Search Results (784)

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects more than 6 million people worldwide, predominantly in Latin America. Current chemotherapy relies on Benznidazole (Bz) and Nifurtimox, which are associated with adverse effects and limited efficacy during chronic infection, underscoring the need for new therapeutic options. Natural products remain an important source of bioactive molecules for antiparasitic drug discovery. In this study, 34 extracts obtained from 18 Brazilian plant species were evaluated for anti-T. cruzi activity. After cytotoxicity assessment, extracts were screened against intracellular amastigotes (Tulahuen strain, DTU VI) and bloodstream trypomastigotes (Y strain, DTU II). Most samples exhibited low toxicity toward mammalian cells (LC₅₀ > 120 μg/mL). Among them, the inflorescence extract of Piper claussenianum (Miq.) C. DC. (PCFLD) showed the highest activity. At 20 μg/mL, PCFLD reduced intracellular parasite burden by 94%, with an EC₅₀ of 3.6 ± 0.36 μg/mL and a selectivity index of 20. Against trypomastigotes, the extract displayed an EC₅₀ of 11.56 ± 5.88 μg/mL and a selectivity index of 11. In an acute murine model, PCFLD (10 mg/kg/day) reduced peak parasitemia by 40%, outperforming Bz at the same dose. These findings identify P. claussenianum as a promising source of anti-T. cruzi compounds. Full article

Climate variability can modulate zoonotic disease risk by altering interactions among wildlife hosts, vectors, and human environments, yet long-term evidence linking large-scale climate oscillations to natural plague systems remains scarce. We investigated the influence of El Niño–Southern Oscillation (ENSO)-related climate variability on rodent host dynamics in a long-established plague focus in Jianchuan County, southwestern China. Using continuous monthly surveillance data from 1978 to 2025, we analyzed population dynamics of two ecologically distinct plague hosts—the wild rodent Apodemus chevrieri and the domestic rodent Rattus tanezumi—together with flea infection rates and local climate variables. Generalized additive models showed that ENSO, quantified by the Southern Oscillation Index (SOI), exerted significant delayed effects on both rodent populations, with El Niño conditions consistently associated with increased host abundance. Wavelet coherence analyses revealed synchronized ENSO–rodent oscillations at dominant 2–3-year periodicities, indicating persistent large-scale climate forcing. In contrast, responses to local environmental factors differed between species: surface temperature strongly constrained the wild rodent A. chevrieri, whereas the domestic R. tanezumi showed weaker thermal sensitivity, consistent with buffering by human-modified indoor habitats. Flea infection rates declined as rodent densities increased, suggesting a dilution effect within the host–vector system. By integrating long-term wildlife surveillance, climate indicators, and vector data, this study provides empirical evidence that ENSO-driven climate variability plays a central role in regulating plague source activity at the human–animal–environment interface. These findings highlight the value of climate-informed, ecology-based surveillance frameworks for anticipating periods of elevated plague risk and strengthening early warning systems in endemic regions. Full article

The rapid emergence and dissemination of antimicrobial resistance (AMR) among bacterial pathogens, particularly the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), represents one of the most pressing global public health challenges, contributing to increased morbidity, mortality, and healthcare costs. The limited development of new antibiotic classes over the past two decades has intensified the search for structurally novel antimicrobial agents and adjuvants capable of overcoming multidrug resistance. Natural products continue to serve as an invaluable source of anti-infective drug leads owing to their remarkable structural diversity and broad spectrum of biological activities. Mangrove ecosystems, located at the interface of terrestrial and marine environments, harbor highly diverse microbial communities, including fungi that have evolved under extreme environmental conditions and produce a wide range of unique secondary metabolites. Beyond their ecological significance, mangrove-associated fungi have emerged as prolific producers of bioactive compounds with promising antibacterial activity against multidrug-resistant pathogens. This review comprehensively summarizes recent advances (2018–2026) in the discovery of antibacterial metabolites from mangrove-associated fungi active against ESKAPE pathogens, which discusses their structural diversity, reported antimicrobial activities, and emerging strategies for accelerating natural product discovery, including genome mining, metabolomics, OSMAC, adaptive laboratory evolution, and artificial intelligence-assisted approaches. A total of 139 chemically distinct metabolites (Compounds 1–139) isolated from mangrove-associated fungi are critically reviewed, highlighting their potential as promising leads for the development of next-generation antimicrobial agents against ESKAPE pathogens. Full article

