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Pregnancy is a transformative period marked by profound physical and emotional changes, with far-reaching consequences for both mother and child. Emerging research has illustrated the pivotal role of a mother's diet during pregnancy in influencing the prenatal gut microbiome and subsequently shaping the neurodevelopment of her offspring. The intricate interplay between maternal gut health, nutrition, and neurodevelopmental outcomes has emerged as a captivating field of investigation within developmental science. Acting as a dynamic bridge between mother and fetus, the maternal gut microbiome, directly and indirectly, impacts the offspring's neurodevelopment through diverse pathways. This comprehensive review delves into a spectrum of studies, clarifying putative mechanisms through which maternal nutrition, by modulating the gut microbiota, orchestrates the early stages of brain development. Drawing insights from animal models and human cohorts, this work underscores the profound implications of maternal gut health for neurodevelopmental trajectories and offers a glimpse into the formulation of targeted interventions able to optimize the health of both mother and offspring. The prospect of tailored dietary recommendations for expectant mothers emerges as a promising and accessible intervention to foster the growth of beneficial gut bacteria, potentially leading to enhanced cognitive outcomes and reduced risks of neurodevelopmental disorders.
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As the burden of type 2 diabetes (T2D) continues to escalate globally, there is a growing need for novel, less-invasive biomarkers capable of early diabetes detection and monitoring of disease progression. Liquid biopsy, recognized for its minimally invasive nature, is increasingly being applied beyond oncology, and nevertheless shows its potential when the collection of the tissue biopsy is not possible. This diagnostic approach involves utilizing liquid biopsy markers such as cell-free nucleic acids, extracellular vesicles, and diverse metabolites for the molecular diagnosis of T2D and its related complications. In this context, we thoroughly examine recent developments in T2D liquid biopsy research. Additionally, we discuss the primary challenges and future prospects of employing liquid biopsy in the management of T2D. Prognosis, diagnosis and monitoring of T2D through liquid biopsy could be a game-changing technique for personalized diabetes management.
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Ácidos Nucleicos Livres , Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , Células Neoplásicas Circulantes , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Biomarcadores Tumorais/metabolismo , Biópsia Líquida/métodos , Vesículas Extracelulares/metabolismo , Ácidos Nucleicos Livres/metabolismo , Células Neoplásicas Circulantes/patologiaRESUMO
The rapid development of antimicrobial resistance due to broad antibiotic utilisation in the healthcare and food industries and the non-availability of novel antibiotics represents one of the most critical public health issues worldwide. Current advances in nanotechnology allow new materials to address drug-resistant bacterial infections in specific, focused, and biologically safe ways. The unique physicochemical properties, biocompatibility, and wide range of adaptability of nanomaterials that exhibit photothermal capability can be employed to develop the next generation of photothermally induced controllable hyperthermia as antibacterial nanoplatforms. Here, we review the current state of the art in different functional classes of photothermal antibacterial nanomaterials and strategies to optimise antimicrobial efficiency. The recent achievements and trends in developing photothermally active nanostructures, including plasmonic metals, semiconductors, and carbon-based and organic photothermal polymers, and antibacterial mechanisms of action, including anti-multidrug-resistant bacteria and biofilm removal, will be discussed. Insights into the mechanisms of the photothermal effect and various factors influencing photothermal antimicrobial performance, emphasising the structure-performance relationship, are discussed. We will examine the photothermal agents' functionalisation for specific bacteria, the effects of the near-infrared light irradiation spectrum, and active photothermal materials for multimodal synergistic-based therapies to minimise side effects and maintain low costs. The most relevant applications are presented, such as antibiofilm formation, biofilm penetration or ablation, and nanomaterial-based infected wound therapy. Practical antibacterial applications employing photothermal antimicrobial agents, alone or in synergistic combination with other nanomaterials, are considered. Existing challenges and limitations in photothermal antimicrobial therapy and future perspectives are presented from the structural, functional, safety, and clinical potential points of view.
