Oxymatrine protects articular chondrocytes from IL-1ß-induced damage through autophagy activation via AKT/mTOR signaling pathway inhibition.

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease characterized by persistent articular cartilage degeneration and synovitis. Oxymatrine (OMT) is a quinzolazine alkaloid extracted from the traditional Chinese medicine, matrine, and possesses anti-inflammatory properties that may help regulate the pathogenesis of OA; however, its mechanism has not been elucidated. This study aimed to investigate the effects of OMT on interleukin-1ß (IL-1ß)-induced damage and the potential mechanisms of action. METHODS: Chondrocytes were isolated from Sprague-Dawley rats. Toluidine blue and Collagen II immunofluorescence staining were used to determine the purity of the chondrocytes. Thereafter, the chondrocytes were subjected to IL-1ß stimulation, both in the presence and absence of OMT, or the autophagy inhibitor 3-methyladenine (3-MA). Cell viability was assessed using the MTT assay and SYTOX Green staining. Additionally, flow cytometry was used to determine cell apoptosis rate and reactive oxygen species (ROS) levels. The protein levels of AKT, mTOR, LC3, P62, matrix metalloproteinase-13, and collagen II were quantitatively analyzed using western blotting. Immunofluorescence was used to assess LC3 expression. RESULTS: OMT alleviated IL-1ß-induced damage in chondrocytes, by increasing the survival rate, reducing the apoptosis rates of chondrocytes, and preventing the degradation of the cartilage matrix. In addition, OMT decreased the ROS levels and inhibited the AKT/mTOR signaling pathway while promoting autophagy in IL-1ß treated chondrocytes. However, the effectiveness of OMT in improving chondrocyte viability under IL-1ß treatment was limited when autophagy was inhibited by 3-MA. CONCLUSIONS: OMT decreases oxidative stress and inhibits the AKT/mTOR signaling pathway to enhance autophagy, thus inhibiting IL-1ß-induced damage. Therefore, OMT may be a novel and effective therapeutic agent for the clinical treatment of OA.

Eye Rubbing in Chinese Patients With Keratoconus: A Multicenter Analysis.

PURPOSE: To investigate the eye rubbing habits of Chinese patients with keratoconus. METHODS: This study was carried out from 2018 to June 2022 at Shandong Eye Hospital, Qingdao Eye Hospital, and Henan Eye Hospital. The study compared the number of patients who rubbed their eyes between medical records and second time questionnaires, eye rubbing of patients with myopia and patients with keratoconus, and disease severity between patients with keratoconus. A questionnaire survey of ophthalmologists was conducted to determine their degree of awareness that eye rubbing is a risk factor for keratoconus. RESULTS: The study assessed 799 patients with keratoconus and 798 control patients, and 97 ophthalmologists. The average proportion of patients with keratoconus who rubbed their eyes was 31.0% in the medical records with an increasing trend related to the increase in ophthalmologists' awareness, 66.6% after the second follow-up, and 25.4% among patients with myopia. After multivariate analysis, the following variables showed significant results: eye rubbing frequency more than 10 times/day (odds ratio [OR], 9.168; P < .001); rubbing with knuckles (OR, 9.804; P = .001); and prone sleep position (OR, 12.427; P < .001). The proportion of patients who rubbed their eyes with stage IV keratoconus was 71.9%, 18.9% higher than those with stage I, 4.8% higher than stage II, and 17.8% higher than stage III. CONCLUSIONS: The proportion of Chinese patients with keratoconus who rubbed their eyes was relatively high. The main reasons for the low proportions reported were lack of attention. Clinical attention should be paid to eye rubbing in patients with keratoconus who should be educated to avoid it. [J Refract Surg. 2023;39(10):712-718.].

Lung cancer screening adherence among people living with and without HIV: An analysis of an integrated health system in Florida, United States (2012-2021).

