ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Nocardiosis is an uncommon infectious disease that bears certain similarities to tuberculosis, with a continuous increase in its incidence and a poor prognosis. In traditional Chinese medicine, the leaves of Cajanus cajan (L.) Millsp. are employed to treat wounds, malaria, coughs, and abdominal pain. AIM OF THE STUDY: In this study, we investigated the effects and mechanisms of longistylin A (LGA), a natural stilbene isolated from C. cajan, as a potential antibiotic against nocardiosis. MATERIALS AND METHODS: LGA was isolated from the leaves of C. cajan and assessed using a minimum bactericidal concentration (MBC) determination against Nocardia seriolae. Multi-omics analysis encompassing genes, proteins, and metabolites was conducted to investigate the impact of LGA treatment on N. seriolae. Additionally, quantitative analysis of 40 cytokinins in N. seriolae mycelium was performed to assess the specific effects of LGA treatment on cytokinin levels. Cryo-scanning electron microscopy was utilized to examine morphological changes induced by LGA treatment, particularly in the presence of exogenous trans-zeatin-O-glucoside (tZOG). The therapeutic effect of LGA was investigated by feeding N. seriolae-infected largemouth bass. RESULTS: LGA exhibited significant efficacy against N. seriolae, with MBC value of 2.56 µg/mL. Multi-omics analysis revealed that LGA disrupted glycerophospholipid metabolism and hormone biosynthesis by notably reducing the expression of glycerol-3-phosphate dehydrogenase and calmodulin-like protein. Treatment with LGA markedly disrupted 12 distinct cytokinins in N. seriolae mycelium. Additionally, the addition of exogenous tZOG counteracted the inhibitory effects of LGA on filamentous growth, resulting in mycelial elongation and branching. Furthermore, LGA treatment improved the survival rate of largemouth bass infected with N. seriolae. CONCLUSIONS: We found for the first time that LGA from C. cajan exhibited significant efficacy against N. seriolae by interfering with glycerophospholipid metabolism and cytokinin biosynthesis.
Subject(s)
Anti-Bacterial Agents , Cajanus , Cytokinins , Glycerophospholipids , Nocardia , Nocardia/metabolism , Nocardia/drug effects , Cytokinins/pharmacology , Cytokinins/biosynthesis , Cytokinins/metabolism , Glycerophospholipids/metabolism , Glycerophospholipids/biosynthesis , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Plant LeavesABSTRACT
Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to â¼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.
Subject(s)
Glioblastoma , Nanoparticles , Neoplasms , Humans , Glioblastoma/diagnostic imaging , Glioblastoma/therapy , Phototherapy/methods , Brain , Blood-Brain Barrier , Coloring Agents , Theranostic Nanomedicine/methods , Nanoparticles/therapeutic use , Cell Line, TumorABSTRACT
We use low-molecular-weight branched polyethylenimine (PEI) to produce cytocompatible reduced graphene oxide quantum dots (rGOQD) as a photothermal agent and covalently bind it with the photosensitizer IR-820. The rGOQD/IR820 shows high photothermal conversion efficiency and produces reactive oxygen species (ROS) after irradiation with near-infrared (NIR) light for photothermal/photodynamic therapy (PTT/PDT). To improve suspension stability, rGOQD/IR820 was PEGylated by anchoring with the DSPE hydrophobic tails in DSPE-PEG-Mal, leaving the maleimide (Mal) end group for covalent binding with manganese dioxide/bovine serum albumin (MnO2/BSA) and targeting ligand cell-penetrating peptide (CPP) to synthesize rGOQD/IR820/MnO2/CPP. As MnO2 can react with intracellular hydrogen peroxide to produce oxygen for alleviating the hypoxia condition in the acidic tumor microenvironment, the efficacy of PDT could be enhanced by generating more cytotoxic ROS with NIR light. Furthermore, quercetin (Q) was loaded to rGOQD through π-π interaction, which can be released in the endosomes and act as an inhibitor of heat shock protein 70 (HSP70). This sensitizes tumor cells to thermal stress and increases the efficacy of mild-temperature PTT with NIR irradiation. By simultaneously incorporating the HSP70 inhibitor (Q) and the in situ hypoxia alleviating agent (MnO2), the rGOQD/IR820/MnO2/Q/CPP can overcome the limitation of PTT/PDT and enhance the efficacy of targeted phototherapy in vitro. From in vivo study with an orthotopic brain tumor model, rGOQD/IR820/MnO2/Q/CPP administered through tail vein injection can cross the blood-brain barrier and accumulate in the intracranial tumor, after which NIR laser light irradiation can shrink the tumor and prolong the survival times of animals by simultaneously enhancing the efficacy of PTT/PDT to treat glioblastoma.
