This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
Humans ; Neoplasms/pathology* ; Biomarkers ; Prognosis ; Oceans and Seas ; China/epidemiology*

Six new bisabolane-type phenolic sesquiterpenoids, including plakordiols A-D (1-4), (7R, 10R)-hydroxycurcudiol (5) and (7R, 10S)-hydroxycurcudiol (6) were isolated from the marine sponge Plakortis simplex collected from the South China Sea. Their structures were determined based on extensive analysis of spectroscopic data. Their configurations were assigned by coupling constant analysis, NOESY correlations, and the modified Mosher's method. Furthermore, their cytotoxic and antibacterial activities were evaluated.
Animals ; Anti-Bacterial Agents/pharmacology* ; China ; Molecular Structure ; Monocyclic Sesquiterpenes/pharmacology* ; Pacific Ocean ; Plakortis/chemistry*

PURPOSE: Despite the well-known anti-inflammatory effects of vitamin D in periodontal health, its mechanism has not been fully elucidated. In the present study, the effect of vitamin D on strengthening E-cadherin junctions (ECJs) was explored in human gingival keratinocytes (HGKs). ECJs are the major type of intercellular junction within the junctional epithelium, where loose intercellular junctions develop and microbial invasion primarily occurs. METHODS: HOK-16B cells, an immortalized normal human gingival cell line, were used for the study. To mimic the inflammatory environment, cells were treated with tumor necrosis factor-alpha (TNF-α). Matrix metalloproteinases (MMPs) in the culture medium were assessed by an MMP antibody microarray and gelatin zymography. The expression of various molecules was investigated using western blotting. The extent of ECJ development was evaluated by comparing the average relative extent of the ECJs around the periphery of each cell after immunocytochemical E-cadherin staining. Vitamin D receptor (VDR) expression was examined via immunohistochemical analysis. RESULTS: TNF-α downregulated the development of the ECJs of the HGKs. Dissociation of the ECJs by TNF-α was accompanied by the upregulation of MMP-9 production and suppressed by a specific MMP-9 inhibitor, Bay 11-7082. Exogenous MMP-9 decreased the development of ECJs. Vitamin D reduced the production of MMP-9 and attenuated the breakdown of ECJs in the HGKs treated with TNF-α. In addition, vitamin D downregulated TNF-α-induced nuclear factor kappa B (NF-κB) signaling in the HGKs. VDR was expressed in the gingival epithelium, including the junctional epithelium. CONCLUSIONS: These results suggest that vitamin D may avert TNF-α-induced downregulation of the development of ECJs in HGKs by decreasing the production of MMP-9, which was upregulated by TNF-α. Vitamin D may reinforce ECJs by downregulating NF-κB signaling, which is upregulated by TNF-α. Strengthening the epithelial barrier may be a way for vitamin D to protect the periodontium from bacterial invasion.
Bays ; Blotting, Western ; Cadherins ; Cell Line ; Down-Regulation ; Epithelial Attachment ; Epithelium ; Gelatin ; Humans ; Intercellular Junctions ; Keratinocytes ; Matrix Metalloproteinase 9 ; Matrix Metalloproteinases ; NF-kappa B ; Periodontium ; Receptors, Calcitriol ; Tumor Necrosis Factor-alpha ; Up-Regulation ; Vitamin D ; Vitamins

Inferior meatal antrostomy (IMA) is a widely performed surgical technique to treat postoperative maxillary mucocele. The method is safe and easy to perform, without major complications compared with other approaches. Facial pain after IMA is a rare clinical entity that can be challenging to diagnose and treat. The authors present an unusual case of acute facial neuralgia triggered by cold air that developed after IMA. The antrostomy was located at the anterior-most part of the inferior meatus, and the inlet size was relatively large compared with the size of the remaining sinus. Surgical narrowing of the antrostomy inlet using endoscopy dramatically reduced the symptoms, and symptom relief was maintained for up to one year after surgery.
Bays ; Cartilage ; Endoscopy ; Facial Neuralgia ; Facial Pain ; Methods ; Mucocele ; Transplants

