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Background and Objectives: With increases in cancer incidence and the number of cancer survivors, the demand for cancer management is growing. However, studies on dental prosthetic treatment for patients with cancer are rare. We aim to investigate the dental prosthetic treatment in patients with cancer aged ≥65 years after expanded health insurance coverage. Materials and Methods: This retrospective study included patients who were treated with implants and removable dentures at Ulsan University Hospital in South Korea between June 2015 and June 2023. Data on age, sex, cancer location, comorbid systemic diseases, number of remaining teeth, dental prosthetic treatment history, type of dental prosthetic treatment, and insurance coverage status were extracted from patient medical records and panoramic radiographs. The influence of multiple variables on dental prosthetic treatment was analyzed using the Chi-square and Fisher's exact tests. Results: The study included 61 patients with cancer (32 men, 29 women; average age: 70.9 years). Among them, 56 (91.8%) had insurance coverage benefits, and 34 (55.7%) received treatments such as implants, removable partial dentures, or complete dentures for the first time. Treatment types included 37 (60.7%) cases of implant prostheses and 24 (39.3%) conventional removable dentures. No statistical differences were observed in the type of dental prosthetic treatment according to sex, age, cancer location, number of systemic diseases, and dental prosthetic treatment history (p > 0.05). Patients with <10 remaining teeth received treatment with conventional removable dentures, which was statistically significant (p < 0.001). Conclusions: Of the 61 patients, 56 (91.8%) received insurance benefits, and 34 (55.7%) underwent dental prosthetic treatment for the first time. Within the limitations of this retrospective study, the expanded health insurance coverage alleviated the unmet demand for dental prosthetic treatment. As cancer prevalence continues to increase, expanding customized health insurance coverage is crucial to meet this demand. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fifth most common cause of cancer-related death worldwide. Early detection is crucial for improving survival rates and treatment outcomes. However, accurate GC-specific biomarkers remain unknown. This study aimed to identify the metabolic differences between intestinal metaplasia (IM) and GC to determine the pathways involved in GC. A metabolic analysis of IM and tissue samples from 37 patients with GC was conducted using ultra-performance liquid chromatography with tandem mass spectrometry. Overall, 665 and 278 significant features were identified in the aqueous and 278 organic phases, respectively, using false discovery rate analysis, which controls the expected proportion of false positives among the significant results. sPLS-DA revealed a clear separation between IM and GC samples. Steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and arginine and proline metabolism were the most significantly altered pathways. The intensity of 11 metabolites, including N1, N2-diacetylspermine, creatine riboside, and N-formylkynurenine, showed significant elevation in more advanced GC. Based on pathway enrichment analysis and cancer stage-specific alterations, we identified six potential candidates as diagnostic biomarkers: aldosterone, N-formylkynurenine, guanosine triphosphate, arginine, S-adenosylmethioninamine, and creatine riboside. These metabolic differences between IM and GC provide valuable insights into gastric carcinogenesis. Further validation is needed to develop noninvasive diagnostic tools and targeted therapies to improve the outcomes of patients with GC. [ABSTRACT FROM AUTHOR]

Introduction: Basicervical femoral neck fracture (FNF) is an uncommon type of femoral neck fracture and is associated with an increased risk of fixation failure due to its inherent instability. The purpose of this study was to compare the surgical parameters and reoperation rate between the use of a multiple cannulated screw (MCS) and fixed angle device (FAD) in treating basicervical FNFs. Methods: We retrospectively reviewed the records of 885 patients who underwent internal fixation between May 2004 and August 2019 to determine basicervical FNF with at least 12 months of follow-up. Among the identified 77 patients with basicervical FNF, 17 patients who underwent multiple cannulated screw (MCS) fixation and 36 patients who underwent fixed angle device (FAD) fixation were included. We compared the rates of fracture-site collapse and reoperations according to the fixation device. Results: Among the 53 patients with basicervical FNF, 13 patients (24.5%) sustained surgical complications (8 collapses of fracture site and 5 reoperations). The reoperation rate in the MCS group was significantly higher than that in the FAD group (23.5% vs. 2.8%, p = 0.016), without any significant difference in the collapse of the fracture site (11.8% vs. 16.7%, p = 0.642). Conclusions: Although basicervical FNF was rare among hip fractures, fracture site collapse was prevalent and prone to fixation failure. Surgeons should keep this in mind, and consider FAD for basicervical FNF. [ABSTRACT FROM AUTHOR]

