Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance.

The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.

Symbiotic Wolbachia in mosquitoes and its role in reducing the transmission of mosquito-borne diseases: updates and prospects.

Mosquito-borne diseases such as malaria, dengue fever, West Nile virus, chikungunya, Zika fever, and filariasis have the greatest health and economic impact. These mosquito-borne diseases are a major cause of morbidity and mortality in tropical and sub-tropical areas. Due to the lack of effective vector containment strategies, the prevalence and severity of these diseases are increasing in endemic regions. Nowadays, mosquito infection by the endosymbiotic Wolbachia represents a promising new bio-control strategy. Wild-infected mosquitoes had been developing cytoplasmic incompatibility (CI), phenotypic alterations, and nutrition competition with pathogens. These reduce adult vector lifespan, interfere with reproduction, inhibit other pathogen growth in the vector, and increase insecticide susceptibility of the vector. Wild, uninfected mosquitoes can also establish stable infections through trans-infection and have the advantage of adaptability through pathogen defense, thereby selectively infecting uninfected mosquitoes and spreading to the entire population. This review aimed to evaluate the role of the Wolbachia symbiont with the mosquitoes (Aedes, Anopheles, and Culex) in reducing mosquito-borne diseases. Global databases such as PubMed, Web of Sciences, Scopus, and pro-Quest were accessed to search for potentially relevant articles. We used keywords: Wolbachia, Anopheles, Aedes, Culex, and mosquito were used alone or in combination during the literature search. Data were extracted from 56 articles' texts, figures, and tables of the included article.

Orobanche crenata Forssk. Extract Affects Human Breast Cancer Cell MCF-7 Survival and Viral Replication.

BACKGROUND: Breast cancer (BC) is the leading cause of death worldwide. The severity of BC strictly depends on the molecular subtype. The less aggressive hormone-positive subtype is treated with adjuvant endocrine therapy (AET), which causes both physical and psychological side effects. This condition strongly impacts the adherence and persistence of AET among oncologic patients. Moreover, viral infections also constitute a serious problem for public health. Despite their efficacy, antiviral agents present several therapeutic limits. Accordingly, in the present work, we investigated the antitumor and antiviral activities of Orobanche crenata Forssk. (O. crenata), a parasitic plant, endemic to the Mediterranean basin, traditionally known for its beneficial properties for human health. METHODS: The MTT assay was carried out to evaluate the cytotoxic effect of O. crenata leaf extract (OCLE) on human breast cancer cells (MCF-7 and MDA-MB-231) and the primary HFF-1 cell line. The lactic dehydrogenase (LDH) assay was performed on MCF-7 cells to analyze necrotic cell death. The antioxidant effect of OCLE was evaluated by intracellular determination of the reactive oxygen species and thiol groups, by DPPH and ABTS assays. The antiviral activity of OCLE was determined against Poliovirus 1, Echovirus 9, Human respiratory syncytial virus, Adenovirus type 2 and type 5, Coxsackievirus B1 (CoxB1) and B3 (CoxB3), Herpes simplex type 1 (HSV-1) and type 2 (HSV-2), and ß-Coronavirus by the plaque reduction assay. RESULTS: The extract, after 24 h of incubation, did not affect MDA-MB-231 and HFF-1 cell viability. However, at the same time point, it showed a dose-dependent inhibitory effect on MCF-7 cells, with an increase in LDH release. OCLE exhibited free radical scavenging activity and significantly increased non-protein thiol levels in MCF-7 cells. OCLE effectively inhibited HSV-1, HSV-2, CoxB1, and CoxB3 replication. CONCLUSIONS: The overall results showed an interesting inhibitory effect of OCLE on both MCF-7 cell survival and viral replication.

Anti-Candidal Activity of the Parasitic Plant Orobanche crenata Forssk.

