Cancer affects millions of individuals worldwide. Thus, there is an increased need for the development of novel effective therapeutic approaches. Tumorigenesis is often coupled with immunosuppression ...which defeats the anticancer immune defense mechanisms activated by the host. Novel anticancer therapies based on the use of immune checkpoint inhibitors (ICIs) are very promising against both solid and hematological tumors, although still exhibiting heterogeneous efficacy, as well as tolerability. Such a differential response seems to derive from individual diversity, including the gut microbiota (GM) composition of specific patients. Experimental evidence supports the key role played by the GM in the activation of the immune system response against malignancies. This observation suggests to aim for patient‑tailored complementary therapies able to modulate the GM, enabling the selective enrichment in microbial species, which can improve the positive outcome of ICI‑based immunotherapy. Moreover, the research of GM‑derived predictive biomarkers may help to identify the selected cancer population, which can benefit from ICI‑based therapy, without the occurrence of adverse reactions and/or cancer relapse. The present review summarizes the landmark studies published to date, which have contributed to uncovering the tight link existing between GM composition, cancer development and the host immune system. Bridging this triangle of interactions may ultimately guide towards the identification of novel biomarkers, as well as integrated and patient‑tailored anticancer approaches with greater efficacy.
In this paper, we report on the synthesis of a new hybrid photocatalytic material activated by natural sunlight irradiation. The material consists of multiferroic nanoparticles of bismuth ferrite ...(BFO) modified through the growth of the Fe-based MIL-101 framework. Material characterization, conducted using various techniques (X-ray diffraction, transmission electron microscopy, FTIR, and X-ray photoelectron spectroscopies), confirmed the growth of the MIL-101 metal–organic framework on the BFO surface. The obtained system possesses the intrinsic photo-degradative properties of BFO nanoparticles significantly enhanced by the presence of MIL-101. The photocatalytic activity of this material was tested in antibacterial experiments conducted under natural sunlight exposure within the nanocomposite concentration range of 100–0.20 µg/ml. The MIL-modified BFO showed a significant decrease in both Minimum Inhibiting Concentration and Minimum Bactericide Concentration values compared to bare nanoparticles. This confirms the photo-activating effect of the MIL-101 modification. In particular, they show an increased antimicrobial activity against the tested Gram-positive species and the ability to begin to inhibit the growth of the four
Escherichia coli
strains, although at the maximum concentration tested. These results suggest that the new nanocomposite BiFeO
3
@MOF has been successfully developed and has proven to be an effective antibacterial agent against a wide range of microorganisms and a potential candidate in disinfection processes.
Primary solid tumors originate close to pre-existing tissue vasculature, initially growing along such tissue blood vessels, and this phenomenon is important for the metastatic potential which ...frequently occurs in highly vascularized tissues. Unfortunately, preclinic and clinic anti-angiogenic approaches have not been very successful, and multiple factors have been found to contribute to toxicity and tumor resistance. Moreover, tumors can highlight intrinsic or acquired resistances, or show adaptation to the VEGF-targeted therapies. Furthermore, different mechanisms of vascularization, activation of alternative signaling pathways, and increased tumor aggressiveness make this context even more complex. On the other hand, it has to be considered that the transitional restoration of normal, not fenestrated, microvessels allows the drug to reach the tumor and act with the maximum efficiency. However, these effects are time-limited and different, depending on the various types of cancer, and clearly define a specific "normalization window." So, new horizons in the therapeutic approaches consist on the treatment of the tumor with pro- (instead of anti-) angiogenic therapies, which could strengthen a network of well-structured blood vessels that facilitate the transport of the drug.
Vascular pericytes are an important cellular component in the tumor microenvironment, however, their role in supporting cancer invasion is poorly understood. We hypothesized that PDGF-BB could be ...involved in the transition of human retinal pericytes (HRPC) in cancer-activated fibroblasts (CAF), induced by the 92.1 uveal melanoma (UM) cell line. In our model system, HRPC were conditioned by co-culturing with 92.1UM for 6 days (cHRPC), in the presence or absence of imatinib, to block PDGF receptor-β (PDGFRβ). The effects of the treatments were tested by wound healing assay, proliferation assay, RT-PCR, high-content screening, Western blot analysis, and invasion assay. Results showed profound changes in cHRPC shape, with increased proliferation and motility, reduction of NG2 and increase of TGF-β1, α-SMA, vimentin, and FSP-1 protein levels, modulation of PDGF isoform mRNA levels, phospho-PDGFRβ, and PDGFRβ, as well as phospho-STAT3 increases. A reduction of IL-1β and IFNγ and an increase in TNFα, IL10, and TGF-β1, CXCL11, CCL18, and VEGF mRNA in cHRPC were found. Imatinib was effective in preventing all the 92.1UM-induced changes. Moreover, cHRPC elicited a significant increase of 92.1UM cell invasion and active MMP9 protein levels. Our data suggest that retinal microvascular pericytes could promote 92.1UM growth through the acquisition of the CAF phenotype.
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.
(
) 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
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
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.
