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1.
Bull Math Biol ; 86(7): 83, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38842602

5-Aminolevulinic Acid (5-ALA) is the only fluorophore approved by the FDA as an intraoperative optical imaging agent for fluorescence-guided surgery in patients with glioblastoma. The dosing regimen is based on rodent tests where a maximum signal occurs around 6 h after drug administration. Here, we construct a computational framework to simulate the transport of 5-ALA through the stomach, blood, and brain, and the subsequent conversion to the fluorescent agent protoporphyrin IX at the tumor site. The framework combines compartmental models with spatially-resolved partial differential equations, enabling one to address questions regarding quantity and timing of 5-ALA administration before surgery. Numerical tests in two spatial dimensions indicate that, for tumors exceeding the detection threshold, the time to peak fluorescent concentration is 2-7 h, broadly consistent with the current surgical guidelines. Moreover, the framework enables one to examine the specific effects of tumor size and location on the required dose and timing of 5-ALA administration before glioblastoma surgery.


Aminolevulinic Acid , Brain Neoplasms , Computer Simulation , Glioblastoma , Mathematical Concepts , Models, Biological , Protoporphyrins , Surgery, Computer-Assisted , Glioblastoma/surgery , Glioblastoma/drug therapy , Glioblastoma/pathology , Glioblastoma/diagnostic imaging , Aminolevulinic Acid/administration & dosage , Humans , Brain Neoplasms/surgery , Protoporphyrins/administration & dosage , Protoporphyrins/metabolism , Surgery, Computer-Assisted/methods , Animals , Photosensitizing Agents/administration & dosage , Optical Imaging/methods , Fluorescent Dyes/administration & dosage
2.
PLoS One ; 19(6): e0300602, 2024.
Article En | MEDLINE | ID: mdl-38829894

OBJECTIVES: Describing mitochondrial oxygenation (mitoPO2) and its within- and between-subject variability over time after 5-aminolevulinic acid (ALA) plaster application in healthy volunteers. DESIGN: Prospective cohort study. SETTING: Measurements were performed in Leiden University Medical Center, the Netherlands. PARTICIPANTS: Healthy volunteers enrolled from July to September 2020. INTERVENTIONS: Two ALA plasters were placed parasternal left and right, with a 3-hour time interval, to examine the influence of the calendar time on the value of mitoPO2. We measured mitoPO2 at 4, 5, 7, 10, 28, and 31 hours after ALA plaster 1 application, and at 4, 5, 7, 25, and 28 hours after ALA plaster 2 application. PRIMARY AND SECONDARY OUTCOME MEASURES: At each time point, five mitoPO2 measurements were performed. Within-subject variability was defined as the standard deviation (SD) of the mean of five measurements per timepoint of a study participant. The between-subject variability was the SD of the mean mitoPO2 value of the study population per timepoint. RESULTS: In 16 completed inclusions, median mitoPO2 values and within-subject variability were relatively similar over time at all time points for both plasters. An increase in overall between-subject variability was seen after 25 hours ALA plaster time (19.6 mm Hg vs 23.9 mm Hg after respectively 10 and 25 hours ALA plaster time). CONCLUSIONS: The mitoPO2 values and within-subject variability remained relatively stable over time in healthy volunteers. An increase in between-subject variability was seen after 25 hours ALA plaster time warranting replacement of the ALA plaster one day after its application. TRIAL REGISTRATION: ClinicalTrials.gov with trial number NCT04626661.


Healthy Volunteers , Oxygen , Humans , Male , Female , Adult , Oxygen/metabolism , Prospective Studies , Mitochondria/metabolism , Middle Aged , Aminolevulinic Acid/administration & dosage , Oxygen Consumption , Young Adult , Netherlands
3.
Artif Cells Nanomed Biotechnol ; 52(1): 270-277, 2024 Dec.
Article En | MEDLINE | ID: mdl-38696132

Spherical gold/polyacrylic acid (Au/PAA) polymer-inorganic Janus nanoparticles (JNPs) with simultaneous therapeutic and targeting functions were fabricated. The obtained Au/PAA JNPs were further selectively functionalized with folic acid (FA) and thiol PEG amine (SH-PEG-NH2) on Au sides to provide superior biocompatibility and active targeting, while the other PAA sides were loaded with 5-aminolevulinic acid (5-ALA) to serve as a photosensitizer (PS) for photodynamic therapeutic (PDT) effects on MCF-7 cancer cells. The PS loading of 5-ALA was found to be 83% with an average hydrodynamic size and z-potential of 146 ± 0.8 nm and -6.40 mV respectively for FA-Au/PAA-ALA JNPs. The in vitro PDT study of the JNPs on MCF-7 breast cancer cells under 636 nm laser irradiation indicated the cell viability of 24.7% ± 0.5 for FA-Au/PAA-ALA JNPs at the IC50 value of 0.125 mM. In this regard, the actively targeted FA-Au/PAA-ALA JNPs treatment holds great potential for tumour therapy with high cancer cell-killing efficacy.