Candida albicans (C. albicans) and Candida glabrata (C. glabrata) are part of the human microbiome. However, they possess numerous virulence factors, which confer them the ability to cause both local and systemic infections. Candidiasis can involve multiple organs, including the eye. In the present study, we investigated the anti-candidal activity and the re-epithelizing effect of Orobanche crenata leaf extract (OCLE). By the microdilution method, we demonstrated an inhibitory effect of OCLE on both C. albicans and C. glabrata growth. By crystal violet and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of OCLE to inhibit the biofilm formation and the viability of yeast cells, respectively. By germ tube and adhesion assays, we proved the capacity of OCLE to affect the morphological transition of C. albicans and the adhesion of both pathogens to human retinal pigment epithelial cells (ARPE-19), respectively. Besides, by MTT and wound healing assay, we evaluated the cytotoxic and re-epithelizing effects of OCLE on ARPE-19. Finally, the Folin-Ciocalteu and the ultra-performance liquid chromatography-tandem mass spectrometry revealed a high content of phenols and the presence of several bioactive molecules in the extract. Our results highlighted new properties of O. crenata, useful in the control of Candida infections.

Correction: Genovese et al. In Vitro Antibacterial, Anti-Adhesive and Anti-Biofilm Activities of Krameria lappacea (Dombey) Burdet & B.B. Simpson Root Extract against Methicillin-Resistant Staphylococcus aureus Strains. Antibiotics 2021, 10, 428.

The authors would like to make the following corrections to the published paper [...].

In Vitro Antibacterial, Anti-Adhesive and Anti-Biofilm Activities of Krameria lappacea (Dombey) Burdet & B.B. Simpson Root Extract against Methicillin-Resistant Staphylococcus aureus Strains.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious threat to public health, due to its large variety of pathogenetic mechanisms. Accordingly, the present study aimed to investigate the anti-MRSA activities of Krameria lappacea, a medicinal plant native to South America. Through Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass spectrometry, we analyzed the chemical composition of Krameria lappacea root extract (KLRE). The antibacterial activity of KLRE was determined by the broth microdilution method, also including the minimum biofilm inhibitory concentration and minimum biofilm eradication concentration. Besides, we evaluated the effect on adhesion and invasion of human lung carcinoma A549 cell line by MRSA strains. The obtained results revealed an interesting antimicrobial action of this extract, which efficiently inhibit the growth, biofilm formation, adhesion and invasion of MRSA strains. Furthermore, the chemical analysis revealed the presence in the extract of several flavonoid compounds and type-A and type-B proanthocyanidins, which are known for their anti-adhesive effects. Taken together, our findings showed an interesting antimicrobial activity of KLRE, giving an important contribution to the current knowledge on the biological activities of this plant.

Antimicrobial, Antioxidant, and Cytotoxic Activities of Juglans regia L. Pellicle Extract.

The difficulty to treat resistant strains-related hospital-acquired infections (HAIs) promoted the study of phytoextracts, known sources of bioactive molecules. Accordingly, in the present study, the pharmacological activities of Juglans regia (L.) pellicle extract (WPE) were investigated. The antiviral effect was tested against Herpes simplex virus type 1 and 2, Poliovirus 1, Adenovirus 2, Echovirus 9, Coxsackievirus B1 through the plaque reduction assay. The antibacterial and antifungal activities were evaluated against medically important strains, by the microdilution method. DPPH and superoxide dismutase (SOD)s-like activity assays were used to determine the antioxidant effect. Besides, the extract was screened for cytotoxicity on Caco-2, MCF-7, and HFF1 cell lines by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also evaluated. Interestingly, WPE inhibited Herpes simplex viruses (HSVs) replication, bacterial and fungal growth. WPE showed free radical scavenging capacity and inhibited superoxide anion formation in a dose-dependent manner. These effects could be attributed to the high content of phenols and flavonoids, which were 0.377 ± 0.01 mg GE/g and 0.292 ± 0.08 mg CE/g, respectively. Moreover, WPE was able to reduce Caco-2 cell viability, at both 48 h and 72 h. The promising results encourage further studies aimed to better elucidate the role of WPE in the prevention of human infectious diseases.

Antibacterial and anti-biofilm activities of walnut pellicle extract (Juglans regia L.) against coagulase-negative staphylococci.

