Search Results (72)

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Background/Objectives: The rapid emergence of multidrug-resistant bacterial infections demands innovative non-antibiotic therapeutic strategies. Dual-modal photoresponse therapy integrating photodynamic (PDT) and photothermal (PTT) effects offers a promising rapid antibacterial approach, yet designing single-material systems with synergistic enhancement remains challenging. This study aims to develop uniform Cu-based metal–organic framework micrometer cubes (Cu-BN) for efficient PDT/PTT synergy. Methods: Cu-BN cubes were synthesized via a one-step hydrothermal method using Cu(NO₃)₂ and 2-amino-p-benzoic acid. The material’s dual-mode responsiveness to visible light (420 nm) and near-infrared light (808 nm) was characterized through UV–Vis spectroscopy, photothermal profiling, and reactive oxygen species (ROS) generation assays. Antibacterial efficacy against multidrug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was quantified via colony counting under dual-light irradiation. Results: Under synergistic 420 + 808 nm irradiation for 15 min, Cu-BN (200 μg/mL) achieved rapid eradication of multidrug-resistant E. coli (99.94%) and S. aureus (99.83%). The material reached 58.6 °C under dual-light exposure, significantly exceeding single-light performance. Photodynamic analysis confirmed a 78.7% singlet oxygen (¹O₂) conversion rate. This enhancement stems from PTT-induced membrane permeabilization accelerating ROS diffusion, while PDT-generated ROS sensitized bacteria to thermal damage. Conclusions: This integrated design enables spatiotemporal PDT/PTT synergy within a single Cu-BN system, establishing a new paradigm for rapid-acting, broad-spectrum non-antibiotic antimicrobials. The work provides critical insights for developing light-responsive biomaterials against drug-resistant infections. Full article

Background: There has been a reduction in successful H. pylori eradication rates recently, which is largely attributed to increasing antibiotic resistance. In areas of high dual clarithromycin and metronidazole resistance such as ours, Maastricht VI/Florence guidelines recommend bismuth quadruple therapy (BQT) as first line of therapy; however, the availability of bismuth was poor in Ireland until recently. Similarly, tetracycline, a component of BQT, is restricted locally, with doxycycline (D) being approved and reimbursed for most indications. Aims: To assess the efficacy of BQT-D therapy for H. pylori eradication in an Irish cohort. Methods: All patients testing positive for H. pylori in three Irish referral centres by urea breath test, stool antigen, or histology were treated prospectively with BQT-D (bismuth subcitrate 120 mg QDS, metronidazole 400 mg TDS, doxycycline 100 mg BD and esomeprazole 40 mg BD) for 14 days. Eradication was evaluated with a urea breath test (UBT) >4 weeks after therapy cessation or by stool antigen testing, as available. Outcomes were recorded and analysed according to demographics and H. pylori treatment history of the patients. Results: 217 patients completed post-eradication testing. Of which, 124 (57%) were female, with a mean age 52 years. 180 patients (83%) were treatment-naïve. A total of 165/180 (92%) of the treatment-naïve patients had successful eradication. There was no association between eradication and gender or age in this cohort (p = 0.3091, p = 0.962 respectively). A total of 29 patients received this therapy as second-line therapy, of which 22 (76%) had successful eradication. Eight patients received the regimen as rescue therapy, with seven (88%) having successful eradication. No serious adverse events were reported. Eleven individuals (6.5%) commented on the complicated nature of the regimen, with 11 tablets being taken at five intervals daily. Conclusions: BQT-D as first-line therapy for H. pylori infection is highly effective in a high dual-resistance population, achieving >90% eradication. BQT-D as a second-line treatment performed less well. Our data support BQT-D as a first-line treatment. Full article

The emergence of multidrug-resistant (MDR) bacteria and biofilm-associated infections has created a significant hurdle for conventional antibiotics, prompting the exploration of alternative strategies. Photodynamic therapy (PDT), a technique that utilizes photosensitizers activated by light to produce ROS, has emerged as a beacon of hope in the fight against MDR microorganisms. Among the natural photosensitizers, hypocrellins (A and B) have shown remarkable potential with their dual-mode photodynamic action, generating ROS via both Type I (electron transfer) and Type II (singlet oxygen) pathways. This unique action disrupts bacterial biofilms and inactivates MDR pathogens. The amphiphilic nature of hypocrellins further enhances their promise, enabling deep biofilm penetration and ensuring potent antibacterial effects even in hypoxic environments, surpassing the capabilities of synthetic photosensitizers. This study critically examines the antimicrobial properties of hypocrellin-based PDT, emphasizing its mechanisms, advantages over traditional antibiotics, and effectiveness against MDR pathogens. Comparative analysis with other photosensitizers, the role of nanotechnology-enhanced delivery systems, and future clinical applications are explored. Its combination with nanotechnology enhances therapeutic outcomes, providing a viable alternative to conventional antibiotics. Further clinical research is essential to optimize its application and integration into antimicrobial treatment protocols. Full article

