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1.
Lab Invest ; : 102104, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945481

ABSTRACT

The glycosaminoglycan hyaluronan (HA) plays an important role in tumor progression. However, its biological and clinical significance in papillary thyroid cancer (PTC) remains unknown. Immunohistochemistry was performed to examine HA expression in tissues from PTC patients. Two PTC cell lines were treated with HA synthesized inhibitor against HA production to assess its function. Serum HA levels from 107 PTC patients, 30 Hashimoto thyroiditis, and 45 normal controls (NC) were measured by chemiluminescence immunoassay. HA levels in FNA washouts obtained from thyroid nodules and lymph nodes (LNs) were measured by chemiluminescence immunoassay. Area under the curve (AUC) were computed to evaluate HA`s clinical value. HA was highly expressed in PTC. Reducing HA production significantly inhibited PTC cell proliferation and invasion. Importantly, serum HA levels in PTC were significantly higher than in NCs and Hashimoto thyroiditis and allowed distinguishing of thyroid cancers from NCs with high accuracy (AUC=0.782). Moreover, elevated serum HA levels in PTC correlate with LN metastasis. HA levels in fine needle aspiration (FNA) washouts from PTC patients were significantly higher than in benign controls, with a high AUC value (0.8644) for distinguishing PTC from benign controls. Furthermore, HA levels in FNA washouts from metastatic LN were significantly higher than in non-metastatic LN, with a high AUC value (0.8007) for distinguishing metastatic LNs from non-metastatic LNs. HA in serum and FNA washout exhibited a potential significance for PTC diagnosis and indicator for LN metastasis in patients with PTC.

2.
Front Pharmacol ; 15: 1404738, 2024.
Article in English | MEDLINE | ID: mdl-38835657

ABSTRACT

Background: The efficacy of Chinese herbal medicine (CHM) in managing irritable bowel syndrome with diarrhea (IBS-D) accompanied by anxiety and depression remains uncertain. Thus, a systematic review was carried out employing meta-analysis and network pharmacology to ascertain the efficacy and underlying mechanisms of CHM therapy. Methods: By conducting a systematic review, including literature search, screening, and data extraction, we identified 25 randomized controlled trials to assess CHM's effectiveness in treating irritable bowel syndrome alongside anxiety and depression. Network pharmacology was utilized to scrutinize the metabolite utility of CHM in addressing this condition. Potential primary mechanisms were synthesized using information sourced from the PubMed database. Results: Twenty-five studies, including 2055 patients, were analyzed, revealing significant treatment efficacy for IBS-D in the trial group compared to controls [OR = 4.01, 95% CI (2.99, 5.36), I2 = 0%] Additionally, treatment for depression [SMD = -1.08, 95% CI (-1.30, -0.86), p < 0.00001, I2 = 68%; SDS: SMD = -1.69, 95% CI (-2.48, -0.90), p < 0.0001, I2 = 96%] and anxiety [HAMA: SMD = -1.29, 95% CI (-1.68, -0.91), p < 0.00001, I2 = 89%; SAS: SMD = -1.75, 95% CI (-2.55, -0.95), p < 0.00001, I2 = 96%] significantly improved in the trial group. Furthermore, the trial group exhibited a significantly lower disease relapse rate [OR = 0.30, 95% CI (0.20, 0.44), p < 0.00001, I2 = 0%]. CHM treatment consistently improved IBS severity (IBS-SSS) and symptom scores. Network pharmacology analysis identified key chemical metabolites in traditional Chinese medicine formulations, including Beta-sitosterol, Stigmasterol, Quercetin, Naringenin, Luteolin, Kaempferol, Nobiletin, Wogonin, Formononetin, and Isorhamnetin. Utilizing the STRING database and Cytoscape v3.9.0 software, a protein-protein interaction (PPI) network revealed the top eight key targets: IL-6, TNF, PPARG, PTGS2, ESR1, NOS3, MAPK8, and AKT1, implicated in anti-inflammatory responses, antioxidant stress modulation, and neurotransmitter homeostasis maintenance. Conclusion: Chinese Herbal Medicine (CHM) offers a promising and safe treatment approach for patients dealing with Diarrheal Irritable Bowel Syndrome (IBS-D) accompanied by anxiety and depression; thus, indicating its potential for practical implementation. The most active metabolites of CHM could simultaneously act on the pathological targets of IBS-D, anxiety, and depression.The diverse scope of CHM's therapeutic role includes various aspects and objectives, underscoring its potential for broad utilization.