Objective: This review aimed to evaluate the existing literature to determine the incidence and associated risk factors of cochlear implant complications. Data Sources: A comprehensive literature search was conducted across PubMed, Web of Science, Embase, and Scopus up to 12 April 2025. Methods: The review protocol was registered on PROSPERO (ID: CRD420251012225) on 15 March 2025, and the systematic review was performed according to PRISMA guidelines. Results: We included a total of 100 records based on 81 studies with 42,167 patients. The overall incidence was 13.7%. Major complications occurred in 5.2%, with device failure being the most common at 2.8%. Minor complications affected 7.8%, with superficial wound infections being most frequent at 2.3%. Vestibular complications (vertigo/dizziness) were prevalent at 12.4%. Adults had significantly higher overall and major complication rates compared to pediatric patients. The mastoidectomy with posterior tympanotomy approach (MPTA) was associated with lower rates (5.4%) than the suprameatal approach (SMA) (7.8%). A significant temporal trend showed decreased complication rates from 8.9% in the early era (1991–2010) to 4.1% in the recent era (2011–2025). Significant risk factors were identified including older age at implantation, inner ear malformations, chronic otitis media, previous otologic surgery, and longer surgery duration. A substantial heterogeneity was present across the included studies (I² up to 93.6%), and the evidence base was predominantly retrospective in nature, which limits the certainty of these estimates. Conclusions: Cochlear implantation appears to be a generally safe procedure. However, these findings should be interpreted with caution. The high heterogeneity, predominantly retrospective study designs, inconsistent complication definitions, and detected publication bias collectively limit the certainty of the pooled estimates. Standardized complication reporting, prospective multicenter designs, and consensus-based outcome definitions are essential to strengthen the evidence base and guide safer clinical practice. Full article

Vulvovaginal candidiasis (VVC) is a common mucosal infection that predominantly affects reproductive-aged women. Although conventional antifungal agents remain the primary treatment option, there is growing interest in developing alternative therapeutic approaches that can enhance antifungal efficacy while potentially reducing treatment burden. Natural products have emerged as valuable sources of bioactive compounds with antifungal potential, offering opportunities for novel combination-based therapies. Ebselen (EB), an organoselenium compound with potent redox-modulating and antifungal properties, and its structurally related analogs represent promising candidates for such strategies. Likewise, black seed oil (BSO), derived from Nigella sativa, and its major active constituent, thymoquinone (TQ), have demonstrated antifungal activity against Candida species, supporting their investigation as natural product-based partners in synergistic antifungal combinations. Commercially prepared BSO and purified TQ were tested across a range of concentrations in a broth microdilution assay in combination with EB and novel organoselenium analogs, including Ebselen Oxide (EB-Ox) and N-octyl-1,2-benzisoselenazol-3(2H)-one (APM C6). Minimum inhibitory concentrations (MICs) for single agents and combinations were determined, and the resulting datasets were analyzed using the web-based Synergy Finder platform. EB, EB-Ox, and APM C6 showed consistent synergy with BSO and TQ against C. albicans (clinical isolate S1), as indicated by positive synergy scores relative to monotherapies. Full article

Fusarium oxysporum f. sp. lycopersici (Fol) is a destructive soil-borne pathogen responsible for major global losses in tomato production, within a context of increasingly constrained fungicide use in intensive farming systems. Sustainable alternatives to chemical fungicides are urgently needed, and microbial secondary metabolites represent a promising source of antifungal compounds. This study explores the antifungal potential of secondary metabolites produced by a natural isolate of Beauveria bassiana (Bb758) previously reported to exhibit strong biocontrol activity against Fol. LC-HRMS metabolomic profiling revealed a chemically diverse metabolite profile dominated by amino acid-derived compounds, peptides and alkaloids. Purification of the crude extract by column chromatography and reverse-phase HPLC yielded beauvericin and several 2,5-diketopiperazines as the main bioactive constituents. These compounds were identified by NMR and LC-HRMS analyses. The antifungal activity of beauvericin (BEA), cyclo(l-Phe-l-Pro) (CFP) and fractions was evaluated against spore germination and germ tube development of Fol. BEA exhibited dose-dependent but limited activity, showing significant inhibition only at high concentrations (100 μg mL⁻¹). In contrast, CFP showed significantly higher antifungal activity than BEA, inhibiting both germination and germ tube formation at concentrations as low as 10 μg mL⁻¹. These results identify CFP as a promising antifungal compound targeting the early infection stages of Fol and highlight fungal-derived diketopiperazines as candidate molecules for sustainable disease management strategies. Full article

