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Overcoming melanin interference in melanocyte photodynamic therapy with a pyrene-derived two-photon photosensitizer
No full textPhotodynamic therapy (PDT) is primarily applied in the treatment of skin diseases. However, conventional PDT is less effective for melanoma, a type of skin cancer that contains melanin pigment, due to melanin's broad absorption spectrum in the ultraviolet–visible region. This reduces the effectiveness of traditional photosensitizers (PSs) in PDT. Here, we introduced pyrene based two-photon (TP) PSs that are easy to synthesize. Among the π-extended pyrene derivatives, we have confirmed the synergetic generation of reactive oxygen species (ROS) with asymmetric pyrene (Py3). We proposed a mechanism explaining the higher ROS generation efficiency of Py3 compared with that of the symmetric derivatives through theoretical calculations. Py3 effectively stains the plasma membrane of melanoma cells and demonstrates superior PDT efficacy compared with Chlorin e6. As the melanin content increases in melanoma cells, cell death significantly decreases under visible light excitation; notably, it is minimally affected by TP irradiation at 750 nm. In 3D multicellular tumor spheroids with a high melanin content, Py3 showed high PDT efficacy through TP irradiation, whereas under visible light irradiation, PDT efficacy decreased. In experiments involving the injection of Py3 into the tail of mice with B16F10 and 4 T1 tumor models, followed by TP-PDT, we observed significant inhibition of tumor growth and high biocompatibility. Our results indicate a promising TP-PDT method for treating melanomas
Analysis of the spatial and morphological characteristics of oligodendrocytes from images of in vitro culture
No full textOligodendrocytes (OLs) are glial cells responsible for the formation of myelin sheaths in the central nervous system. The characteristic features of the oligodendrocyte lineage, ranging from proliferative and migratory oligodendrocyte progenitor cells (OPC) to myelinating mature OLs, can be observed in vitro cultures of OL lineage cells. Here, we introduce a method for analyzing the spatial distribution of OPCs, which reflects their capacity for proliferation and migration, and the morphological complexity of mature OLs, which reflects their capacity for myelin formation, from immunostaining images of in vitro OL cultures. Through the methods described, we have demonstrated the tendency for OPCs to cluster in an environment with epidermal growth factor (EGF), and the differing morphological complexity of mature OLs according to culture medium and duration of differentiation. • The proliferative and migratory characteristics of OPCs can be evaluated by analyzing their spatial distribution. • The myelin-forming capacity of mature OLs can be measured by analyzing their morphological complexity. • Image-based analyses may be a substitute for more convoluted experiments to assess OL function
3D Bioprinting Strategies for Articular Cartilage Tissue Engineering
No full textArticular cartilage is the avascular and aneural tissue which is the primary connective tissue covering the surface of articulating bone. Traumatic damage or degenerative diseases can cause articular cartilage injuries that are common in the population. As a result, the demand for new therapeutic options is continually increasing for older people and traumatic young patients. Many attempts have been made to address these clinical needs to treat articular cartilage injuries, including osteoarthritis (OA); however, regenerating highly qualified cartilage tissue remains a significant obstacle. 3D bioprinting technology combined with tissue engineering principles has been developed to create biological tissue constructs that recapitulate the anatomical, structural, and functional properties of native tissues. In addition, this cutting-edge technology can precisely place multiple cell types in a 3D tissue architecture. Thus, 3D bioprinting has rapidly become the most innovative tool for manufacturing clinically applicable bioengineered tissue constructs. This has led to increased interest in 3D bioprinting in articular cartilage tissue engineering applications. Here, we reviewed current advances in bioprinting for articular cartilage tissue engineering
Clinician-Driven Reanalysis of Exome Sequencing Data From Patients With Inherited Retinal Diseases
