Role of Oral Microbiota Dysbiosis in the Development and Progression of Oral Lichen Planus.

Oral lichen planus (OLP) is a chronic inflammatory autoimmune disease of the oral cavity with malignant potential affecting 1.01% of the worldwide population. The clinical patterns of this oral disorder, characterized by relapses and remissions of the lesions, appear on buccal, lingual, gingival, and labial mucosa causing a significant reduction in the quality of life. Currently, there are no specific treatments for this disease, and the available therapies with topical and systemic corticosteroids only reduce symptoms. Although the etiopathogenesis of this pathological condition has not been completely understood yet, several exogenous and endogenous risk factors have been proposed over the years. The present review article summarized the underlying mechanisms of action involved in the onset of OLP and the most well-known triggering factors. According to the current data, oral microbiota dysbiosis could represent a potential diagnostic biomarker for OLP. However, further studies should be undertaken to validate their use in clinical practice, as well as to provide a better understanding of mechanisms of action and develop novel effective intervention strategies against OLP.

Methylation­sensitive restriction enzyme­droplet digital PCR assay for the one­step highly sensitive analysis of DNA methylation hotspots.

DNA methylation is an epigenetic modification that plays a key role in several cellular processes mediating the fine regulation of gene expression. Aberrant DNA methylation is observed in a wide range of pathologies, including cancer. Since these DNA modifications are transferred to the cell progenies and are stable over the time, the analysis of DNA methylation status has been proposed for diagnostic and prognostic purposes in cancer. Currently, DNA bisulfite conversion is the gold standard method for the high­throughput analysis of DNA methylation alterations. However, bisulfite treatment induces DNA fragmentation affecting its quality for the downstream analyses. In this field, it is mandatory to identify novel methods to overcome the limits of conventional approaches. In the present study, the Methylation­Sensitive Restriction Enzyme­droplet digital PCR (MSRE­ddPCR) assay was developed as a novel sensitive method for the analysis of DNA methylation of short genomic regions, combining the MSRE assay with the high­sensitivity ddPCR and using an exogenous methylation sequence as control. Setup and validation experiments were performed analyzing a methylation hotspot of the Solute Carrier Family 22 Member 17 in DNA samples derived from melanoma cell lines as well as from tissues and serum samples obtained from patients with melanoma and healthy controls. Compared with the standard MSRE approaches, the MSRE­ddPCR assay is more appropriate for the analysis of DNA methylation (methDNA) in samples with low amounts of DNA (up to 0.651 ng) showing a greater sensitivity. These findings suggested the potential clinical application of MSRE­ddPCR paving the way to the analysis of other methDNA hotspots in different tumors.

Influence of H-bond competitors on the solvent-dependent structures of an octaurea-calix[4]tube.

A novel octaurea-calix[4]tube (UC4T) has been synthesized in three steps from the original Beer's p-tert-butylcalix[4]tube ionophore. In a polar solvent (DMSO-d6), UC4T rapidly interconverts between two identical conformations with C2v symmetry for the two calix[4]arene subunits. However, in a less polar solvent mixture (CDCl3/DMSO-d6, 98 : 2), UC4T adopts a highly distorted asymmetric structure, which hinders the formation of typical tetraurea calix[4]arene capsular assemblies. The complexation of potassium (or barium) cations inside the dioxyethylene ionophoric binding site of UC4T triggers a C2v to C4v symmetry rearrangement of the two calix[4]arene subunits. This rearrangement leads to the formation of a transient capsular dimeric species observed in solution upon the addition of KI or BaCl2·2H2O to a solution (CDCl3/DMSO-d6, 98 : 2) of the macrocycle. X-ray studies confirm UC4T's ability to adopt different asymmetric conformations, depending on its interactions with solvent molecules. Two distinct crystal forms (α and ß) of UC4T have been obtained, each displaying divergent calix[4]arene subunits with pinched-cone conformations. These conformations exhibit distinctive head-to-tail (α) or head-to-head/tail-to-tail (ß) orientations of the ureido groups, which are involved in hydrogen bonding with solvent molecules. Notably, the pseudo-capsular 1D supramolecular polymeric arrays observed in the ß form of UC4T assemble to create large parallel solvent channels.