Although lung cancer is a leading cause of death among people living with HIV (PLWH), limited research exists characterizing real-world lung cancer screening adherence among PLWH. Our objective was to compare low-dose computed tomography (LDCT) adherence among PLWH to those without HIV treated at one integrated health system. Using the University of Florida's Health Integrated Data Repository (01/01/2012-10/31/2021), we identified PLWH with at least one LDCT procedure, using Current Procedural Terminology codes(S8032/G0297/71271). Lung cancer screening adherence was defined as a second LDCT based on the Lung Imaging Reporting and Data System (Lung-RADS®). Lung-RADS categories were extracted from radiology reports using a natural language processing system. PLWH were matched with 4 randomly selected HIV-negative patients based on (+/- 1 year) age, Lung-RADS category, and calendar year. Seventy-three PLWH and 292 matched HIV-negative adults with at least one LDCT were identified. PLWH were more likely to be male (66% vs.52%,p < 0.04), non-Hispanic Black (53% vs.23%,p < 0.001), and live in an area of high poverty (45% vs.31%,p < 0.001). PLWH were more likely to be diagnosed with lung cancer after first LDCT (8% vs.0%,p < 0.001). Seventeen percent of HIV-negative and 12% of PLWH were adherent to LDCT screenings. Only 25% of PLWH diagnosed with category 4A were adherent compared to 44% of HIV-negative. On multivariable analyses, those with older age (66-80 vs.50-64 years) and with either Medicaid, charity-based, or other government insurance (vs. Medicare) were less likely to be adherent to LDCT screenings. PLWH may have poorer adherence to LDCT compared to their HIV-negative counterparts.

Lung Cancer Screening Adherence Among People with HIV Treated at an Integrated Health System in Florida.

We evaluated low-dose computed tomography (LDCT) adherence among people with HIV (PWH) treated at University of Florida (UF). From the UF Health Integrated Data Repository, we identified PWH who underwent at least one LDCT procedure (January 1, 2012-October 31, 2021). Lung cancer screening adherence was defined as having a second LDCT within recommended observation window, based on the Lung Imaging Reporting and Data System (Lung-RADS®). We identified 73 PWH with a history of at least one LDCT. PWH were mostly male (66%), non-Hispanic Black (53%), and living in urban (86%), high poverty (45%) areas. Almost 1 in 10 of PWH were diagnosed with lung cancer after their first LDCT. Overall, 48% and 41% of PWH were diagnosed with Lung-RADS categories 1 and 2, respectively. We observed that 12% of PWH were adherent to LDCT. Only 25% of PWH diagnosed with category 4A were adherent. PWH may have poor adherence to lung cancer screening.

A Computable Phenotype for the Identification of Sexual and Gender Minorities in Electronic Health Records.

Sexual gender minorities, including lesbian, gay, and bisexual (LGB) individuals face unique challenges due to discrimination, stigma, and marginalization, which negatively impact their well-being. Electronic health record (EHR) systems present an opportunity for LGB research, but accurately identifying LGB individuals in EHRs is challenging. Our study developed and validated a rule-based computable phenotype (CP) to identify LGB individuals and their subgroups using both structured data and unstructured clinical narratives from a large integrated health system. Validating against a sample of 537 chart-reviewed patients, our three best performing CP algorithms balancing different performance metrics, each achieved sensitivity of 1.000, PPV of 0.982, and F1-score of 0.875 in identifying LGB individuals, respectively. Applying the three best-performing CPs, our study also found that the LGB population is younger and experiences a disproportionate burden of adverse health outcomes, particularly mental health distress.

A conversational agent system for dietary supplements use.

BACKGROUND: Dietary supplements (DS) have been widely used by consumers, but the information around the efficacy and safety of DS is disparate or incomplete, thus creating barriers for consumers to find information effectively. Conversational agent (CA) systems have been applied to healthcare domain, but there is no such system to answer consumers regarding DS use, although widespread use of DS. In this study, we develop the first CA system for DS use. METHODS: Our CA system for DS use developed on the MindMeld framework, consists of three components: question understanding, DS knowledge base, and answer generation. We collected and annotated 1509 questions to develop a natural language understanding module (e.g., question type classifier, named entity recognizer) which was then integrated into MindMeld framework. CA then queries the DS knowledge base (i.e., iDISK) and generates answers using rule-based slot filling techniques. We evaluated the algorithms of each component and the CA system as a whole. RESULTS: CNN is the best question classifier with an F1 score of 0.81, and CRF is the best named entity recognizer with an F1 score of 0.87. The system achieves an overall accuracy of 81% and an average score of 1.82 with succ@3 + score of 76.2% and succ@2 + of 66% approximately. CONCLUSION: This study develops the first CA system for DS use using the MindMeld framework and iDISK domain knowledge base.

MTM1 plays an important role in the regulation of zinc tolerance in Saccharomyces cerevisiae.

