BACKGROUND: Female vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease of the vulva and its etiology is unknown. The main clinical symptoms are itching, burning and dyspareunia, and there is a lack of effective treatment.
METHODS: Clinical and follow-up data of women with VLS who underwent 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) from January 2023 to December 2023 in the department of obstetrics and gynecology, Qilu Hospital of Shandong University, were retrospectively analyzed. According to the inclusion and exclusion criteria, 36 patients with VLS who received ineffective conventional treatment (intractable VLS) were enrolled. Objective signs and subjective symptoms of vulvar lesions were recorded before treatment and 6 months after the end of treatment according to corresponding scoring criteria. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI).
RESULTS: All patients received six sessions of ALA-PDT treatment and follow-up visits. After ALA-PDT treatment, 24 of 36 (66.67%) patients\' itching symptoms completely disappeared, 10 of 36 (27.78%) patients\' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56%) patients\' symptoms were not significantly relieved. 16 of 36 (44.4%) patients\' itching symptoms completely disappeared, 9 of 36 (25%) patients\' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56%) patients still had severe pain. Compared to 22 patients with dyspareunia before treatment, only 9 patients still had dyspareunia with varying degrees of dyspareunia relief after treatment. Clinical signs improved significantly in the patients after ALA-PDT treatment. The total scores of clinical signs were (5.31±1.67 vs 3.67±1.71) before and after treatment. All patients showed improvement in DLQI after treatment. The main side effects of ALA-PDT were pain, erythema and swelling which were transient and tolerable. All patients were \"satisfied\" or \"very satisfied\" with the results of the treatment.
CONCLUSIONS: ALA-PDT is a safe and effective treatment for women with intractable vulva lichen sclerosus.

5-Aminolevulinic acid (ALA), as a novel plant growth regulator, is a critical precursor for the biosynthesis of porphyrin compounds in all organisms. Many studies have reported that exogenous ALA treatment could improve fruit sweetness. However, the mechanism by which ALA promotes the increase in sugar content in fruit remains unclear. In this study, we found that ALA significantly promoted sucrose accumulation and SPS (sucrose phosphate synthase) activity in peach fruit. At 14, 28, 42, 50 and 60 days after ALA treatment, sucrose content of fruit was increased by 23%, 43%, 37%, 40% and 16%, respectively, compared with control treatment, and SPS enzyme activity was increased by 21%, 28%, 47%, 37% and 29%, respectively. Correlation analysis showed that the sucrose content of peach fruit under ALA treatment was significantly positively correlated with SPS activity. Subsequently, bioinformatics was used to identify SPS gene family members in peach fruit, and it was found that there were four members of the PpSPS gene family, distributed on chromosomes 1, 7 and 8, named PpSPS1, PpSPS2, PpSPS3 and PpSPS4, respectively. The results of qRT-PCR showed that PpSPS2 and PpSPS3 were highly expressed in response to ALA during fruit development, and the expression of PpSPS2 was positively correlated with SPS activity and sucrose accumulation in peach fruit. The results of tobacco subcellular localization showed that PpSPS2 was mainly distributed in the cytoplasm and nucleus, while PpSPS3 was mainly distributed in the nucleus. The results of this study will lay the foundation for further study on the functions of PpSPS and the regulation of sugar metabolism during the development and ripening of peach fruit by ALA.

5-Aminolevulinic acid (5-ALA) is a prodrug of porphyrin IX (PpIX). Disadvantages of 5-ALA include poor stability, rapid elimination, poor bioavailability, and weak cell penetration, which greatly reduce the clinical effect of 5-ALA based photodynamic therapy (PDT). Presently, a novel targeting nanosystem was constructed using gold nanoparticles (AuNPs) as carriers loaded with a CSNIDARAC (CC9)-targeting peptide and 5-ALA via Au-sulphur and ionic bonds, respectively, and then wrapped in polylactic glycolic acid (PLGA) NPs via self-assembly to improve the antitumor effects and reduce the side effect. The successful preparation of ALA/CC9@ AuNPs-PLGA NPs was verified using ultraviolet-visible, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The analyses revealed good sphericity with a particle size of approximately140 nm, Zeta potential of 10.11 mV, and slow-controlled release characteristic in a weak acid environment. Confocal microscopy revealed targeting of NCL-H460 cells by NPs by actively internalising CC9 and avoiding the phagocytic action of RAW264.7 cells, and live fluorescence imaging revealed targeting of tumours in tumour-bearing mice. Compared to free 5-ALA, the nanosystem displayed amplified anticancer activity by increasing production of PpIX and reactive oxygen species to induce mitochondrial pathway apoptosis. Antitumor efficacy was consistently observed in three-dimensionally cultured cells as the loss of integrity of tumour balls. More potent anti-tumour efficacy was demonstrated in xenograft tumour models by decreased growth rate and increased tumour apoptosis. Histological analysis showed that this system was not toxic, with lowered liver toxicity of 5-ALA. Thus, ALA/CC9@AuNPs-PLGA NPs deliver 5-ALA via a carrier cascade, with excellent effects on tumour accumulation and PDT through passive enhanced permeability and retention action and active targeting. This innovative strategy for cancer therapy requires more clinical trials before being implemented.