Gastritis, one of the most common gastrointestinal disorders, damages the stomach lining as it causes a disproportion between the protective and ruinous factors of the gastric system. Cabbage (CB) is widely used to treat gastric lesions but requires the addition of natural sweeteners to counteract its distinct bitter taste. Therefore, this study sought to determine whether the combination of chestnut honey (CH)—which is known for its dark brown color and high kynurenic acid (KA) content—or KA-increased CH (KACH) with CB (CH + CB or KACH + CB) exerts synergistic effects for improving both taste and efficacy. Before confirming the gastroprotective effects in indomethacin (INDO)-induced rats, the anti-inflammatory activities of CH + CB and KACH + CB were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. As a result, treatment with either CH + CB or KACH + CB downregulated pro-inflammatory cytokine levels in LPS-stimulated RAW 264.7 macrophages by regulating the translocation of nuclear factor kappa B. Furthermore, both CH + CB and KACH + CB not only enhanced the levels of antioxidant enzymes but also triggered the activation of nuclear factor erythroid-related factor 2. Based on these effects, CH + CB or KACH + CB effectively protected the gastric mucosa in INDO-induced rats. Therefore, this study suggests that CH + CB and KACH + CB exert stronger gastroprotective effects when used together. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is characterized by a poor prognosis, with its five-year survival rate lower than that of any other cancer type. Gemcitabine, a standard treatment for pancreatic cancer, often has poor outcomes for patients as a result of chemoresistance. Therefore, novel therapeutic targets must be identified to overcome gemcitabine resistance. Here, we found that SLC38A5, a glutamine transporter, is more highly overexpressed in gemcitabine-resistant patients than in gemcitabine-sensitive patients. Furthermore, the deletion of SLC38A5 decreased the proliferation and migration of gemcitabine-resistant PDAC cells. We also found that the inhibition of SLC38A5 triggered the ferroptosis signaling pathway via RNA sequencing. Also, silencing SLC38A5 induced mitochondrial dysfunction and reduced glutamine uptake and glutathione (GSH) levels, and downregulated the expressions of GSH-related genes NRF2 and GPX4. The blockade of glutamine uptake negatively modulated the mTOR-SREBP1-SCD1 signaling pathway. Therefore, suppression of SLC38A5 triggers ferroptosis via two pathways that regulate lipid ROS levels. Similarly, we observed that knockdown of SLC38A5 restored gemcitabine sensitivity by hindering tumor growth and metastasis in the orthotopic mouse model. Altogether, our results demonstrate that SLC38A5 could be a novel target to overcome gemcitabine resistance in PDAC therapy. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of pancreatic cancer with a poor prognosis and low survival rates. The prognostic and predictive biomarkers of PDAC are still largely unknown. The receptor CD74 was recently identified as a regulator of oncogenic properties in various cancers. However, the precise molecular mechanism of CD74 action in PDAC remains little understood. We investigated the role of CD74 by silencing CD74 in the pancreatic cancer cell line Capan-1. CD74 knockdown led to reductions in cell proliferation, migration, and invasion and increased apoptosis. Moreover, silencing CD74 resulted in the decreased expression and secretion of S100A8 and S100A9. An indirect co-culture of fibroblasts and tumor cells revealed that fibroblasts exposed to conditioned media from CD74 knockdown cells exhibited a reduced expression of inflammatory cytokines, suggesting a role of CD74 in influencing cytokine secretion in the tumor microenvironment. Overall, our study provides valuable insights into the critical role of CD74 in regulating the oncogenic properties of pancreatic cancer cells and its influence on the expression and secretion of S100A8 and S100A9. Taken together, these findings indicate CD74 as a potential diagnostic biomarker and therapeutic target for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: In computer-assisted diagnostics for pancreatic cancer, attributes featuring irregular contours and indistinct boundaries on CT images present challenges in acquiring high-quality annotations. In response to this issue, we have devised an innovative self-supervised learning algorithm, engineered to enhance the differentiation of malignant and benign lesions. This innovation obviates the necessity for radiologist intervention, thus facilitating the precise classification of pancreatic cancer. By employing a pseudo-lesion segmentation self-supervised learning model, which capitalizes on automatically generated high-quality training data, we have managed to significantly elevate the performance of both convolutional neural network-based and transformer-based deep learning models. The aim of this study was to develop a novel deep learning (DL) model without requiring large-annotated training datasets for detecting pancreatic cancer (PC) using computed tomography (CT) images. This retrospective diagnostic study was conducted using CT images collected from 2004 and 2019 from 4287 patients diagnosed with PC. We proposed a self-supervised learning algorithm (pseudo-lesion segmentation (PS)) for PC classification, which was trained with and without PS and validated on randomly divided training and validation sets. We further performed cross-racial external validation using open-access CT images from 361 patients. For internal validation, the accuracy and sensitivity for PC classification were 94.3% (92.8–95.4%) and 92.5% (90.0–94.4%), and 95.7% (94.5–96.7%) and 99.3 (98.4–99.7%) for the convolutional neural network (CNN) and transformer-based DL models (both with PS), respectively. Implementing PS on a small-sized training dataset (randomly sampled 10%) increased accuracy by 20.5% and sensitivity by 37.0%. For external validation, the accuracy and sensitivity were 82.5% (78.3–86.1%) and 81.7% (77.3–85.4%) and 87.8% (84.0–90.8%) and 86.5% (82.3–89.8%) for the CNN and transformer-based DL models (both with PS), respectively. PS self-supervised learning can increase DL-based PC classification performance, reliability, and robustness of the model for unseen, and even small, datasets. The proposed DL model is potentially useful for PC diagnosis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), the most prevalent neurodegenerative disease, is characterized by progressive and irreversible impairment of cognitive functions. However, its etiology is poorly understood, and therapeutic interventions are limited. Our preliminary study revealed that wasp venom (WV) from Vespa velutina nigrithorax can prevent lipopolysaccharide-induced inflammatory signaling, which is strongly implicated in AD pathogenesis. Therefore, we examined whether WV administration can ameliorate major AD phenotypes in the 5xFAD transgenic mouse model. Adult 5xFAD transgenic mice (6.5 months of age) were treated with WV by intraperitoneal injection at 250 or 400 μg/kg body weight once weekly for 14 consecutive weeks. This administration regimen improved procedural, spatial, and working memory deficits as assessed by the passive avoidance, Morris water maze, and Y-maze tasks, respectively. It also attenuated histological damage and amyloid-beta plaque formation in the hippocampal region and decreased expression levels of pro-inflammatory factors in the hippocampus and cerebrum, while it reduced oxidative stress markers (malondialdehyde in the brain and liver and 8-hydroxy-2′-deoxyguanosine in the plasma). Overall, these findings suggest that long-term administration of WV may alleviate AD-related symptoms and pathological phenotypes. [ABSTRACT FROM AUTHOR]

Data regarding driver mutation profiles in tonsillar squamous cell carcinomas (TSCCs) remain scarce, limiting the understanding of its pathogenesis and unexpected behavior in the updated staging system. We investigated the incidence of clinically relevant mutations and their contribution in the prognosis of the condition, and their association with human papillomavirus (HPV) infection and adjuvant therapy. We subjected 43 surgically resected TSCC samples to targeted next-generation sequencing, determined their HPV status using polymerase chain reaction, and performed The Cancer Genomic Atlas and Gene Set Enrichment analyses. Thirty-five TSCC samples (81.4%) showed at least one oncogenic/likely oncogenic mutation among twenty-nine cancer-related genes. The top five mutated genes were TP53 (46.5%), PIK3CA (25.6%), PTEN (18.6%), EGFR (16.3%), and SMAD4 (14.0%). The EGFR pathway was the most frequently affected (51.2%), followed by the p53 (48.8%), PI3K (39.5%), and RTK (34.9%) pathways. The gene set enrichment analysis confirmed that the genes involved in signal transduction, such as growth factor receptors and second messengers, EGFR tyrosine kinase inhibitors, and PI3K signaling pathways, were mostly related with TSCCs. TP53 mutation was an independent prognostic factor predicting worse overall survival in the adjuvant therapy group. RTK mutations were related to survival in all patients and in the HPV-positive group, but multivariate analyses showed no significance. In conclusion, oncogenic/likely oncogenic mutations were relatively high in TSCCs, and TP53 and RTK mutations may be candidate predictors for poor prognosis in the adjuvant therapy and HPV-positive groups, respectively, under the updated staging system. [ABSTRACT FROM AUTHOR]