BACKGROUND: Acquisition and distribution of zinc supports a number of biological processes. Various molecular factors are involved in zinc metabolism but not fully explored. BASIC PROCEDURES: Spontaneous mutants were generated in yeast with excess zinc culture followed by whole genome DNA sequencing to discover zinc metabolism related genes by bioinformatics. An identified mutant was characterized through metallomic and molecular biology methods. MAIN FINDINGS: Here we reported that MTM1 knockout cells displayed much stronger zinc tolerance than wild type cells on SC medium when exposed to excess zinc. Zn accumulation of mtm1Δ cells was dramatically decreased compared to wild type cells under excessive zinc condition due to MTM1 deletion reduced zinc uptake. ZRC1 mRNA level of mtm1Δ cells was significantly higher than that in the wild-type strain leading to increased vacuolar zinc accumulations in mtm1Δ cells. The mRNA levels of ZRT1 and ZAP1 decreased in mtm1Δ cells contributing to less Zn uptake. The zrc1Δmtm1Δ double knockout strain exhibited Zn sensitivity. MTM1 knockout did not afford resistance to excess zinc through an effect mediated through an influence on levels of ROS. Superoxide dismutase 2 (Sod2p) activity in mtm1Δ cells was severely impaired and not restored through Zn supplementation. Meanwhile, additional Zn showed no significant effect on the localization and expression of Mtm1p. PRINCIPAL CONCLUSIONS: Our study reveals the MTM1 gene plays an important role in the regulation of zinc homeostasis in yeast cells via changing zinc uptake and distribution. This discovery provides new insights for better understanding biochemical communication between vacuole and mitochondrial in relation to zinc-metabolism.

Dracocephalum heterophyllum (DH) Exhibits Potent Anti-Proliferative Effects on Autoreactive CD4+ T Cells and Ameliorates the Development of Experimental Autoimmune Uveitis.

Experimental autoimmune uveitis (EAU) is a CD4+ T cell-mediated organ-specific autoimmune disease and has been considered as a model of human autoimmune uveitis. Dracocephalum heterophyllum (DH) is a Chinese herbal medicine used in treating hepatitis. DH suppressed the production of inflammatory cytokines through the recruitment of myeloid-derived suppressor cells (MDSCs) to the liver. However, it remains elusive whether DH can directly regulate CD4+ T cell biology and hence ameliorates the development of CD4+ T cell-mediated autoimmune disease. In the current study, we found that DH extract significantly suppressed the production of pro-inflammatory cytokines by CD4+ T cells. Further study showed that DH didn't affect the activation, differentiation, and apoptosis of CD4+ T cells. Instead, it significantly suppressed the proliferation of conventional CD4+ T cells both in vitro and in vivo. Mechanistic study showed that DH-treated CD4+ T cells were partially arrested at the G2/M phase of the cell cycle because of the enhanced inhibitory phosphorylation of Cdc2 (Tyr15). In addition, we demonstrated that treatment with DH significantly ameliorated EAU in mice through suppressing the proliferation of autoreactive antigen specific CD4+ T cells. Taken together, the current study indicates that DH-mediated suppression of CD4+ T cell proliferation may provide a promising therapeutic strategy for treating CD4+ T cell-mediated diseases.

[Clinical effect of acupoint thread-embedding therapy at different intervals in the intervention of metabolic syndrome].

OBJECTIVE: To investigate the clinical effect of acupoint thread-embedding therapy at different intervals in the treatment of metabolic syndrome, and to find the optimal treatment interval. METHODS: A total of 70 patients with metabolic syndrome were randomly divided into treatment group 1 (n＝35)and treatment group 2(n＝35). Both groups were given acupoint thread-embedding therapy at Zhongwan (CV12), bilateral Liangmen (ST21), bilateral Huaroumen (ST24), bilateral Tianshu (ST25), bilateral Daimai (GB26), Guanyuan (CV4), bilateral Dachangshu (BL25), bilateral Pishu (BL20), bilateral Zusanli (ST36), bilateral Yinlingquan (SP9), and bilateral Fenglong (ST40), and the treatment interval was 7 d for treatment group 1 and 14 d for treatment group 2. Each course of treatment was 42 d, and both groups were treated for 2 courses. Waist circumfe-rence (WC), hip circumference (HC), waist-hip ratio (WHR), body mass index (BMI), serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and glycosylated hemoglobin (Hb1Ac) were measured before and after treatment to analyze clinical outcome, and adverse reactions were recorded. RESULTS: After treatment, both groups had significant reductions in WC, HC, WHR, BMI, TG, LDL-C, FPG and Hb1Ac (P<0.05) and a significant increase in HDL-C (P<0.05). Compared with treatment group 1, treatment group 2 had significant increases in WC, WHR, BMI, TG, LDL-C, FPG and Hb1Ac (P<0.05) and a significant reduction in HDL-C (P<0.05). There was no significant difference in the incidence rate of adverse reactions between the two groups (P>0.05). CONCLUSION: Under the premise of ensuring efficacy and safety, an interval of 7 d is the optimal interval for acupoint thread-embedding therapy in the clinical intervention of metabolic syndrome.

