-
Plant Physiology Jun 2024Photomixotrophic growth A (PmgA) is a pleiotropic regulator essential for growth under photomixotrophic and prolonged high-light (HL) conditions in the cyanobacterium...
Photomixotrophic growth A (PmgA) is a pleiotropic regulator essential for growth under photomixotrophic and prolonged high-light (HL) conditions in the cyanobacterium Synechocystis sp. PCC 6803. The overall similarity with the anti-sigma factor of the bacterial partner-switching system indicates that PmgA exerts a regulatory function via phosphorylation of its target proteins. In this study, we performed an in vitro phosphorylation assay and protein-protein interaction analysis and found that PmgA interacts with four anti-sigma antagonist homologs, Ssr1600, Slr1856, Slr1859, and Slr1912, but specifically phosphorylates Ssr1600. Phenotypic analyses using the set of gene disruption and overexpression strains of pmgA and ssr1600 revealed that phosphorylation by PmgA is essential for the accumulation of Ssr1600 protein in vivo. The ssr1600-disrupted mutant showed similar phenotypes as those previously reported for the pmgA-disrupted mutant, namely, no obvious phenotype just after the shift to HL, but higher chlorophyll content, 5-aminolevulinic acid synthesis activity, and psaAB transcript levels than those in the wild-type after 6 hours. These findings indicate that the phosphorylated form of Ssr1600 works as the output of the partner-switching system to coordinately repress chlorophyll biosynthesis and accumulation of photosystem I during HL acclimation.
PubMed: 38833609
DOI: 10.1093/plphys/kiae323 -
Frontiers in Immunology 2024
Topics: Humans; Cellular Microenvironment; Animals; Skin Diseases; Epithelial Cells; Skin
PubMed: 38831926
DOI: 10.3389/fimmu.2024.1428209 -
PloS One 2024Describing mitochondrial oxygenation (mitoPO2) and its within- and between-subject variability over time after 5-aminolevulinic acid (ALA) plaster application in healthy...
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.
Topics: Humans; Male; Female; Healthy Volunteers; Adult; Oxygen; Prospective Studies; Mitochondria; Middle Aged; Aminolevulinic Acid; Oxygen Consumption; Young Adult; Netherlands
PubMed: 38829894
DOI: 10.1371/journal.pone.0300602 -
International Journal of Biological... Jun 202417α-Hydroxyprogesterone (17α-OH-PROG) is an important intermediate with a wide range of applications in the pharmaceutical industry. Strategies based on efficient...
Production of 17α-hydroxyprogesterone using an engineered biocatalyst with efficient electron transfer and improved 5-aminolevulinic acid synthesis coupled with a P450 hydroxylase.
17α-Hydroxyprogesterone (17α-OH-PROG) is an important intermediate with a wide range of applications in the pharmaceutical industry. Strategies based on efficient electron transfer and cofactor regeneration were used for the production of 17α-OH-PROG. Here, CYP260A1, Fpr and Adx were expressed using a double plasmid system, resulting in higher biotransformation efficiency. Further optimization of reaction conditions and addition of polymyxin B increased the production of 17α-OH-PROG from 12.52 mg/L to 102.37 mg/L after 12 h of biotransformation. To avoid the addition of external 5-aminolevulinic acid (ALA) as a heme precursor for the P450 enzyme, a modified C5 pathway was introduced into the engineered strain, further reducing the overall process cost. The resulting whole-cell biocatalyst achieved the highest biotransformation yield of 17α-OH-PROG reported to date, offering a promising strategy for commercial application of P450 enzymes in industrial production of hydroxylated intermediates.
PubMed: 38825287
DOI: 10.1016/j.ijbiomac.2024.132831 -
BMC Biomedical Engineering Jun 2024Visualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical...
BACKGROUND
Visualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical need exists for real-time intraoperative visualization of breast carcinomas during BCS. We previously demonstrated the ability of a prototype imaging device to identify breast carcinoma in excised surgical specimens following 5-aminolevulinic acid (5-ALA) administration. However, this prototype device was not designed to image the surgical cavity for remaining carcinoma after the excised lumpectomy specimen is removed. A new handheld fluorescence (FL) imaging prototype device, designed to image both excised specimens and within the surgical cavity, was assessed in a clinical trial to evaluate its clinical utility for first-in-human, real-time intraoperative imaging during index BCS.
RESULTS
The imaging device combines consumer-grade imaging sensory technology with miniature light-emitting diodes (LEDs) and multiband optical filtering to capture high-resolution white light (WL) and FL digital images and videos. The technology allows for visualization of protoporphyrin IX (PpIX), which fluoresces red when excited by violet-blue light. To date, patients have received bodyweight (BW) 5-ALA orally 2-4 h before imaging to facilitate the accumulation of PpIX within tumour cells. Tissue types were identified based on their colour appearance. Breast tumours in sectioned lumpectomies appeared red, which contrasted against the green connective tissues and orange-brown adipose tissues. In addition, ductal carcinoma in situ (DCIS) that was missed during intraoperative standard of care was identified at the surgical margin at <1 mm depth. In addition, artifacts due to the surgical drape, illumination, and blood within the surgical cavity were discovered.
CONCLUSIONS
This study has demonstrated the detection of a grossly occult positive margin intraoperatively. Artifacts from imaging within the surgical cavity have been identified, and potential mitigations have been proposed.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01837225 (Trial start date is September 2010. It was registered to ClinicalTrials.gov retrospectively on April 23, 2013, then later updated on April 9, 2020, to reflect the introduction of the new imaging device.).