Simple Summary: Though women account for approximately 30% of newly diagnosed head and neck cancer, women have comprised only 17% of the study population in landmark clinical trials so far. Caution is therefore required when applying research outcomes directly to women in actual clinical practice. We hypothesized that there is no difference in treatment strategies and their effect on survival in treating locally advanced head and neck squamous cell carcinoma (LA-HNSCC) in the real world. We aimed to compare multidisciplinary treatment modalities and their outcomes by sex in 445 patients with stage III to IVB LA-HNSCC. In our overall and propensity-matched cohorts, there were no significant differences in the treatment strategy or OS by gender. In the present era, in which a multidisciplinary approach is emphasized, we conclude that there is no apparent sex-based disparity in the treatment modalities and outcomes in treating LA-HNSCC. We aimed to compare treatment modalities and outcomes by gender in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We characterized the sex-specific differences and compared the overall survival (OS) between male and female patients in a multicenter cohort of LA-HNSCC. To minimize the observed confounding, propensity score matching was utilized. The study included 445 patients; 385 (86.5%) were men and 60 (13.5%) were women. In terms of age, smoking habits, drinking habits, and primary tumor locations, there was a significant imbalance in sex before the matching. Propensity score matching yielded 60 patient pairs, with no statistical difference between the sexes in terms of their characteristics. As for the treatment strategies, there were no significant differences between the sexes before (p = 0.260) and after (p = 0.585) the propensity score matching. When comparing the survival probabilities between the sexes, OS was not significantly different in the overall (HR 1.02; 95% CI 0.59–1.76; p = 0.938) and propensity-score-matched population (HR 1.46; 95% CI 0.68–3.17; p = 0.331). These results suggest that there was no difference in prognosis by gender in the treatment modalities and outcomes of LA-HNSCC in real-world practice. [ABSTRACT FROM AUTHOR]

The activities of daily living (ADL) ability level of an elderly patient is an important indicator in determining the patient's degree of degenerative brain disease and is mainly evaluated through face-to-face interviews with doctors and patients in hospitals. It is impossible to determine the exact ADL ability of a patient through such a temporary interview, and the pursuit of accurate ADL ability evaluation technology is a very important research task worldwide. In this paper, in order to overcome the limitations of the existing ADL evaluation method mentioned above, first of all, a self-organized IoT architecture in which IoT devices autonomously and non-invasively measure a patient's ADL ability within the context of the patient's daily living place was designed and implemented. Second, a remote rehabilitation treatment concept for enhancing the patient's ADL ability we call an "e-coaching framework", in which a doctor remotely gives an instruction in a specific ADL scenario, and the patient's ability to understand and perform the instruction can be measured on-line and in real time, was additionally developed on top of the self-organized IoT architecture. In order to verify the possibility of remote rehabilitation treatment through the proposed architecture, various remotely directed ADL scenarios were performed and the accuracy of the measurements was verified. [ABSTRACT FROM AUTHOR]

Background and Objectives: There is no consensus regarding the surface treatment method for achieving optimal bonding strength between zirconia and resin cements. We evaluated the effect of hot-etching with 9% hydrofluoric acid (HF) gel using the Zirconia Etchant Cloud System on zirconia surfaces and the consequent shear bond strength (SBS) of different resin cements to such surface-treated zirconia ceramics. Materials and Methods: Forty-five zirconia specimens were randomly assigned to surface-treatment groups (n = 15/group): no treatment (control, CT); sandblasting with 110-μm Al2O3 at an air pressure of 1 bar for 10 s (SB); hot-etching with 9% HF gel (HE). Post-treatment, specimens were examined using scanning electron microscopy (SEM) and surface roughness (SR) analysis. After treatment, self-adhesive resin cements (Maxcem Elite, MAZIC Cem, RelyX U200, 3M ESPE: Maplewood, MN, USA) were bonded to zirconia specimens, which were stored in distilled water at 37 °C for 24 h. All specimens were then subjected to SBS testing, using a universal testing machine, until failure. Data were analyzed using one-way analysis of variance and Tukey's post hoc test (α = 0.05). Results: In the SEM images, roughness was greater in SB than in HE specimens. Ra and Rt values were highest in SB, followed by HE, and CT specimens. HE specimens showed significantly higher SBS values than CT or SB specimens (p < 0.05). MAZIC Cem cement, with 10-methacryloyloxydcyl dihydrogen phosphate yielded the highest SBS values. Conclusions: Hot-etching with 9% HF gel in a safe shell formed uniformly small, defined holes on the zirconia surface and achieved significantly higher SBS values than sandblasting (p < 0.05). Zirconia prostheses can be bonded micromechanically with resin cement, without the deterioration of properties due to t-m transformation, using chemical acid etching with the Zirconia Etchant Cloud System. [ABSTRACT FROM AUTHOR]

This study investigated the effects of wasp venom (WV) from the yellow-legged hornet, Vespa velutina, on scopolamine (SCO)-induced memory deficits in mice, as well as the antioxidant activity in HT22 murine hippocampal neuronal cells in parallel comparison with bee venom (BV). The WV was collected from the venom sac, freeze-dried. Both venoms exhibited free radical scavenging capabilities in a concentration-dependent manner. In addition, the venom treatment enhanced cell viability at the concentrations of ≤40 µg/mL of WV and ≤4 µg/mL of BV in glutamate-treated HT22 cells, and increased the transcriptional activity of the antioxidant response element (ARE), a cis-acting enhancer which regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)-downstream antioxidant enzymes. Concurrently, WV at 20 µg/mL significantly increased the expression of a key antioxidant enzyme heme oxygenase 1 (HO-1) in HT22 cells despite no significant changes observed in the nuclear level of Nrf2. Furthermore, the intraperitoneal administration of WV to SCO-treated mice at doses ranged from 250 to 500 µg/kg body weight ameliorated memory impairment behavior, reduced histological injury in the hippocampal region, and reduced oxidative stress biomarkers in the brain and blood of SCO-treated mice. Our findings demonstrate that WV possess the potential to improve learning and memory deficit in vivo while further study is needed for the proper dose and safety measures and clinical effectiveness. [ABSTRACT FROM AUTHOR]

