Francesca Sisto

University of Milan | UNIMI · Department of Biomedical, Surgical , and Dental Sciences

Helicobacter pylori (Hp) infection affects nearly half of the global population. Current therapeutic options include the administration of a combination of antibiotics and proton pump inhibitors, although antimicrobial resistance rise remains a big concern. Phenolic monoterpenes, e.g., eugenol, vanillin, carvacrol, and thymol, have always attracted...

The antimicrobial properties of one of the most important secondary metabolites, Eugenol (EU), inspired us to design and synthesize three different series of derivatives enhancing its parent compound's anti-Helicobacter pylori activity. Thus, we prepared semisynthetic derivatives through (A) diazo aryl functionalization, (B) derivatization of the h...

The microbial biofilm has been defined as a “key virulence factor” for a multitude of microorganisms associated with chronic infections. Its multifactorial nature and variability, as well as an increase in antimicrobial resistance, suggest the need to identify new compounds as alternatives to the commonly used antimicrobials. The aim of this study...

Medicinal plants are utilized around the globe for the treatment of a wide range of ailments. This study is an attempt to document the utilization of medicinal plants across the four different cultural groups residing in the rural and remote villages of the northern districts of the Union territory of Jammu and Kashmir, India. To gather information...

Ethnopharmacological relevance Achillea erba-rotta subsp. moschata (Wulfen) I.Richardson (syn. A. moschata Wulfen) (Asteraceae) is an alpine endemic plant whose aerial parts are harvested by the locals mainly for the digestive properties. Despite its widespread use, few studies have been conducted to date to verify its properties. Aim of the study...

This study evaluated the in vitro activity of the arylaminoartemisinin GC012, readily obtained from dihydroartemisinin (DHA), against clinical strains of Helicobacter pylori (H. pylori) with different antibiotic susceptibilities in the planktonic and sessile state. The activity was assessed in terms of bacteriostatic and bactericidal potential. The...

In this study, the interaction between benzothiazole (BTA, concentration of a drug required for 50% inhibition in vitro (IC50) = 0.77 mM) and benzimidazole (BIA, IC50 = 2.14 mM) with urease was quantitatively assessed, using UV-Vis, molecular fluorescence, and circular dichroism. The results showed that both compounds interact with urease by a stat...

A new cationic Pt(II) complex bearing 8-aminoquinoline as chelating ligand (called Pt-8AQ) was evaluated against two human carcinomas, one mesothelioma, and three glioblastoma cell lines. The in vitro comparison to the clinically approved CisPt showed a minor activity of Pt-8AQ against carcinoma and mesothelioma, whereas a significant activity of P...

This is the first study of its kind conducted with the aim to document and conserve the ethnomedicinal knowledge of plants used to cure dental diseases in Buner, Pakistan and to provide starting point for future pharmacological studies about new herbal drugs used for dental disorders. Several field trips were conducted in 2018-19 to collect indigen...

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental a...

Nonsteroidal aromatase inhibitors (NSAIs) are well-established drugs for the therapy of breast cancer. However, they display some serious side effects, and their efficacy can be compromised by the development of chemoresistance. Previously, we have reported different indazole-based carbamates and piperidine-sulphonamides as potent aromatase inhibit...

This study reports on the synthesis, structural assessment, microbiological screening against several strains of H. pylori and antiproliferative activity against human gastric adenocarcinoma (AGS) cells of a large series of carvacrol-based compounds. Structural analyses consisted of elemental analysis, 1 H/ 13 C/ 19 F NMR spectra and crystallograph...

The aim of the work is to assess the antimicrobial activities of Cell Free Supernatants (CFS) and Membrane Vesicles (MVs), produced by Lactobacillus reuteri DSM 17938, versus Gram-positive and Gram-negative bacteria and investigate their metabolic profiles. The Minimum Inhibitory Concentration was determined through the broth microdilution method a...

Background Adipose tissue derived MSCs engineered with the tumor necrosis factor-related apoptosis-inducing ligand protein (MSCs-TRAIL) have a significant anticancer activity. MSCs, without any genetic modifications, exposed to high doses of chemotherapeutic agents are able to uptake the drug and release it in amount affecting tumor proliferation....

Introduction: Biofilm is a complex aggregation of microorganisms characterized by the presence of a dynamic, adhesive and protective extracellular matrix composed of polysaccharides, proteins and nucleic acids. It is estimated that the vast majority of human infections are related to the biofilm in which the microorganisms reside and communicate w...

Helicobacter pylori colonizes approximately 50% of the world’s population, and it is the cause of chronic gastritis, peptic ulcer disease, and gastric cancer. The increase of antibiotic resistance is one of the biggest challenges of our century due to its constant increase. In order to identify an alternative or adjuvant strategy to the standard an...

