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1.
Biology (Basel) ; 13(7)2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39056713

ABSTRACT

The objective of this study was to explore the dynamic changes in the gut microbiota of Simmental calves before weaning and to compare the microbial composition and functionality between healthy calves and those with diarrhea. Fourteen neonatal Simmental calves were divided into a healthy group (n = 8) and a diarrhea group (n = 6). Rectal stool samples were collected from each calf on days 1, 3, 5, 7, 9, 12, 15, 18, 22, 26, 30, 35, and 40. High-throughput sequencing of the 16S rRNA gene V1-V9 region was conducted to examine changes in the gut microbiota over time in both groups and to assess the influence of diarrhea on microbiota structure and function. Escherichia coli, Bacteroides fragilis, and B. vulgatus were the top three bacterial species in preweaning Simmental calves. Meanwhile, the major functions of the fecal microbiota included "metabolic pathways", "biosynthesis of secondary metabolites", "biosynthesis of antibiotics", "microbial metabolism in diverse environments", and "biosynthesis of amino acids". For calves in the healthy group, PCoA revealed that the bacterial profiles on days 1, 3, 5, 7, and 9 differed from those on days 15, 18, 22, 26, 30, 35, and 40. The profiles on day 12 clustered with both groups, indicating that microbial structure changes increased with age. When comparing the relative abundance of bacteria between healthy and diarrheic calves, the beneficial Lactobacillus johnsonii, Faecalibacterium prausnitzii, and Limosilactobacillus were significantly more abundant in the healthy group than those in the diarrhea group (p < 0.05). This study provides fundamental insights into the gut microbiota composition of Simmental calves before weaning, potentially facilitating early interventions for calf diarrhea and probiotic development.

2.
PLoS One ; 19(7): e0307269, 2024.
Article in English | MEDLINE | ID: mdl-39018284

ABSTRACT

Urtica cannabina L. (UL) has been used clinically for centuries because of its anti-inflammatory properties. This study aimed to investigate the underlying mechanisms and anti-inflammatory effects of different UL concentrations in zebrafish. To elucidate UL's anti-inflammatory properties, two inflammation zebrafish models were designed 1) by severing the zebrafish's caudal fin to assess the repairing effect of UL on the tail inflammation, and 2) by inducing lipopolysaccharides (LPS)-mediated intestinal inflammation to assess the protective and reparative effects of UL on intestinal inflammation at the histological and genetic levels. Furthermore, the effect of UL on the LPS-induced intestinal flora changes was also assessed. After caudal fin resection, a scar formed on the tail of the zebrafish, and the area of the caudal fin increased by 1.30 times as much as that of the control group (P < 0.01). Moreover, this tail scar was alleviated after 10 mg/g UL supplementation but not after 30 mg/g UL dose. LPS decreased the feed intake and body weight of the zebrafish; however, these effects were reversed after 10 and 30 mg/g doses of UL. In addition, the LPS treatment also reduced the intestinal goblet cells by 49% in the zebrafish when compared with the control, which was significantly restored after 10 and 30 mg/g UL treatments. At the genetics level, the expression of the pro-inflammatory cytokine genes (TNF-α, IL6, and IL8) showed that 10 and 30 mg/g UL doses could rescue LPS-induced expression. The gut microbiota analysis revealed changes in the abundance of four major bacterial phyla in the 10 and 30 mg/g UL-treated groups, with an increased probiotic Bacteroidota and decreased pathogenic bacteria. These results indicate that UL strongly inhibits inflammation caused by caudal fin removal and LPS-induced inflammatory changes in the zebrafish intensity, suggesting that UL is a feed additive that could be developed to improve resistance to inflammation in livestock.


