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1.
J Hazard Mater ; 474: 134697, 2024 May 27.
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.

2.
Biochem Pharmacol ; : 116327, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38823457

ABSTRACT

With intensified aging of the society, the increased age-associated diseases that threatens the quality of life for the elderly. Adipose tissue, a vital energy reservoir with endocrine functions, is one of the most vulnerable tissues in aging, which in turn influence systematic aging process, including metabolic dysfunction. However, the underlying mechanism are 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 improves 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.

3.
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.

4.
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.

5.
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.

6.
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.

7.
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.

8.
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.

9.
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
10.
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
11.
Toxicol Lett ; 397: 1-10, 2024 May 06.
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.

12.
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
13.
Nat Prod Res ; : 1-10, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563116

ABSTRACT

Phytochemical investigation of the roots of Saposhnikovia divaricata (Turcz.) Schischk resulted in the isolation of twelve coumarin derivatives including one new 3,4-dihydroisocoumarin (1) and eleven known 3,4-unsubstituted coumarins (2-12). Structural elucidation of compounds 1-12 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. LPS-induced RAW264.7 inflammatory cell model was used to determine the potential antiinflammation activity of all the isolated compounds in vitro. The results showed that compound 3 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages (IC50 = 4.54 ± 1.71 µM), more active than the positive control (L-NMMA).

14.
Front Pharmacol ; 15: 1337161, 2024.
Article in English | MEDLINE | ID: mdl-38606170

ABSTRACT

Ethnopharmacological relevance: Murrayae Folium et Cacumen (MFC) is a plant considered to be a traditional Chinese medicine with culinary value as well. The dry leaves and twigs of Murraya paniculata and M. exotica are used to treat stomach aches, rheumatism, toothaches, swelling, and insect and snake bites. They are also used to prepare spicy chicken dishes. Aim of the review: This review comprehensively summarizes the available information on the botanical characterization, phytochemistry, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC. Methods: Relevant scientific literature up to August 2023 was included in the study. Chinese and English studies on MFC were collected from databases, including PubMed, Elsevier, Web of Science, Springer, Science Direct, Wiley, ACS, and CNKI (Chinese). Doctoral and Master's dissertations were also included. Results: In total, 720 compounds have been identified and reported in the literature, including flavonoids, coumarins, alkaloids, sterols, phenylpropenols, organic acids, spirocyclopentenones, and volatile oils. Flavonoids and coumarins are the two most important bioactive compounds responsible for these pharmacological activities. MFC has anti-inflammatory, anti-bacterial, anti-microbial, anti-diabetic, anti-tumor, anti-oxidant, anti-depressant, potential anti-Alzheimer's disease, chondroprotective, and analgesic properties. The pharmacological effects include interrupting the STAT3/NF-κB/COX-2 and EGFR signaling pathways, downregulating EpCAM expression, inhibiting NF-κB and ERK signals, inhibiting the EP/cAMP/PKA signaling pathway and miR-29a/Wnt/ß-catenin signaling activity, and upregulating Foxo3a expression. Conclusion: This review demonstrates that the chemical constituents, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC support its use in traditional Chinese botanical medicines. MFC contains a wide range of chemical compounds. Flavonoids and coumarins promote strong pharmacological activity and, are low-toxicity natural phytomedicines that are widely used in medicine, food, ornamentation, and cosmetics, making MFC a promising compound for development and use in the treatment of several medical conditions.

15.
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
16.
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.

17.
Bioresour Technol ; 402: 130756, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38688393

ABSTRACT

DBD low-temperature plasma (DLTP) is recognized as one of the most efficient technologies for treating cotton stalks. This study investigates the impact of various conditions on the gas production characteristics of cotton stalks (CS) and delves into the DLTP decomposition kinetics of CS and CSC in oxygen-enriched (30 % O2/Ar) and CO2 atmospheres. The decomposition rates of CS followed the order CO2 > N2 > Ar. The decomposition behavior of CSC in oxygen-enriched DLTP (30 % O2/Ar) aligned well with the chemical reaction model. The activation energies for CSC decomposition at 900 °C and 1000 °C were determined to be 23.8 kJ/mol and 33.8 kJ/mol, respectively. Moreover, the reaction rate decreased at higher carbonization temperatures, which proved to be detrimental to the decomposition of CSC. The DLTP decomposition of CSC in CO2 exhibited consistency with the fitting results of the unreacted shrinking core model, revealing an observed activation energy of 19.4 kJ/mol.