Aminolevulinic Acid , Breast Neoplasms , Gold , Photochemotherapy , Photosensitizing Agents , Humans , MCF-7 Cells , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Aminolevulinic Acid/chemistry , Aminolevulinic Acid/pharmacology , Gold/chemistry , Gold/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Nanoparticles/chemistry , Acrylic Resins/chemistry , Female , Folic Acid/chemistry , Cell Survival/drug effects
4.
Eur Rev Med Pharmacol Sci ; 28(8): 3268-3274, 2024 Apr.
Article En | MEDLINE | ID: mdl-38708485

BACKGROUND: We describe the first case of a pediatric patient with acute intermittent porphyria and severe chronic porphyric neuropathy treated with givosiran, a small-interfering RNA that drastically decreases delta-aminolevulinic acid production and reduces porphyric attacks' recurrence. CASE REPORT: A 12-year-old male patient with refractory acute intermittent porphyria and severe porphyric neuropathy was followed prospectively for 12 months after givosiran initiation (subcutaneous, 2.5 mg/kg monthly). Serial neurological, structural, and resting-state functional magnetic resonance imaging (MRI) evaluations were performed, including clinical scales and neurophysiological tests. Delta-aminolevulinic acid urinary levels dropped drastically during treatment. In parallel, all the administered neurological rating scales and neurophysiological assessments showed improvement in all domains. Moreover, an improvement in central motor conduction parameters and resting-state functional connectivity in the sensory-motor network was noticed. At the end of the follow-up, the patient could walk unaided after using a wheelchair for 5 years. CONCLUSIONS: A clear beneficial effect of givosiran was demonstrated in our patient with both clinical and peripheral nerve neurophysiologic outcome measures. Moreover, we first reported a potential role of givosiran in recovering central motor network impairment in acute intermittent porphyria (AIP), which was previously unknown. This study provides Class IV evidence that givosiran improves chronic porphyric neuropathy.


Acetylgalactosamine/analogs & derivatives , Porphyria, Acute Intermittent , Humans , Male , Porphyria, Acute Intermittent/drug therapy , Child , Acetylgalactosamine/therapeutic use , Aminolevulinic Acid/analogs & derivatives , Aminolevulinic Acid/urine , Magnetic Resonance Imaging , Pyrrolidines/therapeutic use , Uridine/analogs & derivatives , Uridine/therapeutic use , Uridine/administration & dosage , Recovery of Function , Chronic Disease , Treatment Outcome
5.
Lasers Med Sci ; 39(1): 131, 2024 May 16.
Article En | MEDLINE | ID: mdl-38750381

Photodynamic therapy (PDT) is a targeted treatment method that utilizes a photosensitizer (PS) to induce cytotoxicity in malignant and non-malignant tumors. Optimization of PDT requires investigation of the selectivity of PS for the target tissues, irradiating light source, irradiation wavelengths, fluence rate, fluence, illumination mode, and overall treatment plan. In this study, we developed the Multi-mode Automatized Well-plate PDT LED Laboratory Irradiation System (MAWPLIS), an innovative device that automates time-consuming well plate light dosage/PS dose measurement experiment. The careful control of LED current and temperature stabilization in the LED module allowed the system to achieve high optical output stability. The MAWPLIS was designed by integrating a 3-axis moving system and motion controller, a quick-switching LED controller unit equipped with interchangeable LED modules capable of employing multiple wavelengths, and a TEC system. The proposed system achieved high optical output stability (1 mW) within the range of 0-500 mW, high wavelength stability (5 nm) at 635 nm, and high temperature stability (0.2 °C) across all radiation modes. The system's validation involved in vitro analysis using 5-ALA across varying concentrations, incubation periods, light exposures, and wavelengths in HT-29 colon cancer and WI-38 human lung fibroblast cell lines. Specifically, a combination of 405 nm and 635 nm wavelengths was selected to demonstrate enhanced strategies for colon cancer cell eradication and system validation. The MAWPLIS system represents a significant advancement in photodynamic therapy (PDT) research, offering automation and standardization of time-intensive experiments, high stability and precision, and improved PDT efficacy through dual-wavelength integration.


