Roberto Di Marco

Background/Objectives: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colonic mucosa, resulting from a complex interplay between epithelial barrier dysfunction, dysregulated immune responses, and alterations in the gut microbiota. Despite advances in therapeutic strategies, current treatments for UC remain suboptimal. Many conventional and biologic therapies are associated with systemic side effects due to non-specific distribution, which can limit their long-term use. Novel acting therapies are needed for ulcerative colitis. This study evaluated the efficacy of intracolonic Rifamycin SV in situ gelling formulation (CB-01-35) in a rat model of oxazolone-induced colitis. Methods: Acute colitis was induced in female Wistar rats using oxazolone. Animals were treated for three days with CB-01-35 (80 mg/kg, intracolonic), Vehicle, Asacol, or dexamethasone. Clinical parameters, colon weight, macroscopic damage score (MDS), mucosal damage area, and histological score were assessed. Results: CB-01-35 significantly reduced MDS compared with Vehicle (p < 0.05) and showed a trend toward reduced mucosal damage area (p = 0.06). Histological analysis confirmed significant improvement, with reduced leukocyte infiltration and epithelial damage. No significant effects were observed on body weight or colon weight. Comparator treatments showed limited or inconsistent efficacy. Conclusions: CB-01-35 demonstrated therapeutic activity in this preclinical model, supporting further investigation as a locally acting treatment for colitis. These findings represent an initial proof-of-concept and warrant confirmation in larger and mechanistic studies.

Background: Lactic acid bacteria are increasingly being studied for their immunomodulatory activity and protective effects against pathogens. Limosilactobacillus fermentum DSM 34872, isolated from human breast milk, was evaluated for its prophylactic potential using Galleria mellonella as an alternative preclinical model. Results: The antimicrobial activity of L. fermentum against Salmonella enterica subsp. enterica serovar Typhimurium or Enterococcus faecalis was first assessed in vitro by the overlay assay. In vivo, G. mellonella larvae were orally administered with L. fermentum via gavage and exposed to pathogens. Survival rates, melanization score, and expression of immune-related genes ( dorsal, relish, gallerimycin, gloverin ) were evaluated in both the gut and hemolymph using RT-qPCR at 4 and 24 h after infection. Conclusion: L. fermentum showed antibacterial activity in vitro. In vivo, pre-treatment with L. fermentum significantly increased survival and delayed mortality. The melanization score supported the in vivo survival results. Gene expression analysis revealed modulation of key immune markers in both the gut and hemolymph, suggesting controlled immune activation rather than hyperinflammation in L. fermentum pretreated groups. Prophylactic oral administration of L. fermentum protected against lethal bacterial infections in G. mellonella , altering both local and systemic immune responses. These results highlight the potential of L. fermentum as a promising candidate for future in vivo analyses and confirm G. mellonella as an ethical, economical, and reliable preclinical model for preliminary screening, with the aim of subsequent evaluations in accredited clinical models.

The nasal microbiome represents a complex and dynamic microbial ecosystem that contributes to mucosal defense, epithelial homeostasis, immune regulation, and olfactory function. Increasing evidence indicates that this microbial community actively interacts with host physiology, while alterations in its composition are associated with chronic inflammation, oxidative stress, and olfactory impairment. Such changes have been reported in conditions including chronic rhinosinusitis, allergic rhinitis, and post-viral anosmia. Beyond local effects, chronic nasal inflammation has been hypothesized to influence neuroinflammatory processes and protein aggregation pathways involving α-synuclein and tau, potentially linking nasal microbial imbalance to neurodegenerative mechanisms. However, current evidence remains largely indirect and does not support a causal relationship. This narrative review summarizes current clinical and immunological evidence on the role of the nasal microbiome in olfactory function and dysfunction, highlighting limitations of existing studies and outlining future research directions.

