An Integrative Approach to Treat Parkinson's Disease: Ukgansan Complements L-Dopa by Ameliorating Dopaminergic Neuronal Damage and L-Dopa-Induced Dyskinesia in Mice

Parkinson's disease (PD) is accompanied by motor impairments due to the loss of dopaminergic neurons in the nigrostriatal pathway. Levodopa (L-dopa) has been the gold standard therapy for PD since the 1960s; however, its neurotoxic features accelerate PD progression through auto-oxidation or the induction of dyskinetic movements. Ukgansan (UGS) is a well-known prescription for treating PD in traditional medicines of East Asia, and its anti-PD function has been experimentally evaluated. The present study investigated whether UGS attenuates (1) motor dysfunction and dopaminergic neuronal damage when co-treated with L-dopa and (2) L-dopa-induced dyskinesia (LID) in 6-hydroxydopamine (6-OHDA)-induced PD mice. Although L-dopa was found to reduce motor dysfunctions, it failed to decrease the dopaminergic neuronal damage and increased the expression of dopamine receptor 1 (D1R) and 2 (D2R) in the 6-OHDA-injected mouse striatum. Co-treatment with UGS resulted in normal striatal histology and ameliorated motor impairments. In addition, UGS suppressed the dyskinesia induced by chronic L-dopa treatment while restoring the dopaminergic neurons in the striatum. For the underlying mechanism, UGS reduced the overexpression of D1R-related signaling proteins, such as phosphorylated extracellular signal-regulated kinase, ΔFosB, and c-fos in the striatum. Overall, the results suggest that the effect of UGS could be complementary to L-dopa by ameliorating motor dysfunction, restoring the dopaminergic neurons, and suppressing the dyskinetic movements in PD

Application of photodynamic therapy in gastrointestinal disorders: an outdated or re-emerging technique?

Photodynamic therapy (PDT) is a promising therapeutic modality that involves the administration of a photosensitizer followed by local illumination with a specific wavelength of light in the presence of oxygen. PDT is minimally invasive, has high selectivity for cancer, and has good patient compliance due to the simplicity of the procedure; therefore, PDT is widely used as a palliative and salvage treatment in patients with various gastrointestinal malignancies. When used as a salvage treatment for locoregional failures after definitive chemoradiotherapy for esophageal cancer, favorable results have been reported. PDT in conjunction with biliary stenting is a promising palliative treatment for unresectable cholangiocarcinoma, and can be used as an advanced diagnostic and therapeutic strategy in peritoneal dissemination of gastric cancer. Recent clinical reports of PDT for treating non-resectable pancreatic cancer also show promising results. To widen the application of PDT, the integration of PDT with molecular imaging and nanotechnology is being extensively studied. Based on these new developments, PDT is likely to re-emerge as a valuable technique in the treatment of diverse gastrointestinal diseases

Luciferase-Rose Bengal Conjugates for Single Oxygen Generation by Bioluminescence Resonant Energy Transfer

Conjugates of Rose Bengal and Renilla luciferase generated singlet oxygen upon binding with coelenterazine via bioluminescence resonance energy transfer (BRET). Since the applications of conventional PDT have been limited to superficial lesions due to the limited light penetration in tissue, BRET activated PDT which does not require external light illumination may overcome the limitations of conventional PDT.115Ysciescopu

Accuracy of Administrative Claim Data for Gastric Adenoma After Endoscopic Resection

