Efficacy and safety of a novel 785 nm picosecond neodymium-doped yttrium aluminum garnet laser for the treatment of facial benign pigmented lesions in Asian skin: a pilot study.

BACKGROUND AND OBJECTIVES: Benign pigmented lesions and a general uneven tone in people with skin of color are growing issues that have been presented to dermatologists. To the best of our knowledge, this is the first controlled study to examine the efficacy and safety of using the newly introduced 785 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) picosecond laser to treat facial benign pigmented lesions in Asian patients with diffractive lens array. MATERIALS AND METHODS: A 785 nm Nd:YAG picosecond laser was used to treat 15 healthy female volunteers older than 18 years who had Fitzpatrick skin types II-IV and facial benign pigmented lesions. Each volunteer received five weekly treatments in dual modes. The clinical improvement was assessed by independent investigators and by objectively measuring the melanin index. RESULTS: After the treatment, the melanin and erythema indices decreased, and the pigmented lesions showed clinical improvements. No serious adverse effects were observed during the study period. CONCLUSIONS: A 785 nm Nd:YAG picosecond laser may be safe and effective in treating facial benign pigmented lesions in Asian skin.

Facial Cutaneous Rosai-Dorfman Disease: Dermoscopic Findings with Successful Surgical Treatment.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by an accumulation of activated histiocytes within the affected tissues. It is a heterogeneous disease that includes the classical (nodal) and extra-nodal variants. The cutaneous form of the disease without the characteristic lymphadenopathy is rare and is often misdiagnosed as other dermatologic diseases. Misdiagnosis as lymphoproliferative and infectious diseases such as lymphoma and tuberculosis have been reported in the literature. Herein, we report a case of facial cutaneous RDD with successful surgical treatment. In addition, we provide dermoscopic findings and literature review as dermoscopy can be a useful adjuvant tool in the diagnosis of cutaneous RDD.

Sprr1 and miR-130b contribute to the senescence-like phenotype in aging.

Aging is an inevitable process with senescence being one of its hallmarks. Recent advances have indicated that the elimination of senescent cells can reduce the signs of aging and increase healthy life span. Here, we identify a negative modulator of aging, Sprr1a, and in turn a negative modulator of Sprr1a, miR-130b. We show that reductions in Sprr1a levels, including via miR-130b expression, promotes cell senescence-like phenotype. We find that mediators of senescence, such as inflammatory cytokines and cell cycle regulators, are modulated by the miR-130b and Sprr1a-related pathway. For example, the levels of p16, p53 and p21 become decreased or increased upon the respective expression of Sprr1a versus miR-130b. Further, as shown in relation to p16 levels and ß-galactosidase levels, cells expressing Sprr1a exhibit significant protection from senescence-inducing factors such as radiation or Doxorubicin, suggesting that Sprr1a might contribute to protection against age-related pathologies. Taken together, we introduce two modulators of properties associated with senescence-like phenotype.

An elevated likelihood of stroke, ischemic heart disease, or heart failure in individuals with gout: a longitudinal follow-up study utilizing the National Health Information database in Korea.

Objective: Accumulating evidence from other countries indicates potential associations between gout and cardiovascular diseases; however, the associations of gout with cardiovascular diseases, particularly stroke, ischemic heart disease, and heart failure, remain ambiguous in the Korean population. We hypothesized that individuals with gout are at a higher likelihood of stroke, ischemic heart disease, or heart failure. This study expands upon previous research by ensuring a comparable baseline between patient and control groups and analyzing 16 years of data derived from an extensive healthcare database. Methods: We selected 22,480 patients with gout and 22,480 control individuals from the Korean National Health Insurance Service-Health Screening Cohort database (2002-2019), and matched them at a 1:1 ratio according to sex, age, income, and residence. A Cox proportional hazard model with weighted overlap was employed to examine the relationship between gout and the risk of stroke, ischemic heart disease, or heart failure after adjustment for several covariates. Results: The incidences of stroke, ischemic heart disease, or heart failure in participants with gout were slightly higher than those in controls (stroke: 9.84 vs. 8.41 per 1000 person-years; ischemic heart disease: 9.77 vs. 7.15 per 1000 person-years; heart failure: 2.47 vs. 1.46 per 1000 person-years). After adjustment, the gout group had an 11% (95% confidence interval [CI] = 1.04-1.19), 28% (95% CI = 1.19-1.37), or 64% (95% CI = 1.41-1.91) higher likelihood of experiencing stroke, ischemic heart disease, or heart failure, respectively, than the control group. Conclusion: The present findings suggest that individuals with gout in the Korean population, particularly those aged ≥ 60 years, were more likely to have stroke, ischemic heart disease, or heart failure.