Photochemotherapy , Photosensitizing Agents , Photochemotherapy/methods , Photochemotherapy/instrumentation , Humans , HT29 Cells , Aminolevulinic Acid/administration & dosage
6.
Metab Eng ; 83: 206-215, 2024 May.
Article En | MEDLINE | ID: mdl-38710300

Shewanella oneidensis MR-1 has found widespread applications in pollutant transformation and bioenergy production, closely tied to its outstanding heme synthesis capabilities. However, this significant biosynthetic potential is still unexploited so far. Here, we turned this bacterium into a highly-efficient bio-factory for green synthesis of 5-Aminolevulinic Acid (5-ALA), an important chemical for broad applications in agriculture, medicine, and the food industries. The native C5 pathway genes of S. oneidensis was employed, together with the introduction of foreign anti-oxidation module, to establish the 5-ALA production module, resulting 87-fold higher 5-ALA yield and drastically enhanced tolerance than the wild type. Furthermore, the metabolic flux was regulated by using CRISPR interference and base editing techniques to suppress the competitive pathways to further improve the 5-ALA titer. The engineered strain exhibited 123-fold higher 5-ALA production capability than the wild type. This study not only provides an appealing new route for 5-ALA biosynthesis, but also presents a multi-dimensional modularized engineering strategy to broaden the application scope of S. oneidensis.


Aminolevulinic Acid , Metabolic Engineering , Shewanella , Shewanella/genetics , Shewanella/metabolism , Aminolevulinic Acid/metabolism
8.
J Med Case Rep ; 18(1): 264, 2024 May 30.
Article En | MEDLINE | ID: mdl-38811941

BACKGROUND: Although 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of postoperative cardiac arrest in addition to severe intraoperative hypotension, probably owing to the use of 5-aminolevulinic acid. CASE PRESENTATION: An 81-year-old Japanese man was scheduled to undergo transurethral resection of bladder tumor. The patient took 5-aminolevulinic acid orally 2 hours before entering the operating room. After the induction of anesthesia, his blood pressure decreased to 47/33 mmHg. The patient's hypotension did not improve even after noradrenaline was administered. After awakening from anesthesia, the patient's systolic blood pressure increased to approximately 100 mmHg, but approximately 5 hours after returning to the ward, cardiac arrest occurred for approximately 12 seconds. CONCLUSION: We experienced a case of postoperative cardiac arrest in a patient, probably owing to the use of 5-aminolevulinic acid. Although the cause of cardiac arrest is unknown, perioperative hemodynamic management must be carefully performed in patients taking 5-aminolevulinic acid.


Aminolevulinic Acid , Heart Arrest , Hypotension , Postoperative Complications , Urinary Bladder Neoplasms , Humans , Male , Aminolevulinic Acid/adverse effects , Hypotension/etiology , Hypotension/chemically induced , Aged, 80 and over , Heart Arrest/etiology , Heart Arrest/chemically induced , Urinary Bladder Neoplasms/surgery , Photosensitizing Agents/adverse effects , Photosensitizing Agents/therapeutic use , Intraoperative Complications/chemically induced
9.
Acta Neurochir (Wien) ; 166(1): 212, 2024 May 13.
Article En | MEDLINE | ID: mdl-38739282

PURPOSE: Glioblastoma is a malignant and aggressive brain tumour that, although there have been improvements in the first line treatment, there is still no consensus regarding the best standard of care (SOC) upon its inevitable recurrence. There are novel adjuvant therapies that aim to improve local disease control. Nowadays, the association of intraoperative photodynamic therapy (PDT) immediately after a 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) in malignant gliomas surgery has emerged as a potential and feasible strategy to increase the extent of safe resection and destroy residual tumour in the surgical cavity borders, respectively. OBJECTIVES: To assess the survival rates and safety of the association of intraoperative PDT with 5-ALA FGR, in comparison with a 5-ALA FGR alone, in patients with recurrent glioblastoma. METHODS: This article describes a matched-pair cohort study with two groups of patients submitted to 5-ALA FGR for recurrent glioblastoma. Group 1 was a prospective series of 11 consecutive cases submitted to 5-ALA FGR plus intraoperative PDT; group 2 was a historical series of 11 consecutive cases submitted to 5-ALA FGR alone. Age, sex, Karnofsky performance scale (KPS), 5-ALA post-resection status, T1-contrast-enhanced extent of resection (EOR), previous and post pathology, IDH (Isocitrate dehydrogenase), Ki67, previous and post treatment, brain magnetic resonance imaging (MRI) controls and surgical complications were documented. RESULTS: The Mantel-Cox test showed a significant difference between the survival rates (p = 0.008) of both groups. 4 postoperative complications occurred (36.6%) in each group. As of the last follow-up (January 2024), 7/11 patients in group 1, and 0/11 patients in group 2 were still alive. 6- and 12-months post-treatment, a survival proportion of 71,59% and 57,27% is expected in group 1, versus 45,45% and 9,09% in group 2, respectively. 6 months post-treatment, a progression free survival (PFS) of 61,36% and 18,18% is expected in group 1 and group 2, respectively. CONCLUSION: The association of PDT immediately after 5-ALA FGR for recurrent malignant glioma seems to be associated with better survival without additional or severe morbidity. Despite the need for larger, randomized series, the proposed treatment is a feasible and safe addition to the reoperation.


