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1.
AIDS Behav ; 28(7): 2258-2263, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38526636

ABSTRACT

Italian guidelines recommend HIV pre-exposure prophylaxis (PrEP) only upon satisfying strict eligibility criteria. The objective of this study is to evaluate if PrEP candidates attending a community-based service comply with these criteria and whether these prescribing conditions affect retention in care and sexually transmitted infections (STIs) acquisition. A retrospective analysis was performed on PrEP candidates evaluated from January 2019 to June 2022. Data were collected from self-administered questionnaires and clinical files. The population was divided in subjects with 0/1 (0/1 C) and ≥ 2 (≥ 2 C) criteria. Descriptive statistics and non-parametric tests were employed to describe study population. Incidence of PrEP discontinuation and of STIs was estimated per 100 persons-year of follow up (PYFU), and incidence rate ratio (IRR) was calculated. Univariate and multivariable Cox regression analyses were used to evaluate the association strength between PrEP drop out and other variables. The analyses enrolled 659 individuals: 422 individuals were included in 0/1 C, 237 in ≥ 2 C group, respectively. Inconsistent condom use was the most reported prescribing criteria (399 individuals, 60.6%), followed by a previous STI (186 individuals, 28.2%). 0/1 C exhibited lower STIs incidence. PrEP discontinuation was 29% in 0/1 C and 38% in ≥ 2 C (p = 0.031). Cox model revealed that inconsistent condom use was the only prescribing criteria associated to PrEP persistence. The majority of PrEP candidate did not comply with prescribing conditions. Eligibility criteria failed to identify individuals with better retention in care. Our results suggest that Italian guidelines should be updated removing barriers to prescription.


Subject(s)
HIV Infections , Pre-Exposure Prophylaxis , Retention in Care , Sexually Transmitted Diseases , Humans , Male , Retrospective Studies , Pre-Exposure Prophylaxis/statistics & numerical data , Adult , Female , Sexually Transmitted Diseases/prevention & control , Sexually Transmitted Diseases/epidemiology , HIV Infections/prevention & control , HIV Infections/epidemiology , HIV Infections/drug therapy , Italy/epidemiology , Retention in Care/statistics & numerical data , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Incidence , Middle Aged , Eligibility Determination , Surveys and Questionnaires
2.
Crit Care ; 28(1): 314, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39304944

ABSTRACT

AIMS: Cerebral complications after cardiac arrest (CA) remain a major problem worldwide. The aim was to test the effects of sodium-ß-hydroxybutyrate (SBHB) infusion on brain injury in a clinically relevant swine model of CA. RESULTS: CA was electrically induced in 20 adult swine. After 10 min, cardiopulmonary resuscitation was performed for 5 min. After return of spontaneous circulation (ROSC), the animals were randomly assigned to receive an infusion of balanced crystalloid (controls, n = 11) or SBHB (theoretical osmolarity 1189 mOsm/l, n = 8) for 12 h. Multimodal neurological and cardiovascular monitoring were implemented in all animals. Nineteen of the 20 animals achieved ROSC. Blood sodium concentrations, osmolarity and circulating KBs were higher in the treated animals than in the controls. SBHB infusion was associated with significantly lower plasma biomarkers of brain injury at 6 (glial fibrillary acid protein, GFAP and neuron specific enolase, NSE) and 12 h (neurofilament light chain, NFL, GFAP and NSE) compared to controls. The amplitude of the stereoelectroencephalograph (sEEG) increased in treated animals after ROSC compared to controls. Cerebral glucose uptake was lower in treated animals. CONCLUSIONS: In this experimental model, SBHB infusion after resuscitated CA was associated with reduced circulating markers of cerebral injury and increased sEEG amplitude.


