Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Purpose: The adjusted Global Antiphospholipid Syndrome (APS) Score (aGAPSS) was developed for assessing the probability of thrombotic events in APS patients. This study investigated whether the aGAPSS at diagnosis was associated with poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Materials and Methods: This study included 170 AAV patients who had the results of APS-related antibodies at diagnosis but were not diagnosed with APS. All-cause mortality, end-stage kidney disease (ESKD), cerebrovascular accident, and acute coronary syndrome were considered poor AAV outcomes. The aGAPSS comprises five items, with 5, 4, 4, 3, and 1 points assigned to anticardiolipin antibodies, anti-β2-glycoprotein 1 antibodies, lupus anticoagulants, hyperlipidaemia, and arterial hypertension at AAV diagnosis, respectively. Results: The median age of the 170 patients [93 microscopic polyangiitis (MPA), 44 granulomatosis with polyangiitis (GPA), and 33 eosinophilic GPA (EGPA)] was 63.0 years. The optimal cut-off of the aGAPSS at diagnosis for ESKD during follow-up was set as two using the receiver operating characteristic curve. AAV patients with an aGAPSS ≥2 at diagnosis exhibited a significantly reduced ESKD-free survival rate compared to those with an aGAPSS <2 at diagnosis (p=0.045). Additionally, MPA and GPA patients, excluding EGPA patients for whom the median aGAPSS at diagnosis was close to 0, also showed similar patterns to the results among the 170 patients with AAV (p=0.021). Conclusion This study is the first to demonstrate that the aGAPSS at diagnosis was significantly associated with ESKD during follow-up in AAV patients without APS.

Purpose: The immunological response and adverse effects of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients receiving coronavirus disease-2019 (COVID-19) vaccines remain unclear. We aimed to evaluate the effects of these vaccines on AAV disease activity. Materials and Methods: We reviewed the medical records of 52 patients with AAV who had received at least second doses of the COVID-19 vaccine and evaluated their immunogenicity by measuring the anti-spike (S) antibody (Ab) titer levels using the Roche Elecsys® immunoassay. Responses to the Birmingham Vasculitis Activity Score (BVAS) tool and 36-Item Short Form Survey before and after vaccination were obtained to assess AAV disease activity. Vaccine reactivity was measured using a standardized questionnaire. Results: We enrolled 52 patients with AAV. No differences were found between those who received second and third doses of vaccination in terms of AAV type, disease activity, vaccine type, or the use of immunosuppressive agents, including steroids. The median anti-S Ab titer was 3967.0 after third doses compared to 419.0 after second doses (p=0.001). Except for mycophenolate mofetil (MMF), when immunosuppressants were administered in conjunction with steroids, the Ab titer was higher after the third vaccination than that after the second dose. The BVAS remained unchanged before and after second and third doses. No life-threatening adverse events were reported. Conclusion Although COVID-19 vaccine may not produce sufficient antibodies in patients taking MMF, the vaccine did not exacerbate disease activity or cause severe side effects. Therefore, COVID-19 vaccines should be considered in patients with AAV.

Purpose: Hair disorders, which are often attributed to conditions associated with a shortened anagen growth phase, oxidative stress, and hormonal dysregulation, especially during aging, have profound psychological implications. Currently, only minoxidil has been approved as a topical hair growth solution; thus, alternative therapies for treating hair loss and promoting hair health are urgently needed. Herein, we aimed to develop and assess a novel method to promote hair growth and health using mastic (Pistacia lentiscus) gum and peppermint (Mentha piperita L.) extracts. Materials and Methods: After determining the optimal ratio of mastic gum and peppermint extracts, we performed in vitro and in vivo experiments to verify the efficacy of the 7:3 mastic gum-peppermint mixture (MP73; FHH-MG) for enhancing hair growth and health. Results: Mastic gum significantly promoted cell proliferation and demonstrated synergistic benefits when combined with peppermint extract. In vitro, FHH-MG increased human dermal follicle papilla cell proliferation and demonstrated anti-inflammatory and antioxidant effects. In vivo, treatment with FHH-MG dose-dependently enhanced hair growth and gloss and increased the expression of vascular endothelial growth factor, epidermal growth factor, β-catenin, and insulin-like growth factor-1 in C57BL/6 mice compared to the negative control. Conclusion The novel mixture exhibited hair growth-promoting effects in C57BL/6 mice; thus, FHH-MG may serve as a botanical alternative for hair growth and health promotion.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Methods: Twelve consecutive patients underwent single-level BELIF for lumbar degenerative disease. The technique involves two small portals, one each for endoscopy and instruments. A large PEEK cage was inserted through a posterolateral approach. Clinical outcomes, including a Visual Analog Scale for back and leg pain, the Oswestry Disability Index, and the European Quality of Life-5 Dimensions, were assessed preoperatively and at 3, 6, and 12 months postoperatively. Fusion status was evaluated using computed tomography (CT) at 12 months. Results: The mean patient age was 69.1±7.2 years, with operations predominantly at the L4–5 level (83%). The mean operation time was 149.7±37.4 minutes, and the average surgical drainage was 201.4±59.7 mL. All clinical outcome measures showed significant improvement at 12 months (p<0.05). Fusion was achieved in 83.3% of patients. Cage subsidence (>1 mm) occurred in one patient (8.3%). Complications included one case each of incidental durotomy, wrong-site surgery, and wound dehiscence and three cases of asymptomatic hematoma. Conclusions BELIF using a large PEEK cage demonstrated promising clinical outcomes and fusion rates. The technique offers enhanced visualization and enables direct neural decompression while minimizing tissue trauma. The use of a large PEEK cage may contribute to improved stability and reduced subsidence risk.

Biportal endoscopic spinal surgery (BESS) with interbody fusion is a relatively novel minimally invasive technique that was developed to reduce soft tissue trauma and intraoperative blood loss and shorten recovery time while achieving comparable clinical outcomes for lumbar degenerative diseases. Despite the growing interest in BESS, a comprehensive analysis of its effectiveness, complication rates, and long-term outcomes remains lacking. This systematic review evaluated the clinical outcomes, surgical efficacy, and complication rates of BESS with interbody fusion for lumbar degenerative diseases. Recent literature on endoscopic lumbar interbody fusion was included to expand the scope and gain new perspectives, thereby, providing a comparative analysis that highlighted the advantages, limitations, and emerging trends in minimally invasive spine surgery. This review synthesized current evidence to guide future research and clinical applications. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and using a combination of MeSH (Medical Subject Headings) terms and relevant keywords, PubMed/Medline and Scopus databases were systematically searched for studies published between January 2000 and September 2024. The studies were assessed using the ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) tool to determine the risk of bias. From the 12 studies that provided clinical evidence, the data extracted were patient demographics; operative time; blood loss; clinical outcomes, such as Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores and fusion rates; and complications. The mean operative time ranged from 98 to 206 minutes, with fusion rates between 70% and 95%. Most studies reported significant improvements in VAS scores for back and leg pain and ODI scores. Complications, including dural tears (2.9%–6.4%) and hematomas (1.4%–4.3%), were infrequent but notable. BESS with interbody fusion demonstrated excellent clinical outcomes, high fusion rates, and few complications. Although these results are promising, more randomized controlled trials and long-term studies are required to confirm the broader applicability, particularly in more complex or multilevel spinal pathologies.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.