Search Results (1,453)

Neurodegenerative diseases (NDDs) are a group of progressive diseases affecting neuronal cells in specific areas of the brain, causing cognitive decline and movement impairment. Nowadays, NDDs play a significant role in the global burden of disease, and their incidence is increasing, particularly due to population aging. NDD onset is multi-factorial; based on the current knowledge, genetic, environmental, and cellular factors are believed to contribute to their occurrence and progression. Taking into account that at an early stage, the symptoms are not clearly defined, and diagnosis may be delayed, the development of innovative and non-invasive methodological approaches for early diagnosis of NDDs is strategic for timely and tailored disease management, as well as for the overall improvement of patients’ quality of life. The present review aims to provide, in the first part, an overview based on the current level of knowledge on the environmental risk factors that can explicate a role in the onset of the most common NDDs and on the main pathogenic mechanisms involved in disease initiation and progression. The second part aims to define the current state of the art regarding the significance of Volatile Organic Compounds (VOCs) in the volatome of different human biological matrices (exhaled breath, feces, and skin sebum) as candidate biomarkers of specific NDDs, with the aim of developing non-invasive diagnostic approaches for the early diagnosis and personalized management of the patients. A critical synthesis and discussion on the applied methodological approaches and on the relevant outcomes obtained across the studies is reported. Full article

At many recreational beaches, the health of visitors is protected through water quality monitoring programmes. However, visitors may also be exposed to microbiological pathogens in sand via ingestion, inhalation and skin contact. Microbiological pathogens that can cause human illness may be naturally found in beach sands, or introduced with people, animals or water entering the beach. The World Health Organization has recommended that recreational water safety plans consider microbial pathogens in beach sand. This review shows that a range of faecal and non-faecal pathogens can be detected in beach sand, but difficulty in determining whether exposure occurred via the sand or water means that there is insufficient evidence to link their presence with adverse human health effects. Proactively integrating beach sand testing into recreational water safety programmes will generate data to assess the impact of risk management activities. The use of faecal indicator bacteria to indicate elevated risk from faeces should be a priority where there are potential sources of contamination. This should be complemented with sanitary surveys and analyses that elucidate faecal contamination sources. The inclusion of non-faecal pathogens into monitoring programmes needs further, locally relevant justification through evidence from epidemiological studies and human health risk assessment. Full article

Columnaris disease is a highly contagious infection that affects nearly all freshwater fish species worldwide. Grass carp, one of the most economically significant freshwater fish species in China, is particularly susceptible to the disease, leading to large-scale mortality. Flavobacterium columnare and F. covae are the primary pathogens causing columnaris disease in Chinese grass carp aquaculture. Herein, we compare mortality rates, replication rates of typical columnaris symptoms, histopathological changes, and bacterial content in the tissues of grass carp following infection using four challenge models. The mortality rate in grass carp challenged via intraperitoneal injection was 86.7%. All fish infected via intramuscular and intradermal injections died, while immersion resulted in lower mortality. Gill corrosion rates were 67%, 53%, and 87%, respectively, in the intramuscular injection, intradermal injection, and immersion groups. Correspondingly, skin ulceration rates were 75%, 91%, and 63%. However, surface symptoms in the intraperitoneal injection group were milder. Histopathological analysis revealed similar lesions in grass carp subjected to immersion, intramuscular, and intradermal infection, which differed from carp infected via intraperitoneal injection. The trends in bacterial loads in the gills and skin were similar, although the absolute bacterial content varied between tissues. Bacterial loads in the immersion and intraperitoneal injection groups were lower than those in the other groups. Based on these findings, we determined that the optimal model for simulating columnaris disease in grass carp is the intradermal injection of F. covae in 10–12 cm fish. The infection model generated via intradermal injection resembles natural F. covae infection and can serve as a good tool for evaluating the protective effect of anti-F. covae infection vaccines in grass carp. Full article

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen frequently associated with delayed wound healing, particularly in chronic skin injuries. Its capability to form biofilms, secrete virulence factors, and the faculty to compete with other microorganisms makes it a major challenge in clinical wound management. Recent literature reveals different molecular and cellular mechanisms through which P. aeruginosa disrupts the wound healing process. Findings highlight that it interferes with key phases of healing by modulating host immune responses, degrading extracellular matrix components, and inhibiting keratinocyte migration. Its quorum-sensing systems regulate the expression of critical virulence factors such as exotoxin A, elastases, pyocyanin, and rhamnolipids. Additionally, the production of the biofilm matrix components alginate, and polysaccharides provide protection against host defenses and antibiotics. Interactions with other microorganisms, including antagonistic effects on Staphylococcus epidermidis and synergistic relationships with Staphylococcus aureus, modify the wound microbiota. Promising therapeutic alternatives have shown efficacy in disrupting biofilms and reducing virulence. These insights remark the importance of targeting both P. aeruginosa and its ecological interactions to enhance wound healing outcomes and develop more effective treatments. This review aimed to highlight the pathogenic role of P. aeruginosa and its interactions with other microbial species in the context of skin wound healing. Full article