Subject(s)
Biomarkers , Cardiopulmonary Resuscitation , Disease Models, Animal , Heart Arrest , Animals , Heart Arrest/drug therapy , Heart Arrest/complications , Heart Arrest/therapy , Swine , Biomarkers/blood , Biomarkers/analysis , Cardiopulmonary Resuscitation/methods , Sodium Oxybate/pharmacology , Sodium Oxybate/therapeutic use , Sodium Oxybate/administration & dosage , Brain Injuries/drug therapy , 3-Hydroxybutyric Acid/blood , Male
3.
Int J Mol Sci ; 25(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38542185

ABSTRACT

Photobiology is a challenging research area that aims to explore the interactions between light and living organisms and their biological consequences, with applications in the fields of photomedicine, photo(nano)technology, photosynthesis, and photosensory biology [...].


Subject(s)
Photobiology , Photosynthesis , Light
4.
Int J Mol Sci ; 25(6)2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38542161

ABSTRACT

Photodynamic therapy (PDT) relies on the combined action of a photosensitizer (PS), light at an appropriate wavelength, and oxygen, to produce reactive oxygen species (ROS) that lead to cell death. However, this therapeutic modality presents some limitations, such as the poor water solubility of PSs and their limited selectivity. To overcome these problems, research has exploited nanoparticles (NPs). This project aimed to synthesize a PS, belonging to the BODIPY family, covalently link it to two NPs that differ in their lipophilic character, and then evaluate their photodynamic activity on SKOV3 and MCF7 tumor cell lines. Physicochemical analyses demonstrated that both NPs are suitable for PDT, as they are resistant to photobleaching and have good singlet oxygen (1O2) production. In vitro biological analyses showed that BODIPY has greater photodynamic activity in the free form than its NP-bounded counterpart, probably due to greater cellular uptake. To evaluate the main mechanisms involved in PDT-induced cell death, flow cytometric analyses were performed and showed that free BODIPY mainly induced necrosis, while once bound to NP, it seemed to prefer apoptosis. A scratch wound healing test indicated that all compounds partially inhibited cellular migration of SKOV3 cells.


Subject(s)
Nanoparticles , Photochemotherapy , Photosensitizing Agents/chemistry , Nanoparticles/chemistry , Boron Compounds/pharmacology , Boron Compounds/chemistry , Cell Line, Tumor , Oxygen
5.
Molecules ; 29(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38731582

ABSTRACT

Clinicians often have to face infections caused by microorganisms that are difficult to eradicate due to their resistance and/or tolerance to antimicrobials. Among these pathogens, Pseudomonas aeruginosa causes chronic infections due to its ability to form biofilms on medical devices, skin wounds, ulcers and the lungs of patients with Cystic Fibrosis. In this scenario, the plant world represents an important reservoir of natural compounds with antimicrobial and/or antibiofilm properties. In this study, an extract from the leaves of Combretum micranthum G. Don, named Cm4-p, which was previously investigated for its antimicrobial activities, was assayed for its capacity to inhibit biofilm formation and/or to eradicate formed biofilms. The model strain P. aeruginosa PAO1 and its isogenic biofilm hyperproducer derivative B13 were treated with Cm4-p. Preliminary IR, UV-vis, NMR, and mass spectrometry analyses showed that the extract was mainly composed of catechins bearing different sugar moieties. The phytocomplex (3 g/L) inhibited the biofilm formation of both the PAO1 and B13 strains in a significant manner. In light of the obtained results, Cm4-p deserves deeper investigations of its potential in the antimicrobial field.


Subject(s)
Anti-Bacterial Agents , Biofilms , Catechin , Combretum , Microbial Sensitivity Tests , Plant Extracts , Pseudomonas aeruginosa , Biofilms/drug effects , Pseudomonas aeruginosa/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Catechin/pharmacology , Catechin/chemistry , Combretum/chemistry , Plant Leaves/chemistry , Sugars , Humans
6.
Molecules ; 29(6)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38542921

ABSTRACT

Photodynamic therapy (PDT) is a minimally invasive treatment that uses the combination of a photosensitizing agent (PS) and light to selectively target solid tumors, as well as several non-neoplastic proliferating cell diseases. After systemic administration, PSs are activated by localized irradiation with visible light; in the presence of adequate concentrations of molecular oxygen, this causes the formation of reactive oxygen species (ROS) and subsequent tissue damage. In this study, two series of tetrakis(N-alkylpyridinium-4-yl)porphyrins were synthesized, differing in the presence or absence of a zinc ion in the tetrapyrrole nucleus, as well as in the N-alkyl chain length (from one to twelve carbon atoms). The compounds were chemically characterized, and their effect on cell viability was evaluated using a panel of three tumor cell lines to determine a possible relationship between photodynamic activity and Zn presence/alkyl chain length. The types of cell death mechanisms involved in the effect of the various PSs were also evaluated. The obtained results indicate that the most effective porphyrin is the Zn-porphyrin, with a pendant made up of eight carbon atoms (Zn-C8).