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Anti-Infecciosos , Hipertermia Induzida , Nanoestruturas , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , NanotecnologiaRESUMO
The Campylobacter genus is the leading cause of human gastroenteritis, with the consumption of contaminated poultry meat as the main route of infection. Probiotic bacteria, such as Lactobacillus, Bacillus, Escherichia coli Nissle, and Bifidobacterium species, have a great immunomodulatory capacity and exhibit antipathogenic effects through various molecular mechanisms. Reducing Campylobacter levels in livestock animals, such as poultry, will have a substantial benefit to humans as it will reduce disease transmissibility through the food chain. Moreover, probiotic-based strategies might attenuate intestinal inflammatory processes, which consequently reduce the severity of Campylobacter disease progression. At a molecular level, probiotics can also negatively impact on the functionality of various Campylobacter virulence and survival factors (e.g., adhesion, invasion), and on the associated colonization proteins involved in epithelial translocation. The current review describes recent in vitro, in vivo, and preclinical findings on probiotic therapies, aiming to reduce Campylobacter counts in poultry and reduce the pathogen's virulence in the avian and human host. Moreover, we focused in particular on probiotics with known anti-Campylobacter activity seeking to understand the biological mechanisms involved in their mode of action.
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Infecções por Campylobacter , Campylobacter jejuni , Campylobacter , Doenças das Aves Domésticas , Probióticos , Humanos , Animais , Infecções por Campylobacter/prevenção & controle , Infecções por Campylobacter/veterinária , Infecções por Campylobacter/microbiologia , Galinhas/microbiologia , Probióticos/uso terapêutico , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/microbiologia , Aves DomésticasRESUMO
The prevalence of type 2 diabetes mellitus (T2D) is alarmingly increasing worldwide, urgently calling for a better understanding of the underlying mechanisms in order to step up prevention and improve therapeutic approaches. It is becoming evident that the gut microbiota seem to have an endless capacity to impact T2D. In this study, we profile the gut microbiome patterns in T2D patients from Romania, by using quantitative Real-Time PCR and next generation sequencing. We enrolled a total of 150 individuals (105 T2D patients, 50 of them without metformin treatment and 45 healthy volunteers). The levels of potentially beneficial butyrate-producing bacteria were significantly reduced, while potentially pathogenic microorganisms such as Enterobacteriaceae and Fusobacterium were enriched in T2D patients. We evaluated the correlation between clinical parameters and gut microbiota and identified the genera Bacteroides, Alistipes, Dialister, Bilophila and Sutterella as possible detrimental factors in T2D. Our findings suggest that the gut microbiota may be a potential target in novel approaches to halt the development of T2D-associated complications.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Metformina , Microbiota , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , BacteroidetesRESUMO
Metabolic syndrome (MetSyn) is a major health problem affecting approximately 25% of the worldwide population. Since the gut microbiota is highly connected to the host metabolism, several recent studies have emerged to characterize the role of the microbiome in MetSyn development and progression. To this end, our study aimed to identify the microbiome patterns which distinguish MetSyn from type 2 diabetes mellitus (T2DM). We performed 16S rRNA amplicon sequencing on a cohort of 70 individuals among which 40 were MetSyn patients. The microbiome of MetSyn patients was characterised by reduced diversity, loss of butyrate producers (Subdoligranulum, Butyricicoccus, Faecalibacterium prausnitzii) and enrichment in the relative abundance of fungal populations. We also show a link between the gut microbiome and lipid metabolism in MetSyn. Specifically, low-density lipoproteins (LDL) and high-density lipoproteins (HDL) display a positive effect on gut microbial diversity. When interrogating the signature of gut microbiota in a subgroup of patients harbouring both MetSyn and T2DM conditions, we observed a significant increase in taxa such as Bacteroides, Clostridiales, and Erysipelotrichaceae. This preliminary study shows for the first time that T2DM brings unique signatures of gut microbiota in MetSyn patients. We also highlight the impact of metformin treatment on the gut microbiota. Metformin administration was linked to changes in Prevotellaceae, Rickenellaceae, and Clostridiales. Further research focusing on the microbiome-metabolome patterns is needed to clarify the exact association of various gut microbial communities with the progression of T2DM and the occurrence of various complications in MetSyn patients.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Síndrome Metabólica , Metformina , Butiratos/farmacologia , Clostridiales/genética , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , RNA Ribossômico 16S/genéticaRESUMO
Globally, we are facing a worrying increase in type 1 diabetes mellitus (T1DM) incidence, with onset at younger age shedding light on the need to better understand the mechanisms of disease and step-up prevention. Given its implication in immune system development and regulation of metabolism, there is no surprise that the gut microbiota is a possible culprit behind T1DM pathogenesis. Additionally, microbiota manipulation by probiotics, prebiotics, dietary factors and microbiota transplantation can all modulate early host-microbiota interactions by enabling beneficial microbes with protective potential for individuals with T1DM or at high risk of developing T1DM. In this review, we discuss the challenges and perspectives of translating microbiome data into clinical practice. Nevertheless, this progress will only be possible if we focus our interest on developing numerous longitudinal, multicenter, interventional and double-blind randomized clinical trials to confirm their efficacy and safety of these therapeutic approaches.