Deferiprone: new environmental perspectives. Insights into its sequestering ability vs. different metal cations.

Deferiprone, generally, is considered an important chelating agent for Fe3+ overload. From a literature data analysis, a lack of information on the interaction of this molecule toward a series of metal cations emerged, inducing to fill out the topic. The complexing ability of deferiprone toward Ca2+, Mg2+, Cd2+ and Pb2+ was studied by potentiometry and 1H NMR spectroscopy, in KCl aqueous solutions at different ionic strength values (0.1 ≤ I/mol dm-3 ≤ 1.0) and T = 298.15 K. The same speciation model featured by the ML, ML2, ML3 and ML(OH) (M = metal and L = deferiprone or DFP) species was obtained for Cd2+ and Pb2+; the formation constants calculated at infinite dilution are: logTß = 7.23±0.02, 12.47±0.03, 16.70±0.04, and -2.53±0.04, respectively for Cd2+ and 9.91±0.01, 15.99±0.02, 19.93±0.05 and 0.99±0.02 for Pb2+. Only two species, namely ML and ML2, were determined for Ca2+ and Mg2+, whose formation constants at infinite dilution are respectively: 3.72±0.01 and 6.50±0.02, for the first one, 5.31±0.01 and 9.58±0.01, for the second. The ligand sequestering ability and affinity toward M2+ were evaluated by determining the pL0.5 and pM parameters at different pHs and ionic strengths. The results suggest that deferiprone has the best complexing and sequestering ability toward Pb2+, followed by Cd2+, Mg2+ and Ca2+, respectively. 1H NMR studies confirmed the DFP affinity for Cd2+ and Pb2+, and in combination with DFT calculations showed that metal cations are bound to the hydroxo-oxo moiety of the pyridinone ring. The data reported in this study provide information on the possible employment of a small molecule like deferiprone, as a chelating and sequestering agent for Pb2+ accumulation or overload from environmental and biological matrices.

Ketogenic Diet and Breast Cancer: Recent Findings and Therapeutic Approaches.

Breast cancer (BC), a complex disease with several influencing factors, is significantly impacted by dietary habits. The ketogenic diet (KD), characterized by high fat and low carbohydrate intake, has gained attention as a potential therapeutic approach, but its effects on BC remain unclear. This review seeks to summarize the current knowledge on the principles of the KD, its metabolic influence on BC cells, and the findings of recent clinical trials, in order to elucidate the potential therapeutic role of the KD in BC management. For these purposes, a comprehensive literature review was conducted selecting preclinical and clinical studies that investigate the relationship between the KD and BC. The selection criteria prioritized studies exploring the KD's metabolic effects on BC cells and current clinical trials involving the KD in BC management. The reviewed studies provide a diverse range of findings, with some suggesting potential benefits of the KD in inhibiting tumor growth and improving treatment response. However, robust clinical trials providing clear evidence of the KD's efficacy as a standalone therapeutic approach in BC are still lacking. There are also significant concerns regarding the safety and long-term effects of sustained ketosis in cancer patients. The therapeutic potential of the KD in BC remains an area of active research and debate. While preliminary findings are promising, definitive conclusions are hindered by inconsistent results and limited human trial data. Future research, specifically well-structured, large-scale clinical trials, is necessary to provide a comprehensive understanding of the role of the KD in BC treatment. Until then, caution should be exercised in its application, and patients should continue prioritizing evidence-based, standard-of-care treatments.

Analysis of hsa-miR-19a-3p and hsa-miR-19b-3p modulation and phosphodiesterase type 5 expression in the vaginal epithelium of premenopausal women with genital arousal disorder.