Subject(s)
Photochemotherapy , Porphyrins , Porphyrins/pharmacology , Porphyrins/chemistry , Photosensitizing Agents/chemistry , Light , Carbon
7.
Crit Care ; 27(1): 161, 2023 04 22.
Article in English | MEDLINE | ID: mdl-37087454

ABSTRACT

INTRODUCTION: Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA. METHODS: After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C. RESULTS: Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls. CONCLUSIONS: In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.


Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Heart Injuries , Animals , Swine , Sodium Lactate/pharmacology , Sodium Lactate/therapeutic use , Heart Arrest/complications , Heart Arrest/drug therapy , Vasoconstrictor Agents , Brain/metabolism , Biomarkers/metabolism , Disease Models, Animal
8.
Immun Ageing ; 20(1): 41, 2023 Aug 12.
Article in English | MEDLINE | ID: mdl-37573338

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. In addition to primary brain damage, systemic immune alterations occur, with evidence for dysregulated immune responses in aggravating TBI outcome and complications. However, immune dysfunction following TBI has been only partially understood, especially in the elderly who represent a substantial proportion of TBI patients and worst outcome. Therefore, we aimed to conduct an in-depth immunological characterization of TBI patients, by evaluating both adaptive (T and B lymphocytes) and innate (NK and monocytes) immune cells of peripheral blood mononuclear cells (PBMC) collected acutely (< 48 h) after TBI in young (18-45 yo) and elderly (> 65 yo) patients, compared to age-matched controls, and also the levels of inflammatory biomarkers. RESULTS: Our data show that young respond differently than elderly to TBI, highlighting the immune unfavourable status of elderly compared to young patients. While in young only CD4 T lymphocytes are activated by TBI, in elderly both CD4 and CD8 T cells are affected, and are induced to differentiate into subtypes with low cytotoxic activity, such as central memory CD4 T cells and memory precursor effector CD8 T cells. Moreover, TBI enhances the frequency of subsets that have not been previously investigated in TBI, namely the double negative CD27- IgD- and CD38-CD24- B lymphocytes, and CD56dim CD16- NK cells, both in young and elderly patients. TBI reduces the production of pro-inflammatory cytokines TNF-α and IL-6, and the expression of HLA-DM, HLA-DR, CD86/B7-2 in monocytes, suggesting a compromised ability to drive a pro-inflammatory response and to efficiently act as antigen presenting cells. CONCLUSIONS: We described the acute immunological response induced by TBI and its relation with injury severity, which could contribute to pathologic evolution and possibly outcome. The focus on age-related immunological differences could help design specific therapeutic interventions based on patients' characteristics.

9.
Int J Mol Sci ; 24(4)2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36834543

ABSTRACT

In photodynamic therapy (PDT), a photosensitizer (PS) excited with a specific wavelength, and in the presence of oxygen, gives rise to photochemical reactions that lead to cell damage. Over the past few years, larval stages of the G. mellonella moth have proven to be an excellent alternative animal model for in vivo toxicity testing of novel compounds and virulence testing. In this article, we report a series of preliminary studies on G. mellonella larvae to evaluate the photoinduced stress response by a porphyrin (PS) (TPPOH). The tests performed evaluated PS toxicity on larvae and cytotoxicity on hemocytes, both in dark conditions and following PDT. Cellular uptake was also evaluated by fluorescence and flow cytometry. The results obtained demonstrate how the administration of PS and subsequent irradiation of larvae affects not only larvae survival rate, but also immune system cells. It was also possible to verify PS's uptake and uptake kinetics in hemocytes, observing a maximum peak at 8 h. Given the results obtained in these preliminary tests, G. mellonella appears to be a promising model for preclinical PS tests.