Subject(s)
Gossypium , Plasma Gases , Gossypium/chemistry , Kinetics , Plasma Gases/chemistry , Carbon Dioxide/chemistry , Temperature , Cold Temperature , Oxygen/chemistry
18.
Phytomedicine ; 128: 155394, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38569294

ABSTRACT

BACKGROUND: Current therapeutic agents for AD have limited efficacy and often induce undesirable side effects. Gegen Qinlian tablets (GGQLT) are a well-known clearingheat formula used in clinical treatment of inflammatory diseases. Based on traditional Chinese medicine (TCM) theory, the strategy of clearing-heat is then compatible with the treatment of AD. However, it remains unknown whether GGQLT can exert neuroprotective effects and alleviate neuroinflammation in AD. PURPOSE: This study aimed to evaluate the anti-AD effects of GGQLT and to decipher its intricate mechanism using integrative analyses of network pharmacology, transcriptomic RNA sequencing, and gut microbiota. METHODS: The ingredients of GGQLT were analyzed using HPLC-ESI-Q/TOF-MS. The AD model was established by bilateral injection of Aß1-42 into the intracerebroventricular space of rats. The Morris water maze was used to evaluate the cognitive function of the AD rats. The long-term toxicity of GGQLT in rats was assessed by monitoring their body weights and pathological alterations in the liver and kidney. Reactive astrocytes and microglia were assessed by immunohistochemistry by labeling GFAP and Iba-1. The levels of inflammatory cytokines in the hippocampus were evaluated using ELISA kits, RT-PCR, and Western blot, respectively. The potential anti-AD mechanism was predicted by analyses of RNA-sequencing and network pharmacology. Western blot and immunohistochemistry were utilized to detect the phosphorylation levels of IκBα, NF-κB p65, p38, ERK and JNK. The richness and composition of gut bacterial and fungal microflora were investigated via 16S rRNA and ITS sequencing. RESULTS: Typical ingredients of GGQLT were identified using HPLC-ESI-Q/TOF-MS. GGQLT significantly improved the cognitive function of AD rats by suppressing the activation of microglia and astrocytes, improving glial morphology, and reducing the neuroinflammatory reactions in the hippocampus. RNA-sequencing, network and experimental pharmacological studies demonstrated that GGQLT inhibited the activation of NF-κB/MAPK signaling pathways in the hippocampus. GGQLT could also restore abnormal gut bacterial and fungal homeostasis and no longer-term toxicity of GGQLT was observed. CONCLUSIONS: Our findings, for the first time, demonstrate GGQLT exhibit anti-AD effects and is worthy of further exploration and development.


Subject(s)
Alzheimer Disease , Disease Models, Animal , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Neuroinflammatory Diseases , Rats, Sprague-Dawley , Animals , Gastrointestinal Microbiome/drug effects , Drugs, Chinese Herbal/pharmacology , Alzheimer Disease/drug therapy , Male , Rats , Neuroinflammatory Diseases/drug therapy , Hippocampus/drug effects , Neuroprotective Agents/pharmacology , Homeostasis/drug effects , Tablets , Amyloid beta-Peptides/metabolism , Neuroglia/drug effects , Network Pharmacology , Disease Progression , Cytokines/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.
Fitoterapia ; 174: 105876, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38431027

ABSTRACT

Nine polyacetylenes, including five new compounds named sadivaethynes E-I (1-5), were isolated from the roots of Saposhnikovia divaricata. Structural elucidation of compounds 1-5 was established by extensive spectroscopic analysis, quantum chemical calculations and DP4+ probability analysis. Among them, the absolute configuration of compound 1-2, 4-5 was unambiguous determined by ECD. Also, all compounds were evaluated for cytotoxicity against two human cancer cell lines (A549, HEPG2) in vitro, compound 9 showed moderate inhibitory effect with an IC50 value of 11.66 µM against HEPG2.


Subject(s)
Apiaceae , Polyynes , Humans , Molecular Structure , Polyynes/pharmacology , Polyynes/analysis , Polyynes/chemistry , Plant Roots/chemistry , Plant Extracts/chemistry , Apiaceae/chemistry
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