OBJECTIVES: To estimate the number and risk of imported infections resulting from people visiting Asian and Latin American countries.METHODS: The dataset of visitors to 5 Asian countries with dengue were analyzed for 2016 and 2017, and in the Philippines, Thailand and Vietnam, imported cases of zika virus infection were also reported. For zika virus, a single imported case was reported from Brazil in 2016, and 2 imported cases reported from the Maldives in 2017. To understand the transmissibility in 5 Southeast Asian countries, the estimate of the force of infection, i.e., the hazard of infection per year and the average duration of travel has been extracted. Outbound travel numbers were retrieved from the World Tourism Organization, including business travelers.RESULTS: The incidence of imported dengue in 2016 was estimated at 7.46, 15.00, 2.14, 4.73 and 2.40 per 100,000 travelers visiting Philippines, Indonesia, Thailand, Malaysia and Vietnam, respectively. Similarly, 2.55, 1.65, 1.53, 1.86 and 1.70 per 100,000 travelers in 2017, respectively. It was estimated that there were 60.1 infections (range: from 16.8 to 150.7 infections) with zika virus in Brazil, 2016, and 345.6 infections (range: from 85.4 to 425.5 infections) with zika virus in the Maldives, 2017.CONCLUSION: This study emphasizes that dengue and zika virus infections are mild in their nature, and a substantial number of infections may go undetected. An appropriate risk assessment of zika virus infection must use the estimated total size of infections.
Asia, Southeastern ; Asian Continental Ancestry Group ; Brazil ; Commerce ; Dataset ; Dengue ; Humans ; Incidence ; Indian Ocean Islands ; Indonesia ; Korea ; Latin America ; Malaysia ; Philippines ; Risk Assessment ; Thailand ; Vietnam ; Zika Virus ; Zika Virus Infection

OBJECTIVE: Enhanced technology in computer and internet has driven scale and quality of data to be improved in various areas including healthcare sectors. Machine Learning (ML) has played a pivotal role in efficiently analyzing those big data, but a general misunderstanding of ML algorithms still exists in applying them (e.g., ML techniques can settle a problem of small sample size, or deep learning is the ML algorithm). This paper reviewed the research of diagnosing mental illness using ML algorithm and suggests how ML techniques can be employed and worked in practice. METHODS: Researches about mental illness diagnostic using ML techniques were carefully reviewed. Five traditional ML algorithms-Support Vector Machines (SVM), Gradient Boosting Machine (GBM), Random Forest, Naïve Bayes, and K-Nearest Neighborhood (KNN)-frequently used for mental health area researches were systematically organized and summarized. RESULTS: Based on literature review, it turned out that Support Vector Machines (SVM), Gradient Boosting Machine (GBM), Random Forest, Naïve Bayes, and K-Nearest Neighborhood (KNN) were frequently employed in mental health area, but many researchers did not clarify the reason for using their ML algorithm though every ML algorithm has its own advantages. In addition, there were several studies to apply ML algorithms without fully understanding the data characteristics. CONCLUSION: Researchers using ML algorithms should be aware of the properties of their ML algorithms and the limitation of the results they obtained under restricted data conditions. This paper provides useful information of the properties and limitation of each ML algorithm in the practice of mental health.
Bays ; Forests ; Health Care Sector ; Internet ; Learning ; Machine Learning ; Mental Health ; Residence Characteristics ; Sample Size ; Support Vector Machine

As an important branch of traditional medicines,medicinal marine organisms have many advantages,including biological diversity,remarkable biological activity,especial for the treatment of anti-cancer,anti-virus,anti-coagulation,analgesia,anti-bacterial,cardiovascular and cerebrovascular diseases. In recent years,with the continuous exploration of marine organisms by human beings,many marine organisms with specific biological activities and medicinal prospects have been found,which have attracted great attention around the world and thus called " new hope" to solve human health problems. However,due to the rapid development of modern industry,heavy metal pollution not only poses a great threat to medicinal marine living resources,but also hinders the development of marine biomedical industry and threatens human health. In view of this,this paper introduced the development trend of medicinal marine organisms and the current situation of heavy metal pollution and focusing on the analysis technology and chemical removal technology of heavy metals in medicinal marine organisms,which is to provide reference for the heavy metals control in marine medicines and the development and utilization of marine medicines.
Aquatic Organisms ; China ; Environmental Monitoring ; Medicine, Chinese Traditional ; Metals, Heavy/analysis* ; Water Pollutants, Chemical/analysis*