Subject(s)
Moths , Photochemotherapy , Porphyrins , Animals , Photosensitizing Agents/pharmacology , Photochemotherapy/methods , Porphyrins/chemistry , Models, Animal , Larva
10.
Int J Mol Sci ; 24(5)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36901769

ABSTRACT

In this work, two compounds belonging to the BODIPY family, and previously investigated for their photosensitizing properties, have been bound to the amino-pendant groups of three random copolymers, with different amounts of methyl methacrylate (MMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) in the backbone. The P(MMA-ran-DMAEMA) copolymers have inherently bactericidal activity, due to the amino groups of DMAEMA and to the quaternized nitrogens bounded to BODIPY. Systems consisting of filter paper discs coated with copolymers conjugated to BODIPY were tested on two model microorganisms, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). On solid medium, irradiation with green light induced an antimicrobial effect, visible as a clear inhibition area around the coated disks. The system based on the copolymer with 43% DMAEMA and circa 0.70 wt/wt% of BODIPY was the most efficient in both bacterial species, and a selectivity for the Gram-positive model was observed, independently of the conjugated BODIPY. A residual antimicrobial activity was also observed after dark incubation, attributed to the inherently bactericidal properties of copolymers.


Subject(s)
Anti-Infective Agents , Photochemotherapy , Escherichia coli , Methylmethacrylate , Staphylococcus aureus , Anti-Infective Agents/pharmacology , Methacrylates/pharmacology , Polymers/pharmacology , Anti-Bacterial Agents/pharmacology , Photosensitizing Agents/pharmacology
11.
Molecules ; 28(22)2023 Nov 11.
Article in English | MEDLINE | ID: mdl-38005258

ABSTRACT

Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical-physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Curcumin , Photochemotherapy , Ruthenium , Humans , Photosensitizing Agents/chemistry , Ruthenium/pharmacology , Ruthenium/chemistry , Curcumin/pharmacology , Diarylheptanoids , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Antineoplastic Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
12.
Photochem Photobiol Sci ; 21(7): 1233-1248, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35377108

ABSTRACT

In recent years, antimicrobial Photodynamic Therapy (aPDT) gained increasing attention for its potential to inhibit the growth and spread of microorganisms, both as free-living cells and/or embedded in biofilm communities. In this scenario, compounds belonging to the family of boron-dipyrromethenes (BODIPYs) represent a very promising class of photosensitizers for applications in antimicrobial field. In this study, twelve non-ionic and three cationic BODIPYs were assayed for the inactivation of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. As expected, S. aureus showed to be very sensitive to BODIPYs and mild conditions were sufficient to reach good rates of photoinactivation with both neutral and monocationic ones. Surprisingly, one neutral compound (named B9 in this study) resulted the best BODIPY to photoinactivate P. aeruginosa PAO1. The photoinactivation of C. albicans was reached with both neutral and mono-cationic BODIPYs. Furthermore, biofilms of the three model microorganisms were challenged with BODIPYs in light-based antimicrobial technique. S. aureus biofilms were successfully inhibited with milder conditions than those applied to P. aeruginosa and C. albicans. Notably, it was possible to eradicate 24-h-old biofilms of both S. aureus and P. aeruginosa. In conclusion, this study supports the potential of neutral BODIPYs as pan-antimicrobial PSs.


Subject(s)
Anti-Infective Agents , Photosensitizing Agents , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Biofilms , Boron/pharmacology , Boron Compounds , Candida albicans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Pseudomonas aeruginosa , Staphylococcus aureus
13.
Int J Mol Sci ; 23(17)2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36077597

ABSTRACT

Over the past 30 years, photodynamic therapy (PDT) has shown great development. In the clinical setting the few approved molecules belong almost exclusively to the porphyrin family; but in the scientific field, in recent years many researchers have been interested in other families of photosensitizers, among which BODIPY has shown particular interest. BODIPY is the acronym for 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene, and is a family of molecules well-known for their properties in the field of imaging. In order for these molecules to be used in PDT, a structural modification is necessary which involves the introduction of heavy atoms, such as bromine and iodine, in the beta positions of the pyrrole ring; this change favors the intersystem crossing, and increases the 1O2 yield. This mini review focused on a series of structural changes made to BODIPYs to further increase 1O2 production and bioavailability by improving cell targeting or photoactivity efficiency.