Background: Inappropriate antibiotic use for upper respiratory tract infections (URTIs) is common. However, existing research typically examines single indicators or broad categories of misuse practices, without considering the probabilistic and co-occurring nature of varying behaviours. This study aims to identify and characterise distinct antibiotic behavioural profiles within a general population to inform personalised interventions. Methods: This is a broadly representative population-based study of adult Singapore residents between November 2020 and January 2021. Latent class analysis was first performed to identify distinct profiles, followed by multinomial logistic regression to determine individual characteristics associated with each profile, with interaction effects examined. Results: Amongst 2004 respondents, the majority were “antibiotic appropriates” (53.0%), followed by “antibiotic avoiders” (24.9%), and “antibiotic seekers” (22.2%). “Antibiotic seekers” expected antibiotics for cold/flu, hopped between doctors to source antibiotics, used leftover antibiotics, stopped antibiotic courses prematurely and perceived antibiotics as harmless and useful for treating cold/flu. Individuals with poor knowledge of antibiotic use (AOR 3.71, 95% CI 2.89–4.76, p < 0.001) and antimicrobial resistance (AOR 3.51, 95% CI 1.05–11.76, p = 0.042), low eHealth literacy (AOR 1.34, 95% CI 1.02–1.77, p = 0.038), and high trust in doctors (AOR 2.14, 95% CI 1.44–3.17, p < 0.001) were more likely to be “antibiotic seekers”. Older adults with lower education levels were particularly likely to be “antibiotic seekers”. Conclusions: Approximately one-in-five Singapore residents are antibiotic seekers. Targeted education during multiple clinic visits, given the high trust in doctors, can address antibiotic knowledge gaps and misperceptions, reducing antibiotic misuse. Full article

Oral diseases, encompassing conditions such as periodontitis, head and neck squamous cell carcinoma, pulpitis, and mucosal infections, remain a major global health burden due to their high prevalence and complex, multifactorial pathophysiology. The unique anatomical structure of the oral cavity, together with persistent microbial challenges and dynamic immune responses, imposes substantial limitations on conventional drug delivery strategies. Biomimetic cell membrane-based materials have recently emerged as a promising class of delivery platforms, leveraging natural biological interfaces to confer inherent biocompatibility, immune evasion, prolonged circulation, specific targeting, and biofilm-interactive capabilities. These features position them as a transformative approach for improving therapeutic precision and efficacy in oral disease management. In this review, we provide a systematic and materials-oriented overview of biomimetic cell membrane-based drug delivery systems. Specifically, we discuss: (1) the biological sources, classification, and physicochemical properties of membrane-coated systems, along with their fabrication and engineering strategies; (2) the mechanistic basis of targeting, immune modulation, and nanobiointerface interactions, and their applications across representative oral diseases; and (3) current challenges, including scalable manufacturing, functional controllability, biosafety, and clinical translation. Furthermore, we highlight emerging directions such as stimuli-responsive membrane systems and multifunctional integrated platforms, aiming to provide a conceptual framework for the rational design and clinical advancement of biomimetic drug delivery systems in complex disease settings. Full article

This review examines the bioactive compounds of ginger (Zingiber officinale Roscoe), with a particular focus on metabolites and antimicrobial peptides exhibiting antimicrobial activity. The chemical composition, biological properties, and mechanisms of action of the major ginger-derived compounds are discussed, with emphasis on their antibacterial, antifungal, anti-inflammatory, and antibiofilm potential. Particular attention is given to their antimicrobial spectrum and to potential synergistic interactions with other natural bioactive compounds that may enhance their efficacy against pathogenic microorganisms. Despite their promising therapeutic properties, the application of ginger-derived molecules against skin-associated pathogens remains challenging due to their limited stability, poor bioavailability, and the protective effects of microbial biofilms, which reduce treatment effectiveness and contribute to persistent infections. Current strategies designed to overcome these limitations, including chemical modification, liposomes, nanoemulsions, and hydrogel-based delivery systems, are reviewed. In addition, this review highlights the potential of microalgae-based encapsulation systems as innovative and sustainable platforms for the delivery of ginger bioactives. Owing to their diverse biochemical composition and structural characteristics, microalgae represent a promising source of natural biomaterials for the development of diverse encapsulation strategies. These emerging systems may potentially improve the stability, controlled release, bioavailability, and antibiofilm efficacy of ginger-derived compounds, supporting the development of novel formulations for the management of biofilm-associated skin infections. Full article

Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, biocompatibility, and extracellular matrix-mimicking cues consistent with sustainable, green biomaterials science. This review synthesises recent progress in 3D printing of biopolymer-based scaffolds for bone tissue engineering. We first examine the principal feedstocks—alginate, gelatin and gelatin methacryloyl, collagen, chitosan, silk fibroin, cellulose, and microbial polyesters—and their preparation, crosslinking chemistry, and printability. We then compare extrusion, light-based, and indirect printing technologies and the process–property relationships governing resolution, mechanical competence, and cell viability. Composite and functionalisation strategies, including biopolymer–bioceramic hybrids and controlled delivery of growth factors and antimicrobial agents, are analysed as routes to osteoinduction, vascularisation, and infection control. Finally, we evaluate translational performance in preclinical models and outline central challenges of vascularisation, mechanical–degradation matching, scalability, and regulatory standardisation. Biopolymer 3D printing is positioned as a ve rsatile, sustainable platform whose clinical maturation depends on integrated material, structural, and biological design. Full article

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic bacteria of the Leptospira genus. Currently, 77 genomic species have been described. Leptospira interrogans is the most extensively studied species due to its high prevalence worldwide and the severity of the disease it causes in humans and animals. However, Leptospira santarosai is an important pathogenic species in the Americas, the Caribbean islands, and Taiwan. This species has a high serological diversity: it can infect domestic, wild, and agricultural production animals, causing reproductive problems and substantial economic losses. Additionally, Leptospira santarosai has been detected in water sources and wet soils. In humans, infection with this species can lead to a wide range of clinical manifestations and severe complications. Therefore, this study aimed to synthesize available information on the serological diversity, geographical distribution, natural sources of infection, and human leptospirosis caused by Leptospira santarosai to better understand their role in the leptospirosis transmission cycle. Methods: A systematic review of the literature was conducted, following the criteria established by the PRISMA-2020 guide, the search for scientific articles was conducted in five specialized and multidisciplinary databases (PubMed, Scopus, Web of Science, SciELO, and LILACS), and a search engine (Google Scholar). Two different search strategies (Leptospira santarosai OR L. santarosai) were used. Result: Once the search was carried out in the databases, 2989 scientific articles were identified. These articles underwent a process of identification, screening, eligibility, and inclusion, resulting in 84 articles that met all established inclusion criteria. These articles were included in the qualitative synthesis and elaboration of the systematic review. Conclusions: Leptospira santarosai shows a high serological diversity, with 14 serogroups and 59 serovars. The species has a wide geographic distribution, having been reported on five continents and in 26 countries, and has been described as an infectious agent in at least 24 host animals. It has also been detected in environmental sources such as water and wet soils; 24 serovars have been identified as the causative agents of human leptospirosis, causing clinical manifestations that range from mild to severe forms of the disease and clinical complications such as myocarditis, uveitis, and neuroleptospirosis. Although L. santarosai is considered native to the Americas, it shows an expansion pattern to other continents and countries. Therefore, this pathogenic species of the Leptospira genus represents an important public health problem worldwide. Full article

Refractory thoracic infections require targeted antimicrobial combinations, repeated drainage interventions and often staged surgical procedures of varying complexity grades. In necrotizing pneumonia cases, successful treatment is complete removal of destroyed non-functional parenchyma, pleural cavity debridement, and complete pathogen eradication based on culture-based sensitivity-driven antimicrobials. The latter proves challenging in pan-resistant microbial strains where both medical and surgical treatments demonstrate limited effectiveness. We describe a case of persistent thoracic sepsis due to pan-resistant Pseudomonas receiving sequentially thoracoscopic decortication, thoracotomy for lobectomy, and open thoracostomy as the last treatment option to prevent fatal sepsis in view of non-available antibiotics. The immediate source-control effect raised the question of the ideal timing for selecting an aggressive thoracoplastic procedure despite its deforming nature over any other treatment approach. Full article