OBJECTIVES: The objective of this study was to compare the performance of two popularly used early sepsis diagnostic criteria, systemic inflammatory response syndrome (SIRS) and quick Sepsis-related Organ Failure Assessment (qSOFA), using statistical and machine learning approaches. METHODS: This retrospective study examined patient visits in Emergency Department (ED) with sepsis related diagnosis. The outcome was 28-day in-hospital mortality. Using odds ratio (OR) and modeling methods (decision tree [DT], multivariate logistic regression [LR], and naïve Bayes [NB]), the relationships between diagnostic criteria and mortality were examined. RESULTS: Of 132,704 eligible patient visits, 14% died within 28 days of ED admission. The association of qSOFA ≥2 with mortality (OR = 3.06; 95% confidence interval [CI], 2.96–3.17) greater than the association of SIRS ≥2 with mortality (OR = 1.22; 95% CI, 1.18–1.26). The area under the ROC curve for qSOFA (AUROC = 0.70) was significantly greater than for SIRS (AUROC = 0.63). For qSOFA, the sensitivity and specificity were DT = 0.39, LR = 0.64, NB = 0.62 and DT = 0.89, LR = 0.63, NB = 0.66, respectively. For SIRS, the sensitivity and specificity were DT = 0.46, LR = 0.62, NB = 0.62 and DT = 0.70, LR = 0.59, NB = 0.58, respectively. CONCLUSIONS: The evidences suggest that qSOFA is a better diagnostic criteria than SIRS. The low sensitivity of qSOFA can be improved by carefully selecting the threshold to translate the predicted probabilities into labels. These findings can guide healthcare providers in selecting risk-stratification measures for patients presenting to an ED with sepsis.
Artificial Intelligence ; Bays ; Diagnosis ; Emergency Service, Hospital ; Health Personnel ; Hospital Mortality ; Humans ; Logistic Models ; Machine Learning* ; Medical Informatics ; Methods* ; Mortality ; Odds Ratio ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Sepsis ; Severity of Illness Index ; Systemic Inflammatory Response Syndrome ; Trees

OBJECTIVES: Clusterin (CLU) is known as apolipoprotein J, and has three isoforms with different biological functions. CLU is associated with various diseases such as Alzheimer disease, atherosclerosis, and some malignancies. Recent studies report an association of CLU with inflammation and immune response in inflammatory airway diseases. However, the effect of CLU on mucin secretion of airway epithelial cells has not yet been understood. Therefore, the effect and brief signaling pathway of CLU on MUC5AC (as a major secreted mucin) expression were investigated in human airway epithelial cells. METHODS: In the tissues of nasal polyp and normal inferior turbinate, the presence of MUC5AC and CLU was investigated using immunohistochemical stain and Western blot analysis. In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway of CLU on MUC5AC expression were investigated using immunohistochemical stain, reverse transcription-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and Western blot analysis. RESULTS: In the nasal polyps, MUC5AC and CLU were abundantly present in the epithelium on immunohistochemical stain, and nuclear CLU (nCLU) was strongly detected on Western blot analysis. In human NCI-H292 airway epithelial cells or the primary cultures of normal nasal epithelial cells, recombinant nCLU increased MUC5AC expression, and significantly activated phosphorylation of NF-κB. And BAY 11-7085 (a specific NF-κB inhibitor) and knockdown of NF-κB by NF-κB siRNA (small interfering RNA) significantly attenuated recombinant nCLU-induced MUC5AC expression. CONCLUSION: These results suggest that nCLU induces MUC5AC expression via the activation of NF-κB signaling pathway in human airway epithelial cells.
Alzheimer Disease ; Atherosclerosis ; B-Lymphocytes ; Bays ; Blotting, Western ; Clusterin* ; Epithelial Cells* ; Epithelium ; Humans* ; Immunoenzyme Techniques ; Inflammation ; Mucins ; Nasal Polyps ; NF-kappa B ; Phosphorylation ; Protein Isoforms ; Real-Time Polymerase Chain Reaction ; RNA, Small Interfering ; Turbinates