Practical Training Approaches for Discordant Atopic Dermatitis Severity Datasets: Merging Methods With Soft-Label and Train-Set Pruning.

Objective assessment of atopic dermatitis (AD) is essential for choosing proper management strategies. This study investigated the performance of convolutional neural networks (CNN) models in grading the severity of AD. Five board-certified dermatologists independently evaluated the severity of 9,192 AD images. The severity of AD was evaluated based on an Investigator's Global Assessment (IGA) and six signs of AD. For CNN training, we applied three distinct approaches: 1) ensemble vs. integration 2) hard-label vs. soft-label and 3) train-set pruning. For the IGA prediction, the two best models were chosen based on the macro-averaged AUROC and F-1 score. The ensemble-soft-label-pruning model was chosen based on AUROC 0.943, 0.927 for the internal and external validation set respectively, and integration-soft-label-whole dataset model was chosen based on the F1-score 0.750, 0.721 for the internal and external validation set respectively. CNN models trained by multi-evaluator dataset outperformed the models by an individual evaluator dataset, and they performed better to the dataset in which the assessment of dermatologists was concordant. In conclusion, CNN models for AD could be improved by labeled dataset from multiple evaluators, merging methods with soft-label and train-set pruning.

Tumor microenvironment-responsive histidine modified-hyaluronic acid-based MnO2 as in vivo MRI contrast agent.

Tumor microenvironment (TME)-responsive manganese dioxide (MnO2) nanoparticles as a good T1 contrast agent could reduce unwanted toxicity and improve the accuracy of cancer detection. Despite these distinct advantages of MnO2-based nanoparticles, their synthesis involves multi-step processes with relatively long synthesis times. In this study, we synthesized histidine-modified hyaluronic acid (HA-His), and the prepared HA-His conjugates quickly reduce permanganate to MnO2, leading to facile production of HA-His/MnO2 nanoparticles with good water-dispersibility and stability under biological conditions. The synthesized HA-His/MnO2 nanoparticles readily responded to the TME (low pH, high H2O2, and high glutathione), and they were internalized into SCC7 cells with high CD44 expression. Moreover, the systemically administered HA-His/MnO2 nanoparticles with biocompatibility were specifically accumulated in tumor tissues, thereby efficiently enhancing T1 contrast in MRI. Therefore, the HA-His/MnO2 nanoparticles synthesized herein can be used as a promising T1 contrast agent for tumor MR imaging.

Efficacy and Safety of Cold-Induced Noninvasive Targeted Fat Reduction in Pseudogynecomastia.

BACKGROUND: Treatment options for pseudogynecomastia are limited, and the demand for noninvasive breast fat reduction is increasing. OBJECTIVE: We evaluated the efficacy and safety of a cold-induced lipolysis device for treating pseudogynecomastia. METHODS: In this 16-week prospective trial, a total of 15 male patients with pseudogynecomastia were treated twice with cryolipolysis. The primary endpoint was a change in the chest circumference from baseline at posttreatment week 8. Secondary endpoints were changes in body weight, fat thickness assessed using ultrasonography, independent evaluator- and patient-rated improvement, and Simon's gynecomastia class (SGC) grading. RESULTS: The primary assessment, a reduction of 3.05 cm in the mean chest circumference at 8 weeks post-treatment compared to baseline, was statistically significant. The treatment effect was cumulative, with a steady decrease in chest circumference and fat thickness over the 16-week study period. The mean pain score immediately after the first session of treatment was 2.0±1.36, based on a scale of 0~10, with a score of 10 being the worst pain ever experienced. The pain decreased substantially after the end of the procedure. CONCLUSION: Cryolipolysis was demonstrated to be an effective and safe option for reducing breast fat in pseudogynecomastia. Male with mild to moderate breast enlargement without skin excess can be ideal candidates.

