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Journal of Proteome Research Apr 2024To ensure biological validity in metabolic phenotyping, findings must be replicated in independent sample sets. Targeted workflows have long been heralded as ideal...
To ensure biological validity in metabolic phenotyping, findings must be replicated in independent sample sets. Targeted workflows have long been heralded as ideal platforms for such validation due to their robust quantitative capability. We evaluated the capability of liquid chromatography-mass spectrometry (LC-MS) assays targeting organic acids and bile acids to validate metabolic phenotypes of SARS-CoV-2 infection. Two independent sample sets were collected: (1) Australia: plasma, SARS-CoV-2 positive ( = 20), noninfected healthy controls ( = 22) and COVID-19 disease-like symptoms but negative for SARS-CoV-2 infection ( = 22). (2) Spain: serum, SARS-CoV-2 positive ( = 33) and noninfected healthy controls ( = 39). Multivariate modeling using orthogonal projections to latent structures discriminant analyses (OPLS-DA) classified healthy controls from SARS-CoV-2 positive (Australia; = 0.17, ROC-AUC = 1; Spain = 0.20, ROC-AUC = 1). Univariate analyses revealed 23 significantly different ( < 0.05) metabolites between healthy controls and SARS-CoV-2 positive individuals across both cohorts. Significant metabolites revealed consistent perturbations in cellular energy metabolism (pyruvic acid, and 2-oxoglutaric acid), oxidative stress (lactic acid, 2-hydroxybutyric acid), hypoxia (2-hydroxyglutaric acid, 5-aminolevulinic acid), liver activity (primary bile acids), and host-gut microbial cometabolism (hippuric acid, phenylpropionic acid, indole-3-propionic acid). These data support targeted LC-MS metabolic phenotyping workflows for biological validation in independent sample sets.
Topics: Humans; SARS-CoV-2; Liquid Chromatography-Mass Spectrometry; Chromatography, Liquid; COVID-19; Tandem Mass Spectrometry; Phenotype; Bile Acids and Salts
PubMed: 38484742
DOI: 10.1021/acs.jproteome.3c00797 -
Photodiagnosis and Photodynamic Therapy Apr 2024Onychomycosis, a fungal infection affecting the nail, is characterized by discoloration and thickening of the nail plate and is the most prevalent nail infection...
Onychomycosis, a fungal infection affecting the nail, is characterized by discoloration and thickening of the nail plate and is the most prevalent nail infection globally. We present a case of onychomycosis caused by Trichosporon asahii, a less common etiology. Notably, the patient was successfully treated with a non-traditional antibacterial approach, photodynamic therapy, which has been infrequently documented in the literature for such infections.
Topics: Humans; Onychomycosis; Photochemotherapy; Photosensitizing Agents; Aminolevulinic Acid; Male; Trichosporon; Trichosporonosis; Middle Aged; Female; Basidiomycota
PubMed: 38479606
DOI: 10.1016/j.pdpdt.2024.104045 -
Journal of Nanobiotechnology Mar 2024Breast cancer is the most prevalent malignant tumor among women, with hormone receptor-positive cases constituting 70%. Fulvestrant, an antagonist for these receptors,...
BACKGROUND
Breast cancer is the most prevalent malignant tumor among women, with hormone receptor-positive cases constituting 70%. Fulvestrant, an antagonist for these receptors, is utilized for advanced metastatic hormone receptor-positive breast cancer. Yet, its inhibitory effect on tumor cells is not strong, and it lacks direct cytotoxicity. Consequently, there's a significant challenge in preventing recurrence and metastasis once cancer cells develop resistance to fulvestrant.
METHOD
To address these challenges, we engineered tumor-targeting nanoparticles termed I-fulvestrant-ALA-PFP-FA-NPs. This involved labeling fulvestrant with I to create I-fulvestrant. Subsequently, we incorporated the I-fulvestrant and 5-aminolevulinic acid (ALA) into fluorocarbon nanoparticles with folate as the targeting agent. This design facilitates a tri-modal therapeutic approach-endocrine therapy, radiotherapy, and PDT for estrogen receptor-positive breast cancer.
