Search Results (125)

Gastrointestinal (GI) cancers represent a significant global health burden, with high morbidity and mortality often linked to late-stage detection and metastatic disease. The progression of these malignancies is critically driven by angiogenesis, the formation of new blood vessels, and the surrounding dynamic tumor microenvironment (TME), a complex ecosystem comprising various cell types and non-cellular components. This comprehensive review, based on a systematic search of the PubMed database, synthesizes the existing literature to define the intertwined roles of angiogenesis and the TME in GI tumorigenesis. The TME’s influence creates conditions favorable for tumor growth, invasion, and metastasis, but sometimes induces resistance to current therapies. Available therapeutic strategies for inhibiting angiogenesis involve antibodies and oral tyrosine kinase inhibitors, while immune modulation within the tumor microenvironment is mainly achieved through checkpoint inhibitor antibodies and chemotherapy. Creative emerging strategies encompassing cellular therapies, bispecific antibodies, and new targets such as CD40, DLL4, and Ang2, amongst others, are focused on inhibiting proangiogenic pathways more profoundly, reversing resistance to prior drugs, and modulating the TME to enhance therapeutic efficacy. A deeper understanding of the complex interactions between components of the TME is crucial for addressing the unmet need for novel and effective therapeutic interventions against aggressive GI cancers. Full article

Fixed orthodontic appliances, which are cemented to tooth surfaces, complicate the maintenance of oral hygiene and create a rough surface that is favorable for bacteria attachment. Additionally, the presence of orthodontic appliances may conceive a unique environment that interacts with cariogenic microorganisms, fostering a distinct microbial ecosystem compared to that of the patients without orthodontic appliances, thus increasing the vulnerability of tooth surfaces to demineralization and caries formation. Silver (Ag) has shown strong antimicrobial effects and has been extensively investigated in the medical field. Here, we aim to review the antibacterial properties and potential side effects of silver nanoparticles (AgNPs) when incorporated into orthodontic bonding reagents. This valuation could contribute to the development of novel bonding reagents designed to prevent the formation of white spot lesions and caries during orthodontic treatments. Full article

The oral cavity harbors a highly intricate and dynamic microbial ecosystem of multiple microhabitats supporting diverse microbial populations. As the second most complex microbiome in the human body, surpassed only by the gut, the oral microbiome comprises over 1000 species. Disruptions in the microbial balance have been associated with an increased risk of both oral diseases (dental caries and periodontitis) and systemic conditions, including inflammatory diseases and certain types of cancers. In our pilot study, we purified bacterial DNA from pre-treated, saponin-based, host-depleted saliva samples and performed 16S amplicon sequencing, using Oxford Nanopore Technologies, to identify bacterial composition and investigate changes in the oral microbiota of patients with solid tumors in response to chemotherapy, either alone or in combination with immunotherapy. We found significant reductions in microbial diversity of the oral microbiota following cancer treatment, which may contribute to post-therapeutic complications such as oral mucositis. Moreover, our findings indicate that on the one hand, following chemotherapy treatment the microbial profile is characterized by an increased abundance of Streptococcus, Gemella, and Granulicatella and a decrease in the abundance of Neisseria and Veillonella. On the other hand, post combined treatment, only Streptococcus relative abundance increased, Veillonella exhibited a slight decline, and Haemophilus and Neisseria displayed a marked decrease, whilst Granulicatella and Gemella remained relatively stable. Our findings underline the impact of cancer therapy on the oral microbiome, highlighting the potential for precision-based strategies to restore microbial balance and minimize treatment-related complications. Full article

The oral microbiome, a highly diverse and intricate ecosystem of microorganisms, plays a pivotal role in the maintenance of systemic health. With the oral cavity housing over 700 different bacterial species, the body’s second most diverse microbial community, periodontal pathogens often lead to the dysregulation of immune responses and consequently, neuropsychiatric disorders. Emerging evidence suggests a significant link between the dysbiosis of oral taxa and the progression of neurogenic disorders such as depression, schizophrenia, bipolar disorders, and more. In this paper, we show the relationship between mental health conditions and shifts in the oral microbiome by highlighting inflammatory responses and neuroactive pathways. The connection between the central nervous system and the oral cavity highlights its role as a modulator of mental health. Clinically, these findings have significant importance as dysbiosis could compromise quality of life. The weight of mental health is often compounded with treatment resistance, non-adherence, and relapse, causing a further need for treatment development. This review seeks to underscore the crucial role of the proposed oral–brain axis in hopes of increasing its presence in future intervention strategies and mental health therapies. Full article