Subject(s)
Antineoplastic Agents , Glioblastoma , Graphite , Photochemotherapy , Quantum Dots , Animals , Manganese Compounds/pharmacology , Manganese Compounds/chemistry , Glioblastoma/drug therapy , Quantum Dots/therapeutic use , Heat-Shock Proteins , Reactive Oxygen Species , Tumor Hypoxia , Oxides/pharmacology , Oxides/chemistry , Phototherapy , Hypoxia , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
Practical gas sensing application requires sensors to quantify target analytes with high sensitivity and reproducibility. However, conventional surface enhanced Raman scattering (SERS) sensor lacks reproducibility and quantification arising from variations of "hot spot" distribution and measurement conditions. Here, a ratio-dependent SERS sensor was developed for quantitative label-free gas sensing. Au@Ag-Au nanoparticles (NPs) were filtered onto anodic aluminum oxide (AAO) forming Au@Ag-Au@AAO SERS substrate. 4-MBA was encapsulated in the gap of Au@Ag-Au and served as the internal standard (IS) to calibrate SERS signal fluctuation for improved quantification ability. Combined with headspace sampling method, SO2 residue in traditional Chinese medicine (TCM) can be extracted and captured on the immediate vicinity of Au@Ag-Au surface. The intensity ratio I613 cm-1/I1078 cm-1 showed excellent linearity within the range of 0.5 mg/kg-500 mg/kg, demonstrating superior quantification performance for SO2 detection. Signals for concentration as low as 0.05 mg/kg of SO2 could be effectively collected, much lower than the strictest limit 10 mg/kg in Chinese Pharmacopoeia. Combined with a handheld Raman spectrometer, handy and quantitative TCM quality evaluation in aspect of SO2 residue was realized. This ratiometric SERS sensor functioned well in rapid on-site SO2 quantification, exhibiting excellent sensitivity and simple operability.
Subject(s)
Metal Nanoparticles , Metal Nanoparticles/chemistry , Gold/chemistry , Reproducibility of Results , Silver/chemistry , Medicine, Chinese TraditionalABSTRACT
Type 2 diabetes mellitus (T2DM), a common and frequently occurring disease in contemporary society, has become a global health threat. However, current mainstream methods of prevention and treatment, mainly including oral hypoglycemic drugs and insulin injections, do not fundamentally block the progression of T2DM. Therefore, it is imperative to find new ways to prevent and treat diabetes. Traditional Chinese medicine is characterized by multiple components, pathways, and targets with mild and long-lasting effects. Pharmacological studies have shown that nourishing yin traditional Chinese medicine (NYTCM) can play a positive role in the treatment of T2DM by regulating pathways such as the phosphatidylinositol 3-kinase/serine-threonine kinase, mitogen-activated protein kinase, nuclear factor-kappa B, and other pathways to stimulate insulin secretion, protect and repair pancreatic ß cells, alleviate insulin resistance, ameliorate disordered glucose and lipid metabolism, mitigate oxidative stress, inhibit inflammatory responses, and regulate the intestinal flora. The pharmacologic activity, mechanisms, safety, and toxicity of NYTCM in the treatment of T2DM are also reviewed in this manuscript.
ABSTRACT
Human milk oligosaccharides, including free oligosaccharides and glycoconjugates, exert a key role in neonatal health and development. Changes in free oligosaccharides of milk from different ethnic groups have been documented. In this study, human milk was collected from Han, Hui, and Tibetan populations in northwest China, and differences in N/O-glycome among these three ethnic groups were systematically compared using online high-performance liquid chromatography-tandem mass spectrometry. Among the 63 detected N-glycans, 35 showed significant differences between the three ethnic groups (p < 0.05). Among the 70 detected O-glycans, four neutral O-glycans and six acidic O-glycans exhibited significant differences among the three ethnic groups (p < 0.05), with six acidic O-glycans reported for the first time. Overall, the extent of milk N/O-glycosylation was higher in the Han population than in the Hui or Tibetan groups. This trend was particularly pronounced for the main sialylated N/O-glycans. Except for sulfated O-glycans, which were higher in the milk from Tibetan mothers, the other types of N/O-glycans were present in similar proportions across all ethnic groups. Understanding the composition of N/O-glycans in human milk can help research on the structure-function relationship of glycans.