Background/Objectives: Photothermal therapy (PTT) is an emerging minimally invasive strategy in biomedicine that converts near-infrared (NIR) light into localized heat for the targeted inactivation of pathogens and tumor cells. Methods and Results: In this study, we report the synthesis and characterization of thermoresponsive nanogels composed of poly (N-isopropylacrylamide-co-N-isopropylmethylacrylamide) (PNIPAM-co-PNIPMAM) semi-interpenetrated with polypyrrole (PPy), yielding monodisperse particles of 377 nm diameter. Spectroscopic analyses—including ¹H-NMR, FTIR, and UV-Vis—confirmed successful copolymer formation and PPy incorporation, while TEM images revealed uniform spherical morphology. Differential scanning calorimetry established a volumetric phase transition temperature of 38.4 °C, and photothermal assays demonstrated a ΔT ≈ 10 °C upon 10 min of 850 nm NIR irradiation. In vitro antimicrobial activity tests against Pseudomonas aeruginosa (ATCC 15692) showed a dose-time-dependent reduction in bacterial viability, with up to 4 log CFU/mL. Additionally, gentamicin-loaded nanogels achieved 38.7% encapsulation efficiency and exhibited stimulus-responsive drug release exceeding 75% under NIR irradiation. Conclusions: Combined photothermal and antibiotic therapy yielded augmented bacterial killing, underscoring the potential of PPy-interpenetrated nanogels as smart, dual-mode antimicrobials. Full article

Microorganisms play a dual role in human health, serving as both essential allies and serious threats. Their association with infections led to the development of antimicrobials like penicillin, which revolutionized medicine. However, the emergence of antimicrobial resistance (AMR) has created a global health crisis, rendering many treatments ineffective due to pathogen mutations and acquired resistance mechanisms, particularly among ESKAPE pathogens. This resistance increases morbidity, mortality, and healthcare costs, exacerbated by antibiotic overuse and globalization. Biofilms and sepsis further complicate treatment. Addressing AMR requires new therapies, rational antibiotic use, and innovative approaches for drug discovery. Coordinated global action is essential to ensure future access to effective treatments. Antimicrobial peptides (AMPs) derived from Boana species (Anura, Hylidae) represent a promising alternative in the fight against AMR. These peptides exhibit activity against multidrug-resistant pathogens. Unlike conventional antibiotics, Boana peptides act through a broad mechanism that limits resistance development. Their ability to disrupt bacterial membranes and modulate immune responses makes them ideal candidates for the development of new treatments. These peptides may offer valuable alternatives for treating resistant infections and addressing the global AMR crisis. Full article

Although penicillin transformed antibiotic therapy, rising antimicrobial resistance (AMR) has limited its effectiveness, creating a need for new approaches in wound healing. Antimicrobial peptides (AMPs) are promising candidates due to their rapid membrane-disrupting action, immunomodulatory effects, and ability to target drug-resistant pathogens, though their specific roles in promoting wound healing are still not fully understood. This review aims to provide a comprehensive synthesis of the current evidence on the dual role of AMPs as both antimicrobial and immunomodulatory agents in the context of wound healing. Recent studies published between 2020 and 2025 were comprehensively reviewed, focusing on the mechanisms by which AMPs contribute to pathogen elimination, immune regulation, tissue repair, and inflammation resolution. AMPs not only exhibit rapid membrane-disruptive activities against a wide range of pathogens but also influence immune cell behavior, particularly by promoting macrophage polarization toward a reparative M2 phenotype, modulating cytokine and chemokine network, and maintaining T-cell homeostasis. Their ability to simultaneously control infection and regulate inflammation positions AMPs as promising candidates for advanced wound care strategies. The dual antimicrobial and immunomodulatory functions of AMPs represent a synergistic mechanism essential for effective wound recovery. Understanding and harnessing these properties can drive the development of innovative therapies, such as AMP-integrated smart biomaterials and targeted peptide delivery systems, offering new solutions for both acute and chronic wound management. Full article