BACKGROUND: Few studies have investigated the role of the phosphodiesterase type 5A (PDE5A) isoenzyme in female genital tissue disorders, exclusively taken from cadavers, as well as the epigenetic mechanisms responsible for the regulation of PDE5A levels. AIM: The aim was to study the in vivo association between microRNA (miRNA) expression and the expression levels of PDE5A in women with female genital arousal disorder (FGAD) compared with healthy women. METHODS: Premenopausal women affected by FGAD (cases) and sexually healthy women (control group) underwent microbiopsy of the periclitoral anterior vaginal wall for the collection of tissue samples. Computational analyses were preliminarily performed in order to identify miRNAs involved in the modulation of PDE5A by using miRNA-messenger RNA interaction prediction tools. Differences in the expression levels of miRNAs and PDE5A were finally investigated in cases and control subjects by using the droplet digital polymerase chain reaction amplification system and stratifying women considering their age, number of pregnancies, and body mass index. OUTCOMES: Expression levels of miRNAs were able to target PDE5A and the tissue expression in women with FGAD compared with healthy women. RESULTS: The experimental analyses were performed on 22 (43.1%) cases and 29 (56.9%) control subjects. Two miRNAs with the highest interaction levels with PDE5A, hsa-miR-19a-3p (miR-19a) and hsa-miR-19b-3p (miR-19b), were identified and selected for validation analyses. A reduction of the expression levels of both miRNAs was observed in women with FGAD compared with the control subjects (P < .05). Moreover, PDE5A expression levels were higher in women with FGAD and lower in women without sexual dysfunctions (P < .05). Finally, a correlation between body mass index and the expression levels of miR-19a was found (P < .01). CLINICAL IMPLICATIONS: Women with FGAD had higher levels of PDE5 compared with control subjects; therefore, the administration of PDE5 inhibitors (PDE5 inhibitors) could be useful in women with FGAD. STRENGTHS AND LIMITATIONS: The strength of the current study was to analyze genital tissue obtained in vivo from premenopausal women. A limitation was to not investigate other factors, including endothelial nitric oxide synthetases, nitric oxide, and cyclic guanosine monophosphate. CONCLUSION: The results of the present study indicate that the modulation of selected miRNAs could influence PDE5A expression in genital tissues in healthy women or in those with FGAD. Such findings further suggest that treatment with PDE5 inhibitors, as a modulator of PDE5A expression, could be indicated for women with FGAD.

Binary and ternary complexes of epinephrine with alginate and biologically and environmentally relevant metal cations.

The speciation of epinephrine (Eph -) in the presence of alginate (Alg 2-) and two biological and environmental relevant metal cations (Cu2+, UO2 2+) was investigated at T = 298.15K, I = 0.15-1.00 mol dm-3 in NaCl(aq). The formation of binary and ternary complexes was evaluated and, since epinephrine can behave as a zwitterion, the Eph -/Alg 2- interaction was studied by means of DOSY NMR. The dependence of the equilibrium constants on ionic strength was studied using an extended Debye-Hückel type equation and the SIT approach. The effect of temperature was investigated by means of isoperibolic titration calorimetry: the entropic contribution was the driving force for the Cu2+/Eph - complexes formation. The sequestering ability of Eph - and Alg 2- on Cu2+, evaluated by the pL0.5 calculation, increased with pH and ionic strength. The determination of pM parameter showed that Eph - had a higher Cu2+ affinity with respect to Alg 2-. The formation of Eph -/Alg 2- species was also investigated by UV-Vis spectrophotometry and 1H NMR measurements. The ternary Cu2+/Eph -/Alg 2- and Cu2+/UO2 2+/Eph - interactions were also studied. The "extra-stability" calculated for the mixed ternary species confirmed that their formation was thermodynamically favorable.

Clinical Relevance of Targeted Therapy and Immune-Checkpoint Inhibition in Lung Cancer.