Aminolevulinic Acid , Brain Neoplasms , Glioblastoma , Neoplasm Recurrence, Local , Photochemotherapy , Surgery, Computer-Assisted , Humans , Glioblastoma/surgery , Glioblastoma/drug therapy , Glioblastoma/diagnostic imaging , Aminolevulinic Acid/therapeutic use , Male , Brain Neoplasms/surgery , Brain Neoplasms/drug therapy , Brain Neoplasms/diagnostic imaging , Female , Middle Aged , Photochemotherapy/methods , Neoplasm Recurrence, Local/surgery , Aged , Cohort Studies , Surgery, Computer-Assisted/methods , Photosensitizing Agents/therapeutic use , Adult , Prospective Studies , Neurosurgical Procedures/methods
10.
Microb Pathog ; 191: 106672, 2024 Jun.
Article En | MEDLINE | ID: mdl-38705219

Phytopathogenic fungi significantly threaten global food security, causing substantial yield and quality losses. Sustainable solutions are urgently needed to combat these agricultural pathogens. This study explored the potential of silver (Ag), copper (Cu), and combined Ag/Cu nanoparticles capped with aminolevulinic acid (ALA) as antifungal agents. The nanoparticles (ALAAg, ALACu, and ALAAgCu) were synthesized via photoreduction and characterized using various techniques (UV-Vis, TEM, XRD, Zeta potential). Their antifungal activity against four key plant pathogens (Alternaria grandis, Colletotrichum truncatum, Corynespora cassiicola, and Fusarium oxysporum) was evaluated using poisoned food techniques. Notably, ALAAgCuNPs demonstrated superior antifungal activity compared to a conventional fungicide against two fungal strains. Even at lower concentrations, ALAAgCuNPs exhibited fungistatic effects comparable to those of the control. These promising results suggest the potential of ALAAgCu NPs as a broad-spectrum, potentially eco-friendly alternative for fungal control in plants and seeds. This approach is crucial for ensuring crop health, harvest quality, and food safety.


Aminolevulinic Acid , Antifungal Agents , Copper , Fungi , Metal Nanoparticles , Plant Diseases , Silver , Copper/pharmacology , Copper/chemistry , Silver/pharmacology , Silver/chemistry , Metal Nanoparticles/chemistry , Plant Diseases/prevention & control , Plant Diseases/microbiology , Antifungal Agents/pharmacology , Fungi/drug effects , Aminolevulinic Acid/pharmacology , Microbial Sensitivity Tests , Fusarium/drug effects
11.
Front Biosci (Landmark Ed) ; 29(5): 199, 2024 May 21.
Article En | MEDLINE | ID: mdl-38812322