RESULTS
Our in vivo and in vitro tests showed that the drug-laden nanoparticles effectively zeroed in on tumors. This targeting efficiency was corroborated using SPECT-CT imaging, confocal microscopy, and small animal fluorescence imaging. The I-fulvestrant-ALA-PFP-FA-NPs maintained stability and showcased potent antitumor capabilities due to the synergism of endocrine therapy, radiotherapy, and CR-PDT. Throughout the treatment duration, we detected no notable irregularities in hematological, biochemical, or histological evaluations.
CONCLUSION
We've pioneered a nanoparticle system loaded with radioactive isotope I, endocrine therapeutic agents, and a photosensitizer precursor. This system offers a combined modality of radiotherapy, endocrine treatment, and PDT for breast cancer.
Topics: Animals; Humans; Female; Fulvestrant; Breast Neoplasms; Drug Interactions; Iodine Radioisotopes
PubMed: 38475902
DOI: 10.1186/s12951-024-02309-7 -
Photodiagnosis and Photodynamic Therapy Apr 20245-Aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) is a possible minimally-invasive treatment for high-grade cervical intraepithelial neoplasia (HSIL). The... (Comparative Study)
Comparative Study
Comparison of 5-ALA-PDT and LEEP of cervical squamous intraepithelial neoplasia (CIN2) with high-risk human papillomavirus infection in childbearing age women: A non-randomized controlled polit study.
BACKGROUND
5-Aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) is a possible minimally-invasive treatment for high-grade cervical intraepithelial neoplasia (HSIL). The present study was carried out to assess the effect of 5-ALA-PDT and loop electrosurgical excision procedure (LEEP) in cervical squamous intraepithelial neoplasia (CIN2) combined with high-risk human papillomavirus (HR-HPV) infection.
METHODS
In this study, 190 patients with CIN2 and HR-HPV infection were finally included. They were divided into the LEEP Group (n = 116) and PDT Group (n = 74) according to gynecologist's recommendation and patient's willingness. All patients were followed up at 4-6 months and 12 months after treatment, including HPV testing, cytology, and colposcopy examination.
RESULTS
(1) 4-6 months after treatment, the pathological regression rate was 97.30 % (72/74) in the PDT group and 98.28 % (114/116) in the LEEP group (P = 0.952). The HPV clearance rate was 81.08 % (60/74) in the PDT group and 80.17 % (93/116)in the LEEP group (P = 0.877). (2) 12 months after treatment, the pathological regression rate was 93.24 % (69/74) in the PDT group and 96.55 % (112/116) in the LEEP group (P = 0.486). The recurrence rate of CIN2 was 4.05 % (3/74) in the PDT group and 1.72 % (2/116) in the LEEP group (P = 0.608). The HPV clearance rate was 90.54 % (67/74) in the PDT group and 89.66 % (104/116)in the LEEP group (P = 0.843). The reinfection rate of HR-HPV was 5.41 % (4/74) in the PDT group and 1.72 % (2/116) in the LEEP group (P = 0.322). (3) The adverse reactions in the PDT Group were slightly lower than that in the LEEP Group (P = 0.4956), but the incidence of vaginal bleeding in the PDT group was lower than that in the LEEP group during follow-up.
CONCLUSIONS
The effectiveness of 5-ALA-PDT is similar to LEEP for CIN2 with less side effects. Therefore, 5-ALA-PDT, a non-invasive treatment, may be an effective method for CIN2 patients of childbearing age.
Topics: Humans; Female; Aminolevulinic Acid; Photochemotherapy; Photosensitizing Agents; Papillomavirus Infections; Adult; Uterine Cervical Dysplasia; Electrosurgery; Uterine Cervical Neoplasms; Middle Aged; Young Adult
PubMed: 38467338
DOI: 10.1016/j.pdpdt.2024.104044 -
The EPMA Journal Mar 2024Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is...