Background/Objectives: The skin is a protective barrier against pathogens such as herpes simplex virus type 1 (HSV-1), which causes recurrent and highly prevalent skin infections worldwide. The increasing resistance of HSV-1 to conventional treatments has driven the search for new therapeutic alternatives. In this context, the essential oil of Lippia graveolens (EOL) has demonstrated promising antiviral activity; however, its high volatility limits direct skin application. To overcome this, polymeric nanoparticles (NPs) loaded with EOL were developed to improve its availability and antiviral efficacy. Methods: Nanoformulations were prepared by nanoprecipitation, and their antiviral activity against HSV-1 was evaluated using the plaque reduction assay. The effect of the nanoformulations on skin barrier integrity was assessed using an ex vivo porcine skin model and non-invasive techniques. Results: The NP-EOL exhibited physicochemical properties favorable for skin deposition, including a particle size around 200 nm, a polydispersity index of ≤ 0.2, and negative zeta potential. Moreover, NP-EOL showed 1.85-fold higher antiviral activity against HSV-1 compared with free EOL, while also reducing cytotoxicity in Vero cells. Conclusions: Results demonstrated that the NPs promoted skin hydration without altering pH or transepidermal water loss, suggesting they do not disrupt skin homeostasis. This study supports the potential of NP-based systems as effective topical delivery vehicles for EOL, representing a promising therapeutic alternative against HSV-1 skin infections. Full article

Background: The global health burden of mosquito-borne viruses, including dengue, yellow fever, Zika, and chikungunya, is rising due to climate change and globalisation, which favour mosquito habitat expansion. The genetic diversity of these viruses complicates the development of virus-specific vaccines or antivirals, highlighting the need for pan-viral strategies. As the common vector for these pathogens, mosquitoes and specifically their salivary proteins represent a promising target for such interventions. Mosquito saliva, secreted into the skin during biting, has immunomodulatory effects that can enhance host susceptibility to infection, but these mechanisms are not well defined in humans. Methods: The objective of this study was to determine whether AGS-v PLUS, a vaccine targeting mosquito salivary antigens, could modulate the human skin immune response to mosquito biting and potentially promote antiviral bystander immunity. In a Phase I trial, healthy volunteers were vaccinated with AGS-v PLUS (with or without adjuvant) or placebo, and three weeks later, they were exposed to bites from Aedes albopictus and Aedes aegypti mosquitoes. Skin biopsies from bitten and unbitten sites were analysed by transcriptomic profiling. Results: In placebo recipients, mosquito biting elicited a marked adaptive immune response at 48 h, characterised by CD4⁺ Th1 and CD8⁺ T cell signatures and leukocyte recruitment. While responses to Ae. aegypti and Ae. albopictus bites were broadly similar, those to Ae. albopictus were stronger. Vaccination with AGS-v PLUS, particularly with adjuvant, enhanced Th1 and CD8⁺ T cell-associated gene expression while suppressing pathways linked to neutrophilic inflammation and epithelial stress, which together may provide enhanced antiviral capacity. Conclusions: These findings demonstrate that targeting the host response to mosquito saliva via vaccination can reprogram the skin’s immune response to mosquito bites, supporting a novel and broadly applicable pan-viral strategy to mitigate the impact of arboviral diseases. Full article