Get PDFImportance: Despite advances in next-generation sequencing (NGS), a significant proportion of patients with inherited retinal disease (IRD) remain undiagnosed after initial genetic testing. Exome sequencing (ES) reanalysis in the clinical setting has been suggested as one method for improving diagnosis of IRD. Objective: To investigate the association of clinician-led reanalysis of ES data, which incorporates updated clinical information and comprehensive bioinformatic analysis, with the diagnostic yield in a cohort of patients with IRDs in Korea. Design, Setting, and Participants: This was a multicenter prospective cohort study involving 264 unrelated patients with IRDs, conducted in Korea between March 2018 and February 2020. Comprehensive ophthalmologic examinations and ES analyses were performed, and ES data were reanalyzed by an IRD specialist for single nucleotide variants, copy number variants, mobile element insertions, and mitochondrial variants. Data were analyzed from March to July 2023. Main Outcomes and Measures: Diagnostic rate of conventional bioinformatic analysis and clinician-driven ES reanalysis. Results: A total of 264 participants (151 [57.2%] male; mean [SD] age at genetic testing, 33.6 [18.9] years) were enrolled, including 129 patients (48.9%) with retinitis pigmentosa and 26 patients (9.8%) with Stargardt disease or macular dystrophy. Initial bioinformatic analysis diagnosed 166 patients (62.9%). Clinician-driven reanalysis identified the molecular cause of diseases in an additional 22 patients, corresponding to an 8.3-percentage point increase in diagnostic rate. Key factors associated with new molecular diagnoses included clinical phenotype updates (4 patients) and detection of previously overlooked variation, such as structural variants (9 patients), mitochondrial variants (3 patients), filtered or not captured variants (4 patients), and noncanonical splicing variants (2 patients). Among the 22 patients, variants in 7 patients (31.8%) were observed in the initial analysis but not reported to patients, while those in the remaining 15 patients (68.2%) were newly detected by the ES reanalysis. Conclusions and Relevance: In this cohort study, clinician-centered reanalysis of ES data was associated with improved molecular diagnostic yields in patients with IRD. This approach is important for uncovering missed genetic causes of retinal disease
Facial Telangiectasia as an Initial Notable Symptom of Systemic Sclerosis
No full textSystemic sclerosis (SSc), also called scleroderma, is a rare debilitating autoimmune disease of the connective tissue characterized by microvascular damage, specific immunologic abnormalities, and progressive fibrosis of the skin and internal organs. The disease may be associated with serious visceral complications involving the pulmonary, gastrointestinal, cardiac and renal systems, why early identification is important. Cutaneous telangiectasia was originally one of the diagnostic criteria of the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias), and is now included in the 2013 American College of Rheumatology/European League Against Rheumatism criteria for the diagnosis of SSc. We report herein three cases of SSc who presented our department for telangiectasia, because eruptive telangiectasia on exposed area associated with high titer of antinuclear antibody could be the first sign of SSc
Diagnosis of suprascapular nerve entrapment syndrome based on the infraspinatus muscle cross-sectional area on shoulder MRI
No full textSuprascapular nerve entrapment (SNE) syndrome is a commonly overlooked cause of shoulder weakness and pain. It frequently causes weakness over the posterior and lateral and posterior aspects of the shoulder, as well as pain of infraspinatus muscles. Therefore, we considered that the infraspinatus muscle cross-sectional area (IMCSA) might be a new morphological parameter to analyze SNE syndrome. We assumed that the IMCSA is an important morphologic parameter in SNE syndrome diagnosis. We acquired infraspinatus muscle data from 10 patients with SNE syndrome and from 10 healthy subjects who had undergone magnetic resonance imaging of the shoulder and who revealed no evidence of SNE syndrome. We analyzed the infraspinatus muscle thickness (IMT) and IMCSA at the shoulder on the imaging of the shoulder using our image analysis program. The IMCSA was measured as the whole infraspinatus muscle cross-sectional area that was most atrophied in the sagittal S-MR images. The IMT was measured as the thickest level of infraspinatus muscle. The mean IMT was 29.17 ± 2.81 mm in the healthy subjects and 25.22 ± 3.19 mm in the SNE syndrome group. The mean IMCSA was 1321.95 ± 175.91 mm2 in the healthy group and 1048.38 ± 259.94 mm2 in the SNE syndrome group. SNE syndrome patients had significantly lower IMT (P < .001) and IMCSA (P < .001) than the healthy group. The ROC curve shows that the optimal cutoff point of the IMT was 26.74 mm, with 70.0% sensitivity, 70.0% specificity, and an AUC of 0.83 (95% CI, 0.65-1.00). The best cutoff value of the IMCSA was 1151.02 mm2, with 80.0% sensitivity, 80.0% specificity, and AUC of 0.87 (95% CI, 0.69-1.00). The IMT and IMCSA were both significantly associated with SNE syndrome. And the IMCSA was a highly sensitive diagnostic tool
The effect of human albumin administration on postoperative renal function following major surgery: a systematic review and meta-analysis