Subject(s)
Anti-Inflammatory Agents , Lipopolysaccharides , Zebrafish , Animals , Anti-Inflammatory Agents/pharmacology , Inflammation/drug therapy , Inflammation/pathology , Gastrointestinal Microbiome/drug effects , Food Additives/pharmacology , Animal Feed , Plant Extracts/pharmacology
3.
Chemosphere ; 359: 142299, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761826

ABSTRACT

Sulfur mustard (SM, dichlorodiethyl sulfide) is a potent erosive chemical poison that can cause pulmonary lung, skin and eye disease complications in humans. Currently, there is no designated remedy for SM, and its operation's toxicological process remains unidentified. This work employed zebrafish as a model organism to investigate the toxic manifestations and mechanisms of exposure to SM, aiming to offer novel insights for preventing and treating this condition. The results showed that SM caused a decrease in the survival rate of the zebrafish larvae (LC50 = 2.47 mg/L), a reduction in the hatching rate, an increase in the pericardial area, and small head syndrome. However, T-5224 (a selective inhibitor of c-Fos/activator protein) attenuated the reduction in mortality (LC50 = 2.79 mg/L), the reduction in hatching rate, and the worsening of morphological changes. We discovered that SM causes cartilage developmental disorders in zebrafish larvae. The reverse transcription-quantitative polymerase chain reaction found that SM increased the expression of inflammation-related genes (IL-1ß, IL-6, and TNF-α) and significantly increased cartilage development-related gene expression (fosab, mmp9, and atf3). However, the expression of sox9a, sox9b, and Col2a1a was reduced. The protein level detection also found an increase in c-fos protein expression and a significant decrease in COL2A1 expression. However, T-5224,also and mitigated the changes in gene expression, and protein levels caused by SM exposure. The results of this study indicate that SM-induced cartilage development disorders are closely related to the c-Fos/AP-1 pathway in zebrafish.


Subject(s)
Chondrogenesis , Larva , Mustard Gas , Proto-Oncogene Proteins c-fos , Transcription Factor AP-1 , Zebrafish , Animals , Mustard Gas/toxicity , Larva/drug effects , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-fos/genetics , Chondrogenesis/drug effects , Transcription Factor AP-1/metabolism , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics
4.
Reprod Toxicol ; 127: 108603, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38759877

ABSTRACT

Hypobaric Hypoxia (HH) negatively affects the cardiovascular and respiratory systems as well as gonadal development and the therefore next generation. This study investigated the effects of HH on zebrafish and SD rats, by exposing them to a low-pressure environment at 6000 m elevation for 30 days to simulate high-altitude conditions. It was indicated that parental zebrafish reared amh under HH had increased embryo mortality, reduced hatchability, and abnormal cartilage development in the offspring. Furthermore, the HH-exposed SD rats had fewer reproductive cells and smaller litters. Moreover, the transcriptome analysis revealed the down-regulation of steroid hormone biosynthesis pathways. The expression of the gonad-associated genes (amh, pde8a, man2a2 and lhcgr), as well as the gonad and cartilage-related gene bmpr1a, were also down-regulated. In addition, Western blot analysis validated reduced bmpr1a protein expression in the ovaries of HH-treated rats. In summary, these data indicate the negative impact of HH on reproductive organs and offspring development, emphasizing the need for further research and precautions to protect future generations' health.


Subject(s)
Fertility , Hypoxia , Rats, Sprague-Dawley , Zebrafish , Animals , Female , Male , Bone Development , Embryo, Nonmammalian , Rats
5.
World J Clin Cases ; 12(8): 1481-1486, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38576802

ABSTRACT

BACKGROUND: In recent years, confocal laser endomicroscopy (CLE) has become a new endoscopic imaging technology at the microscopic level, which is extensively performed for real-time in vivo histological examination. CLE can be performed to distinguish benign from malignant lesions. In this study, we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma. CASE SUMMARY: A 63-year-old woman was diagnosed with gastric mucosal lesions, which may be gastric cancer, in the small curvature of the stomach by gastroscopy. She consented to undergo CLE for morphological observation of the gastric mucosa. Through the combination of CLE diagnosis and postoperative pathology, the intraoperative CLE diagnosis was considered to be reliable. According to our experience, CLE can be performed as the first choice for the diagnosis of gastric cancer. CONCLUSION: CLE has several advantages over pathological diagnosis. We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