Mixture of Tomato and Lemon Extracts Synergistically Prevents PC12 Cell Death from Oxidative Stress and Improves Hippocampal Neurogenesis in Aged Mice.

Dietary habits have a great impact on one's health, especially in cognitive decline. Tomato and lemon contain diverse bioactive compounds and possess various effects, including the enhancement of cognitive function. We observed the protective effect of tomato, lemon extract and the mixture of them on H2O2-induced cytotoxicity of PC12 cells. To measure the in vivo effect in a murine model, each extract was orally administered to forty 1-year-old mice for 6 weeks, and a novel object recognition (NOR) test was performed to observe cognitive function, and hippocampal neurogenesis was observed through a doublecortin (DCX) stain. PC12 cell death by oxidative stress was reduced by pretreating with each extract, and a synergistic reduction was observed in the mixture. Newly generated DCX-positive neurons were synergistically increased in the hippocampus by the mixture. NOR test showed a tendency to significantly improve age-related cognitive dysfunction by consuming the mixture of tomato and lemon. In conclusion, tomato and lemon extracts can reduce cellular oxidative stress and increase NOR, likely due to enhanced neurogenesis, while the mixture of the two showed synergistic anti-oxidative effects and hippocampal neurogenesis.

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

The dehiscence process in Panax ginseng seeds and the stigmasterol biosynthesis pathway in terms of metabolomics.

Background: Ginseng, officially known as Panax ginseng Meyer, has been traditionally used as a medicinal herb, particularly in Asia. Ginseng is propagated from seeds; however, seed germination is challenging, especially in its natural environment on farms. The seeds typically exhibit morphophysiological dormancy and require release from both morphological and physiological dormancy before germination. Although some studies have proposed methods for increasing seed germination rates, the underlying mechanisms of its dormancy release process remain unclear. Here, we investigated metabolic alterations during dehiscence in P. ginseng to determine their potential roles in dormancy release. Methods: We compared the ginseng seed metabolome before and after dehiscence and the ginsenoside and phytosterol compositions of the seeds in both periods in the presence of related enzymes. Results: After seed dehiscence, the sugar, amino acid, and squalene concentrations were significantly altered, phytosterols associated with the stigmasterol biosynthesis pathway were increased, while ginsenoside and brassinosteroid levels were not significantly altered. In addition, squalene epoxidase, cycloartenol synthase, 24-methylenesterol C-methyltransferase, and the stigmasterol biosynthesis pathway were activated. Conclusion: Overall, our findings suggest that morphological activities that facilitate ginseng seed growth are the primary phenomena occurring during the dehiscence process. This study improves the understanding of P. ginseng germination processes and promotes further research of its germination and cultivation.

Irradiation with 590-nm yellow light-emitting diode light attenuates oxidative stress and modulates UVB-induced change of dermal fibroblasts.

