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1.
Eur J Dermatol ; 34(3): 260-266, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-39015959

ABSTRACT

Onychomycosis, a fungal nail infection, is primarily caused by dermatophytes, yeasts, and non-dermatophyte moulds (NDMs). The incidence of this disease and the predominance of specific pathogens vary across different regions and evolve. This study aimed to elucidate the epidemiology of onychomycosis and the pattern of causative pathogens in Beijing, and to ascertain the in vitro antifungal susceptibility profiles of Trichophyton rubrum against itraconazole (ITR), terbinafine (TER), and fluconazole (FLU). Involving 245 patients of onychomycosis with positive fungal culture results, the study implemented internal transcribed spacer (ITS) sequencing of ribosomal DNA (rDNA) on all collected samples. The mean age of the participants was 37.93 ± 13.73 years, with a male-to-female ratio of 1.53:1. The prevalence of toenail infections was significantly higher than that of fingernails. Distal and lateral subungual onychomycosis (DLSO) were the most frequent clinical classifications. PCR results indicated that dermatophytes were the most prevalent pathogens, followed by yeasts and NDMs, among which T. rubrum was the most dominant dermatophyte. TER demonstrated high sensitivity to T. rubrum. However, in clinical settings, some patients with onychomycosis exhibit a poor response to TER treatment. The relationship between in vitro antifungal sensitivity and clinical effectiveness is complex, and understanding the link between in vitro MIC values and clinical efficacy requires further investigation.


Subject(s)
Antifungal Agents , Fluconazole , Foot Dermatoses , Itraconazole , Microbial Sensitivity Tests , Onychomycosis , Terbinafine , Humans , Onychomycosis/microbiology , Onychomycosis/drug therapy , Onychomycosis/epidemiology , Male , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Female , Adult , Middle Aged , Terbinafine/pharmacology , Terbinafine/therapeutic use , Foot Dermatoses/microbiology , Foot Dermatoses/drug therapy , Itraconazole/pharmacology , Itraconazole/therapeutic use , Fluconazole/pharmacology , Arthrodermataceae/drug effects , Young Adult , Hand Dermatoses/microbiology , Hand Dermatoses/drug therapy , Hand Dermatoses/epidemiology , China/epidemiology , Prevalence , Trichophyton/drug effects , Aged , Adolescent
2.
Eur J Pharmacol ; 979: 176806, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986830

ABSTRACT

Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-ß1) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.

3.
J Thorac Dis ; 16(4): 2326-2340, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38738261

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD. Methods: Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), FEV1, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected. Results: YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment. Conclusions: YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.

4.
Phytomedicine ; 123: 155188, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38056146

ABSTRACT

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a global health problem with no effective treatment. Isoquercitrin (IQ) alters hepatic lipid metabolism and inhibits adipocyte differentiation. The underlying regulatory mechanisms of IQ in regulating insulin resistance (IR) and lipid metabolism remain unclear. PURPOSE: This study was aimed at investigating the effects of IQ on NASH and deciphering whether the underlying mechanisms are via modulation of galectin-3 mediated IR and lipid metabolism. METHODS: IR-HepG2 cell lines were used to demonstrate the ability of IQ to modulate galectin-3-mediated glucose disposal and lipid metabolism. A 20-week high-fat diet (HFD)-induced NASH model was established in C57BL/6J mice, and the protective effect of IQ on lipid disposal in the liver was verified. Further, the mRNA and protein levels of glucose and lipid metabolism were investigated, and lysophosphatidylcholine (LPC) and acylcarnitine (AC) profiling were performed to characterize the changes in endogenous substances associated with mitochondrial function and lipid metabolism in serum and cells. Furthermore, the pharmacokinetic features of IQ were explored in a rat model of NASH. RESULTS: IQ restored liver function and ameliorated inflammation and lipid accumulationin NASH model mice. Notably, significant regulation of the proteins included fatty acid-generating and transporting, cholesterol metabolism enzymes, nuclear transcription factors, mitochondrial metabolism, and IR-related enzymes was noted to be responsible for the therapeutic mechanisms of IQ against experimental NASH. Serum lipid metabolism-related metabolomic assay confirmed that LPC and AC biosynthesis mostly accounted for the therapeutic effect of IQ in mice with NASH and that IQ maintained the homeostasis of LPC and AC levels. CONCLUSION: This is the first study showing that IQ protects against of NASH by modulating galectin-3-mediated IR and lipid metabolism. The mechanisms responsible for liver protection and improved lipid metabolic disorder by IQ may be related to the suppression of IR and regulation of mitochondrial function and lipid metabolism. Galectin-3 down-regulation represents a potentially novel approach for the treatment and prevention of NASH.