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Diabetes Mellitus Tipo 1/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal , Diabetes Mellitus Tipo 1/terapia , Método Duplo-Cego , Disbiose/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Head and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, EpsteinBarr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.
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Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Microambiente Tumoral , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinogênese/genética , Prognóstico , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/patologiaRESUMO
Epoxy nanocomposites derived from linseed oil, reinforced with graphene oxide (GO) and montmorillonite (MMT) nanostructures, were synthesized. The nanohybrids were developed by enriching the structure of MMT and GO with primary amines through a common and simplified method, which implies physical interactions promoted by ultrasonic processing energy. The influence of the new nanoreinforcing agents along with neat ones on the overall properties of the biobased epoxy materials for coating applications was assessed. Interface formation through surface compatibility was contained by the lower values of activation energy calculated from differential scanning calorimetry (DSC) curves, along with a consistent 70% increase in the cross-linking density when amine-modified MMT was used. Thermomechanical characteristics of the biobased epoxy nanocomposites were explained through the interaction of the functional groups over the curing process of epoxidized linseed oil (ELO), giving a 15 °C higher Tg value increase. Furthermore, the low surface energy values suggested an intrinsic antibacterial activity, as proved by a significant decrease of CFU against Staphylococcus aureus bacterial strains on the 0.25% reinforced coatings.
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INTRODUCTION: Gut microbes pose challenges like colon inflammation, deadly diarrhea, antimicrobial resistance dissemination, and chronic disease onset. Development of early, rapid and specific diagnosis tools is essential for improving infection control. Point-of-care testing (POCT) systems offer rapid, sensitive, low-cost and sample-to-answer methods for microbe detection from various clinical and environmental samples, bringing the advantages of portability, automation, and simple operation. AREAS COVERED: Rapid detection of gut microbes can be done using a wide array of techniques including biosensors, immunological assays, electrochemical impedance spectroscopy, mass spectrometry and molecular biology. Inclusion of Internet of Things, machine learning, and smartphone-based point-of-care applications is an important aspect of POCT. In this review, the authors discuss various fast diagnostic platforms for gut pathogens and their main challenges. EXPERT OPINION: Developing effective assays for microbe detection can be complex. Assay design must consider factors like target selection, real-time and multiplex detection, sample type, reagent stability and storage, primer/probe design, and optimizing reaction conditions for accuracy and sensitivity. Mitigating these challenges requires interdisciplinary collaboration among scientists, clinicians, engineers, and industry partners. Future efforts are essential to enhance sensitivity, specificity, and versatility of POCT systems for gut microbe detection and quantification, advancing infectious disease diagnostics and management.
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Técnicas Biossensoriais , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Testes Imediatos , Técnicas Biossensoriais/métodos , Aprendizado de MáquinaRESUMO
Methotrexate (MTX) is a folic acid antagonist routinely used in cancer treatment, characterized by poor water solubility and low skin permeability. These issues could be mitigated by using drug delivery systems, such as functionalized gold nanoparticles (AuNPs), known for their versatility and unique properties. This study aimed to develop multi-shell AuNPs functionalized with MTX for the improvement of MTX antitumoral, antioxidant, and biocompatibility features. Stable phosphine-coated AuNPs were synthesized and functionalized with tailored polyethylene glycol (PEG) and short-branched polyethyleneimine (PEI) moieties, followed by MTX covalent binding. Physicochemical characterization by UV-vis and Fourier-transform infrared spectroscopy (FTIR) spectroscopy, dynamic light scattering (DLS), scanning transmission electron microscopy (STEM), and X-ray photoelectron spectroscopy (XPS) confirmed the synthesis at each step. The antioxidant activity of functionalized AuNPs was determined using DPPH radical scavenging assay, ferric ions' reducing antioxidant power (FRAP), and cupric reducing antioxidant capacity (CUPRAC) assays. Biocompatibility and cytotoxicity were assessed using MTT and LDH assays on HaCaT human keratinocytes and CAL27 squamous cell carcinoma. MTX functionalized AuNPs demonstrated enhanced antioxidant activity and a pronounced cytotoxic effect on the tumoral cells compared to their individual components, highlighting their potential for improving cancer therapy.