Recently, light-emitting diode (LED)-based devices have emerged as effective and safe tools for the treatment of photoaged skin. However, few studies have been conducted to elucidate the underlying mechanism behind the effect on photoageing of LED light. In this study, we induced photoageing of human dermal fibroblasts (HDFs) with Ultraviolet B (UVB) irradiation and evaluated the ability of 590-nm LED radiation to induce recovery from oxidative stress, restore collagen formation and regulate inflammatory changes. Photoageing was induced in cultured human dermal fibroblasts (HDFs) using UVB irradiation of 50 mJ/cm2 . Then, the photoaged HDFs were irradiated with LED using a custom-built 590-nm LED device which emits light with an intensity of 38 mW/cm2 (irradiated for 900 s with 34.2 J/cm2 of total energy). LED irradiation significantly attenuated UVB-induced reactive oxygen species generation and UVB-induced phosphorylation of JNK, c-Fos and c-Jun. In addition, the procollagen levels were recovered significantly, and MMP-9 levels were significantly suppressed after LED irradiation. The UVB-induced phosphorylation levels of NF-κB and pro-inflammatory enzyme COX-2 also significantly decreased. Our results suggest that 590-nm yellow light irradiation may be an effective and safe anti-oxidative and anti-inflammatory treatment modality for photoaged skin.

Utilization of Ultrasonography in Dermatology: Two Case Reports of Calcinosis Cutis.

Development of newer generation of cost-effective ultrasonic devices in recent years has increased the use of ultrasonography in dermatology. Several lesions can be diagnosed and managed using ultrasonography. Calcinosis cutis involves the deposition of insoluble calcium salts in the cutaneous and subcutaneous tissues. On ultrasonography, it specifically presents as hyperechoic deposits with a posterior acoustic shadowing artifact due to the acoustic properties of calcium. A 62-year-old female patient presented with a solitary, skin-colored, palpable nodule on the inner side of the right lower leg. The lesion was beneath the intact skin and detectable only on palpation. However, ultrasonography demonstrated a clear delineation of the lesion, showing hyperechoic deposits with a posterior acoustic shadow (15 MHz, linear probe). Skin biopsy and curettage were performed, revealing histological features consistent with calcinosis cutis. Four weeks after the procedure, ultrasonography performed to evaluate the outcome of treatment, showed recurrence. Another 18-year-old female patient presented with a skin-colored deep-seated nodule on the left temple. On ultrasonography, linear hyperechoic deposits with a posterior acoustic shadow were visible. Skin biopsy was performed, and histopathologic features showed calcified material in the subcutaneous tissue. These two cases of calcinosis cutis highlight the diagnostic value of ultrasonography in dermatology.

Practical Application of Novel Test Methods to Evaluate the Potency of Botulinum Toxin: A Comparison Analysis among Widely Used Products in Korea.

The safe and effective dosing of botulinum neurotoxins (BoNTs) requires accurate and reliable methods to measure their potency. Several novel methods have been introduced over the past decade; however, only few studies have compared the potency of BoNT products with that of the LD50 and other alternative assays. Therefore, the objective of this study was to comparatively evaluate widely used BoNT products using various test methods. Four types of BoNTs (prabotulinumtoxin A, onabotulinumtoxin A, neubotulinumtoxin A, and letibotulinumtoxin A) were used in this study. The estimated potency was assessed using the LD50 assay, and the total BoNT type A protein levels were measured using the enzyme-linked immunosorbent assay (ELISA). The in vitro efficacy of the BoNTs was determined using fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) assays. The results showed differences in the total amount of BoNT protein and the cleavage activity of SNAP-25 within all types of BoNTs. The SPR study seemed to be useful for evaluating the potency by specifically measuring intact 19S neurotoxin, and these results provide new insights for assessing different BoNT products.

Phase I Trial of Intra-arterial Administration of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Patients with Multiple System Atrophy.