This review article is an effort to summarize the medicinal plant status, history, research, prospects and limitation in Pakistan. Therapeutic plants are the important part of the healthcare system. Over 400.000 higher plants species are identified so far; of which about 10% are utilized by different communities for medicinal purposes. In Pakistan,...

Surgical site infections (SSIs) represent the most common nosocomial infections, and surgical sutures are optimal surfaces for bacterial adhesion and biofilm formation. Staphylococcus spp., Enterococcus spp., and Escherichia coli are the most commonly isolated microorganisms. The aim of this research was to evaluate the antibiofilm activity of a me...

The genome of Helicobacter pylori encodes for carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α- and β-CA classes, which together with urease, have a pivotal role in the acid acclimation of the microorganism within the human stomach. Recently, in the exoproteome of H. pylori, a CA with no indication of the corresponding class was identified....

Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid patt...

An Italian certified Neem seed oil was characterized through the color analysis, the HPLC phenolic fingerprint and the preliminary evaluation of the cytotoxicity profile against the human macrophage (THP-1) cell line. Moreover, a wide screening of its enzyme inhibitory profile, antimicrobial activity towards Helicobacter pylori, several Candida spp...

In this study, the in vitro stability of cisplatin (CisPt) and cationic platinum(II)-complex (caPt(II)-complex) and their in vitro activity (antiproliferative and anti-angiogenic properties) were investigated against three aggressive human tumor cell lines. caPt(II)-complex shown a high stability until 9 days of treatment and displayed a significan...

Aims: The aim of this research is to verify the presence of Legionella in human dental plaque. Methods: 65 adult patients not treated with systemic or local antibiotics at least 2 months before the time of sample collection were enrolled for plaque collection between September 2015 and December 2016. A brief questionnaire about lifestyle and hea...

Objectives: To describe clinical characteristics and outcome of Clostridium difficile infection (CDI) patients in Internal Medicine, to identify ribotypes (RTs); to evaluate the association between RT and patient clinical characteristics and report outcome. Methods: One year prospective cohort study. Clinical data, Barthel Index (BI) and outcome...

The interaction of (S)-(-)-usnic acid (2) and fumarprotocetraric acid (3), isolated from Cladonia rappii (lichen), and commercial (R)-(+)-usnic acid (1) with urease was investigated in vitro by molecular spectroscopy at pH 7.4 and kinetics experiments using jack bean type III urease. All lichen compounds tested interact with urease by statistic que...

Human mesenchymal stromal cells (MSCs) have been widely investigated both for regenerative medicine and their antinflammatory/immunomodulatory capacity. However, their ability to home pathological tissues suggested the development of strategies for using MSCs as carrier to deliver drug into tumor microenvironment. MSCs obtained from different tissu...

Antibacterial and cytotoxic activities of cyclohexane, dichloromethane, methanol, and aqueous extracts of Cantharellus cibarius were tested. Broth microdilution assay was performed against 10 bacterial strains (Staphylococcus aureus, S. epidermidis, Micrococcus luteus, Bacillus subtilis, Enterococcus feacalis, Escherichia coli, Klebsiella pneumonia...

Background: A new tool for the drug delivery is based on the use of Mesenchymal Stromal Cells (MSCs) loaded in vitro with anti-cancer drugs. Unfortunately, the restricted lifespan of MSCs represents a significant limitation to produce them in high amounts and for long time studies. Immortalized MSCs from adipose tissue (hASC) have been generated a...

Introduction: Malignant pleural mesothelioma (MPM) is a rare fatal asbestos-related malignancy originating in the mesothelial cells of the pleura. A platinum-based doublet containing a third-generation antifolate is the front-line standard of care whilst there are no approved second-line treatments for MPM which remains a disease setting to test t...

Background: Clostridium difficile-associated disease (CDAD) is the most common infectious antibiotic-associated diarrhea and is a growing health care problem. Prevention of Clostridium difficile infection focuses on clinical and epidemiologic infection control measures. Methods: Between 2008 and 2009, we conducted a retrospective study that show...

The in vitro activity of the new artemisinin derivative artemisone as well as other molecules of the same class against Helicobacter pylori and their effects when combined with standard antibiotics were evaluated. Since H. pylori can be internalised into gastric epithelial cells, the effects of artemisinin, dihydroartemisinin and artemisone against...

Objective: Gingival tissue is composed of cell types that contribute to the body's defense against many agents in oral environment, wound healing and tissue regeneration. Thanks to their easy and scarcely invasive withdrawal procedure, interdental papilla provide a good source of mesenchymal stromal cells (GinPa-MSCs). We isolated GinPa-MSCs and v...