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Antioxidantes , Ouro , Nanopartículas Metálicas , Metotrexato , Metotrexato/farmacologia , Metotrexato/administração & dosagem , Metotrexato/química , Ouro/química , Humanos , Nanopartículas Metálicas/química , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Linhagem Celular Tumoral , Polietilenoglicóis/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Polietilenoimina/química , Células HaCaT , Queratinócitos/efeitos dos fármacosRESUMO
BACKGROUND: This study provides a comprehensive analysis of Acinetobacter baumannii in aquatic environments and fish microbiota by integrating culture-dependent methods, 16S metagenomics, and antibiotic resistance profiling. METHODS: A total of 83 A. baumannii isolates were recovered using culture-dependent methods from intra-hospital infections (IHI) and wastewater (WW) and surface water (SW) samples from two southern Romanian cities in August 2022. The antibiotic susceptibility was screened using disc diffusion, microdilution, PCR, and Whole Genome Sequencing assays. RESULTS: The highest microbial load in the analyzed samples was found in Glina, Bucharest, for both WW and SW samples across all investigated phenotypes. For Bucharest isolates, the resistance levels corresponded to fluoroquinolones > aminoglycosides > ß-lactam antibiotics. In contrast, A. baumannii from upstream SW samples in TârgoviÈte showed the highest resistance to aminoglycosides. The blaOXA-23 gene was frequently detected in IHI, WW, and SW isolates in Bucharest, but was absent in TârgoviÈte. Molecular phylogeny revealed the presence of ST10 in TârgoviÈte isolates and ST2 in Bucharest isolates, while other minor STs were not specifically correlated with a sampling point. Using 16S rRNA sequencing, significant differences in microbial populations between the two locations was identified. The low abundance of Alphaproteobacteria and Actinobacteria in both locations suggests environmental pressures or contamination events. CONCLUSIONS: These findings indicate significant fecal contamination and potential public health risks, emphasizing the need for improved water quality monitoring and management.
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In this work results are presented on the evaluation of HAp, HApSr, HAp_CS, and HApSr_CS layers deposited on Ti substrates regarding L929 cell viability and cytotoxicity as well as antimicrobial activity against Staphylococcus aureus, in connection with their physicochemical properties. The HAp and HApSr layers generated by radio-frequency magnetron sputtering technique were further covered with chitosan by a matrix-assisted pulsed laser evaporation technique. During the plasma depositions, the Ti substrates were heated externally by a home-made oven above 100 °C. The HApSr_CS layers generated on the unpolished Ti substrates at 100 °C and 400 °C showed the highest biocompatibility properties and antimicrobial activity against Staphylococcus aureus. The morphology of the layer surfaces, revealed by scanning electron microscopy, is dependent on substrate temperature and substrate surface roughness. The optically polished surfaces of Ti substrates revealed grain-like and microchannel structure morphologies of the layers deposited at 25 °C substrate temperature and 400 °C, respectively. Chitosan has no major influence on HAp and HApSr layer surface morphologies. X-ray photoelectron spectroscopy indicated the presence of Ca 2p3/2 peak characteristic of the HAp structure even in the case of the HApSr_CS samples generated at a 400 °C substrate temperature. Fourier transform infrared spectroscopy investigations showed shifts in the wavenumber positions of the P-O absorption bands as a function of Sr or chitosan presence in the HAp layers generated at 25, 100, and 400 °C substrate temperatures.