Residential buildings must now be designed and retrofitted as adaptive climate–health–work systems rather than as static housing units. This structured literature review synthesises peer-reviewed journal and conference evidence on residential taxonomy, ventilation, indoor environmental quality, overheating, airborne infection resilience, post-pandemic occupancy changes and future performance benchmarks. The review shows that single-family and multifamily buildings remain the most practical first-order categories because they differ in envelope exposure, ventilation pathways, system ownership, governance, retrofit feasibility and occupant control. Single-family dwellings generally provide greater household autonomy, roof-based renewable potential and room-level intervention flexibility, but can also carry higher envelope losses, lower density and stronger dependence on occupant operation. Multifamily buildings benefit from compactness and shared infrastructure, yet face additional risks from common services, vertical shafts, stack effects, corridor pressurisation, inter-zonal airflow and collective maintenance. Ventilation evidence indicates that natural, exhaust-only, supply, balanced heat-recovery, hybrid, demand-controlled and filtration-based strategies cannot be ranked universally; their effectiveness depends on climate, airtightness, pollutant source, occupancy, maintenance and governance. This review further shows that overheating, cooling-demand growth, airborne infection preparedness and remote work are shifting residential performance from winter-centric energy efficiency toward year-round thermal resilience, clean-air delivery and prolonged-occupancy functionality. A future taxonomy is therefore proposed around adaptive performance attributes, including thermal resilience, clean-air capacity, ventilation controllability, energy flexibility, remote-work readiness, vulnerability and retrofit potential. The core contribution is a hypothesis-generating, decision-support and benchmark-development framework for aligning residential design, retrofit and policy with health, indoor environmental quality, energy efficiency and carbon performance. Full article

Cowpea (Vigna unguiculata (L.) Walp.) is a legume valued in several countries for its nutritional quality, low input requirements, and economic profitability. However, cowpea productivity is significantly constrained by anthracnose disease caused by Colletotrichum species. Enhancing host resistance through the introgression of resistance alleles from landraces and wild relatives offers a promising strategy for durable disease management. This study evaluated 20 cowpea landraces and 18 V. unguiculata ssp. dekindtiana accessions for resistance to anthracnose under natural field infection. The cultivars Ife Brown and V. vexillata line TVNu-428 were included as susceptible and resistant checks, respectively. The experiment was laid in an alpha lattice design (8 × 5) with three replications arranged. Anthracnose symptoms characterized by enlarged light-brown lesions surrounded by reddish-brown halos were produced on all the accessions and the symptoms progressed throughout the assessment period. Five V. unguiculata ssp. dekindtiana accessions (TVNu-113, TVNu-1506, TVNu-1222, TVNu-420, and TVNu-136) and three cowpea landrace accessions (TVu-14076, TVu-17556, and TVu-17567) were identified as promising sources of anthracnose resistance. These accessions represent valuable genetic resources for broadening the cowpea resistance gene pool and support the strategic utilization of wild cowpea germplasm in breeding programs. Full article

Herpes simplex virus type 1 (HSV-1) remains a significant pathogen, particularly in immunocompromised patients. The emergence of drug-resistant strains necessitates alternative therapeutic agents. Lentinula edodes (LE), Hypsizygus marmoreus, and Pleurotus eryngii are edible mushrooms with recognized medicinal properties. However, their effects on drug-resistant HSV-1 remain unclear. This study characterized metabolites from high-temperature/high-pressure (121 °C) water extracts of fresh and dried fruiting bodies and evaluated anti-HSV-1 activities using in vitro and in silico approaches. Metabolic profiles were analyzed by electrospray ionization–quadrupole time-of-flight mass spectrometry. Antiviral activity against HSV-1 KOS (wild-type) and HSV-1 dxpiii (drug-resistant) strains was assessed by plaque assays and qPCR. Molecular docking and network pharmacology were performed on candidate compounds. LE extract from dried mushroom tended to show the highest levels of selected major bioactive constituents, along with greater antioxidant activities. All extracts significantly inhibited viral infection and gene expression in both strains. LE extract from dried mushroom modulated the expression of NFKB1 and IL6. Molecular docking analysis revealed that eritanidine showed a predicted binding affinity to HSV-1 DNA polymerase (−7.95 kcal/mol). Additionally, eritanidine, 5′-methylthioadenosine, and 3-indoleacrylic acid were predicted to interact with TNF and MAPK1. Several compounds also demonstrated favorable drug-likeness properties. Overall, these mushroom extracts are promising natural sources of antiviral agents against HSV-1, including drug-resistant variants. Full article