Honey bees and other pollinators are key to functioning natural and managed ecosystems. However, their health is threatened by many factors, including pesticides. Spraying fungicides during flowering of fruit trees is widespread even though it directly exposes pollinators to these fungicides. Here, we report a series of experiments designed to understand how the combination of propiconazole and carbendazim, marketed in China as Chunmanchun^®, affects honey bee health. With an acute oral toxicity of 23.8 μg a.i./bee over 24 h in the laboratory, we considered the acute mortality risk from normal Chunmanchun^® applications as relatively low. However, our comprehensive studies revealed other diverse effects: Chunmanchun^® reduced memory after classic conditioning by approximately 25% and altered the activity of protective enzymes and the composition of the honey bees’ gut microbiota. Specifically, the genus Lactobacillus was decreased by ~13%, and Bartonella and Snodgrassella were increased by ~10% and ~7.5%, respectively. The gut metabolome was also disrupted in diverse ways, possibly as a functional consequence of the microbiome changes. Thus, we demonstrated numerous sublethal effects of the combination of propiconazole and carbendazim, which adds to the growing evidence that agrochemicals and fungicides in particular can harm pollinator health in subtle ways that are not captured in simple mortality assays. Full article

Inflammatory bowel disease (IBD) represents a chronic inflammatory disorder of the gastrointestinal tract with a multifactorial etiology that remains incompletely elucidated. Accumulating evidence implicates dysregulation of the intestinal micro-ecosystem, aberrant neuroimmune interactions, and compromised epithelial barrier integrity as key contributors to IBD pathogenesis. While oral administration remains the predominant therapeutic approach, the acidic gastric milieu and enzymatic catabolism markedly compromise drug efficacy. Consequently, selecting an optimal drug delivery method has become a pressing issue in IBD management. As a drug delivery platform, hydrogels, distinguished by their favorable biocompatibility, biodegradability, and injectability, can shield drugs from the harsh gastrointestinal environment. This review offers an innovative and comprehensive analysis of the interactions among various hydrogel application forms, delivery routes, and loaded substances, summarizing the advantages of different types of hydrogels in terms of their anti-inflammatory properties and maintenance of intestinal flora homeostasis, as well as discussing the limitations of current hydrogel deliver systems and looking to the future. Full article

While periodontitis is increasingly linked to systemic disorders through the oral–gut axis, the molecular mediators driving gut microbiota dysbiosis and barrier disruption remain elusive. Hepatocyte growth factor (HGF), a novel regulator of inflammatory bone loss in periodontitis, may serve as a critical communicator between oral infection and distal intestinal pathology. This study investigates how HGF overexpression modulates the gut microbial ecosystem and intestinal barrier integrity in a transgenic periodontitis model. In this study, we combined 16S rRNA sequencing of fecal microbiota with comprehensive gut barrier assessments, including systemic markers (D-lactate, LPS, and DAO ELISA), structural integrity (villous morphology), and molecular analysis (ZO-1, occludin, and NOD2 immunohistochemistry), using HGF-overexpressing transgenic (HGF-Tg) mice with periodontitis. The results demonstrated that HGF increased gut permeability in the context of periodontitis, as evidenced by elevated serum levels of D-lactate and LPS compared to wild type (WT) mice. In addition, gut villous morphology disorder was observed in HGF-Tg mice with periodontitis. HGF also diminished the protein level of occludin and upregulated NOD2 expression in mice with periodontitis. Moreover, HGF-Tg mice with periodontitis exhibited significant dysbiosis of gut microbiota, with reduced levels of probiotics (e.g., Faecalibaculum). Notably, HGF also increased the enrichment of the periodontitis-associated pathogens (e.g., Desulfovibrio and Streptococcus) in the gut. Microbial functions, particularly metabolic pathways, were significantly altered by HGF when periodontitis occurred. Some microorganisms like g_Desulfovibrio may play a role in gut barrier disorder in HGF-Tg mice with periodontitis. Overall, our findings position HGF as a novel orchestrator of oral–gut crosstalk, where its overexpression reshapes gut microbial ecology toward a “leaky gut” phenotype to compromise intestinal barrier integrity, further deepening our understanding of the oral–gut axis. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuronal loss, affecting millions worldwide. Emerging evidence highlights the oral microbiome—a complex ecosystem of bacteria, fungi, viruses, and protozoa as a significant factor in cognitive health. Dysbiosis of the oral microbiome contributes to systemic inflammation, disrupts the blood–brain barrier, and promotes neuroinflammation, processes increasingly implicated in the pathogenesis of AD. This review examines the mechanisms linking oral microbiome dysbiosis to cognitive decline through the oral–brain and oral–gut–brain axis. These interconnected pathways enable bidirectional communication between the oral cavity, gut, and brain via neural, immune, and endocrine signaling. Oral pathogens, such as Porphyromonas gingivalis, along with virulence factors, including lipopolysaccharides (LPS) and gingipains, contribute to neuroinflammation, while metabolic byproducts, such as short-chain fatty acids (SCFAs) and peptidoglycans, further exacerbate systemic immune activation. Additionally, this review explores the influence of external factors, including diet, pH balance, medication use, smoking, alcohol consumption, and oral hygiene, on oral microbial diversity and stability, highlighting their role in shaping cognitive outcomes. The dynamic interplay between the oral and gut microbiomes reinforces the importance of microbial homeostasis in preserving systemic and neurological health. The interventions, including probiotics, prebiotics, and dietary modifications, offer promising strategies to support cognitive function and reduce the risk of neurodegenerative diseases, such as AD, by maintaining a diverse microbiome. Future longitudinal research is needed to identify the long-term impact of oral microbiome dysbiosis on cognition. Full article