BACKGROUND: This study is aimed at investigating the safety and tolerability of the intra-arterial administration of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with multiple system atrophy- (MSA-) cerebellar type (MSA-C). METHODS: This was a single-center, open-label phase I clinical trial in patients with MSA-C. A three-stage dose escalation scheme (low-dose, 3.0 × 105 cells/kg; medium-dose, 6.0 × 105 cells/kg; high-dose, 9.0 × 105 cells/kg) was applied to determine the maximum tolerated dose of intra-arterial administration of BM-MSCs based on the no-observed-adverse-effect level derived from the toxicity study. The occurrence of adverse events was evaluated 1 day before and 1, 14, and 28 days after BM-MSC therapy. Additionally, we assessed changes in the Unified MSA Rating Scale (UMSARS) score 3 months after BM-MSC treatment. RESULTS: One serious adverse drug reaction (ADR) of leptomeningeal enhancement following the intra-arterial BM-MSC administration occurred in one patient in the low-dose group. The safety review of the Internal Monitoring Committee interpreted this as radiological evidence of the blood-brain barrier permeability for MSCs. No other ADRs were observed in the medium- or high-dose groups. In particular, no ischemic lesions on diffusion-weighted images were observed in any of the study participants. Additionally, the medium- and high-dose groups tended to show a slower increase in UMSARS scores than the low-dose group during the 3-month follow-up. CONCLUSION: The present study confirmed that a single intra-arterial administration of autologous BM-MSCs is a safe and promising neuroprotective strategy in patients with MSA-C.

The Impact of SARS-CoV-2 (COVID-19) Pandemic on International Dermatology Conferences in 2020.

To limit the spread of the SARS-CoV-2 (COVID-19) outbreak, humans have been significantly restricted in their ability to travel and interact with others worldwide. Consequently, dermatology conferences were forced to adapt to such changes. The aim of this study is to investigate the impact of COVID-19 on international dermatology conferences. We retrospectively investigated decisions made for international dermatology conferences scheduled for 2020. Thirty-three major conferences were analyzed. Their data were obtained from their respective websites (data was accessed 2 June 2021). Among 33 conferences analyzed, 13 (39.4%) were conducted as scheduled, nine (27.3%) were canceled, eight (24.3%) were postponed to 2021 or 2022, and three (9.1%) were delayed but conducted in 2020. The number of the cancellation (44.4%) and postponement (75%) was the largest in the second quarter of the year. During the fourth quarter, most conferences were held on schedule (70%) but were run virtually. Eight out of 13 virtual conferences shortened their duration (61.5%). Most (90.9%) conferences have decided on the schedule of their meetings for 2021 or 2022 while three (9.1%) remain undecided. Twelve (40%) are planned to run virtually, eight (26.7%) have opted for a hybrid form, five (16.7%) are planned to run in-person, four (13.3%) have not decided on the format, and one (3.3%) has been canceled. Virtual and hybrid conference formats have facilitated people to share knowledge despite the travel restrictions posed by the COVID-19 pandemic. Such formats are environmentally friendly, are able to attract a large audience, and save delegates time and costs involved in attending. Therefore, virtual platforms should continue to be integrated within conferences in the post-pandemic era.

Real-World Three-Year Clinical Outcomes of Biolimus-Eluting Stents versus Other Contemporary Drug-Eluting Stents in Patients with Acute Myocardial Infarction Patients: Data from the Korea Acute Myocardial Infarction Registry (KAMIR).

INTRODUCTION: Biolimus-eluting stents (BES) are known to be superior to bare-metal stents. This study aims to evaluate the safety and efficacy of BES compared to other drug-eluting stents (DES) based on big data from the Korea Acute Myocardial Infarction Registry (KAMIR). METHODS: The study analyzed a total of 9,759 acute myocardial infarction (AMI) patients who underwent percutaneous coronary intervention (PCI) with DES. Total death, cardiac death, recurrent MI, revascularization, stent thrombosis, target lesion failure (TLF, composite of cardiac death, recurrent myocardial infarction (MI), and target lesion revascularization), and major adverse cardiac events (MACE, composite of total death, recurrent MI, and revascularization) were analyzed in patients with AMI up to three years. Study populations were divided into BES (n = 2,020), everolimus-eluting stents (EES, n = 5,293), and zotarolimus-eluting stents (ZES, n = 2,446) groups. RESULTS: To adjust baseline potential confounders, an inverse probability weighting (IPTW) analysis was performed. After IPTW, at three years, total death (7.2%, 8.6%, and 9.5%, P < 0.001), cardiac death (4.1%, 5.3%, and 6.6%, P < 0.001), recurrent MI (1.6%, 2.6%, and 3.2%, P < 0.001), TLF (6.5%, 8.1%, and 9.1%, P < 0.001), and MACE (15.8%, 17.5%, and 18.2%, P < 0.001) were lowest in the BES group compared with the other DES groups in AMI patients. During the 3-year clinical follow-up, the BES group showed better outcomes of MACE (hazard ratio (HR), 0.773; 95% confidence interval (CI), 0.676-0.884; P < 0.001), TLF (HR, 0.659; 95% CI, 0.538-0.808; P < 0.001), total death (HR, 0.687; 95% CI, 0.566-0.835; P < 0.001), and cardiac death (HR,0.593; 95% CI, 0.462-0.541; P < 0.001) than the EES groups. CONCLUSIONS: In this study, BES was superior to EES or ZES in reducing total death, cardiac death, TLF, and MACE in AMI patients.