BACKGROUND/AIMS: Administrative databases provide valuable information for large-cohort studies. This study aimed to evaluate the diagnostic accuracy of an administrative database for resected gastric adenomas. METHODS: Data of patients who underwent endoscopic resection for benign gastric lesions were collected from three hospitals. Gastric adenoma cases were identified in the hospital database using International Classification of Diseases (ICD) 10-codes. The non-adenoma group included patients without gastric adenoma codes. The diagnostic accuracy for gastric adenoma was analyzed based on the pathological reports of the resected specimen. RESULTS: Among 5,095 endoscopic resections with codes for benign gastric lesions, 3,909 patients were included in the analysis. Among them, 2,831 and 1,078 patients were allocated to the adenoma and non-adenoma groups, respectively. Regarding the overall diagnosis of gastric adenoma with ICD-10 codes, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.7%, 88.5%, 95.2%, and 96.8%, respectively. There were no significant differences in these parameters between the tertiary and secondary centers. CONCLUSION: Administrative codes of gastric adenoma, according to ICD-10 codes, showed good accuracy and can serve as a useful tool to study prognosis of these patients in real-world data studies in the future

Dramatic reduction of distant pancreatic metastases using local light activation of verteporfin with nab-paclitaxel

Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metastases at the time of diagnosis. Treatment strategies geared towards reclassifying these patients as surgical candidates by reducing metastatic burden represents the most promising approach to improve long-term survival. We describe a photodynamic therapy (PDT) based approach that, in combination with the first-line chemotherapeutic nab-paclitaxel, effectively addresses distant metastases in three separate orthotopic PDAC models in immunodeficient mice. In addition to effectively controlling local tumor growth, PDT plus nab-paclitaxel primes the tumor to elicit systemic effects and reduce or abrogate metastases. This combination dramatically inhibits (up to 100%) the eventual development of metastases in models of early stage PDAC, and completely eliminates metastasis in 55% of animals with already established distant disease in late-stage models. Our findings suggest that this light activation process initiates local biological and/or physiological changes within the tumor microenvironment that can be leveraged to treat both localized and distant disease, and potentially reclassify patients with previously inoperable disease as surgical candidates

The Effect of Intervention for Improving Colonoscopy Quality Is Associated with the Personality Traits of Endoscopists

BACKGROUND/AIMS: This study investigated whether the personality traits of endoscopists are associated with the effect of interventions for the improvement of colonoscopy quality. METHODS: This prospective, multicenter, single-blind study was performed with 13 endoscopists in three health screening centers over a 12-month period. Quality indicators (QIs), including adenoma detection rate (ADR), polyp detection rate (PDR), and withdrawal time, were measured every 3 months. Consecutive interventions for the improvement of colonoscopy quality were conducted every 3 months, which included the personal notification of QIs, the in-group notification of QIs, and finally a targeted quality education session. The personality traits of each endoscopist were evaluated for perfectionism, fear of negative evaluation, and cognitive flexibility after the last QI assessment. RESULTS: A total of 4,095 colonoscopies were evaluated to measure the QIs of the individual endoscopists for 12 months. The mean ADR, PDR, and withdrawal time of the 13 endoscopists were 32.3%, 47.7%, and 394 seconds at baseline and increased to 39.0%, 55.1%, and 430 seconds by the end of the study (p=0.003, p=0.006, and p=0.004, respectively). Among the three interventions, only quality education significantly improved QIs: ADR, 36.0% to 39.0% (odds ratio, 1.28; 95% confidence interval, 1.01 to 1.63). The improvement of ADR and PDR by education was significantly associated with perfectionism (r=0.617, p=0.033 and r=0.635, p=0.027, respectively) and fear of negative evaluation (r=0.704, p=0.011 and r=0.761, p=0.004, respectively). CONCLUSIONS: Education can improve colonoscopy quality, and its effect size is associated with an endoscopist\u27s personal traits such as perfectionism and fear of negative evaluation (Clinical-Trials.gov Registry NCT03796169)