Juglans regia L. (common walnut) is a deciduous tree belonging to Juglandaceae family. Since ancient time, walnut was widely used in traditional medicine for its antioxidant, antidiabetic, antimicrobial, anti-inflammatory, anti-atherogenic and liver-protective effects. In this work, the antibacterial and anti-biofilm activities of walnuts pellicle extract against coagulase-negative staphylococci were evaluated. Qualitative chemical analysis was performed by the thin layer chromatography. UPLC-Ms/Ms was used to identify the chemical composition of J. regia extract. The total flavonoid and phenolic contents were determined by the Aluminium chloride and Folin-Ciocalteu methods, respectively. The extract showed antibacterial activity with MIC ranging from 3.60 to 461.75 µg/ml and MBC ranging from 461.75 to >461.75 µg/ml. Furthermore, it significantly reduced biofilm biomass and cell viability in a dose-dependent manner. Biological activities of J. regia extract may be due to its high flavonoid and phenolic contents. The obtained results are promising and they deserve further scientific investigations.

Phytochemical composition and biological activities of Orobanche crenata Forssk.: a review.

The genus Orobanche includes about 100 different species. Among them, Orobanche crenata Forssk. (Orobanchaceae family), commonly known as broomrape, is a holoparasitic plant, noxious to legume crops that inhabits mainly in the Mediterranean basin. The aim of this review is to evaluate and organise the available reports on O. crenata. Our research revealed that the plant is edible, relatively safe to ingest, historically used for the treatment of skin infections, ulcers and bowel disorders. In addition, it represents a rich source of nutrients, antioxidant, antitumor and antimicrobial compounds. Phytochemical studies revealed the presence of twenty-two molecules, identified from different parts of the plant. The Prediction of Activity Spectra for Substances (PASS) analysis allowed predicting the biological activity of each compound. Furthermore, biological properties of O. crenata extracts were reported. Therefore, here we elucidate the botanic, phytochemical and biological profile of O. crenata, shedding light on a little characterised plant.

Streptococcus agalactiae in pregnant women: serotype and antimicrobial susceptibility patterns over five years in Eastern Sicily (Italy).

Streptococcus agalactiae (also known Group B Streptococcus or GBS) represents the main pathogen responsible for early- and late-onset infections in newborns. The present study aimed to determine the antimicrobial susceptibility pattern and the capsular serotypes of GBS isolated in Eastern Sicily over 5 years, from January 2015 to December 2019. A total of 3494 GBS were isolated from vaginal swabs of pregnant women (37-39 weeks), as recommended by the Centers for Disease Control and Prevention. Capsular polysaccharide's typing of GBS was determined by a commercial latex agglutination test containing reagents to serotypes I-IX. The antimicrobial resistance pattern of GBS was determined through the disk diffusion method (Kirby-Bauer) and the double-disk diffusion test on Mueller-Hinton agar plates supplemented with 5% defibrinated sheep blood, according to the guidelines of the Clinical and Laboratory Standards Institute. Serotypes III (1218, 34.9%) and V (1069, 30.6%) were the prevalent colonizers, followed by not typable (570, 16.3%) and serotypes Ia (548, 15.7%), Ib (47, 1.3%), II (40, 1.1%), and IV (2, 0.1%). All 3494 clinical isolates were susceptible to cefditoren and vancomycin. Resistance to penicillin, ampicillin, levofloxacin, clindamycin, and erythromycin was observed in 6 (0.2%), 5 (0.1%), 161 (4.6%), 1090 (31.2%), and 1402 (40.1%) of the strains, respectively. Most of erythromycin-resistant GBS (1090/1402) showed the cMLSB phenotype, 276 the M phenotype, and 36 the iMLSB phenotype. Our findings revealed a higher prevalence of serotype III and a relevant resistance rate, among GBS strains, to the most frequently used antibiotics in antenatal screening.

Targeting Metabolic Consequences of Insulin Resistance in Polycystic Ovary Syndrome by D-chiro-inositol and Emerging Nutraceuticals: A Focused Review.