Subject(s)
Colostrum , Tandem Mass Spectrometry , Female , Pregnancy , Infant, Newborn , Humans , Tandem Mass Spectrometry/methods , Colostrum/chemistry , Ethnicity , Milk, Human/chemistry , Polysaccharides/chemistry , Oligosaccharides/chemistryABSTRACT
Di(2-ethylhexyl) phthalate (DEHP) is regarded as a priority environmental pollutant. This study explored the adsorption and accumulation of DEHP within the ginseng-soil system and the mechanism of DEHP toxicity to ginseng (Panax ginseng C.A. Meyer). Under exposure to 22.10 mg/kg DEHP in soil, DEHP mainly accumulated in ginseng leaves (20.28 mg/kg), stems (4.84 mg/kg) and roots (2.00 mg/kg) after 42 days. The oxidative damage, metabolism, protein express of ginseng were comprehensively measured and analyzed. The results revealed that MDA presented an activation trend in ginseng stems and leaves after 42 days of DEHP exposure, while the opposite trend was observed for POD. Levels of ginsenoside metabolites Rg2, Rg3, Rg5, Rd, Rf and CK decreased in the ginseng rhizosphere exudates under DEHP stress. Further investigations revealed that DEHP disrupts ginsenoside synthesis by inducing glycosyltransferase (GS) and squalene synthase (SS) protein interactions. Molecular docking indicated that DEHP could stably bind to GS and SS by intermolecular forces. These findings provide new information on the ecotoxicological effect of DEHP on ginseng root.
Subject(s)
Diethylhexyl Phthalate , Ginsenosides , Panax , Phthalic Acids , Soil Pollutants , Diethylhexyl Phthalate/metabolism , Soil , Soil Pollutants/analysis , Panax/metabolism , Molecular Docking SimulationABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside â ¡ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Interferon Type I , Animals , Mice , Humans , Interferon Type I/pharmacology , Interferon Type I/therapeutic use , Influenza, Human/drug therapy , Signal Transduction , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Immunity, InnateABSTRACT
PURPOSE: To determine the incidence of the documentation of athlete failure of preparticipation sports physicals. METHODS: This was a retrospective observational study that involved review of preparticipation examination physical form documentation from multiple clinicians for all student athletes who participated in athletics during the 2018 to 2019 academic year at Galveston Independent School District (GISD). We collected the reasons for failure to pass the preparticipation physical examination. RESULTS: Of the approximately 800 student athlete forms reviewed, 183 forms indicated individual athletes failed the visual acuity or cardiovascular portions of the preparticipation physical examination. DISCUSSION: Athlete failures of the preparticipation physical examination may cause delays in sports participation, and time and monetary costs to students and their parents. Inconsistences in guidelines used to clear athletes as well as variation in form completion impacts whether athletes reportedly failed or passed the examination. Mass participation screening becomes a safety net for communities for athletes who may not have primary care providers to encourage follow-up with a regular clinician for previously undiagnosed medical issues and standardizing guideline use and form completion across clinicians who do these exams may improve numbers of athletes who are cleared to play sports. CONCLUSION: Focusing on preventable and addressable preparticipation examination failures may help clinicians who perform these exams, while also establishing a safety net for previously undiagnosed medical conditions. Instituting yearly vision checks, addressing cardiovascular issues, and encouraging yearly follow-up with primary care clinicians can more readily address physical and mental health issues and will provide more comprehensive care to student athletes.