Subject(s)
Insulin Resistance , Non-alcoholic Fatty Liver Disease , Quercetin/analogs & derivatives , Mice , Animals , Rats , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Galectin 3/genetics , Galectin 3/metabolism , Galectin 3/pharmacology , Lipid Metabolism , Mice, Inbred C57BL , Liver , Diet, High-Fat/adverse effects , Glucose/metabolism , Lipids
5.
Clin Cosmet Investig Dermatol ; 16: 3165-3170, 2023.
Article in English | MEDLINE | ID: mdl-37937316

ABSTRACT

Herpes zoster is typically a blister rash involving a single skin group, caused by the reactivation of primary varicella zoster virus infection. Disseminated herpes zoster refers to the presence of more than 20 small blisters outside the primary or adjacent skin, which is rare and usually occurs in individuals with weakened immune function. This case described a patient diagnosed with disseminated herpes zoster, with a decrease in CD4 count (379 cells/mm3) and certain skin lesions. He was subsequently screened positive for HIV. Also, we summarized other studies on the CD4 value of HIV patients with herpes zoster. Overall, for herpes zoster patients with decreased CD4 levels and certain skin manifestations, such as diffuse, ulcerative, or pustular lesions, clinicians should be aware of HIV infection.

6.
Clin Cosmet Investig Dermatol ; 16: 2557-2559, 2023.
Article in English | MEDLINE | ID: mdl-37745275

ABSTRACT

We report the case of a patient with Lymphocytic thrombophilic arteritis (LTA) with a history of 67 years. This is a relatively rare disease with no recognised guidelines for diagnosis and treatment. The long medical history from birth of this patient and the lack of positive progression may provide some new ideas for the treatment of this disease.

7.
Phys Imaging Radiat Oncol ; 27: 100474, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37560512

ABSTRACT

Inter- and intra-fractional prostate motion can deteriorate the dose distribution in extremely hypofractionated intensity-modulated proton therapy. We used verification CTs and prostate motion data calculated from 1024 intra-fractional prostate motion records to develop a voxel-wise based 4-dimensional method, which had a time resolution of 1 s, to assess the dose impact of prostate motion. An example of 100 fractional simulations revealed that motion had minimal impact on planning dose, the accumulated dose in 95 % of the scenarios fulfilled the clinical goals for target coverage (D95 > 37.5 Gy). This method can serve as a complementary measure in clinical setting to guarantee plan quality.

8.
Sci Total Environ ; 892: 164747, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37295518

ABSTRACT

The emerging contaminants metformin (MET) and its degradation product guanylurea (GUA) are released into aquatic environments through wastewater treatment plants (WWTPs). Thus, the environmental risks of wastewater with more treatments may be underestimated due to the lower effect concentration of GUA and the higher detected concentration of GUA in treated wastewater in comparison with MET. In this study, we aimed to investigate the combined toxicity mode of MET and GUA to Brachionus calyciflorus by simulating the degrees of wastewater treatments through adjustments to the ratio of MET and GUA in medium. The results showed that the 24 h-LC50 of MET, GUA, their mixtures of equal concentrations and the mixtures of equal toxic units to B. calyciflorus were 907.44, 544.53, 1185.82 and 940.52 mg/L, respectively, demonstrating GUA is significantly more toxic than MET. An antagonistic interaction between MET and GUA was found in mixture toxicity assessments. Compared with the control, MET treatments only significantly affected the intrinsic rate of population increase of rotifers (rm), while all life-table parameters were significantly affected by GUA. In addition, at medium and high concentrations (120 and 600 µmol/L), the net reproductive rate (R0) and rm of rotifers under GUA were significantly lower than those under MET. Notably, increased proportion of GUA relative to MET in binary-mixture treatments resulted in increased survival risk and reduced fecundity of rotifers. Moreover, the responses of population dynamics to exposures of MET and GUA were mainly attributed to the reproduction of rotifer, indicating that an improved wastewater treatment process is necessary to protect aquatic ecosystems. The study highlights the importance of considering the combined toxicity of emerging contaminants and degradation product in environmental risk assessment, especially the unintentional transformations of parent compound in treated wastewater.