3.
Water Sci Technol ; 89(11): 3021-3034, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38877628

ABSTRACT

Drainage modeling that accurately captures urban storm inundation serves as the foundation for flood warning and drainage scheduling. In this paper, we proposed a novel coupling ideology that, by integrating 2D-1D and 1D-2D unidirectional processes, overcomes the drawback of the conventional unidirectional coupling approach that fails to properly represent the rainfall surface catchment dynamics, and provides more coherent hydrological implications compared to the bidirectional coupling concept. This paper first referred to a laboratory experimental case from the literature, applied and analyzed the coupling scheme proposed in this paper and the bidirectional coupling scheme that has been widely studied in recent years, compared the two coupling solutions in terms of the resulting accuracy and applicability, and discussed their respective strengths and weaknesses to validate the reliability of the proposed method. The verified proposed coupling scheme was then applied to the modeling of a real drainage system in a region of Nanjing, China, and the results proved that the coupling mechanism proposed in this study is of practical application value.


Subject(s)
Cities , Floods , Hydrodynamics , Models, Theoretical , China , Sewage , Drainage, Sanitary
4.
Int J Mol Sci ; 25(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891905

ABSTRACT

The DABB proteins, which are characterized by stress-responsive dimeric A/B barrel domains, have multiple functions in plant biology. In Arabidopsis thaliana, these proteins play a crucial role in defending against various pathogenic fungi. However, the specific roles of DABB proteins in Brassica napus remain elusive. In this study, 16 DABB encoding genes were identified, distributed across 10 chromosomes of the B. napus genome, which were classified into 5 branches based on phylogenetic analysis. Genes within the same branch exhibited similar structural domains, conserved motifs, and three-dimensional structures, indicative of the conservation of BnaDABB genes (BnaDABBs). Furthermore, the enrichment of numerous cis-acting elements in hormone induction and light response were revealed in the promoters of BnaDABBs. Expression pattern analysis demonstrated the involvement of BnaDABBs, not only in the organ development of B. napus but also in response to abiotic stresses and Sclerotinia sclerotiorum infection. Altogether, these findings imply the significant impacts of BnaDABBs on plant growth and development, as well as stress responses.


Subject(s)
Brassica napus , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins , Stress, Physiological , Brassica napus/genetics , Brassica napus/microbiology , Brassica napus/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/genetics , Genome, Plant , Ascomycota/genetics , Plant Diseases/microbiology , Plant Diseases/genetics
5.
J Hazard Mater ; 474: 134697, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38823102

ABSTRACT

Airborne pathogens severely threaten public health worldwide. Air disinfection is essential to ensure public health. However, excessive use of disinfectants may endanger environmental and ecological security due to the residual disinfectants and their by-products. This study systematically evaluated disinfection efficiency, induction of multidrug resistance, and the underlying mechanisms of disinfectants (NaClO and H2O2) on airborne bacteria. The results showed that airborne bacteria were effectively inactivated by atomized NaClO (>160 µg/L) and H2O2 (>320 µg/L) after 15 min. However, some bacteria still survived after disinfection by atomized NaClO (0-80 µg/L) and H2O2 (0-160 µg/L), and they exhibited significant increases in antibiotic resistance. The whole-genome sequencing of the resistant bacteria revealed distinct mutations that were responsible for both antibiotic resistance and virulence. This study also provided evidences and insights into possible mechanisms underlying the induction of antibiotic resistance by air disinfection, which involved intracellular reactive oxygen species formation, oxidative stress responses, alterations in bacterial membranes, activation of efflux pumps, and the thickening of biofilms. The present results also shed light on the role of air disinfection in inducing antibiotic resistance, which could be a crucial factor contributing to the global spread of antibiotic resistance through the air.