Subject(s)
Sports Medicine , Sports , Humans , Mass Screening , Physical Examination , Schools , Costs and Cost AnalysisABSTRACT
Studies have confirmed that the health hazards of patients with lower limb injuries combined with osteoporosis are more obvious. This study is mainly based on the Taiwan National Health Insurance Database, and through big data analysis, it shows that the combined treatment of traditional Chinese medicine (TCM) is helpful to the health of patients with lower limb injuries combined with osteoporosis. A total of 9989 combined TCM-treated patients and 19,978 2:1 sex-, age-, and index-year-matched controls who did not receive TCM treatment were selected from the Taiwan National Health Insurance Database. Cox proportional hazards analyzes were performed to compare fracture surgery, inpatient, and all-cause mortality during a mean follow-up period of 17 years. A total of 5406/8601/2564 enrolled-subjects (14.11%/25.46%/5.53%) had fracture surgery/inpatient/all-cause mortality, including 1409/2543/552 in the combined TCM group (14.11%/25.46%/5.53%) and 3997/6058/2012 in the control group (20.01%/30.32%/10.07%). Cox proportional hazard regression analysis showed a lower rate of fracture surgery, inpatient and all-cause mortality for subjects in the combined TCM group (adjusted hazard ratios [HR] = 0.723; 95% confidence intervals [CI] = 0.604-0.810, P < .001; adjusted hazard ratios [HR] = 0.803; 95% CI = 0.712-0.950, P = .001; adjusted HR = 0.842; 95% CI = 0.731-0.953, P = .007, respectively). After 10 years of follow-up, the cumulative incidence of fracture surgery in patients combining TCM treatment seems to be half of that without combining TCM treatment those are shown in Kaplan-Meier analysis with statistically significant (log rank, P < .001, P < .001, and P = .010, respectively). This study hopes to provide clinicians with the option of combined TCM treatment for patients of lower limbs injuries combined with osteoporosis, so that such patients will be associate with a lower risk of fracture surgery, inpatient or all-cause mortality.
Subject(s)
Drugs, Chinese Herbal , Fractures, Bone , Osteoporosis , Humans , Medicine, Chinese Traditional , Cohort Studies , Retrospective Studies , Osteoporosis/complications , Osteoporosis/drug therapy , Taiwan/epidemiology , Lower Extremity , Drugs, Chinese Herbal/therapeutic useABSTRACT
This study investigates the impact of various zinc supplementation methods on anemia in rats induced by phenylhydrazine (PHZ) and in 5/6-nephrectomized anemic rats. We compare oral zinc sulfate (ZnSO4) supplementation, oyster Crassostrea gigas supplementation, and hard clam Meretrix lusoria supplementation on red blood cell (RBC) levels. Oral zinc-rich oyster supplementation (2.70 mg Zn (30 g oyster)/day/rat) effectively corrects anemia in both experimental groups. Rats orally fed oysters for four days exhibit similar effectiveness as those receiving a single ZnSO4 injection (0.95 mg Zn (4.18 mg ZnSO4â 7H2O)/rat). In contrast, oral ZnSO4 supplementation (2.70 mg Zn (11.88 mg ZnSO4â 7H2O)/day/rat) does not significantly increase RBC levels, suggesting better zinc absorption from oysters. A placebo group of anemic rats supplemented with hard clams, similar in composition to oysters but much lower in zinc, did not change RBC counts. This supports oysters' high zinc content as the key to correcting anemia. Oysters also contain high iron levels, offering a potential solution for iron-deficiency anemia while supporting bone marrow erythropoiesis. In summary, oral oyster supplementation emerges as an effective strategy to correct anemia in rats with added zinc and iron support for erythropoiesis.
Subject(s)
Anemia , Crassostrea , Rats , Animals , Zinc , Anemia/drug therapy , Dietary Supplements , Iron/therapeutic useABSTRACT
Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field.
Subject(s)
Drugs, Chinese Herbal , Nanoparticles , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional , Biological Availability , Nanotechnology , Drug Delivery SystemsABSTRACT
Ataxia telangiectasia and Rad3-related protein (ATR) is a critical component of the DNA damage response and a potential target in the treatment of cancers. An ATR inhibitor, BAY 1895344, was evaluated for its use in differentiated thyroid cancer (DTC) therapy. BAY 1895344 inhibited cell viability in four DTC cell lines (TPC1, K1, FTC-133, and FTC-238) in a dose-dependent manner. BAY 1895344 treatment arrested DTC cells in the G2/M phase, increased caspase-3 activity, and caused apoptosis. BAY 1895344 in combination with either sorafenib or lenvatinib showed mainly synergistic effects in four DTC cell lines. The combination of BAY 1895344 with dabrafenib plus trametinib revealed synergistic effects in K1 cells that harbor BRAFV600E. BAY 1895344 monotherapy retarded the growth of K1 and FTC-133 tumors in xenograft models. The combinations of BAY 1895344 plus lenvatinib and BAY 1895344 with dabrafenib plus trametinib were more effective than any single therapy in a K1 xenograft model. No appreciable toxicity appeared in animals treated with either a single therapy or a combination treatment. Our findings provide the rationale for the development of clinical trials of BAY 1895344 in the treatment of DTC.