BACKGROUND: Due to its non-invasive and widely applicable features, photodynamic therapy (PDT) has been a prominent treatment approach against cancer in recent years. However, its widespread application in clinical practice is limited by the dark toxicity of photosensitizers and insufficient penetration of light sources. This study assessed the anticancer effects of a novel photosensitizer 5-(4-amino-phenyl)-10,15,20-triphenylporphyrin with diethylene-triaminopentaacetic acid (ATPP-DTPA)-mediated PDT (hereinafter referred to as ATPP-PDT) under the irradiation of a 450-nm blue laser on colorectal cancer (CRC) in vivo and in vitro. METHODS: After 450-nm blue laser-mediated ATPP-PDT and the traditional photosensitizer 5-aminolevulinic acid (5-ALA)-PDT treatment, cell viability was detected through Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Reactive oxygen species (ROS) generation was quantified by flow cytometry and fluorescence microscopy. Western blotting and transcriptome RNA sequencing and functional experiments were used to evaluate cell apoptosis and its potential mechanism. Anti-tumor experiment in vivo was performed in nude mice with subcutaneous tumors. RESULTS: ATPP-DTPA had a marvelous absorption in the blue spectrum. Compared with 5-ALA, ATPP-DTPA could achieve significant killing effects at a lower dose. Owing to generating an excessive amount of ROS, 450-nm blue laser-mediated PDT based on ATPP-DTPA resulted in evident growth inhibition and apoptosis in CRC cells in vitro. After transcriptome RNA sequencing and functional experiments, p38 MAPK signaling pathway was confirmed to be involved in the regulation of apoptosis induced by 450-nm blue laser-mediated ATPP-PDT. Additionally, animal studies using xenograft model confirmed that ATPP-PDT had excellent anti-tumor effect and reasonable biosafety in vivo. CONCLUSIONS: PDT mediated by 450-nm blue laser combined with ATPP-DTPA may be a novel and effective method for the treatment of CRC.


Apoptosis , Colorectal Neoplasms , Mice, Nude , Photochemotherapy , Photosensitizing Agents , Reactive Oxygen Species , Photochemotherapy/methods , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/radiotherapy , Apoptosis/drug effects , Animals , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Humans , Reactive Oxygen Species/metabolism , Mice , Cell Line, Tumor , Xenograft Model Antitumor Assays , Mice, Inbred BALB C , Lasers , Cell Survival/drug effects , Aminolevulinic Acid/pharmacology , Aminolevulinic Acid/therapeutic use
12.
Carbohydr Polym ; 336: 122114, 2024 Jul 15.
Article En | MEDLINE | ID: mdl-38670775

5-aminolevulinic acid (5-ALA) has been fully demonstrated as a biodegradable, without resistance, and pollution-free pesticide. However, the lack of targeting and the poor adhesion result in a low utilization rate, limiting its practical application. Herein, a dew-responsive polymer pro-pesticide Pec-hyd-ALA was successfully synthesized by grafting 5-ALA onto the pectin (PEC) backbone via acid-sensitive acylhydrazone bonds. When the pro-pesticide is exposed to acid dew on plant surfaces at night, 5-ALA is released and subsequently converted to photosensitize (Protoporphyrin IX, PpIX)in plant cells, leading to its accumulation and promoting photodynamic inactivation (PDI). An inverted fluorescence microscope has verified the accumulation of tetrapyrrole in plant cells. In addition, the highly bio-adhesive PEC backbone effectively improved the wetting and retention of 5-ALA on leaves. The pot experiment also demonstrated the system's control effect on barnyard grass. This work provides a promising approach to improving the herbicidal efficacy of 5-ALA.


Aminolevulinic Acid , Herbicides , Pectins , Photosensitizing Agents , Pectins/chemistry , Herbicides/chemistry , Herbicides/pharmacology , Aminolevulinic Acid/chemistry , Aminolevulinic Acid/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Protoporphyrins/chemistry , Protoporphyrins/pharmacology , Plant Leaves/chemistry , Wettability
13.
Acta Derm Venereol ; 104: adv19459, 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38596905

Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic keratosis. Qualitative research exploring patient experiences of pain and skin reactions during these treatments is scarce. To address this, semi-structured interviews were conducted of 10 patients aged 60-81 years with symmetrically distributed actinic keratoses 4 weeks after split-face treatment with conventional red light photodynamic therapy and simulated daylight photodynamic therapy. The participants were recruited from an ongoing clinical randomized trial. Interviews (median length 35 min) were conducted between June 2022 and January 2023, audio-recorded, transcribed verbatim, and analysed qualitatively using content analysis, as described by Graneheim and Lundman. Participants reported that conventional red light photodynamic therapy was very painful during illumination and transiently painful in the post-treatment period, while simulated daylight photodynamic therapy was almost painless during illumination and led to minor post-treatment pain. Also, skin reactions were more intense and longer-lasting with conventional red light photodynamic therapy than with simulated daylight photodynamic therapy. Most participants expressed a treatment preference for simulated daylight photodynamic therapy but had reservations about its unestablished long-term effectiveness. This study underscores the considerable pain associated with conventional red light photodynamic therapy, and the pivotal importance of shared decision-making when selecting the most appropriate treatment.