Candidiasis is a common fungal infection, with Candida tropicalis infections being relatively rare. These infections develop into skin fungal infections under conditions such as broad-spectrum antibiotic use, diabetes, and immunosuppression. Traditionally, antifungal drugs have been the primary treatment; however, issues like hepatotoxicity and the need for long-term use persist. Consequently, new treatment approaches are essential. Most previous reports have focused on Candida albicans, with fewer addressing Candida tropicalis. This study reports a case where a patient with a skin Candida tropicalis infection was treated with a combination of surgery and ALA photodynamic therapy(635 nm, 120 J/cm2, 177 mW/cm2). After just one session of this combined treatment, the patient achieved significant clinical remission. Therefore, the combination of surgery and ALA-PDT may offer a safe and effective treatment option.

The versatile applications of 5-aminolevulinic acid (5-ALA) across the fields of agriculture, livestock, and medicine necessitate a cost-efficient biomanufacturing process. In this study, we achieved the economic viability of biomanufacturing this compound through a systematic engineering framework. First, we obtained a 5-ALA synthase (ALAS) with superior performance by exploring its natural diversity with divergent evolution. Subsequently, using a genome-scale model, we identified and modified four key targets from distinct pathways in Escherichia coli, resulting in a final enhancement of 5-ALA titers up to 21.82 g/l in a 5-l bioreactor. Furthermore, recognizing that an imbalance of redox equivalents hindered further titer improvement, we developed a dynamic control system that effectively balances redox status and carbon flux. Ultimately, we collaboratively optimized the artificial redox homeostasis system at the transcription level with other cofactors at the feeding level, demonstrating the highest recorded performance to date with a titer of 63.39 g/l for the biomanufacturing of 5-ALA.

BACKGROUND: Oral 5-aminolevulinic acid for transurethral resection of bladder tumor reduces bladder cancer recurrence compared with standard white-light transurethral resection of bladder tumor. However, data regarding risks of adverse events with this drug are unclear. The aim of the present study was to identify risk factors associated with oral 5-aminolevulinic acid induced adverse events in photodynamic diagnosis-transurethral resection of bladder tumor.
METHODS: We studied 104 cases of 5-aminolevulinic acid-photodynamic diagnosis-transurethral resection of bladder tumor from October 2021 to April 2023, administering 20 mg/kg 5-aminolevulinic acid orally at least 2 h pre-surgery. Four major adverse events associated with 5-aminolevulinic acid were selected to identify risk factors for their occurrence, including perioperative hypotension, nausea and/or vomiting, photosensitivity, and liver dysfunction. Univariate and multivariate analyses were conducted to identify the risk factors of those adverse events.
RESULTS: Perioperative hypotension (11.5 %), nausea and/or vomiting (37.5 %) photosensitivity (31.7 %), and liver dysfunction (51.9 %) were observed. Multivariate analyses revealed that spinal anesthesia was associated with hypotension (p = 0.02), whereas advanced age (p < 0.01) and higher body mass index (p < 0.01) were associated with nausea and/or vomiting. Also, male sex (p < 0.01) and longer operative time (p = 0.01) were associated with photosensitivity, and renin-angiotensin system inhibitors use was associated with postoperative liver dysfunction (p < 0.01).
CONCLUSIONS: For elderly male obese patients taking renin-angiotensin system inhibitors, particular attention is needed during the perioperative period of photodynamic diagnosis-transurethral resection of bladder tumor under spinal anesthesia due to the higher risk of onset of the adverse events involved in oral administration of 5-aminolevulinic acid.