Subject(s)
Metformin , Rotifera , Water Pollutants, Chemical , Animals , Metformin/toxicity , Wastewater , Ecosystem , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/analysis , Risk Assessment , Pharmaceutical Preparations
9.
Angew Chem Int Ed Engl ; 62(22): e202303229, 2023 May 22.
Article in English | MEDLINE | ID: mdl-36952314

ABSTRACT

Naphthospironone A, a polyhydroxy cagelike bioactive natural product, was synthesised for the first time in this study. The spiro[bicyclo[3.2.1]octane-pyran] core was constructed by an acid-promoted epoxide-opening lactonisation and a base-induced intramolecular aldol-type cyclisation.

10.
Ultrasound Med Biol ; 49(3): 723-733, 2023 03.
Article in English | MEDLINE | ID: mdl-36509616

ABSTRACT

The goal of this study was to assess the feasibility of three models for detecting hydronephrosis through ultrasound images using state-of-the-art deep learning algorithms. The diagnosis of hydronephrosis is challenging because of varying and non-specific presentations. With the characteristics of ready accessibility, no radiation exposure and repeated assessments, point-of-care ultrasound becomes a complementary diagnostic tool for hydronephrosis; however, inter-observer variability still exists after time-consuming training. Artificial intelligence has the potential to overcome the human limitations. A total of 3462 ultrasound frames for 97 patients with hydronephrosis confirmed by the expert nephrologists were included. One thousand six hundred twenty-eight ultrasound frames were also extracted from the 265 controls who had normal renal ultrasonography. We built three deep learning models based on U-Net, Res-UNet and UNet++ and compared their performance. We applied pre-processing techniques including wiping the background to lessen interference by YOLOv4 and standardizing image sizes. Also, post-processing techniques such as adding filter for filtering the small effusion areas were used. The Res-UNet algorithm had the best performance with an accuracy of 94.6% for moderate/severe hydronephrosis with substantial recall rate, specificity, precision, F1 measure and intersection over union. The Res-UNet algorithm has the best performance in detection of moderate/severe hydronephrosis. It would decrease variability among sonographers and improve efficiency under clinical conditions.


Subject(s)
Deep Learning , Hydronephrosis , Humans , Artificial Intelligence , Ultrasonography , Algorithms , Hydronephrosis/diagnostic imaging
11.
Postepy Dermatol Alergol ; 40(6): 734-740, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38282887

ABSTRACT

Introduction: Recent studies have confirmed the possibility of using upadacitinib for treating atopic dermatitis (AD). However, there is no meta-analysis to summarize and quantify the efficacy and safety of the drug, especially for adolescents with AD. Aim: To evaluate the overall efficacy and safety of upadacitinib in adults and adolescents with AD. Material and methods: We developed this systematic review and meta-analysis according to PRISMA guidelines. Risk-of-bias assessment tool, RoB2 (revised version 2019) was used for quality assessment. Results: Four RCTs were enrolled in the analysis, 3 of which on both adults and adolescents, while the other on adults only. For either adults or adolescents, the group treated with upadacitinib all had better performance than controls: EASI-75 (adults): RR = 4.68, 95% CI: 4.09, 5.35; NRS4 (adults): RR = 4.07, 95% CI: 3.15, 5.25; EASI-75 (adolescents): RR = 4.16, 95% CI: 2.70, 6.42; NRS4 (adolescents): RR = 4.52, 95% CI: 2.49, 8.21. Furthermore, upadacitinib 30 mg was more effective than 15 mg. For serious AEs, upper respiratory tract infection and headache, there was no significant difference between the upadacitinib group and controls. However, the treatment of upadacitinib may increase the risk of nasopharyngitis, increase blood creatine phosphokinase and cause acne. Conclusions: Upadacitinib seems to be a promising drug for AD. More long-term and larger-sized randomized clinical trials are required to further assess the safety and efficacy of upadacitinib for AD.