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Cancer is a very aggressive disease and one of mankind's most important health problems, causing numerous deaths each year. Its etiology is complex, including genetic, gender-related, infectious diseases, dysbiosis, immunological imbalances, lifestyle, including dietary factors, pollution etc. Cancer patients also become immunosuppressed, frequently as side effects of chemotherapy and radiotherapy, and prone to infections, which further promote the proliferation of tumor cells. In recent decades, the role and importance of the microbiota in cancer has become a hot spot in human biology research, bringing together oncology and human microbiology. In addition to their roles in the etiology of different cancers, microorganisms interact with tumor cells and may be involved in modulating their response to treatment and in the toxicity of anti-tumor therapies. In this review, we present an update on the roles of microbiota in cancer with a focus on interference with anticancer treatments and anticancer potential.
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Progressão da Doença , Neoplasias , Humanos , Neoplasias/microbiologia , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/etiologia , Animais , Antineoplásicos/uso terapêutico , Microbiota , Microbioma Gastrointestinal/efeitos dos fármacos , DisbioseRESUMO
The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic has advanced our understanding of the host-microbiome-virus interplay. Several studies in various geographical regions report that SARS-CoV-2 infection disrupts the intestinal microbiota, allowing pathogenic bacteria such as Enterobacteriaceae to thrive, and triggering more severe disease outcomes. Here, we profile the microbiota of 30 individuals, 15 healthy controls and 15 type 2 diabetes (T2D) patients, before and after coronavirus disease 2019 (COVID-19). Despite similar viral loads in both patients and controls, SARS-CoV-2 infection led to exacerbated microbiome changes in T2D patients, characterized by higher levels of Enterobacteriaceae, loss of butyrate producers and an enrichment in fungi such as Candida spp. and Aspergillus spp. Several members of the microbiota were associated with more severe clinical and inflammatory (IL-8 and IL-17) parameters. Future studies to delineate the connection between cytokine release and microbiota disturbances will enhance our understanding of whether these microbial shifts directly impact the cytokine storm in COVID-19 patients or whether they are consecutive to the critical disease.
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The essential oil of Achillea setacea was isolated by hydrodistillation and characterized by GC-MS. The antioxidant and antimicrobial activity of Achillea setacea essential oil was evaluated, as well as its biocompatibility (LDH and MTT methods). DPPH, FRAP, and CUPRAC methods were applied for antioxidant activity evaluation, while qualitative and quantitative assays (inhibition zone diameter, minimum inhibitory concentration, and minimum fungicidal concentration), NO release (by nitrite concentration determination), and microbial adhesion capacity to the inert substrate (the biofilm microtiter method) were used to investigate the antimicrobial potential. A total of 52 compounds were identified by GC-MS in A. setacea essential oil, representing 97.43% of the total area. The major constituents were borneol (32.97%), 1,8-cineole (14.94%), camphor (10.13%), artemisia ketone (4.70%), α-terpineol (3.23%), and γ-eudesmol (3.23%). With MICs ranging from 0.78 to 30 µg/mL, the A. setacea essential oil proved to inhibit the microbial adhesion and induce the NO release. To the best of our knowledge, the present study reports for the first time the antimicrobial activity of A. setacea EO against clinically and biotechnologically important microbial strains, such as Shigella flexneri, Listeria ivanovii, L. innocua, Saccharomyces cerevisiae, Candida glabrata, Aspergillus niger, Rhizopus nigricans, Cladosporium cladosporioides, and Alternaria alternata, demonstrating its antimicrobial applications beyond the clinical field.
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The use of MAPLE synthesized thin films based on BG and VD3 for improving the osseointegration and corrosion protection of Ti-like implant surfaces is reported. The distribution of chemical elements and functional groups was shown by FTIR spectrometry; the stoichiometry and chemical functional integrity of thin films after MAPLE deposition was preserved, optimal results being revealed especially for the BG+VD3_025 samples. The morphology and topography were examined by SEM and AFM, and revealed surfaces with many irregularities, favoring a good adhesion of cells. The thin films' cytotoxicity and biocompatibility were evaluated in vitro at the morphological, biochemical, and molecular level. Following incubation with HDF cells, BG57+VD3_ 025 thin films showed the best degree of biocompatibility, as illustrated by the viability assay values. According to the LDH investigation, all tested samples had higher values compared to the unstimulated cells. The evaluation of cell morphology was performed by fluorescence microscopy following cultivation of HDF cells on the obtained thin films. The cultivation of HDF's on the thin films did not induce major cellular changes. Cells cultured on the BG57+VD3_025 sample had similar morphology to that of unstimulated control cells. The inflammatory profile of human cells cultured on thin films obtained by MAPLE was analyzed by the ELISA technique. It was observed that the thin films did not change the pro- and anti-inflammatory profile of the HDF cells, the IL-6 and IL-10 levels being similar to those of the control sample. The wettability of the MAPLE thin films was investigated by the sessile drop method. A contact angle of 54.65° was measured for the sample coated with BG57+VD3_025. Electrochemical impedance spectroscopy gave a valuable insight into the electrochemical reactions occurring on the surface.