Background: Drug toxicity currently represents the main challenge of tumour chemotherapy. Our group recently developed a new method for drug delivery inspired by the 'Trojan Horse' concept. Human mesenchymal stem cells (hMSCs) have been shown to play the role of new 'horses' in delivering anti-tumour agents, without involving any genetic manipulat...

Mesenchymal stromal cells (MSCs) are considered an important therapeutic tool in cancer therapy. They possess intrinsic therapeutic potential and can also be in vitro manipulated and engineered to produce therapeutic molecules that can be delivered to the site of diseases, through their capacity to home pathological tissues. We have recently demons...

Background aims: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered...

Introduction: In the context of drug delivery, mesenchymal stromal cells (MSCs) from bone marrow and adipose tissue have emerged as interesting candidates due to their homing abilities and capacity to carry toxic loads, while at the same time being highly resistant to the toxic effects. Amongst the many sources of MSCs which have been identified,...

The present study evaluated the anti-Helicobacterpylori activity of Alchemilla glabra Neygenf. (A. sect. Alchemilla), A. monticola Opiz (A. sect. Plicatae S.E. Fröhner), A. fissa Günther & Schummel (A. sect. Calycinae (Buser) Buser) and A. viridiflora Rothm. (A. sect. Calycinae), and identified ellagic acid and quercetin-3-O-β-glucoside. Anti-H. py...

Crocus sativus L. is known in herbal medicine for the various pharmacological effects of its components, but no data are found in literature about its biological properties toward Helicobacter pylori, Plasmodium spp. and Leishmania spp. In this work, the potential anti-bacterial and anti-parasitic effects of crocin and safranal, two important bioac...

Background aims: In attempting to develop new strategies to circumvent the immunosuppression associated with glioblastoma (GB), novel approaches have been designed using dendritic cell (DC)-based vaccination, which is considered a promising strategy to attack high-grade glioma. In previous studies, we demonstrated that human mesenchymal stromal ce...

Clostridium difficile is one of the most important agent of hospital infection with increasing rate of incidence [4]. During a prospective study conducted between 15th March 2011 and 15th March 2012, 142 C. difficile associated disease (CDAD) cases from four internal medicine wards of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in...

Mesenchymal stromal cells (MSCs) have been proposed for delivering anticancer agents because of their ability to home tumor microenvironment. We found that MSCs can acquire strong anti-tumor activity after priming with Paclitaxel (PTX) through their capacity to uptake and then release the drug. Because MSCs secrete a high amount of membrane microve...

To improve the drug delivery efficiency on target cells many strategies have been developed including also Mesenchymal Stromal Cells (MSCs) approaches. In a previous study, we found that bone-marrow-derived MSCs (BM-MSCs) were able to incorporate and release the anti-tumor and anti-angiogenic drug Paclitaxel (PTX). In this study, we evaluated the s...

Traditional antibiotic therapy is based on the oral or systemic injection of antibiotics that are often unable to stop a deep infection (eg, osteomyelitis). We studied whether or not bone marrow stromal cells (BM-MSCs) are able to uptake and release ciprofloxacin (CPX), a fluoroquinolone considered the drug of choice for the treatment of chronic os...

Current leukaemia therapy focuses on increasing chemotherapy efficacy. Mesenchymal stromal cells (MSCs) have been proposed for carrying and delivery drugs to improve killing of cancer cells. We have shown that MSCs loaded with Paclitaxel (PTX) acquire a potent anti-tumour activity. We investigated the effect of human MSCs (hMSCs) and mouse SR4987 l...

Many strategies, including those based on genetically modified Mesenchymal Stromal Cells (MSCs), have been developed in recent years in order to obtain high concentrations of anticancer drugs effective on tumor mass. In previous studies, we showed that human and murine bone marrow-derived MSCs (BM-MSCs) and human skin-derived stromal fibroblasts (h...

The main goal in cancer chemotherapy is to drive the drug into the tumor microenvironment to kill as many cancer cells as possible while producing the lowest collateral toxicity. Previously, we have shown that human bone marrow derived mesenchymal stromal cells (hBM-MSCs) exposed to Paclitaxel (PTX) were able to uptake and subsequently release the...

We evaluated a three-step algorithm for laboratory diagnosis of Clostridium difficile-associated diarrhoea (CDAD). First, stool specimens were screened using an EIA test for glutamate dehydrogenase detection. Screen-positive specimens were tested by a rapid cytotoxintoxin A/B assay and subjected to stool culture. All cultures positive for C. diffic...

Characterization of Mesenchymal Stem Cells expanded from human bone marrow. The MSC feature of the expanded cell population has been confirmed by their capacity to differentiate into adipocyte (A), osteoblasts (B) and condhroblasts (C) under specific stimulation. Figure 1D shows unstimulated MSCs (Negative Control). The box on the right shows the p...