Background: Vitiligo is a chronic, progressive skin disorder characterized by the development of sharply demarcated depigmented patches due to the loss of melanocytes. Alopecia areata (AA) is an autoimmune condition that presents with sudden, non-scarring hair loss affecting the scalp or other body areas. Objective: To evaluate serum granulysin (GNLY) levels in patients with vitiligo and AA to explore its potential role in the pathogenesis and activity of both diseases. Methods: A total of 80 participants were included: 65 patients and 15 healthy controls. Patients were divided into four groups: active vitiligo (n = 25), stable vitiligo (n = 25), active AA (n = 15), and a control group (n = 15). Serum GNLY levels were measured and analyzed in relation to clinical and dermoscopic features. Results: No significant correlation was found between GNLY levels and either age or Vitiligo Area Scoring Index in vitiligo patients. However, serum GNLY levels showed a significant association with the Vitiligo Disease Activity score. GNLY levels did not correlate with sex or the starburst pattern. In contrast, significant associations were found between elevated GNLY levels and dermoscopic signs of activity, including ill-defined lesion borders, satellite lesions, perifollicular pigmentation, and loss of pigment network. Both vitiligo and AA patients exhibited significantly higher GNLY levels than controls, with the highest concentrations observed in the active vitiligo group. Conclusions: The significant rise in serum GNLY levels in vitiligo and AA suggests a pathogenic role, with higher levels in active vitiligo indicating its potential utility as a biomarker for monitoring disease activity. Full article

Dermatophytes are highly infectious pathogenic fungi that colonize keratinized tissues like skin, hair, and nails, causing superficial infections such as tinea capitis, onychomycosis, tinea corporis, and tinea pedis in humans and animals. In immunocompromised patients, they may invade deeper tissues and organs, leading to severe or life-threatening conditions if untreated or inadequately managed. While most infections respond to topical antifungals, some require complex treatment and show resistance to standard therapies. Therefore, novel antifungal agents are needed. We investigated the antidermatophytic activity of imidazole-thiosemicarbazides against Microsporum canis, Trichophyton spp., and Chrysosporium spp. using the broth microdilution method, comparing results to ketoconazole and amphotericin B through minimal inhibitory concentration (MIC), half-maximal inhibitory concentration (IC₅₀), and selectivity index (SI). Iodine- and bromine-substituted compounds showed the strongest activity, with MICs of 15.15 (IC₅₀ < 1 μM; SI > 213) and 73.46 μg/mL (IC₅₀ < 1 μM; SI > 846) against T. tonsurans, and 3.87 (IC₅₀ = 7.21 μM; SI > 29.6) and 7.38 μg/mL (IC₅₀ = 11.06 μM; SI = 76.6) against M. canis. In silico analysis revealed interactions with α-keratin and lanosterol-14-α demethylase (the azole target enzyme), suggesting enhanced drug retention and action. These findings support these compounds as promising leads for further antifungal development. Full article

In the spring of 2023, a disease outbreak occurred in Lake Taihu in China, which caused a large number of deaths of H. nobilis. In order to investigate the cause of morbidity and mortality of the H. nobilis, the diseased fish were collected for histopathological and etiological studies. Histopathological observation revealed that substantial inflammatory cell infiltration was observed around skin lesion in diseased fish, extensive degeneration and necrosis were observed in the hepatic parenchymal cells, the spleen exhibited congestion, and the kidney showed congestion. A bacterial strain, C1, isolated from diseased H. nobilis was identified as Iodobacter fluviatilis through 16S rRNA gene sequencing and biochemical phenotypic characterization. Experimental infection of the fish via intramuscular injection induced a localized abscess in a subset of fish. Antimicrobial susceptibility testing revealed that the isolate was susceptible to aminoglycosides, tetracyclines, quinolones and amphenicols, but resistant to sulfonamides commonly used in aquaculture. Here, we describe an association between I. fluviatilis and skin lesions in H. nobilis. Furthermore, we report the biochemical characteristics and drug resistance profile of the isolated bacteria. These findings also facilitate further investigations into the role of I. fluviatilis associated with skin diseases of H. nobilis and other freshwater fish. Full article

Over the past years, with the growing interest in sustainable biomaterials, marine collagen has been emerging as an interesting alternative to bovine collagen. It is more easily absorbed by the body and has higher bioavailability. In this study, collagen was extracted from Dicentrarchus labrax (sea bass) skin, a fishery by-product, thus valorizing waste streams while reducing environmental impact. To overcome the intrinsic weak mechanical of collagen, it was combined with chitosan to produce composite scaffolds for skin tissue engineering. The incorporation of collagen proved crucial for scaffold performance: (i) it promoted the formation of an open-pore architecture, favorable for cell infiltration and proliferation; (ii) it enhanced swelling behavior suitable for exudate absorption and maintenance of a moist wound environment; (iii) by tuning the chitosan/collagen ratio, it enabled us to control the degradation rate; (iv) it conferred antioxidant properties; and (iv) by adjusting collagen/chitosan concentrations, it allowed fine-tuning of mechanical properties, ensuring sufficient strength to resist stresses encountered during wound healing. In vitro assays demonstrated that the scaffolds were non-cytotoxic and effectively supported mouse adipose tissue fibroblasts’ adhesion and proliferation. Finally, all formulations exhibited marked bactericidal activity against the human pathogen Staphylococcus aureus and the methicillin-resistant Staphylococcus aureus, with a Log reduction greater than 3 (a reduction of at least 99.9% in bacterial growth) compared to the control. Collectively, these findings highlight collagen not only as a sustainable resource but also as a functional component that drives the structural, physicochemical, biological, and antimicrobial performance of chitosan/collagen scaffolds for skin tissue engineering. Full article