Optimized-SopungSunkiwon, a Herbal Formula, Attenuates A β

Alzheimer’s disease (AD), the most common form of dementia, is an age-related neurodegenerative disease that is characterized by memory dysfunction, neuronal cell damage, and neuroinflammation. It is believed that AD-related pathology is mostly due to the overproduction of Aβ, especially the oligomeric form (AβO), in the brain. Evidence of the effects of multifunctional medicinal herbs in the treatment of AD has been steadily increasing. Optimized-SopungSunkiwon (OSS), a multiherbal formulation that is composed of six medicinal herbs derived from SopungSunkiwon, is a traditional medicine that is prescribed for neurodegenerative disorders in elderly patients. We previously reported that OSS showed an antiamnesic and memory enhancing effect in mice, but it is unknown whether OSS has a protective effect against AβO neurotoxicity. In this study, we investigated the effects of OSS in AD models induced by AβO in vitro and in vivo. We found that OSS protected neuronal cells and inhibited the generation of nitric oxide and reactive oxygen species against AβO toxicity in vitro. These results were confirmed by in vivo data that oral administration of OSS for 14 days attenuated memory impairments and neuronal cell death by modulating gliosis, glutathione depletion, and synaptic damage in the mouse hippocampus induced by AβO

The Defined TLR3 Agonist, Nexavant, Exhibits Anti-Cancer Efficacy and Potentiates Anti-PD-1 Antibody Therapy by Enhancing Immune Cell Infiltration

Nexavant was reported as an alternative to the TLR3 agonist of Poly(I:C) and its derivatives. The physicochemical properties, signaling pathways, anti-cancer effects, and mechanisms of Nexavant were investigated. The distinctive characteristics of Nexavant compared to that of Poly(I:C) were demonstrated by precise quantification, enhanced thermostability, and increased resistance to RNase A. Unlike Poly(I:C), which activates TLR3, RIG-I, and MDA5, Nexavant stimulates signaling through TLR3 and RIG-I but not through MDA5. Compared to Poly(I:C), an intratumoral Nexavant treatment led to a unique immune response, immune cell infiltration, and suppression of tumor growth in various animal cancer models. Nexavant therapy outperformed anti-PD-1 antibody treatment in all the tested models and showed a synergistic effect in combinational therapy, especially in well-defined cold tumor models. The effect was similar to that of nivolumab in a humanized mouse model. Intranasal instillation of Nexavant led to the recruitment of immune cells (NK, CD4+ T, and CD8+ T) to the lungs, suppressing lung metastasis and improving animal survival. Our study highlighted Nexavant’s defined nature for clinical use and unique signaling pathways and its potential as a standalone anti-cancer agent or in combination with anti-PD-1 antibodies

Factors Affecting Endoscopic Curative Resection of Gastric Cancer in the Population-Based Screening Era

Background/Aims Since population-based screening for gastric cancer in Korea was implemented, endoscopic treatment of early gastric cancer has become increasingly popular. This study investigates factors affecting endoscopic curative resection of early gastric cancer in population-based screening for gastric cancer. Methods We retrospectively reviewed data of patients with newly diagnosed gastric cancer who underwent treatment at Seoul St. Mary’s Hospital. All patients completed questionnaires about clinical information, including interval between surveillance tests for gastric cancer. Results Of 469 gastric cancer patients, 147 (31.3%) had undergone curative endoscopic resection, 260 (55.4%) had undergone curative surgical resection, and 62 (13.3%) underwent non-curative resection or were in an inoperable state. Patients with curative endoscopic resection had fewer alarm symptoms/signs than other groups. In multivariate analysis, regular surveillance endoscopy was the only factor predicting curative endoscopic resection (odds ratio [OR], 6.099; 95% confidence interval [CI], 2.532–14.933). In addition, patients undergoing gastric cancer screening had a significantly higher rate of endoscopic curative resection compared with subjects who had never been screened. (1-year interval: OR, 49.969; 95% CI, 6.340–393.827, 2-year interval: OR, 15.283; 95% CI, 1.833–127.406, over 2-year interval: OR, 10.651; 95% CI, 1.248–90.871). Shorter screening test intervals were associated with higher rates of endoscopic curative resection. Conclusions Regular surveillance testing was the independent factor predicting curative endoscopic resection of gastric cancer