Lung cancer (LC) represents the second most diagnosed tumor and the malignancy with the highest mortality rate. In recent years, tremendous progress has been made in the treatment of this tumor thanks to the discovery, testing, and clinical approval of novel therapeutic approaches. Firstly, targeted therapies aimed at inhibiting specific mutated tyrosine kinases or downstream factors were approved in clinical practice. Secondly, immunotherapy inducing the reactivation of the immune system to efficiently eliminate LC cells has been approved. This review describes in depth both current and ongoing clinical studies, which allowed the approval of targeted therapies and immune-checkpoint inhibitors as standard of care for LC. Moreover, the present advantages and pitfalls of new therapeutic approaches will be discussed. Finally, the acquired importance of human microbiota as a novel source of LC biomarkers, as well as therapeutic targets to improve the efficacy of available therapies, was analyzed. Therapy against LC is increasingly becoming holistic, taking into consideration not only the genetic landscape of the tumor, but also the immune background and other individual variables, such as patient-specific gut microbial composition. On these bases, in the future, the research milestones reached will allow clinicians to treat LC patients with tailored approaches.

Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant.

BACKGROUND: Gut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well as to improve the efficacy of certain anti-cancer treatments. Among the most characterized probiotics, Lactobacillus rhamnosus GG (LGG) is currently utilized in clinics to alleviate diarrhea, mucositis or intestinal damage which might be associated with several triggers, including Clostridium difficile infections, inflammatory gut diseases, antibiotic consumption, chemotherapy or radiation therapy. Here, we investigate whether LGG cell-free supernatant (LGG-SN) might exert anti-proliferative activity toward colon cancer and metastatic melanoma cells. Moreover, we assess the potential adjuvant effect of LGG-SN in combination with anti-cancer drugs. METHODS: LGG-SN alone or in combination with either 5-Fuorouracil and Irinotecan was used to treat human colon and human melanoma cancer cell lines. Dimethylimidazol-diphenyl tetrazolium bromide assay was employed to detect cellular viability. Trypan blue staining, anti-cleaved caspase-3 and anti-total versus anti-cleaved PARP western blots, and annexin V/propidium iodide flow cytometry analyses were used to assess cell death. Flow cytometry measurement of cellular DNA content (with propidium iodide staining) together with qPCR analysis of cyclins expression were used to assess cell cycle. RESULTS: We demonstrate that LGG-SN is able to selectively reduce the viability of cancer cells in a concentration-dependent way. While LGG-SN does not exert any anti-proliferative activity on control fibroblasts. In cancer cells, the reduction in viability is not associated with apoptosis induction, but with a mitotic arrest in the G2/M phase of cell cycle. Additionally, LGG-SN sensitizes cancer cells to both 5-Fluorouracil and Irinotecan, thereby showing a positive synergistic action. CONCLUSION: Overall, our results suggest that LGG-SN may contain one or more bioactive molecules with anti-cancer activity which sensitize cancer cells to chemotherapeutic drugs. Thus, LGG could be proposed as an ideal candidate for ground-breaking integrated approaches to be employed in oncology, to reduce chemotherapy-related side effects and overcome resistance or relapse issues, thus ameliorating the therapeutic response in cancer patients.

Bioinformatic analysis of the LCN2-SLC22A17-MMP9 network in cancer: The role of DNA methylation in the modulation of tumor microenvironment.