Regulating the innate immune response against infections, particularly drug-resistant bacteria, is a key focus in anti-infection therapy. Cathelicidins, found in vertebrates, are crucial for pathogen resistance. Few studies have explored gecko cathelicidins’ anti-infection properties. Recently, five new cathelicidins (Gj-CATH1-5) were identified in Gekko japonicus. The peptide Gj-CATH5, from G. japonicus, shows promise against Pseudomonas aeruginosa through various mechanisms. This study examined Gj-CATH5’s protective effects using in vitro and in vivo models, finding that it significantly reduced bacterial load in a mouse infection model when administered before or shortly after infection. Flow cytometry and the plate counting method showed that Gj-CATH5 boosts neutrophil and macrophage activity, enhancing chemotaxis, phagocytosis, and bactericidal functions. Gj-CATH5 increases ROS production, MPO activity, and NET formation, aiding pathogen clearance. Its amphipathic α-helical structure supports broad-spectrum bactericidal activity (MBC: 4–8 μg/mL) against Gram-negative and antibiotic-resistant bacteria. Gj-CATH5 is minimally cytotoxic (<8% hemolysis at 200 μg/mL) and preserves cell viability at therapeutic levels. These results highlight Gj-CATH5’s dual role in pathogen elimination and immune modulation, offering a promising approach to combat multidrug-resistant infections while reducing inflammation. This study enhances the understanding of reptilian cathelicidins and lays the groundwork for peptide-based immune therapies against difficult bacterial infections. Full article

Background: Influenza B usually causes mild illness in children. Severe and fatal cases can occur when complicated by secondary Staphylococcus aureus (S. aureus) pneumonia, including community-acquired methicillin-resistant Staphylococcus aureus (MRSA). We present a rare, rapidly progressive fatal case in an adolescent with no known medical history to highlight diagnostic and therapeutic pitfalls. Case Presentation: A 16-year-old boy with no known underlying conditions (unvaccinated for influenza) presented critically ill at “Sf. Ioan” Clinical Emergency Pediatric Hospital in Galați after one week of high fever and cough. He was in respiratory failure with septic shock, requiring immediate intubation and vasopressors. Chest X-ray (CXR) showed diffuse bilateral infiltrates (acute respiratory distress syndrome, ARDS). Initial laboratory tests revealed leukopenia, severe thrombocytopenia, disseminated intravascular coagulation (DIC), rhabdomyolysis, and acute kidney injury (AKI). Reverse transcription polymerase chain reaction (RT-PCR) confirmed influenza B, and blood cultures grew MRSA. Despite maximal intensive care, including mechanical ventilation, antibiotics (escalated for MRSA), antiviral therapy, and cytokine hemoadsorption therapy, the patient developed refractory multi-organ failure and died on hospital day 6. Autopsy revealed bilateral necrotizing pneumonia (NP) without radiographic cavitation, underscoring the diagnostic challenge. Discussion: The initial chest radiography showed diffuse bilateral pulmonary infiltrates, predominantly in the lower zones, with an ill-defined, patchy, and confluent appearance. Such appearance, in our case, was more suggestive of rapid progressive NP caused by MRSA rather than the typical pneumococcal one. This is one of the few reported cases of influenza B–MRSA coinfection with fulminant rhabdomyolysis and autopsy-confirmed necrosis. Our fulminant case illustrates the synergistic virulence of influenza and MRSA. Toxin-producing MRSA strains can cause NP and a “cytokine storm,” causing capillary leak, ARDS, shock, and DIC. Once multi-organ failure ensues, the prognosis is grim despite aggressive care. The absence of early radiographic necrosis and delayed anti-MRSA therapy (initiated after culture results) likely contributed to the poor outcome. Conclusions: Influenza B–MRSA co-infection, though rare, demands urgent empiric anti-MRSA therapy in severe influenza cases with leukopenia or shock, even without radiographic necrosis. This fatal outcome underscores the dual imperative of influenza vaccination and early, aggressive dual-pathogen targeting in high-risk presentations. Full article