Keratosis, Actinic , Photochemotherapy , Humans , Aminolevulinic Acid , Keratosis, Actinic/diagnosis , Keratosis, Actinic/drug therapy , Pain/diagnosis , Pain/etiology , Pain/drug therapy , Photochemotherapy/adverse effects , Photosensitizing Agents/adverse effects , Red Light , Treatment Outcome
14.
Acta Neurochir (Wien) ; 166(1): 163, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38563988

Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over the last decades, prognosis remains poor. Treatment of patients with glioblastoma remains a considerable challenge due to the infiltrative nature of the tumor, rapid growth rates, and tumor heterogeneity. Standard therapy consists of maximally safe microsurgical resection followed by adjuvant radio- and chemotherapy with temozolomide. In recent years, local therapies have been extensively investigated in experimental as well as translational levels. External stimuli-responsive therapies such as Photodynamic Therapy (PDT), Sonodynamic Therapy (SDT) and Radiodynamic Therapy (RDT) can induce cell death mechanisms via generation of reactive oxygen species (ROS) after administration of five-aminolevulinic acid (5-ALA), which induces the formation of sensitizing porphyrins within tumor tissue. Preliminary data from clinical trials are available. The aim of this review is to summarize the status of such therapeutic approaches as an adjunct to current standard therapy in glioblastoma.


Glioblastoma , Humans , Glioblastoma/surgery , Aminolevulinic Acid/therapeutic use , Fluorescence , Temozolomide , Reactive Oxygen Species
15.
Plant Physiol Biochem ; 210: 108083, 2024 May.
Article En | MEDLINE | ID: mdl-38615441

Tomato is an important horticultural cash crop, and low-temperature stress has seriously affected the yield and quality of tomato. 5-Aminolevulinic acid (ALA) is widely used in agriculture as an efficient and harmless growth regulator. It is currently unclear whether exogenous ALA can cope with low-temperature stress by regulating tomato starch content and phenylalanine metabolism. In this study, exogenous ALA remarkably improved the low-temperature tolerance of tomato seedlings. RNA-sequencing results showed that exogenous ALA affected starch metabolism and phenylalanine metabolism in tomato seedling leaves under low-temperature stress. Subsequently, we used histochemical staining, observation of chloroplast microstructure, substance content determination, and qRT-PCR analysis to demonstrate that exogenous ALA could improve the low-temperature tolerance of tomato seedlings by regulating starch content and phenylalanine metabolism (SlPAL, SlPOD1, and SlPOD2). Simultaneously, we found that exogenous ALA induced the expression of SlMYBs and SlWRKYs under low-temperature stress. In addition, dual luciferase, yeast one hybrid, and electrophoretic mobility shift assays indicate that SlMYB4 and SlMYB88 could regulate the expression of SlPOD2 in phenylalanine metabolism. We demonstrated that exogenous ALA could improve the low-temperature tolerance of tomato seedlings by regulating starch content and phenylalanine metabolism.


Aminolevulinic Acid , Phenylalanine , Seedlings , Solanum lycopersicum , Starch , Solanum lycopersicum/metabolism , Solanum lycopersicum/genetics , Solanum lycopersicum/drug effects , Starch/metabolism , Seedlings/metabolism , Seedlings/drug effects , Aminolevulinic Acid/metabolism , Aminolevulinic Acid/pharmacology , Phenylalanine/metabolism , Gene Expression Regulation, Plant/drug effects , Cold Temperature , Plant Proteins/metabolism , Plant Proteins/genetics
16.
J Photochem Photobiol B ; 255: 112907, 2024 Jun.
Article En | MEDLINE | ID: mdl-38677259