The genus Epilobium consists of approximately 200 species that are distributed worldwide. Some of these herbs have been used for the treatment of diarrhea, infection, irritation, and other disorders associated with inflammation. Unlike that of other Epilobium species, there is little scientific understanding of the pharmacological effect of Epilobium amurense subsp. cephalostigma (Hausskn.) C. J. Chen, Hoch & P. H. Raven. In this study, we demonstrated the anti-inflammatory and antioxidative properties of an E. amurense 95% ethanol extract (EACEE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and observed the underlying mechanism of this effect. We measured the productions of nitric oxide (NO) and reactive oxygen species, and examined the actions of EACEE on transcription factors in the macrophages. EACEE reduced NO production and inducible nitric oxide synthase protein levels via the inhibition of the nuclear factor (NF)-κB pathway. Additionally, EACEE suppressed redundant reactive oxygen species production and regulated nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling. Furthermore, EACEE significantly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK). Overall, these results indicate that EACEE exerts anti-inflammatory and antioxidant effects via the activation of Nrf2/HO-1 and inhibition of NF-κB/p38 MAPK signaling. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) accumulation in the hippocampus is an essential event in the pathogenesis of Alzheimer's disease. Insoluble Aβ is formed through the sequential proteolytic hydrolysis of the Aβ precursor protein, which is cleaved by proteolytic secretases. However, the pathophysiological mechanisms of Aβ accumulation remain elusive. Here, we report that rats fed high-phytate diets showed Aβ accumulation and increased apoptotic neuronal cell death in the hippocampus through the activation of the amyloidogenic pathway in the hippocampus. Immunoblotting and immunohistochemical analyses confirmed that the overexpression of BACE1 β-secretase, a critical enzyme for Aβ generation, exacerbated the hippocampal Aβ accumulation in rats fed high-phytate diets. Moreover, we identified that parathyroid hormone, a physiological hormone responding to the phytate-mediated dysregulation of calcium and phosphate homeostasis, plays an essential role in the transcriptional activation of the Aβ precursor protein and BACE1 through the vitamin D receptor and retinoid X receptor axis. Thus, our findings suggest that phytate-mediated dysregulation of calcium and phosphate is a substantial risk factor for elevated Aβ accumulation and apoptotic neuronal cell death in rats. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with metastatic triple-negative breast cancer (mTNBC) have a very poor prognosis. We assume that some mTNBC patients have worse treatment outcomes and defined them as cases of refractory TNBC. We tried to investigate the characteristics and treatment outcomes of our refractory mTNBC cohort selected using a clinical data warehouse (CDW) approach. Between January 1997 and December 2019, TNBC patients were searched for in the breast cancer registry and, among them, pathologically confirmed mTNBC patients were selected as the study cohort (n = 451). Refractory TNBC was defined as cases of TNBC with confirmed distant metastasis within one year after adjuvant treatment. The refractory mTNBC group was younger and had a higher proportion of Ki-67 ≥ 3+ than the nonrefractory group. In addition, a much poorer prognosis existed among mTNBC patients, with an overall survival (OS) of 14.3 months and progression-free survival (PFS) of 4.2 months after first-line palliative chemotherapy compared to an OS of 24.8 months and PFS of 6.2 months in the nonrefractory TNBC group (p < 0.001). Purpose: Triple-negative breast cancer (TNBC) is well known for its aggressive course and poor prognosis. In this study, we sought to investigate clinical, demographic, and pathologic characteristics and treatment outcomes of patients with refractory, metastatic TNBC selected by a clinical data warehouse (CDW) approach. Patients and methods: Data were extracted from the real-time breast cancer registry integrated into the Data Analytics and Research Window for Integrated Knowledge C (DARWIN-C), the CDW of Samsung Medical Center. Between January 1997 and December 2019, a TNBC cohort was searched for in the breast cancer registry, which includes records from more than 40,000 patients. Among them, cases of pathologically confirmed metastatic TNBC (mTNBC) were selected as the cohort group (n = 451). The extracted data from the registry via the CDW platform included clinical, pathological, laboratory, and chemotherapy information. Refractory TNBC was defined as confirmed distant metastasis within one year after adjuvant treatment. Results: This study comprised a total of 451 patients with mTNBC, including 69 patients with de novo mTNBC, 131 patients in the nonrefractory TNBC group with confirmed stage IV disease after one year of adjuvant treatment, and 251 patients with refractory mTNBC, whose disease recurred as stage IV within one year after completing adjuvant treatment. The refractory mTNBC cohort was composed of patients with disease that recurred at stage IV after surgery (refractory mTNBC after surgery) (n = 207) and patients in whom metastasis was confirmed during neoadjuvant chemotherapy (unresectable TNBC due to progression during neoadjuvant chemotherapy) (n = 44). Patients in the refractory mTNBC group were younger than those in the nonrefractory group (median age 46 vs. 51 years; p < 0.001). Considering the pathological findings, the refractory group had a greater proportion of cases with Ki-67 ≥ 3+ than did the nonrefractory group (71% vs. 47%; p = 0.004). During a median 8.4 years of follow-up, the overall survival was 24.8 months in the nonrefractory mTNBC group and 14.3 months in the refractory mTNBC group (p < 0.001), and the median progression-free survival periods were 6.2 months and 4.2 months, respectively (p < 0.001). The median disease-free survival period was 30.1 months in the nonrefractory mTNBC group and only 7.6 months in the refractory mTNBC group. Factors related to metastatic sites affecting overall survival were liver metastasis at diagnosis (p < 0.001) and leptomeningeal involvement (p = 0.001). Conclusions: We revealed that patients with refractory mTNBC had a much poorer prognosis among all mTNBC cases and described the characteristics of this patient group. [ABSTRACT FROM AUTHOR]