12.
Article in English | MEDLINE | ID: mdl-36498239

ABSTRACT

Global warming and environmental pollution have created a unique combination of abiotic and biotic stresses to zooplankton. However, little information is available on the effects of antipsychotic drugs commonly used to treat psychosis, such as chlorpromazine (CPZ), on non-target aquatic organisms in light of global warming. This study investigated how dopamine concentrations (DAC), acute toxicity and chronic toxicity of Brachionus calyciflorus changed in response to CPZ and gradually increasing temperatures. The results showed that the concentration range of rotifer DAC was 1.06~2.51 ng/g. At 18, 25 and 32 °C, the 24 h LC50 was 1.795, 1.242 and 0.833 mg/L, respectively. Compared to the control, exposure to CPZ significantly decreased life expectancy at hatching, the net reproduction rate, generation time, population growth rate and dopamine concentration of B. calyciflorus in all three temperatures (p < 0.05). The toxicity of CPZ to rotifers was increased by high temperature. These findings indicated that CPZ is highly toxic to rotifers, displaying high ecological risks to aquatic ecosystems.


Subject(s)
Antipsychotic Agents , Rotifera , Water Pollutants, Chemical , Animals , Zooplankton , Population Growth , Antipsychotic Agents/toxicity , Chlorpromazine/toxicity , Ecosystem , Dopamine , Water Pollutants, Chemical/toxicity , Rotifera/physiology , Reproduction
13.
Sci Rep ; 12(1): 19429, 2022 11 12.
Article in English | MEDLINE | ID: mdl-36371499

ABSTRACT

A boom in tourism may lead to the enrichment in heavy metals (HMs) in soils. Contamination with HMs poses a significant threat to the security of the soil environment. In this study, topsoil samples were collected from a tourist area of Sayram Lake, and the concentrations of HMs (Cr, Cu, Ni, Pb, Zn and Cd) were determined. With contamination and eco-risk assessment models, correlation analysis, Pb isotope ratios, redundancy analysis and positive matrix factorization (PMF) model, the risks and sources of HMs in the soil were studied. The Igeo results suggested that Cd was the primary pollutant in the tourist area of Sayram Lake. The potential ecological risk index (PERI) showed that the study area was at low risk, and the pollution load index (PLI) indicated that the study area had a moderate contamination level. Qualitative and quantitative analyses apportioned three sources of HMs, namely, natural sources (38.5%), traffic sources (27.2%) and mixed sources (tourist waste and atmospheric deposition) (34.3%). Redundancy analysis results showed that the HMs content was related to SiO2, Al2O3, TiO2, P2O5, MnO, K2O, Fe2O3 and SOC, and heavy metals tended to be stored in soil particles of grain sizes < 32 µm. These findings are expected to provide useful insights into the source identification of HMs in the soils of mountain tourism areas and provide a scientific decision-making basis for sustainable tourism development and for the assessment of ecological service values in the Tianshan Mountains.


Subject(s)
Metals, Heavy , Soil Pollutants , Soil , Lead/analysis , Soil Pollutants/analysis , Cadmium/analysis , Silicon Dioxide/analysis , Environmental Monitoring , Metals, Heavy/analysis , Risk Assessment , Isotopes/analysis , China
14.
Animals (Basel) ; 12(22)2022 Nov 18.
Article in English | MEDLINE | ID: mdl-36428428