Modulation of P-gp expression and PTX sensitivity. (A) The histogram shows the basal expression of P-gp by hMSCs and SR4987 (CTRL), its modulation after 24 hours of treatment with 2 µg/ml paclitaxel (PTX+) or 20 uM Verapamil (VP+). P-gp expression was evaluated by FACS and reported as ratio between fluorescence intensity measured on cells treated w...

Evaluation of apoptosis in hMSCs and SR-4987 after PTX treatment. The evaluation of apoptosis was performed by flow cytometry by the Annexin-V binding assay and confirmed by the quantification of the sub-G1 cell population. Data report the percentage of apoptotic/necrotic cells (mean ± s.d. of three assays). The assays were performed with different...

Mouse SR4987PTX-CM inhibit HUVECs and HMECs proliferation. HUVECs (A) and (C) and HMECs (B) were cultured for 72 hrs in the presence or in the absence of control SR4987-CM and SR4987PTX-CM at different dilutions. SR4987PTX-CM at 1∶2 and 1∶4 dilutions were cytotoxic for HUVECs, while they induced a significant growth inhibition on HMECs. In C photog...

Effects of GFP+ SR4987-PTX on the growth and histology of subcutaneous RFP+U87MG xenografts. At the 2, 4, and 8 week survival time, the tumor xenografts generated by co-injection of RFP+U87MG glioblastoma cells and GFP+SR4987-PTX cells showed significantly smaller diameter compared with tumor generated by injection of glioblastoma cells or by co-in...

Cell cycle analysis by FACS. The histograms show the effects of PTX treatment on hMSCs and SR4987 cell cycle after 24 hours of treatment. The percentages of cells counted in each different cell phase (G0/G1, S and G2/M ) are reported and compared to these found in untreated cells (CTRL). PTX 24 h = cells after 24 h of PTX treatment; PTX 24+24 h = P...

Internalization and kinetics of Fluorescent PTX (PTX-F) decrease in hMSCs. The histogram demonstrates that PTX-F was internalized by hMSCs. The study was conducted by treating hMSCs with PTX-F for 24 hrs. Thereafter, the cells were harvested by trypsin and washed, and then analysed by FACS immediately (time 0) at 8 and 24 hours while maintained res...

Mouse SR4987PTX inhibit B16 melanoma growth in syngeneic C57Bl6 mice. The Figure shows the effect of control SR4987 and primed SR4987PTX (0.4×105) mixed at 1∶5 ratio with B16 melanoma cells (2×105) and injected s.c into syngeneic C57Bl6 mice (see also Table 1). In (A) SR4987PTX induced a significant reduction of B16 tumor volume calculated by measu...

Mesenchymal stromal cells may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that exposure of mouse bone marrow derived stromal cells to Doxorubicin led them to acquire anti-proliferative potential towards co-cultured haematopoietic stem cells (HSCs). We thus hypothesized whether freshly isolated hum...

Recurrence is a major complication of Clostridium difficile-associated diarrhea and occurs in 15 to 20% of patients after discontinuation of therapy. Strains from 53 patients with Clostridium difficile recurrences were fingerprinted by PCR ribotyping. Reinfection with a different strain occurred in 15 out of 53 patients (28,3%), while 38 patients r...

Background: Mesenchymal stem cells (MSCs) may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that simple exposure of bone marrow (BM) derived MSCs to high doses of Doxorubicin, led them to acquire anti-proliferative potential towards co-cultured haematopoitic stem cells (HSCs). We thus hypothesized w...

A variety of new coumarin—thiazole conjugated systems (III) (31 examples) is synthesized by Hantzsch condensation and evaluated for a selective activity against H.

The mesenchymal stromal cell line SR-4987 has been established in our laboratory from the bone marrow of BDF/1 mice. Recent information on mesenchymal stem cells biology and the need to deal with well-characterized cell lines suggest to critically consider the existent data on this cell line by updating them with new investigations on growth parame...

A novel class of coumarin-thiazole conjugated systems (1-31) were synthesized by Hantzsch condensation between alpha-bromo-3-acetyl coumarin and several thiosemicarbazone intermediates. This scaffold was also evaluated for selective antibacterial activity against 20 isolates of H. pylori clinical strains, including four metronidazole resistant ones...

N-substituted-3-carboxamido-coumarin derivatives were prepared and evaluated for selective antibacterial activity against 20 isolates of Helicobacter pylori clinical strains, including five metronidazole resistant ones. Some of them possessed the best activity against H. pylori metronidazole resistant strains with MIC values lower than the drug ref...

UCB (human umbilical cord blood) contains cells able to differentiate into non-haematopoietic cell lineages. It also contains cells similar to primitive ESCs (embryonic stem cells) that can differentiate into pancreatic-like cells. However, few data have been reported regarding the possibility of expanding these cells or the differential gene expre...