Defoliation (DF) on peach (Prunus persica L.) and Japanese apricot (Prunus mume Sieb. et Zucc.) trees caused by a hailstorm in 2017, year 1, was investigated for its effects on growth and fruit yield in South Korea over four years, comparing with recovery effects of the DF trees treated with repeated immediate pruning (IP) right after the storm. Treatments included 0–10, 10–40, 40–70, and 70–100% of DF trees, with 0–10, 10–40, 40–70, and 70–100% of DF + IP trees. The hailstorms increased the damages to shoots for peaches and to shoots and scaffold for Japanese apricot trees in year 1, with fruit yield reduced more than 80% observed on 10–100 DF of both fruit species. The IP treatment increased the number of new shoots in years 2–4 but reduced shoot length and diameter of peach and Japanese apricot trees. Tree canopy in years 2–4 was reduced on 40–100 DF of peach trees and on 70–100 of DF and DF + IP of Japanese apricot trees. The 40–100 DF Japanese apricot trees resulted in a fruit yield index of less than 90% for years 2–4, which was observed on 40–100 DF+IP trees only in year 2 due to balanced tree vegetative and reproductive growth. [ABSTRACT FROM AUTHOR]

The Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative Gram-negative bacterium that causes acute gastroenteritis and food poisoning. S. Typhimurium can survive within macrophages that are able to initiate the innate immune response after recognizing bacteria via various pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs). In this study, we investigated the effects and molecular mechanisms by which agonists of endosomal TLRs—especially TLR3—contribute to controlling S. Typhimurium infection in murine macrophages. Treatment with polyinosinic:polycytidylic acid (poly(I:C))—an agonist of TLR3—significantly suppressed intracellular bacterial growth by promoting intracellular ROS production in S. Typhimurium-infected cells. Pretreatment with diphenyleneiodonium (DPI)—an NADPH oxidase inhibitor—reduced phosphorylated MEK1/2 levels and restored intracellular bacterial growth in poly(I:C)-treated cells during S. Typhimurium infection. Nitric oxide (NO) production increased through the NF-κB-mediated signaling pathway in poly(I:C)-treated cells during S. Typhimurium infection. Intracellular microtubule-associated protein 1A/1B-light chain 3 (LC3) levels were increased in poly(I:C)-treated cells; however, they were decreased in cells pretreated with 3-methyladenine (3-MA)—a commonly used inhibitor of autophagy. These results suggest that poly(I:C) induces autophagy and enhances ROS production via MEK1/2-mediated signaling to suppress intracellular bacterial growth in S. Typhimurium-infected murine macrophages, and that a TLR3 agonist could be developed as an immune enhancer to protect against S. Typhimurium infection. [ABSTRACT FROM AUTHOR]

Umbelliferone (UMB), also known as 7-hydroxycoumarin, is a derivative of coumarin, which is widely found in many plants such as carrots, coriander, and garden angelica. Although many studies have already revealed the various pharmacological properties of UMB, its effect on benign prostatic hyperplasia (BPH) remains unclear. Therefore, the present study aimed to elucidate the underlying mechanism of the anti-proliferative effect of UMB in a human benign prostatic hyperplasia cell line (BPH-1), as well as its ameliorative effect on BPH in testosterone propionate (TP)-induced rats. The results showed that UMB exerts an anti-proliferative effect in BPH-1 cells by modulating the signal transducer and activator of transcription 3 (STAT3)/E2F transcription factor 1 (E2F1) axis. UMB treatment not only inhibited androgen/androgen receptor (AR) signaling-related markers, but also downregulated the overexpression of G1/S phase cell cycle-related markers. In TP-induced rats, UMB administration demonstrated an anti-BPH effect by significantly reducing prostate size, weight, and epithelial thickness. In addition, UMB suppressed cell proliferation by reducing the expression of proliferating cell nuclear antigen (PCNA) and p-STAT3 (Tyr 705) in prostate tissue following TP injection. These findings suggest that UMB has pharmacological effects against BPH. [ABSTRACT FROM AUTHOR]

Many researchers have argued that Western diet (WD)-induced obesity accelerates inflammation and that inflammation is a link between obesity and colorectal cancer (CRC). This study investigated the effect of WDs on the development and progression of colitis-associated colon cancer (CAC) and the efficacy of the anti-obesity agent orlistat on WD-driven CAC in mice. The results revealed that the WD exacerbated CAC in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice, which showed increased mortality, tumor formation, and aggravation of tumor progression. Furthermore, WD feeding also upregulated inflammation, hyperplasia, and tumorigenicity levels through the activation of STAT3 and NF-κB signaling in an AOM/DSS-induced mouse model. In contrast, treatment with orlistat increased the survival rate and alleviated the symptoms of CAC, including a recovery in colon length and tumor production decreases in WD-driven AOM/DSS-induced mice. Additionally, orlistat inhibited the extent of inflammation, hyperplasia, and tumor progression via the inhibition of STAT3 and NF-κB activation. Treatment with orlistat also suppressed the β-catenin, slug, XIAP, Cdk4, cyclin D, and Bcl-2 protein levels in WD-driven AOM/DSS-induced mice. The results of this study indicate that orlistat alleviates colon cancer promotion in WD-driven CAC mice by suppressing inflammation, especially by inhibiting STAT3 and NF-κB activation. [ABSTRACT FROM AUTHOR]

In this study, possible changes in the expression of rat organic cationic transporters (rOCTs) and rat multidrug and toxin extrusion proteins (rMATEs) following treatment with 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) were investigated. Rats received intraperitoneal administrations of 1,25(OH)2D3 for four consecutive days, and the tissues of interest were collected. The mRNA expression of rOCT1 in the kidneys was significantly increased in 1,25(OH)2D3-treated rats compared with the control rats, while the mRNA expressions of rOCT2 and rMATE1 in the kidneys, rOCT1 and N-acetyltransferase-II (NAT-II) in the liver, and rOCT3 in the heart were significantly decreased. Changes in the protein expression of hepatic rOCT1 and renal rOCT2 and rMATE1 were confirmed by western blot analysis. We further evaluated the pharmacokinetics of procainamide (PA) hydrochloride and its major metabolite N-acetyl procainamide (NAPA) in the presence of 1,25(OH)2D3. When PA hydrochloride was administered intravenously at a dose 10 mg/kg to 1,25(OH)2D3-treated rats, a significant decrease in renal and/or non-renal clearance of PA and NAPA was observed. A physiological model for the pharmacokinetics of PA and NAPA in rats was useful for linking changes in the transcriptional and translational expressions of rOCTs and rMATE1 transporters to the altered pharmacokinetics of the drugs. [ABSTRACT FROM AUTHOR]