iDISK: the integrated DIetary Supplements Knowledge base.

OBJECTIVE: To build a knowledge base of dietary supplement (DS) information, called the integrated DIetary Supplement Knowledge base (iDISK), which integrates and standardizes DS-related information from 4 existing resources. MATERIALS AND METHODS: iDISK was built through an iterative process comprising 3 phases: 1) establishment of the content scope, 2) development of the data model, and 3) integration of existing resources. Four well-regarded DS resources were integrated into iDISK: The Natural Medicines Comprehensive Database, the "About Herbs" page on the Memorial Sloan Kettering Cancer Center website, the Dietary Supplement Label Database, and the Natural Health Products Database. We evaluated the iDISK build process by manually checking that the data elements associated with 50 randomly selected ingredients were correctly extracted and integrated from their respective sources. RESULTS: iDISK encompasses a terminology of 4208 DS ingredient concepts, which are linked via 6 relationship types to 495 drugs, 776 diseases, 985 symptoms, 605 therapeutic classes, 17 system organ classes, and 137 568 DS products. iDISK also contains 7 concept attribute types and 3 relationship attribute types. Evaluation of the data extraction and integration process showed average errors of 0.3%, 2.6%, and 0.4% for concepts, relationships and attributes, respectively. CONCLUSION: We developed iDISK, a publicly available standardized DS knowledge base that can facilitate more efficient and meaningful dissemination of DS knowledge.

Detecting associations between dietary supplement intake and sentiments within mental disorder tweets.

Many patients with mental disorders take dietary supplement, but their use patterns remain unclear. In this study, we developed a method to detect signals of associations between dietary supplement intake and mental disorder in Twitter data. We developed an annotated dataset and trained a convolutional neural network classifier that can identify language use pattern of dietary supplement intake with an F1-score of 0.899, a precision of 0.900, and a recall of 0.900. Using the classifier, we discovered that melatonin and vitamin D were the most commonly used supplements among Twitter users who self-diagnosed mental disorders. Sentiment analysis using Linguistic Inquiry and Word Count has shown that among Twitter users who posted mental disorder self-diagnosis, users who indicated supplement intake are more active and express more negative emotions and fewer positive emotions than those who have not mentioned supplement intake.

ALOHA: developing an interactive graph-based visualization for dietary supplement knowledge graph through user-centered design.

BACKGROUND: Dietary supplements (DSs) are widely used. However, consumers know little about the safety and efficacy of DSs. There is a growing interest in accessing health information online; however, health information, especially online information on DSs, is scattered with varying levels of quality. In our previous work, we prototyped a web application, ALOHA, with interactive graph-based visualization to facilitate consumers' browsing of the integrated DIetary Supplement Knowledge base (iDISK) curated from scientific resources, following an iterative user-centered design (UCD) process. METHODS: Following UCD principles, we carried out two design iterations to enrich the functionalities of ALOHA and enhance its usability. For each iteration, we conducted a usability assessment and design session with a focus group of 8-10 participants and evaluated the usability with a modified System Usability Scale (SUS). Through thematic analysis, we summarized the identified usability issues and conducted a heuristic evaluation to map them to the Gerhardt-Powals' cognitive engineering principles. We derived suggested improvements from each of the usability assessment session and enhanced ALOHA accordingly in the next design iteration. RESULTS: The SUS score in the second design iteration decreased to 52.2 ± 11.0 from 63.75 ± 7.2 in our original work, possibly due to the high number of new functionalities we introduced. By refining existing functionalities to make the user interface simpler, the SUS score increased to 64.4 ± 7.2 in the third design iteration. All participants agreed that such an application is urgently needed to address the gaps in how DS information is currently organized and consumed online. Moreover, most participants thought that the graph-based visualization in ALOHA is a creative and visually appealing format to obtain health information. CONCLUSIONS: In this study, we improved a novel interactive visualization platform, ALOHA, for the general public to obtain DS-related information through two UCD design iterations. The lessons learned from the two design iterations could serve as a guide to further enhance ALOHA and the development of other knowledge graph-based applications. Our study also showed that graph-based interactive visualization is a novel and acceptable approach to end-users who are interested in seeking online health information of various domains.