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Urban wastewater treatment plants harbor a large collection of antibiotic resistant enteric bacteria. It is therefore reasonable to hypothesize that workers at such plants would possess a more diverse set of resistant enteric bacteria, compared to the general population. To address this hypothesis, we have compared the fecal microbiome and resistome of 87 workers at wastewater treatment plants (WWTPs) from Romania and the Netherlands to those of 87 control individuals, using shotgun metagenomics. Controlling for potential confounders, neither the total antibiotic resistance gene (ARG) abundance, nor the overall bacterial composition were significantly different between the two groups. If anything, the ARG richness was slightly lower in WWTP workers, and in a stratified analysis the total ARG abundance was significantly lower in Dutch workers compared to Dutch control participants. We identified country of residence, together with recent antibiotic intake in the Dutch population, as the largest contributing factors to the total abundance of ARGs. A striking side-finding was that sex was associated with carriage of disinfectant resistance genes, with women in both Romania and the Netherlands having significantly higher abundance compared to men. A follow up investigation including an additional 313 publicly available samples from healthy individuals from three additional countries showed that the difference was significant for three genes conferring resistance to chemicals commonly used in cosmetics and cleaning products. We therefore hypothesize that the use of cosmetics and, possibly, cleaning products leads to higher abundance of disinfectant resistance genes in the microbiome of the users. Altogether, this study shows that working at a WWTP does not lead to a higher abundance or diversity of ARGs and no large shifts in the overall gut microbial composition in comparison to participants not working at a WWTP. Instead, other factors such as country of residence, recent antibiotic intake and sex seem to play a larger role.
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Desinfetantes , Microbiota , Purificação da Água , Humanos , Feminino , Águas Residuárias , Genes Bacterianos , Bactérias/genética , Antibacterianos/farmacologia , Antibacterianos/análise , Microbiota/genéticaRESUMO
Hydrogels are ideal candidates for the sustained local administration of antimicrobial drugs because they have customizable physicochemical properties that allow drug release kinetics to be controlled and potentially address the issue of systemic side effects. Consequently, the purpose of this study was to use 266 nm-pulsed laser beams to photo-crosslink gelatin methacryloyl hydrogels using Irgacure 2959 as a photo-initiator to reduce the curing time and to have an online method to monitor the process, such as laser-induced fluorescence. Additionally, irradiated chlorpromazine was loaded into the hydrogels to obtain a drug delivery system with antimicrobial activity. These hydrogels were investigated by UV-Vis and FTIR absorption spectroscopy, scanning electron microscopy, and laser-induced fluorescence spectroscopy and their structural and morphological characteristics, swelling behavior, and drug release profile were obtained. As a result the morphology, swelling behavior, and drug release profile were influenced by both the energy of the laser beam and the exposure time. The optimal hydrogel was obtained after 1 min of laser irradiation for Irgacure 2959 at 0.05% w/v concentration and gelatin methacryloyl at 10% w/v concentration. The hydrogels loaded with irradiated chlorpromazine show significant antimicrobial activity against Staphylococcus aureus and MRSA bacteria and a non-cytotoxic effect against L929 fibroblast cell lines.
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Testicular cancer is the most common solid tumor affecting young males. Most testicular cancers are testicular germ cell tumors (TGCTs), which are divided into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). During their development, primordial germ cells (PGCs) undergo epigenetic modifications and any disturbances in their pattern might lead to cancer development. The present study provides a comprehensive review of the epigenetic mechanisms-DNA methylation, histone post-translational modifications, bivalent marks, non-coding RNA-associated with TGCT susceptibility, initiation, progression and response to chemotherapy. Another important purpose of this review is to highlight the recent investigations regarding the identification and development of epigenetic biomarkers as powerful tools for the diagnostic, prognostic and especially for epigenetic-based therapy.