Several features of cancer cells such as proliferation, invasion, metastatic spreading, and drug resistance are affected by their interaction with several tumor microenvironment (TME) components, including neutrophil gelatinase-associated lipocalin (NGAL), solute carrier family 22 member 17 (SLC22A17), and matrix metallopeptidase 9 (MMP9). These molecules play a key role in tumor growth, invasion, and iron-dependent metabolism of cancer cells. However, the precise epigenetic mechanisms underlying the gene regulation of Lipocalin 2 (LCN2), SLC22A17, and MMP9 in cancer still remain unclear. To this purpose, computational analysis was performed on TCGA and GTEx datasets to evaluate the expression and DNA methylation status of LCN2, SLC22A17, and MMP9 genes in different tumor types. Correlation analysis between gene/isoforms expression and DNA methylation levels of LCN2, SLC22A17, and MMP9 was performed to investigate the role of DNA methylation in the modulation of these genes. Protein network analysis was carried out using reverse phase protein arrays (RPPA) data to identify protein-protein interactions of the LCN2-SLC22A17-MMP9 network. Furthermore, survival analysis was performed according to gene expression and DNA methylation levels. Our results demonstrated that LCN2 and MMP9 were mainly upregulated in most tumor types, whereas SLC22A17 was largely downregulated, representing a specific hallmark signature for all gastrointestinal tumors. Notably, the expression of LCN2, SLC22A17, and MMP9 genes was negatively affected by promoter methylation. Conversely, intragenic hypermethylation was associated with the overexpression of SLC22A17 and MMP9 genes. Protein network analysis highlighted the role of the LCN2-SLC22A17-MMP9 network in TME by the interaction with fibronectin 1 and claudin 7, especially in rectal tumors. Moreover, the impact of expression and methylation status of LCN2, SLC22A17, and MMP9 on overall survival and progression free interval was tumor type-dependent. Overall, our analyses provide a detailed overview of the expression and methylation status of LCN2, SLC22A17, and MMP9 in all TCGA tumors, indicating that the LCN2-SLC22A17-MMP9 network was strictly regulated by DNA methylation within TME. Our findings pave the way for the identification of novel DNA methylation hotspots with diagnostic and prognostic values and suitable for epi-drug targeting.

A two-site reactive platform in the synthesis of amino-functionalized amphiphilic molecules via sulfenic acids.

The synthesis of some bolaamphiphiles is described. It is a convergent approach that allows the linkage of a glucosyl derivative to a bis-functionalized platform, via a copper-free Sonogashira cross-coupling. The central core was obtained from the reaction of a suitably substituted bis-sulfoxide with diethynyl benzenes. The intermediates of such reaction are sulfenyl functions that are easily added to one triple bond of the unsaturated molecules. The functionalization at the central core, through the nucleophilic addition of ammonia or piperidine onto the two vinyl sulfonyl groups already present in the backbones of the molecules, opened the way to the preparation of more complex derivatives. The observation of the formation of new stereogenic carbons with an unexpected significantly high diastereoselectivity was justified and supported by preliminary theoretical calculations. The two ending glucosyl moieties were favourably deprotected to afford the amino-functionalized bolaamphiphilic molecules.

Proton transfer mediated recognition of amines by ionizable macrocyclic receptors.

Ammonium ion/carboxylate ion pairing is a key interaction ubiquitous in biological systems, but amine recognition by ionizable molecular receptors, mediated by host-to-guest proton transfer, has too often been overlooked as a design element for molecular recognition. This survey will show that proton transfer mediated recognition is a powerful and versatile tool that can be made to work with different amines and diverse macrocyclic scaffolds, such as crown ethers, calixarenes or pillararenes. We will trace the history of this recognition motif since Cram's first report half a century ago down to the latest applications in supramolecular sensing, drug-delivery and materials science, highlighting along the way the impact of host-to-guest proton transfer on self-assembly and molecular recognition.

Liquid Biopsy and Circulating Biomarkers for the Diagnosis of Precancerous and Cancerous Oral Lesions.

Oral cancer is one of the most common malignancies worldwide, accounting for 2% of all cases annually and 1.8% of all cancer deaths. To date, tissue biopsy and histopathological analyses are the gold standard methods for the diagnosis of oral cancers. However, oral cancer is generally diagnosed at advanced stages with a consequent poor 5-year survival (~50%) due to limited screening programs and inefficient physical examination strategies. To address these limitations, liquid biopsy is recently emerging as a novel minimally invasive tool for the early identification of tumors as well as for the evaluation of tumor heterogeneity and prognosis of patients. Several studies have demonstrated that liquid biopsy in oral cancer could be useful for the detection of circulating biomarkers including circulating tumor DNA (ctDNA), microRNAs (miRNAs), proteins, and exosomes, thus improving diagnostic strategies and paving the way to personalized medicine. However, the application of liquid biopsy in oral cancer is still limited and further studies are needed to better clarify its clinical impact. The present manuscript aims to provide an updated overview of the potential use of liquid biopsy as an additional tool for the management of oral lesions by describing the available methodologies and the most promising biomarkers.