Polycystic ovary syndrome (PCOS) is a complex disorder associated with ovarian dysfunction, infertility, menstrual irregularity, and hormonal impairments. Over the last decade, several studies have shown that some PCOS women have insulin resistance (InsR) and hyperinsulinemia, apart from being overweight or obese. Therefore, a crucial clinical aspect is that PCOS patients might develop glucose intolerance and type 2 diabetes. Insulin-sensitizing drugs have been used as first-line treatment to improve hyperinsulinemia in women with PCOS. Although reducing PCOS symptoms and signs, several used insulin-sensitizer drugs may induce side effects, which reduces compliance. D-chiro-inositol (DCI), which is a naturally occurring stereoisomer of inositol, has been classified as an insulin-sensitizer and seems to mitigate multiple InsR-related metabolic alterations in PCOS with a safe profile. However, according to a multi-targeted design, the supplementation with DCI can be synergistically integrated by combining other potential insulin-sensitizing drugs and/or nutraceuticals. The literature provides the initial support for using several unexplored nutraceutical interventions that may target relevant metabolic abnormalities associated with InsR in PCOS. With a need to promote interest in clinical research, this review aims to discuss the efficacy of DCI and the role of emerging nutraceuticals for managing InsR in PCOS.

Association of oral dysbiosis with oral cancer development.

Oral squamous cell carcinoma (OSCC) is the leading cause of mortality for oral cancer. Numerous risk factors mainly related to unhealthy habits and responsible for chronic inflammation and infections have been recognized as predisposing factors for oral carcinogenesis. Recently, even microbiota alterations have been associated with the development of human cancers. In particular, some specific bacterial strains have been recognized and strongly associated with oral cancer development (Capnocytophaga gingivalis, Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Porphyromonas gingivalis and Prevotella spp.). Several hypotheses have been proposed to explain how the oral microbiota could be involved in cancer pathogenesis by mainly paying attention to chronic inflammation, microbial synthesis of cancerogenic substances, and alteration of epithelial barrier integrity. Based on knowledge of the carcinogenic effects of dysbiosis, it was recently suggested that probiotics may have anti-tumoral activity. Nevertheless, few data exist with regard to probiotic effects on oral cancer. On this basis, the association between the development of oral cancer and oral dysbiosis is discussed focusing attention on the potential benefits of probiotics administration in cancer prevention.

Preliminary in Vitro Studies on Corynebacterium urealyticum Pathogenetic Mechanisms, a Possible Candidate for Chronic Idiopathic Prostatitis?

Corynebacterium urealyticum is a well-known opportunistic uropathogen that can occur with cystitis, pyelonephritis, and urinary sepsis. Although a wide variety of coryneform bacteria have been found from the male genital tract of prostatitis patients, only one clinical case of prostatitis caused by C. urealyticum has been reported. The aim of this study was to evaluate the in vitro tropism of C. urealyticum towards LNCaP (lymph node carcinoma of the prostate) human cells line and the influence of acetohydroxamic acid as an irreversible urease inhibitor on different aspects of its pathogenicity by means of several in vitro tests, such as the determination and analysis of growth curves, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, the production of biofilms, and adhesion to LNCaP and HeLa cell lines. Results have brought new pieces of evidence on the in vitro tropism of C. urealyticum for the human prostate cell line LNCaP and the therapeutic use of the irreversible urease inhibitors such as acetohydroxamic acid (AHA), not only as enzyme blockers to facilitate the removal of encrustations but also as modulators of some pathogenic mechanisms. These interesting preliminary data allow us to assert that there is a real possibility that C. urealyticum is a new candidate for chronic idiopathic prostatitis.

Role of 17ß-Estradiol on Cell Proliferation and Mitochondrial Fitness in Glioblastoma Cells.