OBJECTIVE: The objective of this study is to investigate the variances in transcriptome gene expression of normal oral mucosa-derived mesenchymal stem cell (OM-MSC), oral leukoplakia-derived MSC (OLK-MSC) and oral squamous cell carcinoma-derived MSC(OSCC-MSC). as Additionally, the study aims to compare the in vitro proliferation, migration, invasion ability, and response to photodynamic therapy (PDT) of these three MSC, HOK, DOK, leuk1, and Cal27 cell lines. METHODS: HOK, DOK, leuk1, Cal27 cells were cultured in vitro. 3 MSC cells were obtained from OM, OLK, OSCC tissue (n = 3) and identified through flow cytometry. They were also cultured in vitro for osteogenic and lipogenic-induced differentiation. Based on the Illumina HiSeq high-throughput sequencing platform, OM-MSC, OLK-MSC, OSCC-MSC (n = 3) were subjected to transcriptome sequencing, functional annotation, and enrichment analysis of differentially expressed genes and related genes. CCK8 assay, wound healing assay, and transwell assay were performed to compare the proliferation, migration, and invasion of the seven types of cells. The 7 cells were incubated with 0, 0.125 mM, 0.25 mM, 0.5 mM, 1 mM, and 2 mM of the photosensitizer (5-aminolevulinic acid, 5-ALA) in vitro. Subsequently, they were irradiated with a 150 mM, 635 nm laser for 1 min, and the cell activity was detected using the CCK8 assay after 24 h. The mitochondrial changes in the 7 cells before and after the treatment of PDT were detected using the JC-10 probe, and the changes in ATP content were measured before and after the PDT treatment. RESULTS: OM-MSC, OLK-MSC, and OSCC-MSC expressed positive MSC surface markers. After osteogenic and lipogenic-induced differentiation culture, stained calcium nodules and lipid droplets were visible, meeting the identification criteria of MSC. Pathway enrichment analysis revealed that the differentially expressed genes (DEGs) of OSCC-MSC compared to OLK-MSC were primarily associated with the PI3K-Akt signaling pathway and tumor-related pathways. OSCC-MSC exhibited stronger migratory and invasive abilities compared to Cal27. The IC50 values required for OM, OLK, and OSCC-derived MSC were lower than those required for epithelial cells treated with PDT, which were 1.396 mM, 0.9063 mM, and 2.924 mM, respectively. Cell membrane and mitochondrial disruption were observed in seven types of cells after 24 h of PDT treatment. However, HOK, DOK, leuk1, and Cal27 cells had an ATP content increased. CONCLUSIONS: OLK, OSCC epithelial cells require higher concentrations of 5-ALA for PDT treatment than MSC of the same tissue origin. The concentration of 5-ALA required increases with increasing cell malignancy. Differences in the response of epithelial cells and MSC to PDT treatment may have varying impacts on OLK recurrence and malignancy.


Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , Epithelial Cells , Leukoplakia, Oral , Mesenchymal Stem Cells , Mouth Mucosa , Mouth Neoplasms , Photochemotherapy , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mouth Mucosa/pathology , Mouth Mucosa/cytology , Leukoplakia, Oral/pathology , Leukoplakia, Oral/therapy , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Movement/drug effects , Cell Movement/radiation effects , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/drug therapy , Mouth Neoplasms/therapy , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Photosensitizing Agents/pharmacology , Cell Line, Tumor , Aminolevulinic Acid/pharmacology , Cell Differentiation/drug effects , Transcriptome/drug effects
17.
Bioorg Med Chem ; 105: 117726, 2024 May 01.
Article En | MEDLINE | ID: mdl-38626642

5-Aminolevulinic acid (ALA) and its derivatives, serving as the endogenous precursor of the photosensitizer (PS) protoporphyrin IX (PpIX), successfully applied in tumor imaging and photodynamic therapy (PDT). ALA and its derivatives have been used to treat actinic keratosis (AK), basal cell carcinoma (BCC), and improve the detection of superficial bladder cancer. However, the high hydrophilicity of ALA and the conversion of PpIX to heme have limited the accumulation of PpIX, hindering the efficiency and potential application of ALA-PDT. This study aims to evaluate the PDT activity of three rationally designed series of ALA-HPO prodrugs, which were based on enhancing the lipophilicity of the prodrugs and reducing the labile iron pool (LIP) through HPO iron chelators to promote PpIX accumulation. Twenty-four ALA-HPO conjugates, incorporating amide, amino acid, and ester linkages, were synthesized. Most of the conjugates, exhibited no dark-toxicity to cells, according to bioactivity evaluation. Ester conjugates 19a-g showed promoted phototoxicity when tested on tumor cell lines, and this increased phototoxicity was strongly correlated with elevated PpIX levels. Among them, conjugate 19c emerged as the most promising (HeLa, IC50 = 24.25 ± 1.43 µM; MCF-7, IC50 = 43.30 ± 1.76 µM; A375, IC50 = 28.03 ± 1.00 µM), displaying superior photodynamic anticancer activity to ALA (IC50 > 100 µM). At a concentration of 80 µM, the fluorescence intensity of PpIX induced by compound 19c in HeLa, MCF-7, and A375 cells was 18.9, 5.3, and 2.8 times higher, respectively, than that induced by ALA. In conclusion, cellular phototoxicity showed a strong correlation with intracellular PpIX fluorescence levels, indicating the potential application of ALA-HPO conjugates in ALA-PDT.