Potential Neurotoxic Effects of Glioblastoma-Derived Exosomes in Primary Cultures of Cerebellar Neurons via Oxidant Stress and Glutathione Depletion.

High-grade gliomas are the most fatal brain tumors. Grade 4 gliomas are called glioblastoma multiforme (GBM), which are associated with the poorest survival and a 5-year survival rate of less than 4%. Many patients with GBM developed concomitant cognitive dysfunctions and epilepsy. Although the cognitive decline is well defined in glioblastomas, the neurotoxic factors underlying this pathology are not well understood in GBM patients. In this study, we aimed to investigate whether GBM-derived exosomes play a role in neuronal toxicity. For this purpose, exosomes obtained from T98G and U373 GBM cells were applied to primary neuron culture at different concentrations. Subsequently, MTT, LDH, GSH, TAS, and TOS tests were performed. Both GBM-derived exosomes induced a dose-dependent and statistically significant increase of LDH release in cerebellar neurons. MTT assay revealed as both T98G and U373 GBM-derived exosomes induced dose-dependent neurotoxic effects in cerebellar neurons. To the best of our knowledge, this study is the first study demonstrating the toxic potential of GBM-derived exosomes to primary neurons, which may explain the peritumoral edema and cognitive decline in GBM patients.

Chronic Pesticide Exposure in Farm Workers Is Associated with the Epigenetic Modulation of hsa-miR-199a-5p.

The increasing use of pesticides in intensive agriculture has had a negative impact on human health. It was widely demonstrated how pesticides can induce different genetic and epigenetic alterations associated with the development of different diseases, including tumors and neurological disorders. Therefore, the identification of effective indicators for the prediction of harmful pesticide exposure is mandatory. In this context, the aim of the study was to evaluate the modification of hsa-miR-199a-5p expression levels in liquid biopsy samples obtained from healthy donors and farm workers with chronic exposure to pesticides. For this purpose, the high-sensitive droplet digital PCR assay (ddPCR) was used to detect variation in the expression levels of the selected microRNA (miRNA). The ddPCR analyses revealed a significant down-regulation of hsa-miR-199a-5p observed in individuals exposed to pesticides compared to control samples highlighting the good predictive value of this miRNA as demonstrated by statistical analyses. Overall, the obtained results encourage the analysis of miRNAs as predictive biomarkers of chronic pesticide exposure thus improving the current strategies for the monitoring of harmful pesticide exposure.

Co-Occurrence of Interleukin-6 Receptor Asp358Ala Variant and High Plasma Levels of IL-6: An Evidence of IL-6 Trans-Signaling Activation in Deep Vein Thrombosis (DVT) Patients.

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in several mechanisms, and the alteration of IL-6 signaling leads to the overactivation of various processes including immunity, inflammation, and hemostasis. Although IL-6 increase has been documented in venous thromboembolic diseases, the exact involvement of IL-6 signaling in deep vein thrombosis (DVT) has not been fully understood. Consequently, we investigated the involvement of IL-6 trans-signaling in inflammatory events occurring in DVT, focusing on the role of the interleukin-6 receptor (IL6-R) Asp358Ala variant. The circulating levels of IL-6, soluble IL6-R (sIL6-R), and soluble glycoprotein 130, as well as the Asp358Ala genotyping, were assessed in a consecutive cohort of DVT patients and healthy controls. The results indicated that IL-6 was higher in DVT compared to controls. Moreover, sIL6-R levels were strongly correlated to Asp358Ala variant in both groups, showing a high frequency of this mutation across all samples. Interestingly, our results showed a high frequency of both Asp358Ala mutation and raised IL-6 levels in DVT patients (OR = 21.32; p ≤ 0.01), highlighting that this mutation could explain the association between IL-6 overactivation and DVT outcome. Overall, this study represents a proof of concept for the targeting of IL-6 trans-signaling as a new strategy for the DVT adjuvant therapy.

Identification of the most common BRCA alterations through analysis of germline mutation databases: Is droplet digital PCR an additional strategy for the assessment of such alterations in breast and ovarian cancer families?