6.
Article in English | MEDLINE | ID: mdl-38447648

ABSTRACT

Gelsemium elegans (GE), also known as Duanchangcao, is a plant associated with toxic symptoms related to the abdomen; however, the toxicity caused by GE remains unknown. Gelsemine (GEL) is an alkaloid extracted from GE and is one of the most toxic alkaloids. This study used zebrafish as an animal model and employed high-throughput gene sequencing to identify genes and signaling pathways related to GEL toxicity. Exposure to GEL negatively impacted heart rate, swim bladder development, and activity in zebrafish larvae. Transcriptomics data revealed the enrichment of inflammatory and phagocyte signaling pathways. RT-PCR analysis revealed a decrease in the expression of pancreas-related genes, including the pancreatic coagulation protease (Ctr) family, such as Ctrl, Ctrb 1, and Ctrc, due to GEL exposure. Furthermore, GEL exposure significantly reduced Ctrb1 protein expression while elevating trypsin and serum amylase activities in zebrafish larvae. GEL also resulted in a decrease in pancreas-associated fluorescence area and an increase in neutrophil-related fluorescence area in transgenic zebrafish. This study revealed that GEL toxicity in zebrafish larvae is related to acute pancreatic inflammation.


Subject(s)
Alkaloids , Gelsemium , Animals , Zebrafish/metabolism , Gelsemium/metabolism , Larva/metabolism
7.
Bull Environ Contam Toxicol ; 112(2): 39, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38353786

ABSTRACT

Acetaminophen (N-acetyl-p-aminophenol; APAP) is one of the most widely used analgesics. To examine the toxicity of APAP, we used zebrafish embryos as model animals to detect the effect of APAP on the thyroid system of zebrafish embryos. The zebrafish embryos were exposed to APAP from 4 h post fertilization (4 hpf) until observation. The experimental results showed that APAP caused pericardial edema and decreased pigmentation in the zebrafish embryos or larvae. The APAP treatment caused a decrease in the expression of tpo and thrß in the zebrafish at 36 and 72 hpf. The transcriptomic analysis found that APAP affected retinol metabolism, the metabolism of xenobiotics by cytochrome P450, and the tyrosine metabolism pathway. The harmful effect of APAP on zebrafish embryos might be due to its disrupting effect on the functional regulation of the thyroid hormone system.


Subject(s)
Acetaminophen , Perciformes , Animals , Acetaminophen/toxicity , Zebrafish , Thyroxine , Pigmentation , Thyroid Gland
8.
Environ Geochem Health ; 46(1): 27, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38225481

ABSTRACT

Toxicity observed in aquatic ecosystems often cannot be explained by the action of a single pollutant. Likewise, evaluation standards formulated by a single effect cannot truly reflect the environmental quality requirements. The study of mixtures is needed to provide environmental relevance and knowledge of combined toxicity. In this study, the embryos of Japanese medaka (Oryzias latipes) were treated with individual and binary mixture of copper (Cu) and cadmium (Cd) until 12 days post-fertilization (dpf). Hatching, mortality, development, histology and gene expression were assessed. Our results showed that the highest concentration mixture of Cd (10 mg/L) and Cu (1 mg/L) affected survival, hatching time and hatching success. Occurrence of uninflated swim bladder was the highest (value) with exposure to 10 mg/L Cd. Swim bladder was commonly over-inflated in a mixture (0.1 mg/L Cd + 1.0 mg/L Cu) exposure. Individuals exposed to the mixture (0.1 Cd + 1.0 Cu mg/L) showed up to a 7.69% increase in swim bladder area compared to the control group. The mixtures containing 0.1 or 10 mg/L Cd, each with 1.0 mg/L Cu resulted in significantly increased of Pbx1b expression, higher than any Cd or Cu alone (p < 0.01). In the co-exposure group (0.1/10 Cd + 1.0 Cu mg/L), Pbx1b expression was found at 12 dpf but not 7 dpf in controls. Higher concentrations of Cd may progressively reduce Pbx1b expression, potentially explaining why 75% of individuals in the 10 mg/L Cd group failed to inflate their swim bladders. Additionally, the swim bladder proved to be a valuable bio-indicator for biological evaluation.