Subject(s)
Bacteria , Disinfectants , Disinfection , Hydrogen Peroxide , Hydrogen Peroxide/pharmacology , Disinfectants/pharmacology , Disinfection/methods , Bacteria/drug effects , Bacteria/genetics , Air Microbiology , Biofilms/drug effects , Sodium Hypochlorite/pharmacology , Drug Resistance, Bacterial/genetics , Drug Resistance, Bacterial/drug effects , Anti-Bacterial Agents/pharmacology , Chlorine/pharmacology , Reactive Oxygen Species/metabolism
6.
Biochem Pharmacol ; 225: 116327, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823457

ABSTRACT

With the progressive aging of society, there is an increasing prevalence of age-related diseases that pose a threat to the elderly's quality of life. Adipose tissue, a vital energy reservoir with endocrine functions, is one of the most vulnerable tissues in aging, which in turn influences systematic aging process, including metabolic dysfunction. However, the underlying mechanism is still poorly understood. In this study, we found that NRG4, a novel adipokine, is obviously decreased in adipocyte tissues and serums during aging. Moreover, delivered recombinant NRG4 protein (rNRG4) into aged mice can ameliorate age-associated insulin resistance, glucose disorders and other metabolic disfunction. In addition, rNRG4 treatment alleviates age-associated hepatic steatosis and sarcopenia, accompanied with altered gene signatures. Together, these results indicate that NRG4 plays a key role in the aging process and is a therapeutic target for the treatment of age-associated metabolic dysfunction.


Subject(s)
Adipocytes , Aging , Mice, Inbred C57BL , Neuregulins , Animals , Mice , Neuregulins/metabolism , Neuregulins/genetics , Adipocytes/metabolism , Adipocytes/drug effects , Aging/metabolism , Male , Recombinant Proteins/administration & dosage , Recombinant Proteins/metabolism , Sarcopenia/metabolism , Sarcopenia/prevention & control , Insulin Resistance/physiology
7.
J Mater Chem B ; 12(24): 5812-5822, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38856691

ABSTRACT

Immunotherapy is an important approach in cancer treatment. Transdermal administration is emerging as a promising method for delivering immunotherapeutics. Dissolving microneedles are made mainly of soluble or biodegradable polymers and have garnered widespread attention due to their painlessness, safety, convenience, excellent drug loading capacity, and easy availability of various materials, making them an ideal transdermal delivery system. This review comprehensively summarized the preparation methods, materials, and applications of dissolving microneedles in cancer vaccines, immune checkpoint inhibitors, and adoptive cell therapy. Additionally, the challenges and perspectives associated with their future clinical translation are discussed.


Subject(s)
Administration, Cutaneous , Drug Delivery Systems , Immunotherapy , Needles , Neoplasms , Humans , Neoplasms/therapy , Neoplasms/drug therapy , Animals , Cancer Vaccines/administration & dosage
8.
Toxicol Lett ; 397: 1-10, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38710400

ABSTRACT

Glycolic acid (GA) is extensively used in cosmetic formulations and skin peeling treatments but its adverse effects, notably severe disruption of epidermal structure, limit its clinical utility. However, the detailed impact of GA on epidermal homeostasis, including changes in structure and protein expression over time, is not fully understood. This study employed a reconstructed human epidermis (RHE) model to assess the effects of varying GA concentrations on epidermal proliferation, differentiation, and desquamation at different time points. Through histology, immunofluorescence, and immunohistochemistry, we observed that 35% GA concentration adversely caused abnormal epidermal homeostasis by affecting epidermal proliferation, differentiation and desquamation. Our findings reveal time-specific responses of key proteins to GA: Filaggrin, Involucrin, Loricrin, and Ki67 showed very early responses; KLK10 an early response; and AQP3 and K10 late responses. This research provides a detailed characterization of GA's effects in an RHE model, mimicking clinical superficial peeling and identifying optimal times for detecting GA-induced changes. Our results offer insights for designing interventions to mitigate GA's adverse effects on skin, enhancing the safety and efficacy of GA peeling treatments.