Subject(s)
Adenocarcinoma , Thyroid Neoplasms , Animals , Humans , Thyroid Neoplasms/pathology , Phenylurea Compounds/pharmacology , Phenylurea Compounds/therapeutic use , Sorafenib/pharmacology , Adenocarcinoma/drug therapy , Ataxia Telangiectasia Mutated ProteinsABSTRACT
PURPOSE: Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS. MATERIALS AND METHODS: This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model. RESULTS: A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL² predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17-2.88) and conversion (HR 1.56, 95% CI 1.05-2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91-2.18; ≥50%: HR 1.97, 95% CI 1.1453-3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06-6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years). CONCLUSIONS: AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.
ABSTRACT
Phytochemical investigation on the anti-inflammatory fraction extracted from the whole plant of Euphorbia helioscopia L. led to the isolation of three new ent-atisane diterpenoids (1-3) and five known analogues (4-8). The structures and absolute configurations of the new compounds were elucidated by comprehensive analysis of the NMR, MS, IR, ECD, and X-ray crystallography. It is worth mentioning that compound 3 belongs to a rare class of ent-atisane diterpenoid featuring a hydroxyl group at C-9. Bioactivity investigation showed that compounds 4, 7, and 8 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.
Subject(s)
Diterpenes , Euphorbia , Euphorbia/chemistry , Diterpenes/pharmacology , Diterpenes/chemistry , Magnetic Resonance Spectroscopy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Molecular StructureABSTRACT
PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.
Subject(s)
Metabolome , Prostatic Neoplasms , Humans , Male , Biopsy , Neoplasm Grading , Prostate-Specific Antigen , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Prostatic Neoplasms/urine , Risk Factors , Early Detection of Cancer/methods , Urinalysis/methods , Urine/chemistryABSTRACT
As a renewable carbon source produced from organic wastes by acidogenic fermentation, volatile fatty acids (VFAs) are important intermediates in chemical and biological fields and beneficial to resource recovery and carbon neutrality. Maximizing VFA production by some strategies without additional chemicals is critical to increasing economic and environmental benefits. In this study, the effects of initial organic load (OL) on the performance of VFA production, variations of intermediate metabolites, and the thermogravimetric properties of potato peel waste (PPW) during batch acidogenic fermentation were studied. The results showed that the concentration of VFAs increased with the increase of initial OL, while the VFA yield decreased with the increase of initial OL. When the initial OL was in the range of 28.4 g VS/L-91.3 g VS/L, the fermentation type of PPW was butyric acid fermentation. The highest butyric acid proportion of 61.3% was achieved with the initial OL of 71.5 g VS/L. With the increase of initial OL, the proportion of acetic acid and the utilization rate of protein in the PPW decreased. VFAs were produced from proteins and carbohydrates in the early stage and mainly produced from carbohydrates in the later stage. The production efficiency of VFA was relatively high with the initial OL of 71.5 g VS/L, because more easily-biodegradable compounds were solubilized. The results showed that suitably increased initial OL could accelerate acidogenesis, reduce hydrolysis time, and increase the proportion of butyric acid. The findings in this work suggest that PPW is a promising feedstock for butyric acid biosynthesis and appropriate initial OL is beneficial to VFA production.