PubMed: 38822389
DOI: 10.1186/s42490-024-00079-9 -
Photodiagnosis and Photodynamic Therapy May 2024Dissecting cellulitis of the scalp (DCS) has a significant impact on the physical well-being and body image of the patient. Since DCS often responds poorly to...
Effectiveness of 5-aminolevulinic acid photodynamic therapy in treating dissecting cellulitis of the scalp and pathological changes in skin lesions: A retrospective study.
BACKGROUND
Dissecting cellulitis of the scalp (DCS) has a significant impact on the physical well-being and body image of the patient. Since DCS often responds poorly to conventional treatments, there is a need to identify alternative treatment strategies. This study aimed to explore the effectiveness of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating DCS.
METHODS
Twelve male patients with DCS treated solely with ALA-PDT between June 2022 and June 2023 at our institution were enrolled in this study. Two patients underwent a biopsy before and after treatment for comparison. The efficacy of the treatments was assessed 10 days after treatment by evaluating the symptom scores recorded on medical records and by assessing the photographs acquired before and after treatment. In addition, the impact of the treatment on pain relief and median recurrence rate were also extracted.
RESULTS
Out of the 12 enrolled patients, the majority of the patients (75%) had a significant reduction in the nodules or abscesses. The pain relief was significant in 3 patients (25%), and moderate in 7 patients (58.3%). For the subcutaneous sinus tract symptoms, 3 patients (27.3%) showed moderate improvement, and 7 (63.6%) had a mild improvement. Six patients (75%) had mild improvement in their alopecia. The pathology results showed a decrease in the number of lymphocytes, macrophages, and neutrophils within the skin lesions following the administration of ALA-PDT.
CONCLUSION
ALA-PDT can effectively reduce the DCS symptoms and the number of lymphocytes, macrophages, and neutrophils within the skin lesions.
PubMed: 38821237
DOI: 10.1016/j.pdpdt.2024.104227 -
Frontiers in Bioscience (Landmark... May 2024Due to its non-invasive and widely applicable features, photodynamic therapy (PDT) has been a prominent treatment approach against cancer in recent years. However, its...
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) and .
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 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 . 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 .
CONCLUSIONS
PDT mediated by 450-nm blue laser combined with ATPP-DTPA may be a novel and effective method for the treatment of CRC.
Topics: Photochemotherapy; Colorectal Neoplasms; Apoptosis; Animals; Photosensitizing Agents; Humans; Mice, Nude; Reactive Oxygen Species; Mice; Cell Line, Tumor; Xenograft Model Antitumor Assays; Mice, Inbred BALB C; Lasers; Cell Survival; Aminolevulinic Acid
PubMed: 38812322
DOI: 10.31083/j.fbl2905199 -
Journal of Medical Case Reports May 2024Although 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of...
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.
Topics: Humans; Male; Aminolevulinic Acid; Hypotension; Aged, 80 and over; Heart Arrest; Urinary Bladder Neoplasms; Postoperative Complications; Photosensitizing Agents; Intraoperative Complications
PubMed: 38811941
DOI: 10.1186/s13256-024-04589-x -
Dermatology Practical & Conceptual Apr 2024Basal cell carcinoma (BCC) is the most common skin cancer worldwide and has been reported to have a rising incidence in the last years. Multiple therapeutic modalities... (Review)
Review
INTRODUCTION
Basal cell carcinoma (BCC) is the most common skin cancer worldwide and has been reported to have a rising incidence in the last years. Multiple therapeutic modalities are approved for the treatment of BCC, making it difficult for physicians to choose the most suitable option for every patient. Photodynamic therapy (PDT) using either 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) as photosensitizing agents is an established treatment option for low-risk BCC.
OBJECTIVES
This review aims to summarize the available evidence from randomized clinical trials (RCTs) that utilize either ALA or MAL PDT and compare it with other treatment modalities. The main outcomes related to the effectiveness, adverse events, cosmetic outcomes and pain sensation, along with data from long-term follow-ups will be presented and discussed.
METHODS
Thorough literature searches were conducted through the electronic databases ClinicalTrials. gov and Pubmed/MEDLINE from inception up to 28 March 2023. Only studies in English were included. All relevant data were extracted accordingly from the eligible studies.
RESULTS
Eight RCTs included superficial BCC (sBCC) alone, 7 included nodular BCC (nBCC), 2 included both sBCC and nBCC and 1 included BCC of unspecified subtype. Follow-up duration ranged from 3 months to 5 years. Both ALA-PDT and MAL-PDT demonstrated acceptable efficacy, adverse events, cosmetic outcomes and pain sensation while no major differences were observed between them. PDT was less effective than surgery but with better reported cosmetic outcomes.
CONCLUSIONS
PDT is a safe and efficacious treatment option for sBCC and to a lesser extent nBCC.
PubMed: 38810046
DOI: 10.5826/dpc.1402a105 -
Lasers in Surgery and Medicine Jul 2024Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA... (Clinical Trial)
Clinical Trial
BACKGROUND
Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution.
METHODS
For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale.
RESULTS
Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5 (interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination.
CONCLUSIONS
Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT.
Topics: Humans; Carcinoma, Basal Cell; Pilot Projects; Photochemotherapy; Female; Skin Neoplasms; Male; Aminolevulinic Acid; Aged; Middle Aged; Photosensitizing Agents; Prospective Studies; Injections, Jet; Treatment Outcome; Aged, 80 and over
PubMed: 38804170
DOI: 10.1002/lsm.23793