This work reports the self-organization of dimple nanostructures on a polyethylene naphthalate (PEN) surface where an Ar ion beam was irradiated at an ion energy of 600 eV. The peak-to-peak roughness and diameter of dimple nanostructures were 29.1~53.4 nm and 63.4~77.6 nm, respectively. The electron energy loss spectrum at the peaks and troughs of dimples showed similar C=C, C=O, and O=CH bonding statuses. In addition, wide-angle X-ray scattering showed that Ar ion beam irradiation did not induce crystallization of the PEN surface. That meant that the self-organization on the PEN surface could be due to the ion-induced surface instability of the amorphous layer and not due to the partial crystallinity differences of the peaks and valleys. A nonlinear continuum model described surface instability due to Ar ion-induced sputtering. The Kuramoto–Sivashinsky model reproduced the dimple morphologies numerically, which was similar to the experimentally observed dimple patterns. This preliminary validation showed the possibility that the continuum equation used for metal and semiconductor surfaces could be applied to polymer surfaces where ion beam sputtering occurred. [ABSTRACT FROM AUTHOR]

Preventing exacerbation and seeking to determine the severity of the disease during the hospitalization of chronic obstructive pulmonary disease (COPD) patients is a crucial global initiative for chronic obstructive lung disease (GOLD); this option is available only for stable-phase patients. Recently, the assessment and prediction techniques that are used have been determined to be inadequate for acute exacerbation of chronic obstructive pulmonary disease patients. To magnify the monitoring and treatment of acute exacerbation COPD patients, we need to rely on the AI system, because traditional methods take a long time for the prognosis of the disease. Machine-learning techniques have shown the capacity to be effectively used in crucial healthcare applications. In this paper, we propose a voting ensemble classifier with 24 features to identify the severity of chronic obstructive pulmonary disease patients. In our study, we applied five machine-learning classifiers, namely random forests (RF), support vector machine (SVM), gradient boosting machine (GBM), XGboost (XGB), and K-nearest neighbor (KNN). These classifiers were trained with a set of 24 features. After that, we combined their results with a soft voting ensemble (SVE) method. Consequently, we found performance measures with an accuracy of 91.0849%, a precision of 90.7725%, a recall of 91.3607%, an F-measure of 91.0656%, and an AUC score of 96.8656%, respectively. Our result shows that the SVE classifier with the proposed twenty-four features outperformed regular machine-learning-based methods for chronic obstructive pulmonary disease (COPD) patients. The SVE classifier helps respiratory physicians to estimate the severity of COPD patients in the early stage, consequently guiding the cure strategy and helps the prognosis of COPD patients. [ABSTRACT FROM AUTHOR]

Face masks will be used to prevent pandemic recurrence and outbreaks of mutant SARS-CoV-2 strains until mass immunity is confirmed. The polypropylene (PP) filter is a representative disposable mask material that traps virus-containing bioaerosols, preventing secondary transmission. In this study, a copper thin film (20 nm) was deposited via vacuum coating on a spunbond PP filter surrounding a KF94 face mask to provide additional protection and lower the risk of secondary transmission. Film adhesion was improved using oxygen ion beam pretreatment, resulting in cuprous oxide formation on the PP fiber without structural deformation. The copper-coated mask exhibited filtration efficiencies of 95.1 ± 1.32% and 91.6 ± 0.83% for NaCl and paraffin oil particles, respectively. SARS-CoV-2 inactivation was evaluated by transferring virus-containing media onto the copper-coated PP filters and subsequently adding Vero cells. Infection was verified using real-time polymerase chain reaction and immunochemical staining. Vero cells added after contact with the copper-coated mask did not express the RNA-dependent RNA polymerase and envelope genes of SARS-CoV-2. The SARS-CoV-2 nucleocapsid immunofluorescence results indicated a reduction in the amount of virus of more than 75%. Therefore, copper-coated antiviral PP filters could be key materials in personal protective equipment, as well as in air-conditioning systems. [ABSTRACT FROM AUTHOR]

Cicadae Periostracum (CP), derived from the slough of Cryptotympana pustulata, has been used as traditional medicine in Korea and China because of its diaphoretic, antipyretic, anti-inflammatory, antioxidant, and antianaphylactic activities. The major bioactive compounds include oleic acid (OA), palmitic acid, and linoleic acid. However, the precise therapeutic mechanisms underlying its action in asthma remain unclear. The objective of this study was to determine the antiasthmatic effects of CP in an ovalbumin (OVA)-induced asthmatic mouse model. CP and OA inhibited the inflammatory cell infiltration, airway hyperresponsiveness (AHR), and production of interleukin (IL)7 and Th2 cytokines (IL-5) in the bronchoalveolar lavage fluid and OVA-specific imunoglobin E (IgE) in the serum. The gene expression of IL-5, IL-13, CCR3, MUC5AC, and COX-2 was attenuated in lung tissues. CP and OA might inhibit the nuclear translocation of GATA-binding protein 3 (GATA-3) and retinoic acid receptor-related orphan receptor γt (RORγt) via the upregulation of forkhead box p3 (Foxp3), thereby preventing the activation of GATA-3 and RORγt. In the in vitro experiment, a similar result was observed for Th2 and GATA-3. These results suggest that CP has the potential for the treatment of asthma via the inhibition of the GATA-3/Th2 and IL-17/RORγt signaling pathways. [ABSTRACT FROM AUTHOR]

