NETs. Interestingly, in the presence of neutrophils, S. aureus promotes the proliferation and hyphal growth of C. albicans. Our research has showed substantial differences in the progression of co-infections compared to single-microbial infections, thereby providing scientific evidence for NETs as potential therapeutic targets in the treatment of co-infections.