Phase separation is one of the mechanisms critical for protein function, and its aberrances are associated with cancer development. However, mutations that affect protein phase separation and cancer development have not been systematically identified and analyzed. In this study, we systematically identified the mutations affecting protein liquid–liquid phase separation in multiple cancers. We calculated the phase separation scores alterations for over 1,200,000 mutations across 16 cancer types using the TCGA dataset. We then performed pathway enrichment, kinase, TF enrichment, and survival analysis to identify related biological processes and clinical implications. Nearly 10% of the mutations were defined to affect phase separation in pan-cancer. These mutations occupied a consistent percentage in each cancer type. Extremely influencing mutations accumulate on stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), and skin cutaneous melanoma (SKCM). Moreover, proteins carrying these mutations are enriched in cancer-related pathways, including TGF-beta signaling pathways and polycomb repressive complex. Phase separation of these proteins would be regulated by kinases, including CDK1, CDK2, and EGFR, and transcription factors, including ZNF407, ZNF318, and MGA proteins, to play functions in cancer. Protein–Protein Interaction Network revealed that these phase separation proteins are highly interconnected. Finally, patients carrying mutations that positively affect the protein phase separation are associated with poor prognosis in skin cutaneous melanoma (SKCM) and lung squamous cell carcinoma (LUSC), which could be partially explained by the pathogenicity of these mutations. The study provided a pan-cancer landscape for depicting the association of phase separation and cancer mutations, which would be a rich data resource for understanding the association of cancer mutations and phase separation. Full article

Background/Objective: Neuronal intranuclear inclusion disease (NIID) is characterized by widespread deposition of eosinophilic intranuclear inclusions in multiple systems throughout the body. The aim of this study was to investigate the clinical and phenotypic features of NIID, with a focus on the potential association between the morphological features of fibrils formed by polyG (polyglycine) proteins and cognitive dysfunction in patients with NIID. Methods: This study involved a retrospective collection of clinical data from 15 patients with NIID harboring GGC repeat expansions in the NOTCH2NLC (Notch 2 N-Terminal Like C) gene (including symptoms, signs, biochemical markers, cranial MRI, MMSE, and MoCA cognitive scores). All patients underwent skin biopsy, with one additional autopsy of brain tissue. Some skin samples were stained with hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining with anti-p62 antibody. The remaining skin samples and brain tissue samples obtained from autopsies were analyzed using anti-p62 antibody immunofluorescence (IF) staining and transmission electron microscopy (TEM). The number of GGC repeats was quantified using repeat primer PCR (RP-PCR). Based on ultrastructural characteristics (morphology and diameter), inclusion fibers were classified into two subtypes, and differences in the severity of cognitive impairment between subtypes were compared. Results: The majority of patients in this cohort with NIID were female (73.3%), with an average age of onset of 61.06 ± 7.67 years. The core clinical manifestations were cognitive decline (93.3%) and autonomic dysfunction (93.3%). Cranial MRI revealed characteristic DWI “ribbon sign” in 93.3% of patients, accompanied by lateral ventricle enlargement (93.3%), cerebellar atrophy (86.6%), and high T2-FLAIR signal in the corpus callosum (93.3%). All patients were found to have pathogenic GGC amplification in the NOTCH2NLC gene (median 115, range 88–210). Skin/brain tissue pathology confirmed p62-positive nuclear inclusions, and transmission electron microscopy revealed two fiber subtypes for the first time: type A (Long, thin filamentous, 202.38 ± 42.35 nm) and type B (short rod-shaped, 73.08 ± 11.56 nm). Group analysis indicated that the diameter of fibers was significantly larger in the cognitive impairment group (p < 0.05), and the type B fiber group had lower cognitive levels (p < 0.05) and larger diameters (p < 0.05), suggesting a strong association between type B fibers and severe cognitive impairment and poor prognosis. Conclusions: The presence of two different forms of fibrils, type A and type B, in the inclusion bodies of NIID patients, and the poorer cognitive level of NIID patients in the type B group than that of type A suggest that type B fibrils can be used as a novel pathological marker of severe cognitive impairment and poor prognosis in NIID. Full article