Subject(s)
Oryzias , Water Pollutants, Chemical , Humans , Animals , Copper/toxicity , Cadmium/toxicity , Ecosystem , Urinary Bladder , Water Pollutants, Chemical/toxicity , Embryo, Nonmammalian
9.
J Minim Access Surg ; 20(2): 148-153, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-36695237

ABSTRACT

BACKGROUND: Incidental gall bladder cancer (IGBC) is often discovered unexpectedly in patients after cholecystectomy. Currently, magnetic resonance imaging (MRI) has been widely applied in the pre-operative diagnosis of gall bladder diseases as laparoscopic cholecystectomy developed into the preferred method. AIMS AND OBJECTIVES: This study aimed to evaluate the pre-operative MRI application and laparoscopic management in the IGBCs. MATERIALS AND METHODS: Between January 2011 and January 2020, a total of 7917 patients with gall bladder diseases treated by laparoscopy were enrolled in this study. RESULTS: Amongst 49 patients diagnosed with IGBCs, the incidence of IGBCs in polypoid lesions, biliary pancreatitis, cholecystitis, cholecystocholedocholithiasis and gall bladder stones was 0.42%, 1.19%, 0.62%, 1.20% and 0.49%, respectively. MRI evaluation showed more remarkable pre-operative imaging as compared to ultrasonographic evaluation (40.8 vs. 26.5, P < 0.05). Furthermore, 14 patients were diagnosed with gall bladder cancer through intraoperative histological examination and 11 received laparoscopic extensive resection after cholecystectomy. MRI findings with diffuse thickening of the gall bladder detected IGBCs with 6.1% sensitivity, 96.02 specificity, 0.95% positive predictive values and 99.4% negative predictive values; diffuse thickening of the gall bladder with suspicion of malignancy detected IGBCs with 12.2% sensitivity, 99.1% specificity, 7.6% positive predictive values and 99.5% negative predictive values; focal thickening of the gall bladder detected IGBCs with 16% sensitivity, 99.8% specificity, 32% positive predictive values and 99.5% negative predictive values; moreover, suspicious lesion detected IGBCs with 6.1% sensitivity, 99.6% specificity, 8.8% positive predictive values and 99.4% negative predictive values. CONCLUSIONS: Patients with biliary pancreatitis and cholecystocholedocholithiasis have a higher incidence of IGBC. MRI evaluation could provide more accurate information for the IGBCs, which should be recommended for patients accepting cholecystectomy. MRI findings exhibited an unsatisfactory sensitivity when detecting IGBCs, but they represented high specificity. Pre-operative MRI evaluation and intraoperative histological examination may help some IGBCs to achieve one-stage laparoscopic extensive resection.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1009218

ABSTRACT

OBJECTIVE@#To investigate the clinical effect of modified suspension reduction method combined with percutaneous vertebroplasty in the treatment of osteoporotic thoracolumbar compression fractures.@*METHODS@#From February 2020 to October 2021, 92 patients with thoracolumbar osteoporotic compression fracture were treated by percutaneous vertebroplasty. According to different treatment methods, they were divided into the observation group and the control group. The observation group was treated with modified suspension reduction and then percutaneous vertebroplasty, while the control group was treated with percutaneous vertebroplasty alone. The observation group (47 cases), including 20 males and 27 females, the age ranged from 59 to 76 years old with an average of (69.74±4.50) years old, fractured vertebral bodies:T10(2 cases), T11(7 cases), T12(19 cases), L1(14 cases), L2(5 cases);the control group(45 cases), including 21 males and 24 females, the age ranged from 61 to 78 years old with an average of (71.02±3.58) years old, fractured vertebral bodies:T10(3 cases), T11(8 cases), T12(17 cases), L1(12 cases), L2(5 cases);The leakage of bone cement were observed, the visual analogue scale (VAS), Oswestry lumbar dysfunction index (ODI), anterior vertebrae height (AVH), Cobb angle of kyphosis and the amount of bone cement injected before and after operation were recorded and compared between the two groups.@*RESULTS@#All patients were followed up, ranged from 6 to10 with an average of (8.45±1.73) months. Two patients ocurred bone cement leakage in observation group and 3 patients in control group. AVH of observation group increased (P<0.05) and Cobb angle of injured vertebrae decreased (P<0.05). Cobb angle of injured vertebrae and AVH of the control group were not significantly changed (P>0.05). Cobb angle of injured vertebrae of the observation group was lower than that of control group (P<0.05) and AVH was higher than that of the control group (P<0.05). In the observation group, VAS before operation and 1 week, 3 and 6 months after operation respectively were(7.32±1.05) scores, (3.56±1.18) scores, (1.83±0.67) scores, (1.27±0.34) scores, and ODI were(40.12±14.69) scores, (23.76±10.19) scores, (20.15±6.39) scores, (13.45±3.46) scores. In the control group, VAS before operation and 1 week, 3 and 6 months after operation respectively were(7.11±5.26) scores, (3.82±0.68) scores, (1.94±0.88) scores, (1.36±0.52) scores, and ODI were(41.38±10.23) scores, (25.13±14.22) scores , (20.61±5.82) scores, (14.55±5.27) scores . The scores of VAS and ODI after operation were lower than those before operation (P<0.05), but there was no significant difference between the two groups (P<0.05).@*CONCLUSION@#Modified suspension reduction method combined with PVP surgery for osteoporotic thoracolumbar compression fractures has achieved good clinical results, which can effectively relieve lumbar back pain, restore vertebral height, correct kyphosis, improve lumbar function and patients' quality of life.