Subject(s)
Cell Proliferation , Epidermis , Filaggrin Proteins , Glycolates , Homeostasis , Glycolates/toxicity , Humans , Epidermis/drug effects , Epidermis/metabolism , Homeostasis/drug effects , Cell Proliferation/drug effects , Cell Differentiation/drug effects , Time Factors , Keratinocytes/drug effects , Keratinocytes/metabolism
9.
bioRxiv ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38746305

ABSTRACT

Zika virus (ZIKV) infections cause microcephaly in new-borns and Guillain-Barre syndrome in adults raising a significant global public health concern, yet no vaccines or antiviral drugs have been developed to prevent or treat ZIKV infections. The viral protease NS3 and its co-factor NS2B are essential for the cleavage of the Zika polyprotein precursor into individual structural and non-structural proteins and is therefore an attractive drug target. Generation of a robust crystal system of co-expressed NS2B-NS3 protease has enabled us to perform a crystallographic fragment screening campaign with 1076 fragments. 48 binders with diverse chemical scaffolds were identified in the active site of the protease, with another 6 fragment hits observed in a potential allosteric binding site. Our work provides potential starting points for the development of potent NS2B-NS3 protease inhibitors. Furthermore, we have structurally characterized a potential allosteric binding pocket, identifying opportunities for allosteric inhibitor development.

10.
Front Psychol ; 15: 1344816, 2024.
Article in English | MEDLINE | ID: mdl-38770246

ABSTRACT

This paper examines the diversification of overseas subsidiaries on innovation performance of the parent company. Based on theoretical analysis and a combined Chinese firm dataset from 2000 to 2013, we find that diversification of overseas subsidiaries positively promotes the parent company innovation performance through the spillover effect of innovation capabilities. In addition, we determine that both the overseas and domestic investment layout can positively moderate the main effect. But there are differences between them. In concrete terms, the domestic investment layout plays a substitution effect in developed areas and acts a more pronounced moderating role in state-owned sample. Besides, the overseas investment layout plays a more important substitutive moderating role on non-state-owned enterprises. This research provides a special insight for studying the reverse spillover effect of OFDI in terms of the contribution of subsidiary linkages and offers several recommendations for multinational corporations to enhance the global competitiveness.

11.
Article in English | MEDLINE | ID: mdl-38780504

ABSTRACT

Nine compounds were isolated and identified from ethanolic extracts of Saposhnikovia divaricata, including one new alkaloid (1), one new pentacyclic triterpenoid (9), and seven known alkaloids (2-8). Structural elucidation of compounds 1 and 9 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for antiproliferative activity against two cancer cell lines (LN229, A549) in vitro. Compounds (1-9) showed no significant antiproliferative activity.

12.
Biosensors (Basel) ; 14(5)2024 May 07.
Article in English | MEDLINE | ID: mdl-38785706

ABSTRACT

The development of gel electrophoresis-based biodetection assays for point-of-care analysis are highly demanding. In this work, we proposed a ratiometric gel electrophoresis-based biosensing platform by employing catalytic hairpin assembly (CHA) process functions as both the signal output and the signal amplification module. Two types of nucleic acids, DNA and miRNA, are chosen for demonstration. The proposed strategy indeed provides a new paradigm for the design of a portable detection platform and may hold great potential for sensitive diagnoses.


Subject(s)
Biosensing Techniques , DNA , MicroRNAs , MicroRNAs/analysis , Catalysis , Electrophoresis , Nucleic Acids/analysis
13.
Phytochemistry ; 223: 114133, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38710375

ABSTRACT

Five undescribed elesesterpenes L-U, along with nine known 3,4-seco-lupane-type triterpenoids were isolated from the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu. Elesesterpene L-S, and U were lupane-type triterpenoids, whereas elesesterpene T was an oleanane-type triterpenoid, probably artifact, as suggested by LC-MS analysis. Out of the nine known compounds, five were initially identified in E. sessiliflorus. Moreover, their structures were definitively determined using spectroscopic analyses, and the absolute configurations of elesesterpenes L-M and sachunogenin 3-O-glucoside were clarified using X-ray crystallographic techniques. The absolute configuration of elesesterpene T was determined by measuring and calculating its ECD. In addition, all compounds were tested to examine their ability to inhibit the proliferation of HFLS-RA cells induced by TNF-α in vitro. Elesesterpene M, chiisanogenin, chiisanoside, and 3-methylisochiisanoside significantly inhibited HFLS-RA proliferation.