Background: Malaria remains a major public health concern in Africa, due to the persistence of Plasmodium falciparum gametocytes that sustain transmission post treatment. This study evaluated the effects of artemether–lumefantrine (AL) alone compared with AL combined with a single low-dose of primaquine (SLD-PQ) on gametocyte clearance and infectivity to Anopheles arabiensis post treatment. Methods: A prospective cohort and entomological study were conducted from January to September 2025 in Northwest Ethiopia. Ninety-six microscopically confirmed cases of P. falciparum gametocytemia mono-infection were proportionally assigned to both treatment groups. Follow-up assessments were conducted on days 3, 7, 14, and 28, and mixed-species infections were assessed using molecular diagnostic assays. Additionally, membrane feeding assays (MFAs) were performed to evaluate mosquito infectivity post treatment. Results: Gametocyte prevalence declined faster with AL + SLD-PQ (15.2% on day 3; 0% by day 7) compared to AL alone (28.9% on day 3: p = 0.001; 12.2% by day 7: p = 0.033). Higher baseline gametocyte density strongly predicted mosquito infection (95% in high vs. 59% moderate and 33% low). On day 3 post treatment, 28.6% of cases treated with AL only showed confirmed mosquito infection, compared to 6.8% in the AL + SLD-PQ group (p = 0.001). By day 7, 7.3% of cases remained infectious in the AL-only group, while none were detected in the AL+ SLD-PQ group (p = 0.01). Conclusions: High baseline gametocyte density strongly correlated with increased infectivity. Adding SLD-PQ markedly accelerates gametocyte clearance and completely blocks post-treatment transmission. Submicroscopic gametocytemia contributed to residual transmission in the AL-only group. Incorporation of SLD-PQ alongside AL, in line with WHO recommendations, is advised to enhance post-treatment transmission blocking, with continued surveillance.

Objectives: Upper respiratory tract infections pose a significant challenge for healthcare systems worldwide. Forming biofilms-complex polymicrobial communities encased in an exopolymer matrix plays a pivotal role in the persistence of these infections, contributing to enhanced resistance against conventional treatments and host immune responses. Consequently, developing innovative strategies to disrupt biofilms has become a therapeutic imperative.This study investigated the in vitro efficacy of a hypertonic solution of salsobromoiodic thermal water, in mitigating biofilm formation by key upper respiratory tract pathogens. Methods: Biofilm formation by Staphylococcus aureus , Moraxella catarrhalis , Haemophilus influenzae , Streptococcus pneumoniae , Candida albicans , Candida parapsilosis , and Candida tropicalis was assessed using the MBEC Assay ^® system. The effects of the hypertonic salsobromoiodic thermal water solution were compared with standard saline (0.9 % NaCl). Results: A significant, concentration-dependent reduction in biofilm biomass was observed in all tested microorganisms when treated with the hypertonic solution. This effect was also evident in polymicrobial biofilms, indicating a broad and consistent antibiofilm potential. Conclusions: The hypertonic solution of salsobromoiodic thermal water demonstrated notable in vitro activity against biofilm formation by major upper respiratory tract pathogens. These findings highlight its potential as novel therapeutic approach for managing biofilm-associated respiratory infections and enhancing conventional antimicrobial treatments effectiveness.

Living organisms must adapt and communicate effectively in their environment to survive. Cells communicate through various mechanisms, including releasing growth factors, chemokines, small bioactive molecules, and cell–cell contact. In recent years, a new and sophisticated cell communication mechanism based on extracellular vesicles (EVs) has been described in all three domains of life: archaea, bacteria, and eukaryotes. EVs are small, bilayer proteolipid vesicles released by cells into the extracellular space. This review aims to analyze and compare the current literature on bacterial, archaeal, and eukaryotic EVs and their possible clinical applications. This framework will address three key points: (a) The role of EVs in bacteria, eukaryotes, and archaea. (b) What is the impact of EVs in archaea on disease? (c) How archaea use EVs to communicate with other domains (bacteria/eukaryotes).

Pouchitis is one of the most common long-term complications after ileal pouch–anal anastomosis (IPAA) surgery, with a reported incidence rate of up to 50%. Identifying specific bacteria involved in the pathogenesis has important implications for clinical management. Indeed, antibiotic therapy is a common treatment option, but antibiotic choice and treatment duration can vary depending on the severity of symptoms and the bacteria involved. Ansamycins are effective in the management of antibiotic-dependent pouchitis. Therefore, this study aimed to test the in vitro antibacterial activity of a novel rifamycin gel solution, specifically intended for treating infections associated with pouchitis, with the agar diffusion assay. Furthermore, the in vitro antibacterial activity of rifamycin sodium salt against several bacterial strains involved in pouchitis was compared with the gel formulation. Rifamycin’s in vitro anti-microbial characteristics were not affected by the gel formulation. These results, although preliminary, support the potential of the Rifamycin Gel formulation as a valuable addition to the therapeutic armamentarium for this challenging condition.