Gliomas are the most common primary tumors of the central nervous system (CNS) in the adult. Previous data showed that estrogen affects cancer cells, but its effect is cell-type-dependent and controversial. The present study aimed to analyze the effects of estradiol (E2, 5 nM) in human glioblastoma multiforme U87-MG cells and how it may impact on cell proliferation and mitochondrial fitness. We monitored cell proliferation by xCELLigence technology and mitochondrial fitness by assessing the expression of genes involved in mitochondrial biogenesis (PGC1α, SIRT1, and TFAM), oxidative phosphorylation (ND4, Cytb, COX-II, COX IV, NDUFA6, and ATP synthase), and dynamics (OPA1, MNF2, MNF1, and FIS1). Finally, we evaluated Nrf2 nuclear translocation by immunocytochemical analysis. Our results showed that E2 resulted in a significant increase in cell proliferation, with a significant increase in the expression of genes involved in various mechanisms of mitochondrial fitness. Finally, E2 treatment resulted in a significant increase of Nrf2 nuclear translocation with a significant increase in the expression of one of its target genes (i.e., heme oxygenase-1). Our results suggest that E2 promotes proliferation in glioblastoma cells and regulate the expression of genes involved in mitochondrial fitness and chemoresistance pathway.

Bioinspired benzoxanthene lignans as a new class of antimycotic agents: synthesis and Candida spp. growth inhibition.

In this work we synthetized the bioinspired benzoxanthene lignans (BXLs) 3, 14-22, and the phenazine derivative 23 as potential antimycotic agents. MICs and MFCs against Candida strains were determined. In a preliminary screening, compounds 3, 15, 20, 21, 22 were substantially inactive. Compounds 14 and 17 showed antifungal activity, being able to inhibit the growth of the majority of Candida strains with MIC values in the range 4.6-19.2 µM (14) and 26.0-104.3 µM (17); for three strains, the MICs were lower than those obtained using the antimycotic drug fluconazole. The three BXLs 18, 19 and 23 showed some MIC values lower than that of fluconazole; 18 was also active against two non-albicans Candida strains resistant to fluconazole. Phenazine 23, although active only against one strain (MIC = 1.3 µM), was one order of magnitude more potent than fluconazole. All the BXLs were fungicidal.

In vitro evaluation of biological activities of Orobanche crenata Forssk. leaves extract.

Orobanche crenata Forssk. (Orobanchaceae) is a holoparasitic plant noxious to legumes. Orobanchaceae are well known in traditional medicine for their hypotensive, antihyperglycemic, antispasmodic, analgesic and antimicrobial effects. In this work, the biological activities of the acetonic leaves extract were evaluated. Qualitative chemical analysis was determined through thin layer chromatography. Total phenols and flavonoids content was obtained by the Folin-Ciocalteu and the Aluminium chloride colorimetric methods, respectively. The antimicrobial activity was performed by the broth microdilution method. The extract showed antibacterial activity, particularly against Gram-positive strains, with MIC ranging from 376.00 to 3011.00 µg/ml. Besides, it exhibited antifungal effects on Candida spp. with MIC ranging from 94.10 to 3011.00 µg/ml. In addition, O. crenata inhibited superoxide anion formation and showed a DPPH quenching capacity, particularly at 80 µg/ml. Interestingly, our results are promising thus indicating the importance of O. crenata as a significant source of biologically active natural compounds.

Effects of a new combination of plant extracts plus d-mannose for the management of uncomplicated recurrent urinary tract infections.

Urinary tract infections (UTIs) are an economic burden for public health. The increasing prevalence of resistant bacteria which cause UTIs may be related to the inappropriate prescription of antibiotics. The aim of this preliminary study was to evaluate whether three different combinations of plant extracts plus d-mannose are effective in preventing the recurrence of UTIs. Three groups of patients received three combinations of plant extracts in conjunction with d-mannose. These were: berberine, arbutin and birch (group A); berberine, arbutin, birch and forskolin (group B); and proanthocyanidins (group C). The clinical recurrence of cystitis at the end of treatment and during follow-up was determined by comparison with baseline measurements using the microbiological assessment of urine samples, vaginal swabs and vaginal smear slides. Patients in groups A and B had a lower incidence of episodes of recurrent cystitis during treatment and follow-up, samples with a significantly lower median bacterial load and a reduction of the grade of lactobacillary flora compared to patients in group C.

Nanotechnology approaches for antibacterial drug delivery: Preparation and microbiological evaluation of fusogenic liposomes carrying fusidic acid.