Simple Summary: As the population of the yellow-legged hornet (Vespa velutina) spreads, this study investigated ways to utilize this resource of abundant invasive wasp species. Hymenoptera venoms, including bee venom and wasp venom, have therapeutic potential. Although the venoms are toxic to humans, the elucidation of their composition and working mechanisms has led to discoveries about their potential applications in treatment modalities for a variety of disorders. Therefore, we examined the anti-inflammatory effect of wasp venom from V. velutina in comparison with that of bee venom from honey bee on BV-2 murine microglial cells. Treatment with wasp venom reduced the secretion of nitric oxide and pro-inflammatory cytokines, including interleukin-6 and tumor necrosis factor alpha, from BV-2 cells activated by lipopolysaccharide (LPS). Western blot analysis revealed that wasp venom and bee venom decreased the expression levels of inflammation markers, including inducible nitric oxide synthase and cyclooxygenase-2. In addition, wasp venom decreased the nuclear translocation of nuclear factor κB (NF-κB), which is a key transcription factor in the regulation of cellular inflammatory response. Overall, the findings demonstrated that wasp venom inhibited LPS-induced inflammation in microglial cells by suppressing the NF-κB-mediated signaling pathway, which warrants further studies to confirm its therapeutic potential for neurodegenerative diseases. The aim of this study was to compare the anti-inflammatory effect of wasp venom (WV) from the yellow-legged hornet (Vespa velutina) with that of bee venom (BV) on BV-2 murine microglial cells. WV was collected from the venom sac, freeze-dried, and used for in vitro examinations. WV and BV were non-toxic to BV-2 cells at concentrations of 160 and 12 µg/mL or lower, respectively. Treatment with WV reduced the secretion of nitric oxide and proinflammatory cytokines, including interleukin-6 and tumor necrosis factor alpha, from BV-2 cells activated by lipopolysaccharide (LPS). Western blot analysis revealed that WV and BV decreased the expression levels of inflammation markers, including inducible nitric oxide synthase and cyclooxygenase-2. In addition, WV decreased the nuclear translocation of nuclear factor κB (NF-κB), which is a key transcription factor in the regulation of cellular inflammatory response. Cumulatively, the results demonstrated that WV inhibited LPS-induced neuroinflammation in microglial cells by suppressing the NF-κB-mediated signaling pathway, which warrants further studies to confirm its therapeutic potential for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Fermented soybean products, such as cheonggukjang (Japanese natto), doenjang (soy paste), ganjang (soy sauce), and douchi, are widely consumed in East Asian countries and are major sources of bioactive compounds. The fermentation of cooked soybean with bacteria (Bacillus spp.) and fungi (Aspergillus spp. and Rhizopus spp.) produces a variety of novel compounds, most of which possess health benefits. This review is focused on the preventive and ameliorative potential of fermented soy foods and their components to manage neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Arbitrary upfront dose reduction (UDR) of palliative chemotherapy has often been performed according to the judgement of the physician of older adults with metastatic solid cancer in current practice. UDR might decrease treatment efficacy in older adults but may be helpful for palliation, so selecting older adults who benefit from UDR and the identification of predictors of UDR are required. The authors investigated the prevalence and predictors of UDR through variables of geriatric assessment (GA). Chemotherapy compliance between the UDR and standard dose patient groups was also compared. The results of this study demonstrated that approximately 60% of older adults with metastatic solid cancer received UDR. Poor performance status (PS) and living without a spouse were predictive factors of UDR of first-line palliative chemotherapy, and patients with UDR better-tolerated chemotherapy compared with patients with standard doses. Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (≥70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4–47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3–5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose. [ABSTRACT FROM AUTHOR]

Cornus officinalis, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells. We standardized C. officinalis 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment. [ABSTRACT FROM AUTHOR]

Metastasis is the main cause of cancer-related deaths. Anoikis is a type of apoptosis caused by cell detachment, and cancer cells become anoikis resistant such that they survive during circulation and can successfully metastasize. Therefore, sensitization of cancer cells to anoikis could prevent metastasis. Here, by screening for anoikis sensitizer using natural compounds, we found that pygenic acid A (PA), a natural compound from Prunella vulgaris, not only induced apoptosis but also sensitized the metastatic triple-negative breast cancer cell lines, MDA-MB-231 cells (human) and 4T1 cells (mouse), to anoikis. Apoptosis protein array and immunoblotting analysis revealed that PA downregulated the pro-survival proteins, including cIAP1, cIAP2, and survivin, leading to cell death of both attached and suspended cells. Interestingly, PA decreased the levels of proteins associated with anoikis resistance, including p21, cyclin D1, p-STAT3, and HO-1. Ectopic expression of active STAT3 attenuated PA-induced anoikis sensitivity. Although PA activated ER stress and autophagy, as determined by increases in the levels of characteristic markers, such as IRE1α, p-elF2α, LC3B I, and LC3B II, PA treatment resulted in p62 accumulation, which could be due to PA-induced defects in autophagy flux. PA also decreased metastatic characteristics, such as cell invasion, migration, wound closure, and 3D growth. Finally, lung metastasis of luciferase-labeled 4T1 cells decreased following PA treatment in a syngeneic mouse model when compared with the control. These data suggest that PA sensitizes metastatic breast cancer cells to anoikis via multiple pathways, such as inhibition of pro-survival pathways and activation of ER stress and autophagy, leading to the inhibition of metastasis. These findings suggest that sensitization to anoikis by PA could be used as a new therapeutic strategy to control the metastasis of breast cancer. [ABSTRACT FROM AUTHOR]

There are limited data from prospective controlled trials regarding optimal treatment strategies in patients with primary breast diffuse large B-cell lymphoma (DLBCL). In this phase 2 study (NCT01448096), we examined the efficacy and safety of standard immunochemotherapy and central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX). Thirty-three patients with newly diagnosed primary breast DLBCL received six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and four fixed doses of IT-MTX (12 mg). The median age was 50 years (range, 29–75), and all patients were females. According to the CNS-International Prognostic Index, most patients (n = 28) were categorized as the low-risk group. Among the 33 patients, 32 completed R-CHOP, and 31 completed IT-MTX as planned. With a median follow-up of 46.1 months (interquartile range (IQR), 31.1–66.8), the 2-year progression-free and overall survival rates were 81.3% and 93.5%, respectively. Six patients experienced treatment failures, which included the CNS in four patients (two parenchyma and two leptomeninges) and breast in two patients (one ipsilateral and one contralateral). The 2-year cumulative incidence of CNS relapse was 12.5%. Although standard R-CHOP and IT-MTX without routine radiotherapy show clinically meaningful survival outcomes, this strategy may not be optimal for reducing CNS relapse and warrants further investigation. [ABSTRACT FROM AUTHOR]