Subject(s)
Photochemotherapy , Boron Compounds/chemistry , Boron Compounds/therapeutic use , Fluorescent Dyes/chemistry
14.
Development ; 145(21)2018 10 29.
Article in English | MEDLINE | ID: mdl-30266829

ABSTRACT

The transcription factor Nfix belongs to the nuclear factor one family and has an essential role in prenatal skeletal muscle development, where it is a master regulator of the transition from embryonic to foetal myogenesis. Recently, Nfix was shown to be involved in adult muscle regeneration and in muscular dystrophies. Here, we have investigated the signalling that regulates Nfix expression, and show that JunB, a member of the AP-1 family, is an activator of Nfix, which then leads to foetal myogenesis. Moreover, we demonstrate that their expression is regulated through the RhoA/ROCK axis, which maintains embryonic myogenesis. Specifically, RhoA and ROCK repress ERK kinase activity, which promotes JunB and Nfix expression. Notably, the role of ERK in the activation of Nfix is conserved postnatally in satellite cells, which represent the canonical myogenic stem cells of adult muscle. As lack of Nfix in muscular dystrophies rescues the dystrophic phenotype, the identification of this pathway provides an opportunity to pharmacologically target Nfix in muscular dystrophies.


Subject(s)
MAP Kinase Signaling System , Muscle Development , Myoblasts/metabolism , NFI Transcription Factors/metabolism , rhoA GTP-Binding Protein/metabolism , Animals , Animals, Newborn , Embryo, Mammalian/metabolism , Female , Fetus/metabolism , Gene Expression Regulation, Developmental , Gene Silencing , Male , Mice , NFI Transcription Factors/genetics , Stem Cells/metabolism , Transcription Factors/metabolism , rho-Associated Kinases/metabolism
15.
Photochem Photobiol Sci ; 20(8): 1011-1025, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34260053

ABSTRACT

Photodynamic therapy involves the concomitant action of three components, light with an appropriate wavelength, molecular oxygen, and a molecule, able to absorb an electromagnetic radiation, called photosensitizer (PS). A fundamental aspect is the bioavailability of the PS that is directly related to some physicochemical properties of the PS itself as it should feature a certain degree of lipophilicity to easily cross the cell membrane, however, at the same time, should be sufficiently water-soluble to navigate in the bloodstream. Consequently, the use of a system for drug delivery becomes essential when photosensitizers with a high degree of lipophilicity are considered. In this work, we present three different drug delivery systems, microemulsions, emulsions and liposomes all capable of carrying a PS belonging to the porphyrin family: the tetraphenyl porphyrin (TPP) and the 4-hydroxyphenyl porphyrin (THPP), which show a relevant different degree of lipophilicity. A series of microemulsions (ME) and emulsions (E) were prepared, among which two formulations, one for THPP and one for TPP, have been chosen. The stability of these two carriers was monitored over time and under various temperature conditions. With the same criteria, two liposomal formulations have been also identified and analyzed. The four formulations mentioned above (one ME, one E and two liposomes) have been tested on SKOV3 tumor cell line comparing the photodynamic activity of the porphyrin formulations versus the aqueous/organic (DMSO) solution of the same two PSs. The results show that all the formulations have proved to be excellent carriers and that the liposomal formulation enhance the photodynamic efficacy of both porphyrins.