It is suspected that microbial infections take part in the pathogenesis of diabetes mellitus type 1 (T1DM). Glucose-induced insulin secretion is accompanied by the release of free arachidonic acid ...(AA) mainly by cytosolic- and calcium independent phospholipases A2 (cPLA2 and iPLA2). Insulinoma cell line (INS-1E) was infected with E. coli isolated from the blood culture of a patient with sepsis. Invasion assay, Scanning Electron Microscopy and Transmission Electron Microscopy demonstrated the capacity of E. coli to enter cells, which was reduced by PLA2 inhibitors. Glucose-induced insulin secretion was significantly increased after acute infection (8h) but significantly decreased after chronic infection (72h). PLA2 activities, cPLA2, iPLA2, phospho-cPLA2, and COX-2 expressions were increased after acute and, even more, after chronic E. coli infection. The silencing of the two isoforms of PLA2s, with specific cPLA2- or iPLA2-siRNAs, reduced insulin secretion after acute infection and determined a rise in insulin release after chronic infection. Prostaglandins E2 (PGE2) production was significantly elevated in INS-1E after long-term E. coli infection and the restored insulin secretion in presence of L798106, a specific EP3 antagonist, and NS-398, a COX-2 inhibitor, and the reduction of insulin secretion in presence of sulprostone, a specific EP3 agonist, revealed their involvement in the effects triggered by bacterial infection. The results obtained demonstrated that cPLA2 and iPLA2 play a key role in insulin secretion process after E. coli infection. The high concentration of AA released is transformed into PGE2, which could be responsible for the reduced insulin secretion.
In the present study, the in vitro activity of the sulbactam–durlobactam (SUL–DUR) combination was evaluated against 141 carbapenem-resistant A. baumannii (CRAb) clinical strains collected from six ...Italian laboratories. Over half (54.6%) of these isolates were resistant to colistin. The SUL–DUR combination was active against these CRAb isolates with MIC50 and MIC90 values of 0.5 mg/L and 4 mg/L, respectively. Only eleven isolates were resistant to SUL–DUR with MIC values ranging from 8 to 128 mg/L. The SUL–DUR resistant A. baumannii exhibited several antimicrobial resistance genes (ARGs) such as blaOXA-20, blaOXA-58, blaOXA-66, blaADC-25, aac(6′)-Ib3 and aac(6′)-Ib-cr and mutations in gyrA (S81L) and parC (V104I, D105E). However, in these isolates, mutations Q488K and Y528H were found in PBP3. Different determinants were also identified in these CRAb isolates, including adeABC, adeFGH, adeIJK, abeS, abaQ and abaR, which encode multidrug efflux pumps associated with resistance to multiple antibacterial agents. This is the first report on the antimicrobial activity of SUL–DUR against carbapenem-resistant A. baumannii isolates selected from multiple regions in Italy.
Pericytes are branched cells located in the wall of capillary blood vessels that are found throughout the body, embedded within the microvascular basement membrane and wrapping endothelial cells, ...with which they establish a strong physical contact. Pericytes regulate angiogenesis, vessel stabilization, and contribute to the formation of both the blood-brain and blood-retina barriers by Angiopoietin-1/Tie-2, platelet derived growth factor (PDGF) and transforming growth factor (TGF) signaling pathways, regulating pericyte-endothelial cell communication. Human pericytes that have been cultured for a long period give rise to multilineage progenitor cells and exhibit mesenchymal stem cell (MSC) features. We focused our attention on the roles of pericytes in brain and ocular diseases. In particular, pericyte involvement in brain ischemia, brain tumors, diabetic retinopathy, and uveal melanoma is described. Several molecules, such as adenosine and nitric oxide, are responsible for pericyte shrinkage during ischemia-reperfusion. Anti-inflammatory molecules, such as IL-10, TGFβ, and MHC-II, which are increased in glioblastoma-activated pericytes, are responsible for tumor growth. As regards the eye, pericytes play a role not only in ocular vessel stabilization, but also as a stem cell niche that contributes to regenerative processes in diabetic retinopathy. Moreover, pericytes participate in melanoma cell extravasation and the genetic ablation of the PDGF receptor reduces the number of pericytes and aberrant tumor microvessel formation with important implications for therapy efficacy. Thanks to their MSC features, pericytes could be considered excellent candidates to promote nervous tissue repair and for regenerative medicine.
No studies have evaluated the ultrasound features of the male sex accessory glands in infertile patients with bacterial male accessory gland infection （MAGI） according to the microbiological outcomes ...of bacterial cultures （absent, partial or complete） following antibiotic therapy administration. Therefore, the aim of this study was to evaluate the ultrasound characteristics of the prostate, seminal vesicles, and epididymal tracts after treatment with levofloxacin （a common quinolone antibiotic）, in patients with infections caused by Escherichia coil （a Gram-negative bacterium） according to the Naber＇s classification, which includes the following categories： eradication, eradication with superinfection, persistence and persistence with superinfection. The study was conducted in 100 patients aged 25±8 years （range： 20-40 years） with bacterial MAGI and bacterial cultures positive only for E. coil（colony forming units ≥ 106 per ml）. Retrospective analysis was conducted only on patients treated with oral levofloxacin （500 mg） administered once daily for 28 days who were recruited over the last 5 years. Following antibiotic treatment, patients with microbiological persistence or persistence with superinfection had a significantly higher percentage of ultrasound abnormalities suggestive of prostato-vesiculitis （PV） （30.2% and 36.0%, respectively） or prostato-vesiculo-epididymitis （PVE） （60.2% and 70.0%, respectively） compared with patients with microbiological eradication （PV= 10.2% and PVE=8.2%, respectively） or eradication with superinfection （PV= 18.8% and PVE=21.2%, respectively）. In conclusion, patients with microbiological persistence or persistence plus superinfection showed the highest prevalence of complicated forms of MAGI （PV and PVE）, compared with patients with microbiological eradication or eradication with superinfection.
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