Background: Purpureocillium lilacinum (P. lilacinum) is an emerging filamentous fungus known to cause opportunistic infections, particularly in immunocompromised patients. Formerly known as Paecilomyces lilacinus, this pathogen is widespread in the environment and can lead to a range of infections, from superficial skin lesions to invasive diseases. This article presents a case of deep cutaneous hyalohyphomycosis caused by P. lilacinum in a liver transplant patient, followed by a review of the literature focusing on new antifungal agents. Methods: We reported a brief case description followed by a narrative review of the literature regarding P. lilacinum cutaneous and lymphangitic infections in immunocompromised patients. Results: We conducted a review of the literature over the past 20 years, focusing on the clinical features, diagnostic challenges, and therapeutic outcomes of cutaneous and lymphangitic P. lilacinum infections in immunocompromised hosts. Conclusions: This review highlights the critical importance of early diagnosis through the analysis of biopsy samples using standard microbiological and histological techniques, complemented by innovative molecular biology methods. We also emphasise the role of appropriate antifungal treatment, despite the absence of an established standard of care, particularly in high-risk patients. Furthermore, we review and discuss the current lack of a standardised therapeutic regimen and the potential of novel antifungal agents as promising treatment options for P. lilacinum infections. Full article

Background: Sarcina ventriculi is a bacterium predominantly reported in the stomach and associated with emphysematous gastritis, delayed gastric emptying, gastroparesis, or gastric outlet obstruction. Its prevalence is increasing among patients with a history of organ transplants, immunosuppression, and graft-versus-host disease (GVHD). This bacterium can be detected on histology with characteristic tetrad packet morphology; however, confirmation requires PCR and molecular studies. The role of Sarcina ventriculi in human diseases is not fully understood and has unclear clinical significance. While certain studies point to a possible pathogenic role, others regard its detection as incidental with no clear clinical consequence. Case presentation: Herein, we report a case of a 39-year-old male patient with primary refractory cHL, stage IVb, who underwent an autologous bone marrow transplant (BMT) and an allogeneic stem cell infusion. His post-transplant course was complicated by chronic kidney disease (CKD), malnutrition, depression, myopathy, skin, and colon GVHD. He eventually developed sepsis, was admitted to the ICU and developed multiorgan failure and passed away. The patient developed diarrhea, and the gastrointestinal specialist was consulted and revealed ulcerated ileitis and colitis. Biopsies were taken to evaluate for CMV infection and GVHD. The terminal ileum biopsy mainly revealed ulceration with granulation tissue formation and abundant microorganisms arranged in distinctive tetrads, characteristic of Sarcina ventriculi. The colonic biopsies were consistent with GVHD grade II. Conclusions: The significance of Sarcina microorganisms and their mechanisms of injury remain poorly understood. The identification of Sarcina ventriculi in the terminal ileum, which is an unusual and previously unreported finding, adds a new perspective to our understanding of its pathogenic potential and anatomical distribution. While the patient’s clinical decline was influenced by multiple factors, including GVHD, recurrent sepsis, and multiorgan failure, the role of Sarcina ventriculi as a potential exacerbating factor remains unclear. Full article

The genus Iris is a perfect example of ethnobotanic continuity, where symbolic, medicinal and cultural relevance have provided foundations for many of the ornamental, phytochemical, pharmacological, industrial and ecological applications we know today. The aim of this review is to provide an up-to-date perspective on the past, present and future of this genus at the nexus of various interconnected disciplines, focusing on the most impactful and promising applications. The genus’s most economically relevant areas of importance are ornamental use and the industrial application of orris. Biodiversity studies provide a necessary basis of knowledge for preserving its valuable genetic pool; optimized cultivation technologies ensure the flow of raw materials to various industries; and scientific research opens new niches for applications. Iris extracts and compounds have been shown to be effective against certain human pathogens, including fungi, bacteria, and protozoa. Newly screened species indicate promising antimicrobial and antioxidant bioactivity, hinting at their unexplored potential. New compounds have been isolated and studied, exhibiting pharmacological and immunomodulatory potential. Iris-derived exosomes with skin-protective effects and iris extract-coated nanoparticles that can be applied in phytoremediation are among the newest findings. Novel niches explore the potential of useful microbiomes from wild-sampled irises and the use of allelochemicals as bioherbicides. Current scientific evidence supports the medicinal, ecological and industrial relevance of this genus. Full article