Get PDFOptimal fluid management during major surgery is of considerable concern to anesthesiologists. Although crystalloids are the first choice for fluid management, the administration of large volumes of crystalloids is associated with poor postoperative outcomes. Albumin can be used for fluid management and may protect renal function. However, data regarding the effects of albumin administration on kidney function are conflicting. As such, the present study aimed to investigate the effect of albumin administration on renal function in patients undergoing major surgery and compare its effects with those of crystalloid fluid. The Embase, Medline, Web of Science, Cochrane Library, and KoreaMed databases were searched for relevant studies. The primary endpoint of the meta-analysis was the incidence of postoperative kidney injury, including acute kidney injury and renal replacement therapy. Twelve studies comprising 2311 patients were included; the primary endpoint was analyzed in four studies comprising 1749 patients. Perioperative albumin levels in patients undergoing major surgery did not significantly influence kidney dysfunction (p = 0.98). Postoperative fluid balance was less positive in patients who underwent major surgery and received albumin than in those who received crystalloids. Owing to the limitations of this meta-analysis, it remains unclear whether albumin administration during major surgery is better than crystalloid fluid for improving postoperative renal function
Decision regret after prostate biopsy for prostate cancer diagnosis: a Korean multicenter cohort study
Get PDFBackground: Many people struggle with the choice in a series of processes, from prostate cancer (PCa) diagnosis to treatment. We investigated the degree of regret after the prostate biopsy (PBx) and relevant factors in patients recommended for biopsy for suspected PCa. Methods: From 06/2020 to 05/2022, 198 people who performed PBx at three institutions were enrolled and analyzed through a questionnaire before and after biopsy. Before the biopsy, a questionnaire was conducted to evaluate the sociodemographic information, anxiety scale, and health literacy, and after PBx, another questionnaire was conducted to evaluate the decision regret scale. For patients diagnosed as PCa after biopsy, a questionnaire was conducted when additional tests were performed at PCa staging work-up. Results: 190 patients answered the questionnaire before and after PBx. The mean age was 66.2 ± 7.8 years. Overall, 5.5% of men regretted biopsy, but there was no significant difference between groups according to the PCa presence. Multivariate analysis, to identify predictors for regret, revealed that the case when physicians did not properly explain what the prostate-specific antigen (PSA) test was like and what PSA elevation means (OR 20.57, [95% CI 2.45–172.70], p = 0.005), low media literacy (OR 10.01, [95% CI 1.09–92.29], p = 0.042), and when nobody to rely on (OR 8.49, [95% CI 1.66–43.34], p = 0.010) were significantly related. Conclusions: Overall regret related to PBx was low. Decision regret was more significantly related to media literacy rather than to educational level. For patients with relatively low media literacy and fewer people to rely on in case of serious diseases, more careful attention and counseling on PBx, including a well-informed explanation on PSA test, is helpful
Survival and Risk Factors for Mortality in Infants With Congenital Heart Disease in South Korea
Get PDFBackground/Aim: The survival of patients with congenital heart disease (CHD) has dramatically improved over recent decades. However, a disparity exists depending on the country and medical system. This study aimed to analyze the survival of infants with CHD until the age of 18 years using large-scale population data in South Korea and investigate the effect of neonatal conditions at birth. Patients and Methods: We retrospectively extracted the Korean National Health Insurance Service claims data from January 2002 to December 2020. We included patients diagnosed with CHD who were less than one year of age. The follow-up duration was until their death or until they were censored before the age of 18 years. The CHD lesions were classified hierarchically (conotruncal, severe non-conotruncal, coarctation of the aorta, ventricular septal defect, atrial septal defect, and others). Several neonatal conditions were adopted as risk factors. Results: Overall, 127,958 infants had been diagnosed with CHD and 2,275 died before the age of 18 years. The survival rate of infants with CHD during childhood was 97.9%. The highest childhood mortality rate was associated with non-conotruncal defects (19.7%), followed by conotruncal defects (10.2%). The significant risk factors for childhood mortality were complex CHD, pulmonary hypertension, birth asphyxia, small for gestational age, respiratory distress, pulmonary hemorrhage, bronchopulmonary dysplasia, and convulsions. Conclusion: The survival of infants with CHD has been favorable in South Korea. Several neonatal conditions are risk factors for childhood mortality. Individualized risk assessment and optimal treatment strategies may help improve their survival rate
Effect of Pravastatin on Kidney Function in Patients with Dyslipidemia and Type 2 Diabetes Mellitus: A Multicenter Prospective Observational Study
Get PDFIntroduction: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice. Methods: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety. Results: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30–90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks. Conclusion: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. Trial Registration Number: NCT05107063 submitted October 27, 2021