Objective: This systematic review and meta-analysis aims to evaluate the temporal changes in Helicobacter pylori antibiotic resistance in Russia based on studies published over the past 15 years. Materials and Methods: We conducted a comprehensive literature search in MEDLINE/PubMed, EMBASE, the Russian Science Citation Index, and Google Scholar, following the PRISMA 2020 guidelines. Our meta-analysis was pre-registered in PROSPERO (CRD 420251025636). The inclusion criteria included original research, published in English or Russian in 2011–2024, involving antibiotic susceptibility testing in treatment-naive Russian adults using validated diagnostic methods. Two independent researchers selected studies and extracted data using standardized procedures, with methodological quality assessed via the Newcastle–Ottawa Scale. Pooled resistance rates were calculated using fixed/random-effects models in MedCalc 23.1.5 and Python 3.9.21, with meta-regression investigating temporal trends and subgroup analyses examining regional and methodological variations. Results: We identified 16 studies comprising 1206 H. pylori isolates. The pooled analysis of studies (2011–2025) revealed an overall clarithromycin resistance rate of 15.236%, with a significant temporal increase from 11.903% pre-2015 to 21.024% in 2020–2024 (p = 0.0049). Metronidazole showed consistently high pooled resistance (33.309%), while amoxicillin (1.828%), levofloxacin (19.014%), tetracycline (1.328%), and rifampicin (5.803%) maintained low resistance rates, and dual clarithromycin–metronidazole resistance was observed in 2.793% of isolates. Regional disparities were notable in the two largest cities of Russia, with 18.763% clarithromycin resistance in Moscow versus 28.540% in Saint-Petersburg. Conclusions: Russia surpasses the Maastricht VI Consensus resistance threshold for clarithromycin (15%), necessitating revision of empirical treatment strategies. The significant increase in clarithromycin resistance, potentially exacerbated by antibiotic use during the COVID-19 pandemic, underscores the urgent need for resistance-guided therapies and ongoing national surveillance programs to optimize H. pylori management. Full article

The growing threat of multidrug-resistant bacteria requires innovative therapies beyond traditional antibiotics. This review highlights the potential of endolysin biocomposites using alginate oligosaccharides (AOSs) and modified cellulose (CL) as stabilizers. AOSs could enhance endolysin stability and potentially support colonic fermentation, producing short-chain fatty acids that may synergize with endolysins to combat pathogens and improve gut health. KZ144 and LysPA26 are proposed as optimal candidates for their broad pH range, divalent cation tolerance, and potential effectiveness against Gram-positive and Gram-negative pathogens. Integrating AOSs and CL into biocomposites could offer a novel dual-action strategy against gastrointestinal diseases while potentially reducing antibiotic dependence. Full article

Background: All currently used therapeutic protocols and drugs for Clostridioides difficile infection (CDI) treatment do not have a satisfying success and usually cost a lot. Objectives: To compare the efficacy of vancomycin monotherapy vs modified dual therapy with vancomycin + nifuroxazide as a therapeutic protocol for a medium–severe form of CDI. In addition, the effects of a modified therapeutic protocol with standard monotherapy on the number of stools and stool consistency in a medium–severe CDI will be compared. Materials and Methods: A prospective, randomized, controlled clinical trial that included 60 patients divided into two groups was conducted. One group of patients was treated with vancomycin monotherapy. The other group was treated with the modified therapeutic protocol (vancomycin + nifuroxazide). Results: The modified therapy with vancomycin + nifuroxazide demonstrated enhanced pharmacological efficacy in the management of CDI compared to the standard vancomycin monotherapy. Patients treated with dual therapy reported a significantly lower number of stools in first, second and third control; first control (4.47 ± 2.20 compared to 5.70 ± 1.91 in vancomycin group (p = 0.024)), second control (2.37 ± 0.85 compared to 3.13 ± 0.90 in vancomycin group (p = 0.001)), and third control (1.53 ± 0.51 compared to 1.80 ± 0.61 in vancomycin group (p = 0.035)). Also, the first and third controls noted significant improvements in stool consistency, measured as a decrease in the number of completely watery stools (p = 0.011 and p < 0.001, respectively). Conclusions: Nifuroxazide and vancomycin have demonstrated accelerated improvement in patient status and hold promise as a novel dual therapeutic regimen for managing patients diagnosed with a medium–severe form of CDI. Full article