Breast and ovarian cancer represent two of the most common tumor types in females worldwide. Over the years, several non­modifiable and modifiable risk factors have been associated with the onset and progression of these tumors, including age, reproductive factors, ethnicity, socioeconomic status and lifestyle factors, as well as family history and genetic factors. Of note, BRCA1 and BRCA2 are two tumor suppressor genes with a key role in DNA repair processes, whose mutations may induce genomic instability and increase the risk of cancer development. Specifically, females with a family history of breast or ovarian cancer harboring BRCA1/2 germline mutations have a 60­70% increased risk of developing breast cancer and a 15­40% increased risk for ovarian cancer. Different databases have collected the most frequent germline mutations affecting BRCA1/2. Through the analysis of such databases, it is possible to identify frequent hotspot mutations that may be analyzed with next­generation sequencing (NGS) and novel innovative strategies. In this context, NGS remains the gold standard method for the assessment of BRCA1/2 mutations, while novel techniques, including droplet digital PCR (ddPCR), may improve the sensitivity to identify such mutations in the hereditary forms of breast and ovarian cancer. On these bases, the present study aimed to provide an update of the current knowledge on the frequency of BRCA1/2 mutations and cancer susceptibility, focusing on the diagnostic potential of the most recent methods, such as ddPCR.

Overview of the Clinical and Molecular Features of Legionella Pneumophila: Focus on Novel Surveillance and Diagnostic Strategies.

Legionella pneumophila (L. pneumophila) is one of the most threatening nosocomial pathogens. The implementation of novel and more effective surveillance and diagnostic strategies is mandatory to prevent the occurrence of legionellosis outbreaks in hospital environments. On these bases, the present review is aimed to describe the main clinical and molecular features of L. pneumophila focusing attention on the latest findings on drug resistance mechanisms. In addition, a detailed description of the current guidelines for the disinfection and surveillance of the water systems is also provided. Finally, the diagnostic strategies available for the detection of Legionella spp. were critically reviewed, paying the attention to the description of the culture, serological and molecular methods as well as on the novel high-sensitive nucleic acid amplification systems, such as droplet digital PCR.

Overactivation of IL6 cis­signaling in leukocytes is an inflammatory hallmark of deep vein thrombosis.

Inflammation is a protective response of the body to various injuries, which is strictly regulated by a variety of factors, including immune cells and soluble mediators. However, dysfunction of this defensive mechanism often results in inflammation­driven diseases, such as deep vein thrombosis (DVT). The complex relationship between inflammatory cell activity and DVT has not been fully elucidated. The present study aimed to investigate the role of interleukin­6 (IL6) signaling transduction in DVT. To this aim, the expression levels of transmembrane isoforms of the IL6 receptor (IL6R) and the glycoprotein 130 responsible for the IL6 cis­signaling were evaluated in the peripheral blood mononuclear cells of patients with DVT and of healthy controls. The results indicated that leukocytes from patients with DVT exhibited overexpression of both IL6R and gp130 membrane isoforms and that these were strongly associated with the occurrence of DVT. Overall, the present findings indicated that IL6 cis­signaling may have a direct involvement in the leukocyte activation in DVT and may serve as a predictive biomarker of DVT development.

Biotechnological Applications and Health-Promoting Properties of Flavonols: An Updated View.

Flavonols are a subclass of natural flavonoids characterized by a remarkable number of biotechnological applications and health-promoting properties. They attract researchers' attention due to many epidemiological studies supporting their usage. They are phytochemicals commonly present in our diet, being ubiquitous in the plant kingdom and, in particular, relatively very abundant in fruits and vegetables. All these aspects make flavonols candidates of choice for the valorization of products, based on the presence of a remarkable number of different chemical structures, each one characterized by specific chemical features capable of influencing biological targets inside the living organisms in very different manners. In this review, we analyzed the biochemical and physiological characteristics of flavonols focalizing our attention on the most promising compounds to shed some light on their increasing utilization in biotechnological applications in processing industries, as well as their suitable employment to improve the overall wellness of the humankind.