Early Differentiation of Stress Cardiomyopathy from Acute Anterior Wall Myocardial Using Changing Cardiac Enzyme Patterns.

BACKGROUND: Most patients with acute anterior wall ST elevation myocardial infarction (STEMI) or stress cardiomyopathy (SCMP) show elevations in cardiac enzymes that peak within 24 hours. The changing pattern of cardiac enzymes can be an early clue to the differentiation of anterior STEMI and SCMP. METHODS: This study was a retrospective analysis (matching cases and respective control subjects) performed at a single center. We compared 27 patients with SCMP and 30 patients with anterior STEMI. We used laboratory data included cardiac marker, such as the initial creatine kinase MB (CK-MB) fraction and troponin T (Tn-T), at admission and peak CK-MB and Tn-T at follow up. RESULTS: The mean age was 69.3 ± 14.1 years, and 38.6% of patients were female. The SCMP patients were older, more often female, and had lower left ventricular ejection fractions than the anterior STEMI patients. The initial CK-MB was higher in the anterior STEMI group than in the SCMP group. In contrast, the initial Tn-T level was not significantly different between the 2 groups. Peak CK-MB and Tn-T levels and change from initial levels were significantly greater in the anterior STEMI group than they were in the SCMP group. SCMP could be differentiated from anterior STEMI based on peak CK-MB > 46.65 ng/mL or Tn-T > 1.56 ng/mL. CONCLUSIONS: Follow-up changes in cardiac enzymes can be an effective early tool for differentiating SCMP from anterior STEMI.

Oxygen-generating glycol chitosan-manganese dioxide nanoparticles enhance the photodynamic effects of chlorin e6 on activated macrophages in hypoxic conditions.

This study aimed to investigate the use of glycol chitosan (GC) for the synthesis of MnO2 nanoparticles (NPs) and to evaluate whether the prepared GC-MnO2 NPs enhance the light-triggered photodynamic effects of chlorin e6 (Ce6) via the generation of oxygen and alleviation of hypoxia in lipopolysaccharide (LPS)-activated macrophages (RAW 264.7), which produce excessive amounts of reactive oxygen species (ROS). GC-MnO2 NPs were synthesized by a simple reaction between GC and KMnO4 in water. The prepared GC-MnO2 NPs were spherical in shape, with a mean diameter of approximately 60 nm. The particles effectively generated oxygen via H2O2-induced degradation under hypoxic conditions, which led to an increase in the singlet oxygen levels upon laser irradiation. Furthermore, GC-MnO2 NPs significantly enhanced the light-triggered photodynamic effects of Ce6 on activated macrophages under hypoxic conditions, as shown by the increased levels of cell death and cell membrane damage in activated macrophages. Therefore, these results suggest that GC can be used as an alternative natural polymer for the synthesis of MnO2 NPs and that oxygen-generating GC-MnO2 NPs enhance the light-triggered photodynamic effects of Ce6 on activated macrophages by alleviating hypoxia.