Background: Menopause, a natural phase in a woman’s life, often adversely affects physical, mental, sexual, and emotional well-being due to low estrogen levels. This study examines the impact of vaginal ovules with tocopherol acetate (Filme Gyno-V^® ovules, manufactured by Panin Srl and distributed by Hulka Srl, Italy), 500 mg per ovule, on vaginal health in pre- and menopausal women. Methods: Fifty women aged 50–70 were divided into menopausal (28) and premenopausal (22) cohorts and treated with the ovules for two weeks, with assessments before and after treatment. Results: The findings showed that distressing symptoms of vaginal atrophy, such as dryness, itching, and pain during intercourse, were resolved post-treatment. A molecular analysis revealed a reduction in Escherichia coli in both cohorts and an increase in three species of Lactobacillus in premenopausal patients. Conclusions: This study concludes that Filme Gyno-V ovules may benefit vaginal health by alleviating atrophy symptoms and promoting healthy vaginal microbiota.

Background: The COVID-19 pandemic has made antibiotic resistance (AMR) and healthcare-acquired infections (HAIs) increasingly serious problems. Point-prevalence Surveys (PPS) and other surveillance techniques are essential for antimicrobial management and prevention. Methods: In a hematology department of an Italian hospital, the prevalence of HAI, microbiology, and AMR were examined in this retrospective study in two different periods, namely 2019 and 2021 (pre-pandemic and during the pandemic, respectively). Comparisons were made between patient demographics, hospitalization duration, surveillance swabs, and HAIs. Findings: There was no discernible variation in the prevalence of HAI between 2019 and 2021. Higher rates of HAI were connected with longer hospital stays. Variations in antimicrobial susceptibility and species distribution were found by microbiological analysis. Discussion: The incidence of HAI stayed constant during the epidemic. Nevertheless, shifts in antibiotic susceptibility and microbiological profiles highlight the necessity of continuous monitoring and care. Conclusions: Despite the difficulties of COVID-19, ongoing surveillance and infection control initiatives are crucial for halting HAIs and battling antimicrobial resistance (AMR) in healthcare environments. To fully understand the pandemic’s long-term impact on the spread of infectious diseases and antibiotic resistance, more research is required.

Long-term inflammatory skin disease atopic dermatitis is characterized by dry skin, itching, and eczematous lesions. During inflammation skin barrier protein impairment promotes S. aureus colonisation in the inflamed skin, worsening AD patient’s clinical condition. Proteomic analysis revealed the presence of several immune evasion proteins and virulence factors in S. aureus extracellular vesicles (EVs), suggesting a possible role for these proteins in the pathophysiology of atopic dermatitis. The objective of this study is to assess the efficacy of a wall fragment obtained from a patented strain of C. acnes DSM28251 (c40) and its combination with a mucopolysaccharide carrier (HAc40) in counteract the pathogenic potential of EVs produced by S. aureus ATCC 14458. Results obtained from in vitro studies on HaCaT keratinocyte cells showed that HAc40 and c40 treatment significantly altered the size and pathogenicity of S. aureus EVs. Specifically, EVs grew larger, potentially reducing their ability to interact with the target cells and decreasing cytotoxicity. Additionally, the overexpression of the tight junctions mRNA zona occludens 1 (ZO1) and claudin 1 (CLDN1) following EVs exposure was decreased by HAc40 and c40 treatment, indicating a protective effect on the epidermal barrier’s function. These findings demonstrate how Hac40 and c40 may mitigate the harmful effects of S. aureus EVs. Further investigation is needed to elucidate the exact mechanisms underlying this interaction and explore the potential clinical utility of c40 and its mucopolysaccharide carrier conjugate HAc40 in managing atopic dermatitis.