The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation.
Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.
PubMed: 38463624
DOI: 10.1007/s13167-024-00356-6 -
Internal Medicine (Tokyo, Japan) Mar 2024Hereditary coproporphyria (HCP) is caused by a partial deficiency of coproporphyrinogen oxidase during heme biosynthesis. Givosiran is approved for the treatment of...
Hereditary coproporphyria (HCP) is caused by a partial deficiency of coproporphyrinogen oxidase during heme biosynthesis. Givosiran is approved for the treatment of acute hepatic porphyria. We herein report the case of a 47-year-old woman with HCP. Monthly givosiran administration improved her subjective symptoms and reduced her δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels to the normal range. However, givosiran was discontinued after six months due to a decreased renal function. The patient's ALA and PBG levels remained within the normal ranges, and her HCP-related symptoms resolved more than 2 years after the discontinuation of givosiran.
PubMed: 38462517
DOI: 10.2169/internalmedicine.3284-23 -
Photodiagnosis and Photodynamic Therapy Apr 2024Photodynamic therapy (PDT) is a non-invasive, effective treatment for superficial skin conditions, offering superior cosmetic outcomes compared with traditional...
Photodynamic therapy (PDT) is a non-invasive, effective treatment for superficial skin conditions, offering superior cosmetic outcomes compared with traditional therapies. Bowen's disease (BD) of the nipple-areola complex (NAC) is rare and thus, lacks a standardized treatment approach. This report details the case of a 48-year-old woman who was successfully treated for BD of the NAC using PDT. Over a follow-up period of 30 months, there was no evidence of disease recurrence, underscoring the potential of PDT as a viable treatment option for this rare manifestation of BD.
Topics: Humans; Female; Photochemotherapy; Middle Aged; Bowen's Disease; Nipples; Photosensitizing Agents; Cryotherapy; Skin Neoplasms; Combined Modality Therapy; Breast Neoplasms; Aminolevulinic Acid
PubMed: 38460656
DOI: 10.1016/j.pdpdt.2024.104041 -
PloS One 2024Topical photodynamic therapy (PDT) is an approved and widely used treatment for low-risk basal cell carcinoma (BCC), comprising two sessions with an interval of 1 week.... (Randomized Controlled Trial)
Randomized Controlled Trial
New, simplified versus standard photodynamic therapy (PDT) regimen for superficial and nodular basal cell carcinoma (BCC): A single-blind, non-inferiority, randomised controlled multicentre study.
BACKGROUND
Topical photodynamic therapy (PDT) is an approved and widely used treatment for low-risk basal cell carcinoma (BCC), comprising two sessions with an interval of 1 week. Simplification of the treatment course can be cost-effective, easier to organize, and cause less discomfort for the patients.
METHODS AND FINDINGS
We performed an investigator-initiated, single-blind, non-inferiority, randomized controlled multicentre study with the objective of investigating whether a simpler and more flexible PDT regimen was not >10% less effective than the standard double PDT in the treatment of primary, superficial, and nodular ≤2 mm-thick BCC and evaluate the cosmetic outcome. With a non-inferiority margin of 0.1 and an expected probability complete response of 0.85, 190 tumours were required in each group. Histologically verified BCCs from seven centres in Norway were randomly assigned (1:1) to either receive a new regimen of single PDT with one possible re-treatment of non-complete responding tumours, or the standard regimen. The primary endpoint was the number of tumours with complete response or treatment failure at 36 months of follow-up, assessed by investigators blinded to the treatment regimen. Intention-to-treat and per-protocol analyses were performed. The cosmetic outcome was recorded. The study was registered with ClinicalTrials.gov, NCT-01482104, and EudraCT, 2011-004797-28. A total of 402 BCCs in 246 patients were included; 209 tumours assigned to the new and 193 to the standard regimen. After 36 months, there were 61 treatment failures with the new and 34 failures with the standard regimen. Complete response rate was 69.5% in the new and 81.1% in the standard treatment group. The difference was 11.6% (upper 97.5% CI 20.3), i.e. > than the non-inferiority margin of 10%. Cosmetic outcomes were excellent or good in 92% and 89% following the new and standard regimens, respectively.