Many antibacterial drugs have some difficulty passing through the bacterial cell membrane, especially if they have a high molecular weight or large spatial structure. Consequently, intrinsic resistance is shown by some bacterial strains. Reduced cell membrane permeability is one of the mechanisms of resistance known for fusidic acid (FUS), a bacteriostatic steroidal compound with activity limited to Gram-positive bacteria. Moreover, the lipophilic character of FUS has been shown to cause drug retention inside the bilayers of cell membranes, preventing its diffusion towards target sites inside the cytoplasm. Targeting antimicrobial agents by means of liposomes may be a valid strategy in the treatment of infections refractory to conventional routes of antimicrobial treatment. On this basis, loading of FUS in fusogenic liposomes (FLs) was planned in this study. Fusogenic small unilamellar vesicles loaded with FUS were produced to evaluate their influence on improving the cell penetration and antibacterial activity of the antibiotic. The produced carriers were technologically characterised and were subjected to an in vitro microbiological assay against several strains of Gram-negative and Gram-positive bacteria. The experimental results showed that encapsulating FUS in a liposomal carrier can improve antimicrobial efficacy and reduce the effective concentration required, probably through putative mechanisms of increased diffusion through the bacterial cell membrane. In fact, whilst free FUS was active only on the tested Gram-positive strains, incubation of FUS-loaded FLs exhibited growth inhibitory activity both against Gram-positive and Gram-negative strains. The lowest MICs were obtained against Staphylococcus epidermidis (≤0.15 µg/mL) and Acinetobacter baumannii (37.5 µg/mL) clinical strains.

Anti-Adhesion Activity of A2-type Proanthocyanidins (a Cranberry Major Component) on Uropathogenic E. coli and P. mirabilis Strains.

Urinary tract infections (UTIs) are relatively common in women and may be classified as uncomplicated or complicated, depending upon the urinary tract anatomy and physiology. Acute uncomplicated cystitis (AUC) occurs when urinary pathogens from the bowel or vagina colonize the periurethral mucosa and reach the bladder. The vast majority of episodes in healthy women involving the same bacterial strain that caused the initial infection are thought to be reinfections. About 90% of AUC are caused by uropathogenic Escherichia coli (UPEC), but Proteus mirabilis also plays an important role. Several studies support the importance of cranberry (Vaccinium macrocarpon) proanthocyanidins in preventing adhesion of P-fimbriated UPEC to uroepithelial cells. In this study, we evaluated the in vitro anti-adhesion activity of A2-linked proanthocyanidins from cranberry on a UPEC and Proteus mirabilis strains and their possible influence on urease activity of the latter. A significant reduction of UPEC adhesion (up to 75%) on the HT1376 cell line was observed vs. control. For the strains of P. mirabilis there was also a reduction of adhesion (up to 75%) compared to controls, as well as a reduction in motility and urease activity. These results suggest that A2-type cranberry proanthocyanidins could aid in maintaining urinary tract health.

A tailored health surveillance program unveils a case of MALT lymphoma in an HCV-positive health-care worker.

Non-Hodgkin lymphoma (NHL) may occur among hepatitis C virus (HCV)-infected individuals. HCV is one of the most common blood-borne pathogens transmitted from patients to health-care workers (HCWs). The development of NHL among HCV-infected HCWs has recently been shown. To investigate this issue further a tailored health surveillance program was applied to 3,138 HCWs from four Medical Institutions. To this aim, all employees were screened for both anti-HCV antibodies and HCV-related extrahepatic manifestations. The HCV prevalence rate, similar among all the HCW subgroups, was 7.3%. The occurrence of a gastric mucosa-associated lymphoma tissue (MALT) lymphoma, diagnosed in a physician following a long history of HCV chronic infection, was observed. Molecular characterization of MALT tissue indicated that immunoglobuline gene combinations were those usually found among HCV-associated lymphomas. Furthermore, B-cell expansion exhibited t(14;18) translocation, as a genetic abnormality associated with the development of MALT lymphomas from HCV-positive patients. Overall, these findings support the hypothesis that HCV viral infection potentially affects the pathway of transformation and progression of lymphoma cells. The occurrence of B-cell NHL, among HCV-positive HCWs, is an additional reason to apply the standard precautions to reduce the risk of blood-borne pathogen transmission.