Subject(s)
Cell Proliferation , Eleutherococcus , Plant Leaves , Triterpenes , Tumor Necrosis Factor-alpha , Eleutherococcus/chemistry , Plant Leaves/chemistry , Triterpenes/pharmacology , Triterpenes/chemistry , Triterpenes/isolation & purification , Cell Proliferation/drug effects , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Humans , Molecular Structure , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Structure-Activity Relationship , Cell Line , Dose-Response Relationship, Drug
14.
Clin Cosmet Investig Dermatol ; 17: 1117-1125, 2024.
Article in English | MEDLINE | ID: mdl-38765194

ABSTRACT

Purpose: In the quest for a youthful appearance, women use a variety of anti- aging cosmetics. Defining skin problems is especially important for the selection of anti-aging solutions. However, the skin problems faced by Chinese women at different ages are different. This study aimed at Chinese women aged 20-40 years old and analyzed facial skin aging characteristics of those with old-perceived age. Patients and Methods: The total of 400 standard facial photographs from Chinese female volunteers aged 20-40 was assessed by another 126 Chinese women. The facial areas and skin aging characteristics that influenced age estimation were collected at the same time. Skin aging characteristics, including wrinkles, skin tone, pigmentation and pores, were analyzed based on facial photographs. Groupings were made based on deviation of perceived age from chronological age, and skin aging characteristics among groups were compared. Results: The perceived age of Chinese women aged 20-40 has a moderate correlation with chronological age. Women aged 20-30 generally had an old-perceived age. Deep skin tone was a prominent problem in this age group, with those who had the older-perceived age observed the darker and redder skin tone. Women aged 31-40 were perceived partly old but appeared with wrinkle aggravation, as well as deepening of redness, enlarged pores, and increased pigmentation at the mid-face. The perceived older women also had more visible frown lines and darker skin tone at the upper face. Conclusion: The perceived age of Chinese women aged 20-40 tends to deviate from their chronological age. Women aged 20-30 with old-perceived age are associated with deep skin tone, even found darker and redder in older-perceived women group, while women aged 31-40 are associated with wrinkles and deterioration at mid-face area and upper-face problems drive more attention in older-perceived women group.

15.
Microorganisms ; 12(5)2024 May 20.
Article in English | MEDLINE | ID: mdl-38792859

ABSTRACT

The vaginal microbiota can be classified into five major community state types (CSTs) based on the bacterial content. However, the link between different CST subtypes and vaginal infection remains unclear. Here, we analyzed 2017 vaginal microbiota samples from women of a reproductive age with vaginal infections that were published in the last decade. We found that L. iners was the most dominant in 34.8% of the vaginal samples, followed by L. crispatus (21.2%). CST I was common in healthy individuals, whereas CST III and IV were associated with dysbiosis and infection. CST III-B, IV-A, IV-B, and IV-C0 were prevalent in patients with bacterial vaginosis (BV). Based on the relative abundance of bacteria at the (sub)genus level, a random forest classifier was developed to predict vaginal infections with an area under the curve of 0.83. We further identified four modules of co-occurring bacterial taxa: L. crispatus, Gardnerella, Prevotella, and Bacteroides. The functional prediction revealed that nucleotide biosynthesis pathways were upregulated in patients with human papilloma virus, and carbohydrate degradation pathways were downregulated in patients with BV. Overall, our study identified the bacterial signatures of healthy and infected vaginal microbiota, providing unique insights into the clinical diagnosis and health status prediction of women of a reproductive age.

16.
Alpha Psychiatry ; 25(2): 243-248, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38798818

ABSTRACT

Background: In this study, the effect of magnesium sulfate and labetalol in treating pregnancy-induced hypertension (PIH) and its influence on anxiety and depression in patients are observed, and new ideas for treating anxiety and depression in PIH are introduced. Methods: A retrospective cohort study was conducted to select patients with PlH diagnosed from July 2020 to July 2023 from Affiliated Hospital of Electronic Science and Technology University and Chengdu Women' s and Children's Central Hospital in Chengdu of Sichuan Province. The changes in blood pressure, Edinburgh Postnatal Depression Scale (EPDS), and generalized anxiety disorder 7 (GAD-7) in patients with hypertensive pregnancy were collected and analyzed. Results: In our investigation, 219 patients completed the study, and 36.1% (79/219) of them developed anxiety and depression. According to whether the patients were treated with magnesium sulfate and labetalol, 49 cases were assigned to the magnesium sulfate and labetalol treatment (MSLT) group, and 30 cases were assigned to the conventional treatment (CT) group. Edinburgh Postnatal Depression Scale scores and GAD-7 scores in the MSLT group were significantly lower than those in the CT group, indicating that magnesium sulfate and labetalol can improve anxiety and depression in hypertensive patients during pregnancy. The difference was statistically significant (P < .05). According to the changes in systolic blood pressure, the clinical efficacy of patients was evaluated, and no significant difference in efficacy existed between the MSLT and CT groups. Conclusion: Magnesium sulfate and labetalol can control the blood pressure of patients with PIH and indirectly improve anxiety and depression in patients with PIH, thereby introducing new ideas for the treatment of PIH accompanied by anxiety and depression.