ABSTRACT

Zooplankton bodies are organic-rich micro-environments that support fast bacterial growth. Therefore, the abundance of zooplankton-associated bacteria is much higher than that of free-living bacteria, which has profound effects on the nutrient cycling of freshwater ecosystems. However, a detailed analysis of associated bacteria is still less known, especially the relationship between those bacteria and bacterioplankton. In this study, we analyzed the relationships between Brachionus calyciflorus-associated bacterial and bacterioplankton communities in freshwater using high-throughput sequencing. The results indicated that there were significant differences between the two bacterial communities, with only 29.47% sharing OTUs. The alpha diversity of the bacterioplankton community was significantly higher than that of B. calyciflorus-associated bacteria. PCoA analysis showed that the bacterioplankton community gathered deeply, while the B. calyciflorus-associated bacterial community was far away from the whole bacterioplankton community, and the distribution was relatively discrete. CCA analysis suggested that many environmental factors (T, DO, pH, TP, PO43-, NH4+, and NO3-) regulated the community composition of B. calyciflorus-associated bacteria, but the explanatory degree of variability was only 37.80%. High-throughput sequencing revealed that Raoultella and Delftia in Proteobacteria were the dominant genus in the B. calyciflorus-associated bacterial community, and closely related to the biodegradation function. Moreover, several abundant bacterial members participating in carbon and nitrogen cycles were found in the associated bacterial community by network analysis. Predictive results from FAPROTAX showed that the predominant biogeochemical cycle functions of the B. calyciflorus-associated bacterial community were plastic degradation, chemoheterotrophy, and aerobic chemoheterotrophy. Overall, our study expands the current understanding of zooplankton-bacteria interaction and promotes the combination of two different research fields.

15.
Pharmacol Res ; 186: 106514, 2022 12.
Article in English | MEDLINE | ID: mdl-36252771

ABSTRACT

Multiple drug resistance (MDR) is the major obstacle for both chemotherapy and molecular-targeted therapy for cancer, which is mainly caused by overexpression of ABC transporters or genetic mutation of drug targets. Based on previous studies, we hypothesized that ROS/Nrf2 is the common target for overcoming acquired drug resistance to both targeted therapy and chemotherapy treatments. In this study, we firstly proved that the levels of ROS and Nrf2 were remarkably up-regulated in both H1975 (Gefitinib-resistant lung cancer cells with T790M) and A549/T (paclitaxel-resistant) cells, which is consistent with the clinical database analysis results of lung cancer patients that Nrf2 expression level is negatively related to survival rate. Nrf2 Knockdown with siRNA or tangeretin (TG, a flavonoid isolated from citrus peels) inhibited the MDR cell growth by suppressing the Nrf2 pathway, and efficiently enhanced the anti-tumor effects of paclitaxel and AZD9291 (the third generation of TKI) in A549/T or H1975, respectively. Moreover, TG sensitized A549/T cells-derived xenografts to paclitaxel via inhibiting Nrf2 and its downstream target P-gp, leading to an increased paclitaxel concentration in tumors. Collectively, targeting Nrf2 to enhance ROS may be a common target for overcoming the acquired drug resistance and enhancing the therapeutic effects of chemotherapy and molecular-targeted therapy.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , ErbB Receptors/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Quinazolines/pharmacology , NF-E2-Related Factor 2/genetics , Reactive Oxygen Species , Drug Resistance, Neoplasm , Mutation , Cell Line, Tumor , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Drug Resistance, Multiple
16.
Plant Physiol ; 190(4): 2246-2259, 2022 11 28.
Article in English | MEDLINE | ID: mdl-36047846

ABSTRACT

Fine roots and leaves, the direct interfaces of plants with their external environment along the soil-plant-atmosphere continuum, are at the front line to ensure plant adaptation to their growing habitat. This study aimed to compare the vulnerability to water deficit of fine roots and leaves of woody species from karst and mangrove forests-two water-stressed habitats-against that of timber and ornamental woody species grown in a well-watered common garden. Thus, pressure-volume curves in both organs of 37 species (about 12 species from each habitat) were constructed. Fine roots wilted at a less negative water potential than leaves in 32 species and before branch xylem lost 50% of its hydraulic conductivity in the 17 species with available data on branch xylem embolism resistance. Thus, turgor loss in fine roots can act as a hydraulic fuse mechanism against water stress. Mangroves had higher leaf resistance against wilting and lower leaf-specific area than the karst and common garden plants. Their fine roots had high specific root lengths (SRL) and high capacitance to buffer water stress. Karst species had high leaf bulk modulus, low leaf capacitance, and delayed fine root wilting. This study showed the general contribution of fine roots to the protection of the whole plant against underground water stress. Our findings highlight the importance of water storage in the leaves and fine roots of mangrove species and high tolerance to water deficit in the leaves of mangrove species and the fine roots of some karst species.