CONCLUSIONS
Single PDT with possible re-treatment of primary, superficial, and nodular ≤ 2-mm-thick BCC was significantly less effective than the approved standard double treatment. The cosmetic outcome was favorable and comparable between the two treatment groups.
Topics: Humans; Skin Neoplasms; Photosensitizing Agents; Aminolevulinic Acid; Single-Blind Method; Photochemotherapy; Carcinoma, Basal Cell; Pathologic Complete Response; Treatment Outcome
PubMed: 38457386
DOI: 10.1371/journal.pone.0299718 -
Photodiagnosis and Photodynamic Therapy Apr 2024Kerion, a severe manifestation of tinea capitis caused by dermatophytes, is a fungal skin disease primarily affecting children. This report discusses six cases of... (Review)
Review
Kerion, a severe manifestation of tinea capitis caused by dermatophytes, is a fungal skin disease primarily affecting children. This report discusses six cases of pediatric kerion that were successfully treated with a combination of photodynamic therapy (PDT) and antifungal agents. Additionally, we conducted a literature review, identifying and analyzing six published reports on kerion and tinea capitis. The characteristics and efficacies of these cases are summarized. In summary, early combination therapy and proactive pre-treatment interventions proved effective in maximizing therapeutic outcomes, reducing disease duration and minimizing adverse reactions such as cicatricial alopecia. This approach has emerged as a favorable choice for the treatment of kerion.
Topics: Humans; Photochemotherapy; Antifungal Agents; Photosensitizing Agents; Male; Female; Child; Tinea Capitis; Child, Preschool; Aminolevulinic Acid; Combined Modality Therapy; Adolescent
PubMed: 38452908
DOI: 10.1016/j.pdpdt.2024.104039 -
Advanced Science (Weinheim,... May 2024Glioblastoma (GBM) is hard to treat due to cellular invasion into functioning brain tissues, limited drug delivery, and evolved treatment resistance. Recurrence is...
Glioblastoma (GBM) is hard to treat due to cellular invasion into functioning brain tissues, limited drug delivery, and evolved treatment resistance. Recurrence is nearly universal even after surgery, chemotherapy, and radiation. Photodynamic therapy (PDT) involves photosensitizer administration followed by light activation to generate reactive oxygen species at tumor sites, thereby killing cells or inducing biological changes. PDT can ablate unresectable GBM and sensitize tumors to chemotherapy. Verteporfin (VP) is a promising photosensitizer that relies on liposomal carriers for clinical use. While lipids increase VP's solubility, they also reduce intracellular photosensitizer accumulation. Here, a pure-drug nanoformulation of VP, termed "NanoVP", eliminating the need for lipids, excipients, or stabilizers is reported. NanoVP has a tunable size (65-150 nm) and 1500-fold higher photosensitizer loading capacity than liposomal VP. NanoVP shows a 2-fold increase in photosensitizer uptake and superior PDT efficacy in GBM cells compared to liposomal VP. In mouse models, NanoVP-PDT improved tumor control and extended animal survival, outperforming liposomal VP and 5-aminolevulinic acid (5-ALA). Moreover, low-dose NanoVP-PDT can safely open the blood-brain barrier, increasing drug accumulation in rat brains by 5.5-fold compared to 5-ALA. NanoVP is a new photosensitizer formulation that has the potential to facilitate PDT for the treatment of GBM.
Topics: Animals; Photochemotherapy; Verteporfin; Mice; Photosensitizing Agents; Brain Neoplasms; Drug Delivery Systems; Glioblastoma; Nanoparticles; Disease Models, Animal; Humans; Rats; Liposomes; Cell Line, Tumor; Brain
PubMed: 38445882
DOI: 10.1002/advs.202302872