Subject(s)
Drug Carriers/chemistry , Photochemotherapy , Photosensitizing Agents/chemistry , Porphyrins/chemistry , Cell Line, Tumor , Humans , Liposomes/chemistry
16.
Int J Mol Sci ; 22(13)2021 Jun 24.
Article in English | MEDLINE | ID: mdl-34202773

ABSTRACT

In recent years, antimicrobial photodynamic therapy (aPDT) has received increasing attention as a promising tool aimed at both treating microbial infections and sanitizing environments. Since biofilm formation on biological and inert surfaces makes difficult the eradication of bacterial communities, further studies are needed to investigate such tricky issue. In this work, a panel of 13 diaryl-porphyrins (neutral, mono- and di-cationic) was taken in consideration to photoinactivate Pseudomonas aeruginosa. Among cationic photosensitizers (PSs) able to efficiently bind cells, in this study two dicationic showed to be intrinsically toxic and were ruled out by further investigations. In particular, the dicationic porphyrin (P11) that was not toxic, showed a better photoinactivation rate than monocationic in suspended cells. Furthermore, it was very efficient in inhibiting the biofilms produced by the model microorganism Pseudomonas aeruginosa PAO1 and by clinical strains derived from urinary tract infection and cystic fibrosis patients. Since P. aeruginosa represents a target very difficult to inactivate, this study confirms the potential of dicationic diaryl-porphyrins as photo-activated antimicrobials in different applicative fields, from clinical to environmental ones.


Subject(s)
Biofilms/drug effects , Biofilms/radiation effects , Light , Porphyrins/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Pseudomonas aeruginosa/radiation effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cations , Dose-Response Relationship, Drug , Humans , Molecular Structure , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Porphyrins/chemistry
17.
Chem Res Toxicol ; 33(9): 2381-2389, 2020 09 21.
Article in English | MEDLINE | ID: mdl-32786541

ABSTRACT

Recent studies have raised concerns about e-cigarette liquid inhalation toxicity by reporting the presence of chemicals with European Union CLP toxicity classification. In this scenario, the regulatory context is still developing and is not yet up to date with vaping current reality. Due to the paucity of toxicological studies, robust data regarding which components in e-liquids exhibit potential toxicities, are still inconsistent. In this study we applied computational methods for estimating the toxicity of poorly studied chemicals as a useful tool for predicting the acute toxicity of chemicals contained in e-liquids. The purpose of this study was 3-fold: (a) to provide a lower tier assessment of the potential health concerns associated with e-liquid ingredients, (b) to prioritize e-liquid ingredients by calculating the e-tox index, and (c) to estimate acute toxicity of e-liquid mixtures. QSAR models were generated using QSARINS software to fill the acute toxicity data gap of 264 e-liquid ingredients. As a second step, the potential acute toxicity of e-liquids mixtures was evaluated. Our preliminary data suggest that a computational approach may serve as a roadmap to enable regulatory bodies to better regulate e-liquid composition and to contribute to consumer health protection.


Subject(s)
Electronic Nicotine Delivery Systems , Flavoring Agents/adverse effects , Vaping , Animals , Flavoring Agents/administration & dosage , Flavoring Agents/analysis , Humans , Mice , Principal Component Analysis , Quantitative Structure-Activity Relationship
18.
Photochem Photobiol Sci ; 19(6): 790-799, 2020 Jun.
Article in English | MEDLINE | ID: mdl-33856674

ABSTRACT

Two aza-BODIPY photosensitizes (PSs, compounds 7 and 8), featuring an iodine atom on each pyrrolic unit of their structure, were synthesized in fairly good yields starting from commercial products and tested in vitro on two human cancer cell lines (HCT116 and SKOV3) to assess their photodynamic efficacy. After treating the cell cultures with variable concentrations of 7 or 8 and incubating for the desired incubation time, the cells were irradiated for two hours with a red-light emitting diode (LED) device; afterwards the extent of cell death was determined by MTT assay. Besides the killing effect, the new PSs were also studied to determine further parameters related to photodynamic efficacy, such as the resistance towards photobleaching, the rate of singlet oxygen production, the fluorescence quantum yields, the cellular uptake and the localization inside the cells and, finally, flow cytometric analysis for apoptosis. Considering the results as a whole, these aza-BODIPYs can be considered to be promising photosensitizers because of their IC50 values being below micromolar concentrations and for more rather interesting features. Actually, these molecules have proved to be: (a) quite stable towards photobleaching; (b) good producers of singlet oxygen and (c) highly penetrating the cells with a wide distribution in the cytosol. Furthermore, in accordance with the good rate of singlet oxygen production, the apoptotic cells reach 30% and this allows us to assume a low inflammatory effect of the in vivo PDT treatment; thus a possible in vivo application of these aza-BODIPYs might be plausible.