Subject(s)
Dehydration , Plant Leaves , Xylem , Ecosystem , Soil
17.
Front Pharmacol ; 13: 984611, 2022.
Article in English | MEDLINE | ID: mdl-36059967

ABSTRACT

Objective: To explore the active components and epigenetic regulation mechanism underlying the anti-inflammatory effects of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair (LFP) in carbon tetrachloride (CCl4)-induced rat liver fibrosis. Methods: The main active ingredients and disease-related gene targets of LFP were determined using TCMSP and UniProt, and liver fibrosis disease targets were screened in the GeneCards database. A network was constructed with Cytoscape 3.8.0 and the STRING database, and potential protein functions were analyzed using bioinformatics analysis. Based on these analyses, we determined the main active ingredients of LFP and evaluated their effects in a CCl4-induced rat liver fibrosis model. Serum biochemical indices were measured using commercial kits, hepatocyte tissue damage and collagen deposition were evaluated by histopathological studies, and myofibroblast activation and inflammation were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. High-performance liquid chromatography-mass spectrometry was performed to determine the levels of homocysteine, reduced glutathione, and oxidized glutathione, which are involved in inflammation and oxidative stress. Results: The main active components of LFP were quercetin, kaempferol, and luteolin, and its main targets were α-smooth muscle actin, cyclooxygenase-2, formyl-peptide receptor-2, prostaglandin-endoperoxide synthase 1, nuclear receptor coactivator-2, interleukinß, tumor necrosis factor α, CXC motif chemokine ligand 14, and transforming growth factor ß1. A combination of quercetin, kaempferol, and luteolin alleviated the symptoms of liver fibrosis. Conclusion: The results of this study support the role of LFP in the treatment of liver fibrosis, and reveal that LFP reduces collagen formation, inflammation, and oxidative stress. This study suggests a potential mechanism of action of LFP in the treatment of liver fibrosis.

18.
Ecotoxicology ; 31(6): 1023-1034, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35831721

ABSTRACT

The increasing production of nano-TiO2 has attracted extensive concerns about the ecological consequence and health risk of these compounds in natural ecosystem. However, little is known about its toxicity on zooplankton, especially its possibility to access to the food chain via dietary exposure. To address this concern, the toxic and cumulative effects of nano-TiO2 on an aquatic food chain were explored through two trophic levels independently or jointly including producer and consumer. The results revealed that exposure to suspensions of nanomaterials had negative effects on both producers and consumers. Specifically, nanoparticles reduced the density of algal cells in a concentration-dependent way, and hatching life expectancy, average lifespan, net reproductive rate, and population intrinsic growth rate of rotifers decreased significantly with the concentration of nanomaterials increased (P < 0.05). Notably, nanoparticles accumulated in algal cells and were transferred to consumers through dietary exposure. Biomagnification of nano-TiO2 was observed in this simplified food chain, as many of the biomagnification factor (BMF) values in this study were >1. Exposure concentration, exposure time and their interactions play a strong part in the accumulation of nanoparticles in algae and rotifers. Overall, the present findings confirmed that nano-TiO2 was deleterious to plankton, posing a significant environmental threat to aquatic ecosystems. Graphical abstract.