This review article highlights the surveillance of bacterial, viral, and parasitic diseases in donkey populations in China. Key findings highlight significant threats from Equine herpesviruses (EHV-8 and EHV-1), which cause encephalitis, abortion, and respiratory distress. Several parasitic infections including Giardia duodenalis, Cryptosporidium spp., Enterocytozoon bieneusi, and Toxoplasma gondii present important zoonotic concerns across multiple regions of China. Additionally, this review synthesizes current knowledge on donkey microbiota across various body sites and examines their functional significance in health and disease. The complex relationship between the microbiota and host health represents a critical area of research in donkeys. Recent molecular advancements have enhanced our understanding of the diverse microbial ecosystems inhabiting different body sites in donkeys and their profound impact on health outcomes. As single-stomach herbivores, donkeys possess complex microbial communities throughout their digestive tracts that are essential for intestinal homeostasis and nutritional processing. Significant variations in microbiota composition exist across different intestinal segments, with the hindgut displaying greater richness and diversity compared to the foregut. Beyond the digestive system, distinct microbial profiles have been characterized across various body sites including the skin, oral cavity, reproductive tract, and body secretions such as milk. The health implications of donkey microbiota extend to critical areas including nutrition, immune function, and disease susceptibility. Research demonstrates how dietary interventions, environmental stressors, and physiological states significantly alter microbial communities, correlating with changes in inflammatory markers, antioxidant responses, and metabolic functions. Additionally, specific microbial signatures associated with conditions like endometritis and respiratory disease suggest the potential for microbiota-based diagnostics and therapeutics. The identification of antibiotic-resistant strains of Proteus mirabilis and Klebsiella pneumoniae in donkey meat highlights food safety concerns requiring enhanced monitoring systems and standardized safety protocols. These findings provide a foundation for improved donkey healthcare management, including targeted disease surveillance, microbiota-based interventions, and protective measures for those working with donkeys or consuming donkey-derived products. Full article

Background and aims: Vaginal microbiomes have been classified into five different general categories, termed Community State Type (CSTs), with CST-III and CST-IV often associated with vaginal dysbiosis which makes women more prone to recurrent infections and assisted reproductive technology (ART) failure. Since a healthy microbiome is one of the key steps for successful reproduction, we investigated the impact of modulating the vaginal microbiota through the oral administration of probiotic formula consisting of a consortium of vaginal-specific lactobacilli and prebiotics (Personal Flora 2^®). Methods: We recruited 32 women who had previous failed IVF cycles and were scheduled to undergo ART. We examined the composition of the vaginal microbiota before and after oral probiotic supplementation using 16S ribosomal RNA (rRNA) sequencing technology. Results: Our data show a noticeable modulation of the vaginal microbiome upon probiotic supplementation. In particular, precision probiotic intervention lowers the species diversity, favoring the dominance of Lactobacillus (p = 0.015) and Bifidobacterium (p = 0.000) whilst decreasing the percentage of Atopobium (p = 0.003), Gardnerella (p = 0.022), and Prevotella (p = 0.000). Conclusions: Although CST-III and CST-IV are generally considered detrimental, gynecologists should not refrain from performing IVF in these women if they have been previously subjected to a consortium of precision probiotics treatments, as the administration of specific probiotics reduces the presence of pathogenic bacteria promoting the increase in lactobacilli associated with a healthy vaginal ecosystem, which could impact pregnancy success. Full article