The tapeworms Echinococcus granulosus and Echinococcus multilocularis cause two different clinical manifestations in humans: cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. Both forms of echinococcosis manifest primarily in the liver, while other organs or tissues are less frequently affected. Simultaneous occurrence of CE and AE is extremely rare, and all previously reported patients exhibited affected livers, while simultaneous infection without liver involvement has not yet been described. Herein, we present an exclusively extrahepatic E. granulosus and E. multilocularis coinfection localized between the calf muscles of a patient. Due to progressive painful local swelling, an abscess was suspected, but there was no improvement after the administration of multiple courses of antibiotics. When imaging diagnostics suggested a parasitic origin of the two identified cystic lesions, positive serology for both species indicated a dual infection. Albendazole therapy was started, and extensive surgical excision was performed. Both species were confirmed using PCR and sequencing from intraoperative samples. The current case shows that coinfection without liver involvement can occur, even in patients from low-incidence regions, which should be considered in the differential diagnosis of patients with unusual clinical presentation. Full article

Chronic wounds not only cause significant patient morbidity but also impose a substantial economic burden on the healthcare system. The primary barriers to wound healing include a deficiency of key modulatory factors needed to progress beyond the stalled inflammatory phase and an increased susceptibility to infections. While antimicrobial agents have traditionally been used to treat infections, stem cells have recently emerged as a promising therapy due to their regenerative properties, including the secretion of cytokines and immunomodulators that support wound healing. This study aims to develop an advanced dual-delivery system integrating stem cells and antibiotics. Stem cells have previously been delivered by encapsulation in gelatin methacrylate (GelMA) hydrogels. To explore a more effective delivery method, GelMA was processed into microparticles (MP). Compared to a bulk GelMA hydrogel (HG) encapsulation, GelMA MP supported greater cell growth and enhanced in vitro wound healing activity of human mesenchymal stem cells (hMSCs), likely due to a larger surface area for cell attachment and improved nutrient exchange. To incorporate antimicrobial properties, the broad-spectrum antibiotics penicillin/streptomycin (PS) were loaded into a bulk GelMA hydrogel, which was then cryo-milled into MPs to serve as carriers for hMSCs. To achieve a more sustained antibiotic release, gelatin nanoparticles (NP) were used as carriers for PS. PS was either incorporated during NP synthesis (NP+PS(S)) or absorbed into NP after synthesis (NP+PS(A)). MPs containing PS, NP+PS(S), or NP+PS(A) were tested for their cell carrier functions and antibacterial activities. The incorporation of PS did not compromise the cell-carrying function of MP configurations. The anti-S. aureus activity was detected in conditioned media from MPs for up to eight days—four days longer than from bulk HG containing PS. Notably, the presence of hMSCs prolonged the antimicrobial activity of MPs, suggesting a synergistic effect between stem cells and antibiotics. PS loaded via synthesis (NP+PS(S)) exhibited a delayed initial release, whereas PS loaded via absorption (NP+PS(A)) provided a more immediate release, with potential for sustained delivery. This study demonstrates the feasibility of a dual-delivery system integrating thera Full article

Due to the increasing prevalence of antimicrobial resistance, the efficacy of standard triple therapy for Helicobacter pylori (H. pylori) infection has declined, with eradication rates now falling below 80% in most countries. Although bismuth quadruple therapy and concomitant therapy are advised in regions with high clarithromycin resistance, these treatments commonly cause frequent adverse events and require the use of two or three antibiotics. This review article evaluates the effectiveness of 14-day mono-antibiotic therapies for H. pylori infection through randomized controlled trials conducted from 1 October 2014 to 1 October 2024. The pooled eradication rates for 14-day high-dose amoxicillin/proton pump inhibitor (PPI) dual therapies were 86.1% (3335/3875; 95% confidence interval (CI): 85.1–87.2%) by intention-to-treat (ITT) analysis and 87.3% (3232/3702; 95% CI: 86.2–88.4%) by per-protocol (PP) analysis. For 14-day high-dose amoxicillin/vonoprazan dual therapies, the rates were 87.4% (1085/1241; 95% CI: 85.5–89.2%) by ITT and 93.0% (1044/1124; 95% CI: 91.5–94.5%) by PP. In the penicillin-allergic population, 14-day tetracycline/vonoprazan dual therapy showed eradication rates of 92.0% (138/150) by ITT and 95.1% (135/142) by PP. In conclusion, 14-day tetracycline/vonoprazan dual therapy presents an effective option for eradicating H. pylori in patients allergic to penicillin. For those without a penicillin allergy, first-line treatments can include 14-day mono-antibiotic regimens, such as high-dose amoxicillin/PPI dual, high-dose amoxicillin/vonoprazan dual, and tetracycline/vonoprazan dual therapies. Full article