Dermatosis papulosa nigra (DPN) is a type of benign epidermal hyperplasia that affects the appearance of patients and poses a threat to their physical and mental health. Photodynamic therapy (PDT) has been shown to have the advantages of non-invasiveness, efficacy, and low recurrence in the treatment of skin disorders. However, no studies have been reported on the use of PDT for the treatment of DPN. Therefore, we used PDT for the first time to treat DPN and monitor its efficacy. Forty-five patients with DPN diagnosed at the outpatient clinic of Changzhou First People\'s Hospital were treated with 10 % 5-aminolevulinic acid (ALA) once a week for four consecutive weeks and followed for 3 months. After four treatment sessions, the cure rate among the 45 patients was 71.1 %, and the overall efficacy rate was 93.3 %. The most common adverse reactions were mild erythema, edema, and temporary pigmentation. PDT is expected to become a new and effective treatment for DPN.

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes despite the prevalent recurrence and progression among many patients. In particular, flat urothelial carcinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new-generation photosensitizer, 5-Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

OBJECTIVE: The diagnostic accuracy for cholangiocarcinoma (CCA) is inadequate, necessitating the exploration of novel diagnostic approaches. Protoporphyrin IX (Pp IX), a metabolic product of 5-aminolevulinic acid (5-ALA), emits red fluorescence upon blue light exposure. Because it accumulates selectively in cancer cells, photodynamic diagnosis using 5-ALA (5-ALA-PDD) has been integrated into clinical practice for diverse cancer types. Nevertheless, there is currently no device capable of capturing Pp IX-derived fluorescence for real-time 5-ALA-PDD within the biliary tract, largely due to challenges in device miniaturization.
METHODS: To investigate the feasibility of real-time 5ALA-PDD in CCA, we developed two essential components of the cholangioscopy system: a small-diameter flexible camera and a light guide for emitting blue light. We evaluated the detectability of Pp IX fluorescence using these devices in experimental gels and animal models.
RESULTS: Our camera and light guide were smoothly inserted into the lumen of existing cholangioscopes. Incorporating a long-pass filter at the camera tip enabled efficient detection of red fluorescence without significantly impacting white-light observation. The integration of these devices facilitated clear visualization of red fluorescence from gels containing Pp IX at concentrations of 5 μM or higher. Additionally, when observing subcutaneous human CCA tumor models in nude mice treated with 5-ALA, we successfully demonstrated distinct red fluorescence from Pp IX accumulation in tumors compared to peritumoral subcutaneous areas.
CONCLUSIONS: The integration of our device combination holds promise for real-time 5-ALA-PDD in human CCA, potentially enhancing the diagnostic accuracy for this complex condition.

5-aminolevulinic acid (5-ALA) is an endogenous non-protein amino acid that is frequently used in modern agriculture. This study set out to determine how dietary 5-ALA affected the nonspecific immunity and growth performance of Litopenaeus vannamei. The shrimp were supplemented with dietary 5-ALA at 0, 15, 30, 45, and 60 mg/kg for three months. Transcriptome data of the control group and the group supplemented with 45 mg/kg dietary 5-ALA were obtained using transcriptome sequencing. 592 DEGs were identified, of which 426 were up-regulated and 166 were down-regulated. The pathways and genes associated with growth performance and nonspecific immunity were confirmed using qRT-PCR. The highest survival rate, body length growth rate, and weight gain values were observed in shrimp fed diets containing 45 mg/kg 5-ALA. L. vannamei in this group had a significantly higher total hemocyte count, phagocytosis rate and respiratory burst value than those in the control group. High doses of dietary 5-ALA (45 mg/kg, 60 mg/kg) significantly increased the activities of catalase, superoxide dismutase, oxidized glutathione, glutathione-peroxidase, phenoloxidase, lysozyme, acid phosphatase, and alkaline phosphatase. At the transcriptional level, dietary 5-ALA significantly up-regulated the expression levels of antioxidant immune-related genes. The optimal concentration of 5-ALA supplementation was 39.43 mg/kg, as indicated by a broken line regression. Our study suggested that dietary 5-ALA positively impacts the growth and nonspecific immunity of L. vannamei, providing a novel theoretical basis for further research into 5-ALA as a dietary supplement.