According to the psychological reactance theory, psychological reactance is strongly associated with many adverse outcomes of health promotion messages. This is particularly pertinent when health messages are targeting young adults, as they resist freedom-threatening messages compared to other age groups. However, previous reactance measures either relied on the open-ended thought-listing procedure, or incorporated both antecedents as well as consequences of reactance and state reactance. This study aimed to develop and validate a comprehensive scale to measure the state of psychological reactance specifically toward health promotion messages. To this end, this study was situated in the context of an anti-binge drinking intervention targeting college students. A cross-sectional survey was conducted with 203 Singaporean undergraduate students. The dataset was analyzed by exploratory factor analysis, confirmatory factor analysis, and item analysis. The final 27 items were loaded on eight factors (anger, exaggeration, design derogation, authoritative tone, ineffectiveness, know-it-all attitude, jadedness, and source motive) that accounted for 78.53% of the variance. Each factor showed satisfactory reliability and validity (discriminant, convergent, and predictive). This study specified cognitive reactions by multiple dimensions and examined how they are intertwined with the affective dimension, which is represented by anger. The scale proposed herein will help researchers and practitioners develop sustainable health interventions. [ABSTRACT FROM AUTHOR]

Background: 6′-Sialyllactose (6SL) displays a wide range of the bioactive benefits, such as anti-proliferative and anti-angiogenic activities. However, the therapeutic effects of 6SL on benign prostatic hyperplasia (BPH) remain unknown. Methods: Six-week-old male Wistar rats (n = 40) were used for in vivo experiments. All rats were castrated and experimental BPH was induced in castrated rats by intramuscular injection of testosterone, with the exception of those in the control group. Rats with BPH were administrated finasteride and 0.5 or 1.0 mg/kg 6SL. Furthermore, the inhibitory effects of 6SL on human epithelial BPH cell line (BPH-1) cells were determined in vitro. Results: Rats with BPH exhibited outstanding BPH manifestations, including prostate enlargement, histological alterations, and increased prostate-specific antigen (PSA) levels. Compared to those in the BPH group, rats in the 6SL group showed fewer pathological changes and normal androgen events, followed by restoration of retinoblastoma protein (pRb) and cell cycle-related proteins. In BPH-1 cells, treatment with 6SL significantly suppressed the effects on the androgen receptor (AR), PSA, and E2F transcription factor 1 (E2F1)-dependent cell cycle protein expression. Conclusions: 6SL demonstrated anti-proliferative effects in a testosterone-induced BPH rat model and on BPH-1 cells by regulating the pRB/E2F1–AR pathway. According to our results, we suggest that 6SL may be considered a potential agent for the treatment of BPH. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to simplify and identify the contents of the herbal formula, HBX-5. This study was carried out to evaluate the therapeutic effects of HBX-6 in a mouse model of benign prostatic hyperplasia (BPH). Based on in vitro, we selected a candidate, reconstituted an experimental agent and investigated the effects on testosterone-induced BPH rats. Cell viability was determined by MTT assay in RWPE-1 and WPMY-1 cells. The expression of androgen receptor (AR) was measured in dihydrotestosterone-stimulated RWPE-1 and WPMY-1 cells. BPH was induced in mice by a subcutaneous injection of testosterone propionate for four weeks. Animals were divided into six groups: Group 1, control mice; Group 2, mice with BPH; Group 3, mice with BPH treated with finasteride; Group 4, mice with BPH treated with 200 mg/kg HBX-5; Group 5, mice with BPH treated with 100 mg/kg HBX-6; and Group 6, mice with BPH treated with 200 mg/kg HBX-6. Changes in prostate weight were measured after treatments, and the thickness of the epithelium was evaluated. The expression levels of proteins associated with prostatic cell proliferation and cell cycle-related proteins were determined. Based on previous reports and in vitro results, we selected Cornus officinalis and Psoralea corylifolia among HBX-5 components and reconstituted the experimental agent, and named it HBX-6. The result represented a new herbal formula, HBX-6 that suppressed the pathological alterations in BPH and showed a marked reduction in proliferation-related protein expression compared to mice with BPH. Our results indicate that HBX-6 has a better therapeutic effect in the BPH murine model than those of HBX-5 and finasteride, suggesting the role of HBX-6 as a new BPH remedial agent. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH), an age-dependent disorder with a prevalence percentage of 60% in the 60s, has been found to involve an androgenic hormone imbalance that causes confusion between cell apoptosis and proliferation. Because general medications for BPH treatment have undesirable side effects, the development of effective alternative medicines has been considered. HBX-5 is a newly developed formula with the aim of improving BPH, and is composed of nine medicinal herbs. BPH was induced in the rats by intramuscular injection of testosterone propionate after castration. Rats were divided into six groups, and the efficacy of HBX-5 on testosterone-induced BPH in rats was estimated. In addition, RWPE-1 and WPMY-1 cells were used to demonstrate the effect of HBX-5 on BPH in vitro model. Compared with the control group, HBX-5 administration group suppressed BPH manifestations, such as excessive development of prostate, and increase of serum dihydrotestosterone and 5α-reductase concentrations. Furthermore, immunohistochemistry analysis revealed that HBX-5 significantly decreased the expression of androgen receptor (AR) and proliferating cell nuclear antigen (PCNA). In addition, results of RWPE-1 and WPMY-1 cells showed that HBX-5 inhibited the over-expression of AR and PSA in DHT-induced prostate hyperplastic microenvironments. [ABSTRACT FROM AUTHOR]

The melanin-inducing properties of cirsimaritin were investigated in murine B16F10 cells. Cirsimaritin is an active flavone with methoxy groups, which is isolated from the branches of Lithocarpus dealbatus. Tyrosinase activity and melanin content in murine B16F10 melanoma cells were increased by cirsimaritin in a dose-dependent manner. Western blot analysis revealed that tyrosinase, tyrosinase-related protein (TRP) 1, TRP2 protein levels were enhanced after treatment with cirsimaritin for 48 h. Cirsimaritin also upregulated the expression of microphthalmia-associated transcription factor (MITF) after 24 h of treatment. Furthermore, cirsimaritin induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner after treatment for 15 min. The cirsimaritin-mediated increase of tyrosinase activity was significantly attenuated by H89, a cAMP-dependent protein kinase A inhibitor. These findings indicate that cirsimaritin stimulates melanogenesis in B16F10 cells by activation of CREB as well as upregulation of MITF and tyrosinase expression, which was activated by cAMP signaling. Finally, the melanogenic effect of cirsimaritin was confirmed in human epidermal melanocytes. These results support the putative application of cirsimaritin in ultraviolet photoprotection and hair coloration treatments.