17.
BMC Oral Health ; 24(1): 408, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561756

ABSTRACT

BACKGROUND: Supracrestal gingival tissue dimensions (SGTDs) has been considered to be an essential element of periodontal phenotype (PP) components. This study aimed to explore the relationship between SGTDs and other PP components by digital superposition method that integrated cone beam computed tomography (CBCT) with intraoral scanning. METHODS: This cross-sectional study was conducted at the Stomatology Hospital of Fujian Medical University. Participants were recruited based on the inclusion and exclusion criteria. The data obtained from the digital scanner (TRIOS 3, 3Shape, Denmark) and CBCT images were imported into the TRIOS software (Implant Studio, 3Shape, Denmark) for computing relevant parameters. The significant level was set at 0.05. RESULTS: A total of 83 participants with 498 maxillary anterior teeth were finally included. The mean values of supracrestal gingival height (SGH) and the distance from the cementoenamel junction (CEJ) to the crest of the alveolar ridge (CEJ-ABC) on the buccal site were significantly higher than palatal SGH (SGH-p) and palatal CEJ-ABC (CEJ-ABC-p). Men exhibited taller CEJ-ABC and SGH-p than women. Additionally, tooth type was significantly associated with the SGH, SGH-p and CEJ-ABC-p. Taller SGH was associated with wider crown, smaller papilla height (PH), flatter gingival margin, thicker bone thickness (BT) and gingival thickness (GT) at CEJ, the alveolar bone crest (ABC), and 2 mm apical to the ABC. Smaller SGH-p displayed thicker BT and GT at CEJ, the ABC, and 2 and 4 mm apical to the ABC. Higher CEJ-ABC showed lower interproximal bone height, smaller PH, flatter gingival margin, thinner GT and BT at CEJ, and 2 mm apical to the ABC. Smaller CEJ-ABC-p displayed thicker BT at CEJ and 2 and 4 mm apical to the ABC. On the buccal, thicker GT was correlated with thicker BT at 2 and 4 mm below the ABC. CONCLUSION: SGTDs exhibited a correlation with other PP components, especially crown shape, gingival margin and interdental PH. The relationship between SGTDs and gingival and bone phenotypes depended on the apico-coronal level evaluated. TRIAL REGISTRATION: This study was approved by the Biomedical Research Ethics Committee of Stomatology Hospital of Fujian Medical University (approval no. 2023-24).


Subject(s)
Breast Cyst , Gingiva , Maxilla , Male , Humans , Female , Cross-Sectional Studies , Maxilla/diagnostic imaging , Gingiva/diagnostic imaging , Tooth Crown , Cone-Beam Computed Tomography/methods , China
18.
J Hazard Mater ; 471: 134337, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38640674

ABSTRACT

BACKGROUND: Hexafluoropropylene oxide trimer acid (HFPO-TA), a perfluorooctanoic acid (PFOA) substitute, exhibited strong affinity and capability to activate peroxisome proliferator activated receptor gamma (PPARγ), a lipid metabolism regulator, suggesting potential to induce metabolic toxicities. METHODS: Fertile chicken eggs were exposed to 0, 0.5, 1 or 2 mg/kg (egg weight) HFPO-TA and incubated until hatch. Serum from 0- and 3- month-old chickens were subjected to liquid chromatography ultra-high resolution mass spectrometry for HFPO-TA concentration, while liver, pancreas and adipose tissue samples were collected for histopathological assessments. In ovo PPARγ reporter and silencing system were established with lentivirus microinjection. qRT-PCR and immunohistochemistry were utilized to evaluate the expression levels of PPARγ downstream genes. RESULTS: In 3-month-old animals developmentally exposed to HFPO-TA, adipose tissue hyperplasia, hepatic steatosis, pancreas islet hypertrophy and elevated serum free fatty acid / insulin levels were observed. Results of reporter assay and qRT-PCR indicated HFPO-TA-mediated PPARγ transactivation in chicken embryo. Silencing of PPARγ alleviated HFPO-TA-induced changes, while PPARγ agonist rosiglitazone mimicked HFPO-TA-induced effects. qRT-PCR and immunohistochemistry revealed that FASN and GPD1 were upregulated following developmental exposure to HFPO-TA in 3-month-old animals. CONCLUSIONS: Developmental exposure to HFPO-TA induced persistent metabolic toxicities in chickens, in which PPARγ played a central role.