Subject(s)
Antineoplastic Agents/pharmacology , Boron Compounds/pharmacology , Neoplasms/drug therapy , Photochemotherapy , Photosensitizing Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Boron Compounds/chemical synthesis , Boron Compounds/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Neoplasms/pathology , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry
19.
Bioorg Med Chem ; 28(21): 115737, 2020 11 01.
Article in English | MEDLINE | ID: mdl-33065434

ABSTRACT

A new class of compounds based on the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene core, known as BODIPYs, has attracted significant attention as photosensitizers suitable for application in photodynamic therapy (PDT), which is a minimally invasive procedure to treat cancer. In PDT the combination of a photosensitizer (PS), light, and oxygen leads to a series of photochemical reactions generating reactive oxygen species (ROS) exerting cytotoxic action on tumor cells. Here we present the synthesis and the study of the in vitro photodynamic effects of two BODIPYs which differ in the structure of the substituent placed on the meso (or 8) position of the dipyrrolylmethenic nucleus. The two compounds were tested on three human cancer cell lines of different origin and degree of malignancy. Our results indicate that the BODIPYs are very effective in reducing the growth/viability of HCT116, SKOV3 and MCF7 cells when irradiated with a green LED source, whereas they are practically devoid of activity in the dark. Phototoxicity occurs mainly through apoptotic cell death, however necrotic cell death also seems to play a role. Furthermore, singlet oxygen generation and induction of the increase of reactive oxygen species also appear to be involved in the photodynamic effect of the BODIPYs. Finally, it is worth noting that the two BODIPYs are also able to exert anti-migratory activity.


Subject(s)
Boron Compounds/chemistry , Photosensitizing Agents/chemical synthesis , Apoptosis/drug effects , Boron Compounds/chemical synthesis , Boron Compounds/metabolism , Boron Compounds/pharmacology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Drug Stability , Humans , Light , Neoplasms/drug therapy , Neoplasms/pathology , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/metabolism , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/metabolism , Singlet Oxygen/metabolism
20.
Lasers Med Sci ; 33(6): 1401-1407, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29038970

ABSTRACT

Photosensitizers belonging to the boron-dipyrromethenes (BODIPYs) class were recently found endowed with good efficacy in the antibacterial photodynamic therapy (aPDT) against both Gram-positive and Gram-negative bacteria. In this paper, we report on the remarkable adjuvant effect exerted in this respect by linear polyamidoamines (PAAs), a family of moderately basic polymers obtained by Michael-type polyaddition of amines to bisacrylamides. Three different PAAs (AGMA1, BP-AGMA, and BP-DMEDA) were studied, testing for each two different molecular weight samples (8000 and 24000 Da). At nontoxic concentrations (1 or 10 µg mL-1) all PAAs remarkably improved the killing efficacy of BODIPY upon irradiation with a green LED device (range: from 480 to 580 nm with λmax = 525 nm) up to an energy rate of 16.6 J cm-2. A 6-7 log unit decrease in bacteria survival was observed with concentrations of BODIPY of 1.0 and 0.1 µM in the case of Escherichia coli and Staphylococcus aureus, respectively. The one-way analysis of variance (ANOVA) was used to evaluate the statistical significance of different treatments (n ≥ 3). Thus, the PAA-photosensitizer combination warrants potentially as a new, effective, and mild method of killing bacteria. Moreover, the antibacterial treatment here reported might be successfully applied to defeat the bacterial resistance often encountered with many antibacterial drugs owing to the double action of this two-component treatment.


Subject(s)
Anti-Bacterial Agents/pharmacology , Boron Compounds/pharmacology , Photosensitizing Agents/pharmacology , Polyamines/chemistry , Escherichia coli/drug effects , Humans , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects
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