Subject(s)
Nanoparticles , Water Pollutants, Chemical , Bioaccumulation , Ecosystem , Food Chain , Nanoparticles/toxicity , Titanium/toxicity , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
19.
Can Respir J ; 2022: 9309611, 2022.
Article in English | MEDLINE | ID: mdl-35607595

ABSTRACT

Background: There is no accurate radiological measurement to estimate the severity of pediatrics acute respiratory distress syndrome (PARDS). We validated the effectiveness of an adult radiographic assessment of lung edema (RALE) score in PARDS. Aim: To assess the severity and prognosis of PARDS based on a chest radiograph (CXR) RALE scoring method. Methods: Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria were used to diagnose PARDS. General demographics, pulmonary complications, and 28-day mortality of the patients were recorded. Subgroups were compared by prognosis (survive and death) and etiology (infection and noninfection). Two observers calculated RALE independently. Each quadrant of CXR was scored by consolidation scores 0 (none alveolar opacity), 1 (extent <25%), 2 (extent 25%-50%), 3 (50%-75%), and 4 (>75%) and density scores 1 (hazy), 2 (moderate), and 3 (dense). Quadrant score equals consolidation score times density score. Total score equals to the sum of four quadrants scores. The ROC curve and survival curve were established, and the optimal cutoff score for discrimination prognosis was set. Results: 116 PARDS (72 boys and 44 girls) and 463 CXRs were enrolled. The median age was 25 months (5 months, 60.8 months) and with a mortality of 37.9% (44/116). The agreement between two independent observers was excellent (ICC = 0.98, 95% CI: 0.97-0.99). Day 3 score was independently associated with better survival (p < 0.001). The area under the curve of ROC was 0.773 (95% CI: 0.709-0.838). The cutoff score was 21 (sensitivity 71.7%, specificity 76.5%), and the hazard ratio (HR) was 9.268 (95% CI: 1.257-68.320). The pulmonary complication showed an HR of 3.678 (95% CI: 1.174-11.521) for the discrimination. Conclusion: CXR RALE score can be used in PARDS for discriminating the prognosis and has a better agreement among radiologist and pediatrician. PARDS with pulmonary complications, day 3 score whether greater than 21 points, have a better predictive effectiveness.


Subject(s)
Pediatrics , Pulmonary Edema , Respiratory Distress Syndrome , Adult , Child , Child, Preschool , Female , Humans , Male , Prognosis , Pulmonary Edema/etiology , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Sounds
20.
Cancer Med ; 11(1): 151-165, 2022 01.
Article in English | MEDLINE | ID: mdl-34821082

ABSTRACT

BACKGROUND: To evaluate whether the use of the internal target volume (ITV) delineation method improves the performance of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in terms of survival, acute toxicities, and dose-volume parameters. METHODS: A total number of 477 cervical cancer patients who received concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016 were retrospectively analyzed. They were divided into four groups: the non-ITV (N-ITV) + IMRT, ITV + IMRT, N-ITV + 3DCRT, and ITV + 3DCRT groups, with 76, 41, 327, and 33 patients, respectively. Survival analysis was performed with the Kaplan-Meier and the log-rank tests, and acute toxicity analysis was performed with the chi-squared test and the binary logistic regression test. Using the propensity score matching (PSM) method, 92 patients were matched among the four groups, and their dose-volume parameters were assessed with the Kruskal-Wallis method. RESULTS: The median follow-up time was 49 months (1-119) for overall survival (OS). The 5-year OS rate was 66.4%. The ITV delineation method was an independent prognostic factor for OS (HR [95% CI]: 0.52 [0.27, 0.98], p = 0.044) and progression-free survival (PFS) (HR [95% CI]: 0.59 [0.36, 0.99], p = 0.045). The ITV + IMRT group had the lowest incidence rate (22%) and the N-ITV + IMRT group had the highest incidence rate of grade ≥3 hematological toxicity (HT) (46.1%) among the four groups. The pelvic bone marrow relative V10, V20, and V30 in the N-ITV + IMRT group was higher than those in the ITV + IMRT and N-ITV + 3DCRT groups (p < 0.05). CONCLUSIONS: The use of ITV for IMRT treatment planning was associated with improved overall survival and progression-free survival, with lower HT rate.


Subject(s)
Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Conformal/adverse effects , Radiotherapy, Intensity-Modulated/adverse effects , Uterine Cervical Neoplasms/radiotherapy , Adult , Chemoradiotherapy , Female , Follow-Up Studies , Humans , Middle Aged , Propensity Score , Radiotherapy Dosage , Retrospective Studies , Survival Analysis , Uterine Cervical Neoplasms/mortality
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