Subject(s)
Fluorocarbons , PPAR gamma , Animals , PPAR gamma/genetics , PPAR gamma/metabolism , Fluorocarbons/toxicity , Chick Embryo , Liver/drug effects , Liver/metabolism , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Chickens , Pancreas/drug effects , Pancreas/metabolism
19.
Biochim Biophys Acta Gen Subj ; 1868(7): 130631, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38685534

ABSTRACT

BACKGROUND: Vascular endothelial growth factor (VEGF) is overexpressed in most malignant tumors, which has important impact on tumor angiogenesis and development. Its gene promoter i-motif structure formed by C-rich sequence can regulate gene expression, which is a promising new target for anti-tumor therapy. METHODS: We screened various compounds and studied their effects on VEGF through extensive experiments, including SPR, MST, TO displacement, FRET, CD, ESI-MS, NMR, MTT, clone formation, qPCR, Western blot, dual-luciferase reporter assay, immunofluorescence, cell scrape, apoptosis, transwell assay, and animal model. RESULTS: After extensive screening, bisacridine derivative B09 was found to have selective binding and stabilization to VEGF promoter i-motif, which could down-regulate VEGF gene expression. B09 showed potent inhibition on MCF-7 and HGC-27 cell proliferation and metastasis. B09 significantly inhibited tumor growth in xenograft mice model with HGC-27 cells, showing decreased VEGF expression analyzed through immunohistochemistry. CONCLUSION: B09 could specifically regulate VEGF gene expression, possibly through interacting with promoter i-motif structure. As a lead compound, B09 could be further developed for innovative anti-cancer agent targeting VEGF.


Subject(s)
Acridines , Gene Expression Regulation, Neoplastic , Promoter Regions, Genetic , Vascular Endothelial Growth Factor A , Humans , Animals , Promoter Regions, Genetic/drug effects , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Mice , Gene Expression Regulation, Neoplastic/drug effects , Acridines/pharmacology , Acridines/chemistry , Cell Proliferation/drug effects , Xenograft Model Antitumor Assays , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/metabolism , MCF-7 Cells , Mice, Nude , Cell Line, Tumor , Apoptosis/drug effects , Female , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
20.
Front Pharmacol ; 15: 1270661, 2024.
Article in English | MEDLINE | ID: mdl-38659586

ABSTRACT

Background: Bufei Huoxue capsule (BFHX) is widely used for the clinical treatment of chronic obstructive pulmonary disease (COPD) in China. Objectives: The aim of this study is to explore the effects on COPD and the underlying mechanism of BFHX. The process and methods: In this study, we established a COPD mouse model through cigarette smoke (CS) exposure in combination with lipopolysaccharide (LPS) intratracheal instillation. Subsequently, BFHX was orally administrated to COPD mice, and their pulmonary function, lung pathology, and lung inflammation, including bronchoalveolar lavage fluid (BALF) cell count and classification and cytokines, were analyzed. In addition, the anti-oxidative stress ability of BFHX was detected by Western blotting, and the bacterial diversity, abundance, and fecal microbiome were examined using 16S rRNA sequencing technology. Outcome: BFHX was shown to improve pulmonary function, suppress lung inflammation, decrease emphysema, and increase anti-oxidative stress, whereas 16S rRNA sequencing indicated that BFHX can dynamically regulate the diversity, composition, and distribution of the intestinal flora microbiome and regulate the lysine degradation and phenylalanine metabolism of COPD mice. These results highlight another treatment option for COPD and provide insights into the mechanism of BFHX.

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