Subject(s)
Solanum tuberosum , Fermentation , Bioreactors , Fatty Acids, Volatile , Acids , Carbohydrates , Butyric Acid , Hydrogen-Ion Concentration , SewageABSTRACT
The ingestion of contaminated tea involves the risk of human exposure to residues of neonicotinoids (NEOs). Nevertheless, there is little empirical research about this topic; to bridge the current knowledge gap, we collected 220 samples of various tea products from four geographical areas in China, including unfermented green tea, semi-fermented white tea and oolong tea, completely fermented black tea, and post-fermented dark tea. A total of six NEOs were detected from the tea leaves and infusions, namely, dinotefuran (DIN), thiamethoxam (THM), clothianidin (CLO), imidacloprid (IMI), acetamiprid (ACE), and thiacloprid (THI). The detection frequencies (DFs) and concentrations of all target NEOs were relatively high across the investigated tea samples, and the DIN, IMI and ACE residues measured in some samples exceeded the maximum residue level (MRL) standards for the European Union. Samples representing the Jiangnan area exhibited greater levels of total target NEOs (∑6NEOs) than samples representing the Jiangbei area (p < 0.001). Moreover, dark tea samples were found to have far higher levels of NEO residues than green (p < 0.001), white (p < 0.05), or oolong (p < 0.001) samples. The health risks associated with exposure to NEO residues via tea were small for both children and adults in terms of acute, chronic, and cumulative dietary exposure risk assessments. The transfer rates (TRs) of NEOs observed in white, black, and dark tea infusions gradually decreased after the third brewing time. As such, it is recommended to only consume tea that has been brewed at least three times. The presented results not only describe the extent of NEO contamination in Chinese tea leaves and infusions, but also provide tea drinking guidelines for consumers.
Subject(s)
Camellia sinensis , Insecticides , Adult , Child , Humans , Insecticides/analysis , Neonicotinoids/analysis , Nitro Compounds/analysis , Tea/chemistry , Camellia sinensis/chemistry , ChinaABSTRACT
OBJECTIVE: To observe the expression of local macrophages and related cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) after catgut implantation in "Zusanli"(ST 36) in rats, so as to explore its underlying mechanisms in inducing therapeutic effect. METHODS: A total of 110 male SD rats were randomly divided into blank control group (n=10), catgut embedding (CE) group (n=50), and sham CE group (n=50). The CE and sham CE groups were randomly divided into 8 h, 3 d, 7 d, 14 d and 21 d subgroups after the intervention (n=10 in each time point group). Rats of the CE group were uniformly subjected into catgut embedding at ST36 once, and those of the sham CE group received embedding needle puncture at ST36 without catgut retention, and the blank control group was only grasped and fixed without other treatments. Tissues from the ST36 area in each group were collected at the corresponding time points, and the expression of CD68 in macrophages in the acupoint area was detected by immunofluorescence, the contents of TNF-α and IL-1ß in the acupoint area were detected by ELISA. RESULTS: Following catgut embedment at ST36, the contents of TNF-α and IL-1ß, and macrophage CD68 expression level began to increase at 8 h, peaked at 3 d, and then gradually decreased at 7, 14, and 21 d, being still higher in the CE group than in the blank control group at 21 d (P<0.05). Compared with the blank control group, the contents of TNF-α and IL-1ß, and macrophage CD68 expression were significantly increased at 8 h, and 3, 7, 14 and 21 d in the CE group (P<0.05). Following sham CE at ST36, the content of TNF-α at 8 h and 3 d, IL-1ß at 8 h and 3, 7 and 14 d, and expression of CD68 at 8 h were significantly increased in comparison with the blank control group (P<0.05). Comparison between the CE and sham CE groups showed that the contents of IL-1ß at 3, 7, 14 and 21 d, and contents of TNF-αï¼CD68 expression at 8 h, and 3, 7, 14 and 21 d were significantly higher in the CE group than in the sham CE group (P<0.05). CONCLUSION: Catgut embedding at ST36 can induce an increase levels of inflammatory cytokines TNF-α, IL-1ß and macrophage CD68 in the local microenvironment in rats, which may contribute to its functions in initiating therapeutic effect.
Subject(s)
Catgut , Tumor Necrosis Factor-alpha , Rats , Male , Animals , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/genetics , Interleukin-1beta/genetics , Cytokines , Acupuncture Points , Antigens, Differentiation, Myelomonocytic/genetics , Antigens, CD/geneticsABSTRACT
Acupuncture treatment in local areas is commonly used to treat pain or soreness; however, acupuncture around the neck or shoulder may be a risk factor for pneumothorax. Herein, we report two cases of iatrogenic pneumothorax after acupuncture. These points indicate that physicians should be aware of these risk factors through history-taking before acupuncture. Chronic pulmonary diseases, such as chronic bronchitis, emphysema, tuberculosis, lung cancer, pneumonia, and thoracic surgery, may be associated with a higher risk of iatrogenic pneumothorax after acupuncture. Even if the incidence of pneumothorax should be low under caution and fully evaluated, it is still recommended to arrange further imaging examinations to rule out the possibility of iatrogenic pneumothorax.