The impact of agrochemicals on pollinators, especially honey bees, has drawn significant attention due to its critical implications for worldwide food stability and ecosystems. Given the potential threat of insecticides to honey bees, bees may encounter multiple insecticides simultaneously during foraging. This study investigated the toxic effect of an insecticide mixture (IM) containing acetamiprid (neonicotinoid) and deltamethrin (pyrethroid) on the survival and cognitive appetitive performance of Apis mellifera jemenitica, a vital native pollinator in arid regions of Saudi Arabia. The lethal concentration (LC₅₀) was determined by assessing bees’ mortality rates following exposure to IM through topical and oral routes. Significant bee mortality occurred at 4–48 h post treatment with IM through both exposure routes, showing a trend of increased mortality with higher IM concentrations compared to the control bees. Throughout all tested times, topical exposure proved relatively more effective, resulting in significantly greater bee mortality compared to oral exposure to IM. Food intake declined progressively with rising IM concentrations during oral exposure. The LC₅₀ values of IM at 24 h after treatment were 12.24 ppm for topical and 10.45 ppm for oral exposure. The corresponding LC₁₀, LC₂₀, and LC₃₀ values were 3.75 ppm, 5.63 ppm, and 7.54 ppm for topical exposure and 2.45 ppm, 4.04 ppm, and 5.78 ppm for oral exposure, respectively. The combination index (CI) revealed a synergistic effect (0.43) for topical exposure and antagonistic effects (1.43) for oral exposure, highlighting differential toxicity dynamics. IM exposure significantly impaired cognitive acquisition and memory reinforcement in honey bees, as demonstrated through behavioral assays, indicating potential neurotoxic effects. Learning and memory formation significantly declined at 2, 12, and 24 h after exposure to sublethal concentrations of IM through both topical and oral routes. Thus, evaluating the interactive impact of multiple pesticides on bees’ health and cognitive function is essential, particularly in regions where diverse agrochemicals are routinely utilized. Full article

The oral microbiome, a complex ecosystem of microbes, is crucial for oral health. Imbalances in this ecosystem can lead to various oral diseases. Probiotics, live beneficial bacteria, offer a potential solution by strengthening oral defences. This study aimed to develop and evaluate a novel toothpaste containing Streptococcus salivarius M18, a probiotic strain. After ensuring compatibility with toothpaste ingredients, a stable formulation with desirable properties was created. The toothpaste demonstrated cleaning efficacy and antimicrobial activity against oral pathogens in vitro. A clinical trial involving healthy adults showed that all doses of the probiotic toothpaste significantly increased S. salivarius M18 levels in saliva, with the effect persisting even after discontinuation. These findings suggest that the toothpaste effectively delivers the probiotic to the oral cavity and promotes colonisation. Further research is needed to optimise the formulation and assess its long-term impact on oral health. Full article

Background/Objectives: This paper brings to light the results of extensive research on the dimension of dental care in Romania in terms of priorities and policies defined at the governmental level for a 25-year period (1999–2023). This research aims to present both individual and ecosystem perspectives on the influence of the way oral health strategies are shaped in Romania. Methods: The data collected are analyzed through the prism of the “iron triangle of healthcare”, focusing on the evolution of dental care from the perspective of the interrelationship of three important components: cost, quality, and access to healthcare services. Results: The paper provides insight and clarity into the context in which the doctor–patient relationship is constructed and developed, as well as a vision of how oral health policies should be designed to meet the individual needs of the patient, which will have an impact on the health and quality of life of the whole community. Conclusions: This study emphasizes the need to reconfigure oral health policies in Romania. Despite some input achievements like a considerable number of dentists, the systemic challenges that developed over these 25 years (such as insufficient funding, the reduced reimbursed procedures, and the limited dentists contracting with NHIH) have significantly contributed to a stagnation or decline of the oral health outcomes at the societal level. Full article

Xerostomia is a widespread condition among the elderly, impacting as many as 50% of individuals within this demographic. This review aims to analyze the association between age-related xerostomia and the oral microbial ecosystem. Xerostomia not only induces discomfort but also heightens the susceptibility to oral diseases, including dental caries and infections. The oral microbial ecosystem, characterized by a dynamic equilibrium of microorganisms, is integral to the maintenance of oral health. Dysbiosis, defined as a microbial imbalance, can further aggravate oral health complications in those suffering from xerostomia. This review investigates the composition, diversity, and functionality of the oral microbiota in elderly individuals experiencing xerostomia, emphasizing the mechanisms underlying dysbiosis and its ramifications for both oral and systemic health. A comprehensive understanding of these interactions is vital for the formulation of effective management and prevention strategies aimed at enhancing the quality of life for older adults. Full article