Analyzing Social Media Data to Understand Consumer Information Needs on Dietary Supplements.

Despite the high consumption of dietary supplements (DS), few reliable, relevant, and comprehensive online resources could satisfy information seekers. This research study aims to understand consumer information needs on DS using topic modeling, and to evaluate accuracy in correctly identifying topics from social media. We retrieved 16,095 unique questions posted on Yahoo! Answers relating to 438 unique DS ingredients mentioned in sub-section, "Alternative medicine" under the section, "Health" . We implemented an unsupervised topic modeling method, Correlation Explanation (CorEx) to unveil the various topics in which consumers are most interested. We manually reviewed the keywords of all the 200 topics generated by CorEx and assigned them to 38 health-related categories, corresponding to 12 higher-level groups. We found high accuracy (90-100%) in identifying questions that correctly align with the selected topics. The results could guide us to generate a more comprehensive and structured DS resource based on consumers' information needs.

A novel functional role of nickel in sperm motility and eukaryotic cell growth.

BACKGROUND: Metal ions are essential for numerous life processes. This study aims to investigate the relationship between seminal quality and ion levels in seminal plasma. BASIC PROCEDURES: A total of 205 semen samples were collected and seminal plasma ion levels were examined with inductively-coupled plasma-mass spectrometry. The nickel function was demonstrated by in vitro assay and cell growth. MAIN FINDINGS: The low sperm motility group showed distinctively reduced nickel concentration in seminal plasma compared with the normal sperm motility group. However, arsenic, sulfur, selenium, magnesium and zinc were negatively associated with sperm quality. No significant relationship between other examined cations and semen quality was observed. In vitro assay suggested low concentration of nickel significantly increased sperm total motility and progressive motility. Cell growth assay further confirmed nickel promoted eukaryotic yeast cell growth. Nickel level in seminal plasma may play important functions to determine sperm quality. PRINCIPAL CONCLUSIONS: Our study reveals a strong correlation between S, Mg, Se, Zn, As, Ni and seminal quality as well as discovers a novel functional role of nickel in sperm motility and eukaryotic cell growth. These findings may provide a potential avenue for assessment of sperm quality and treatment of reproduction disorders.

[Strategies on the construction of high-quality microbial natural product library--a review].

The microbial secondary metabolites are always the main source of the natural drugs. The historical paradigm of the deep ocean as a biological 'desert' has shifted to one of a 'rainforest' owing to the isolation of many novel microbes and their associated bioactive compounds. A high quality microbial and its natural product library are crucial for successful drug and other screenings. However, how to build up the library efficiently is still faced with many bottlenecks. To overcome the difficulties and limitations, we reviewed the following strategies: (1) diversifying microbial sources and dereplication; (2) diversifying gene sources and dereplication; (3) diversifying microbial metabolite sources and dereplication; (4) novel methods and technologies for bioactive secondary metabolites, especially the high-throughput synergy screening for multi-target drugs. Bioactive compounds isolated using the above chemical microbiology strategies have not only shown importance in biotechnological and pharmaceutical applications but also increased our understanding of the diversity of microbe, ecosystem functions and the exploitable biology.

High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections.

The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of approximately 20,000 microbial extracts, 12 hits were identified with broad-spectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy.

Exploring a possible way to synthesize novel better antioxidants based on vitamin E: a DFT study.

The promoting effect of heterocyclic ring and heteroatom on the antioxidant properties of vitamin E has been investigated systemically by using density functional theory. The calculated results show that the heteroatom plays a more important role in promoting the antioxidant properties than the heterocyclic ring, indicating that replacing O atom by S or Se is impossible to synthesize the novel better antioxidants. Furthermore, the bond dissociation enthalpy (BDE) and ionization potential (IP) of the corresponding molecules are decreased dramatically when the O atom is replaced by NH. In addition, the calculated results also reveal that reducing the atom number of heterocyclic ring is an ideal way to synthesize novel antioxidants with better antioxidant activity than vitamin E.