Aminolevulinic Acid , Antineoplastic Agents , Drug Screening Assays, Antitumor , Photochemotherapy , Photosensitizing Agents , Humans , Aminolevulinic Acid/pharmacology , Aminolevulinic Acid/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Pyridones/pharmacology , Pyridones/chemistry , Pyridones/chemical synthesis , Cell Line, Tumor , Protoporphyrins/chemistry , Protoporphyrins/pharmacology , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Cell Survival/drug effects , Prodrugs/pharmacology , Prodrugs/chemistry , Prodrugs/chemical synthesis
18.
Photodiagnosis Photodyn Ther ; 46: 104087, 2024 Apr.
Article En | MEDLINE | ID: mdl-38614271

Plantar wart is one of the most recalcitrant types of cutaneous warts with a high recurrence rate. Recalcitrant plantar warts are resistant to traditional treatments such as cryotherapy. Photodynamic therapy (PDT) is a modern, non-invasive method utilized to treat benign and malignant skin disorders. Several previous studies have reported the effective application of PDT treatment for plantar warts. We reported three cases of recalcitrant plantar warts successfully treated with PDT.


Aminolevulinic Acid , Photochemotherapy , Photosensitizing Agents , Warts , Humans , Warts/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Male , Female , Aminolevulinic Acid/therapeutic use , Adult , Treatment Outcome , Young Adult , Foot Dermatoses/drug therapy
19.
Photodiagnosis Photodyn Ther ; 46: 104085, 2024 Apr.
Article En | MEDLINE | ID: mdl-38614272

BACKGROUND: Chronic wounds refer to those that can't reconstruct anatomical and physical functional integrity, and are usually associated with signs of microbial infection. Current therapies include debridement and dressing change, local or systemic application of antibiotics, and medical dressing care, which are not ideal for the healing of chronic wounds. OBJECTIVE: To explore the efficacy and safety of photodynamic therapy (ALA-PDT) for the treatment of chronic infectious wounds. MATERIALS AND METHODS: ALA-PDT was used in ten patients with persistent wound infections and systemic complications who did not respond to conventional treatment. 5 % ALA solution was applied to the wound surface after debridement, incubated for 3 h with light protection, and then irradiated with red light for 20 min. This procedure was repeated every two weeks, and any adverse reactions were recorded. After the end of three treatments, the patients were followed up for 3 months. RESULTS: Patients who exhibit resistance to traditional therapies demonstrate a favorable therapeutic outcome with ALA-PDT, although complications may impede wound healing. All participants successfully underwent ALA-PDT treatment and subsequent monitoring, with 90 % achieving complete healing. Common adverse reactions to ALA-PDT encompass treatment-related pain, temporary erythema, and swelling, all of which are well-tolerated by patients without enduring severe consequences. CONCLUSIONS: ALA-PDT proves to be an efficacious intervention for managing chronic wounds, irrespective of the presence of localized infections or systemic complications.


Aminolevulinic Acid , Photochemotherapy , Photosensitizing Agents , Humans , Photochemotherapy/methods , Male , Female , Photosensitizing Agents/therapeutic use , Middle Aged , Aged , Aminolevulinic Acid/therapeutic use , Chronic Disease , Wound Healing/drug effects , Adult , Wound Infection/drug therapy , Aged, 80 and over
20.
Photodiagnosis Photodyn Ther ; 46: 104098, 2024 Apr.
Article En | MEDLINE | ID: mdl-38642727

Intraductal papillary mucinous neoplasm of the bile tract is a rare biliary tumor characterized by mucin growth within the bile duct. In the early stages, it often presents without significant obstruction, this often leads to its discovery in the advanced stages. We report a case of a 63-year-old female with an intraductal papillary mucinous neoplasm of the bile duct (IPMN-B). The patient had a history of intrahepatic bile duct stones and biliary ascariasis. She gradually developed symptoms such as jaundice and intermittent fever before admission, and a bile duct biopsy confirmed the diagnosis of IPMN-B. Currently, endoscopic photodynamic therapy (PDT) is considered an effective treatment for bile duct cancer. In this case, we performed two sessions of PDT guided by SpyGlass. The patient experienced complete remission postoperatively, and there has been no evidence of tumor recurrence or metastasis in the three years following the procedure.


Bile Duct Neoplasms , Photochemotherapy , Photosensitizing Agents , Humans , Female , Middle Aged , Photochemotherapy/methods , Bile Duct Neoplasms/drug therapy , Photosensitizing Agents/therapeutic use , Adenocarcinoma, Mucinous/drug therapy , Aminolevulinic Acid/therapeutic use
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