Subject(s)
Male , Female , Humans , Middle Aged , Aged , Bone Cements/therapeutic use , Vertebroplasty/methods , Fractures, Compression/surgery , Quality of Life , Treatment Outcome , Spinal Fractures/surgery , Lumbar Vertebrae/injuries , Osteoporotic Fractures/surgery , Kyphosis/surgery , Retrospective Studies
11.
Chemosphere ; 340: 139940, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37634582

ABSTRACT

Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin that causes oxidative damage in various organs. At present, the research studies on AFB1 are primarily focused on its effects on the terrestrial environment and animals. However, its toxicity mechanism in aquatic environments and aquatic animals has not been largely explored. Thus, in this study, zebrafish was used as a model to study the toxicity mechanism of AFB1 on the liver of developing larvae. The results showed that AFB1 exposure inhibited liver development and promoted fat accumulation in the liver. Transcriptome sequencing analysis showed that AFB1 affected liver redox metabolism and oxidoreductase activity. KEGG analysis showed that AFB1 inhibited the expression of gsto1, gpx4a, mgst3a, and idh1 in the glutathione metabolizing enzyme gene pathway, resulting in hepatic oxidative stress. At the same time, AFB1 also inhibited the expression of acox1, acsl1b, pparα, fabp2, and cpt1 genes in peroxidase and PPAR metabolic pathways, inducing hepatic steatosis and lipid droplet accumulation. Antioxidant N-Acetyl-l-cysteine (NAC) preconditioning up-regulated gsto1, gpx4a and idh1 genes, and improved the AFB1-induced lipid droplet accumulation in the liver. In summary, AFB1 induced hepatic oxidative stress and steatosis, resulting in abnormal liver fat metabolism and accumulation of cellular lipid droplets. NAC could be used as a potential preventative drug to improve AFB1-induced fat accumulation.


Subject(s)
Chemical and Drug Induced Liver Injury , Fatty Liver , Animals , Aflatoxin B1/toxicity , Zebrafish/genetics , Acetylcysteine , Larva/genetics
12.
Front Public Health ; 11: 1164952, 2023.
Article in English | MEDLINE | ID: mdl-37397711

ABSTRACT

Theoretical models and empirical evidence suggest an association between volunteering and health outcomes in older adults. However, less is known about existing programs that involve older adults engaging in formal volunteering, especially programs for older volunteers with cognitive impairment. In this review, we summarized and evaluated different types of volunteering-based programs involving older volunteers with and without cognitive impairment. After a non-systematic literature search, we presented eight example volunteer programs. Older volunteers participate in the programs in person or remotely. In five of the programs, older volunteers without cognitive impairment participate in intergenerational engagement, support and referral, home visiting, and dementia care services. The other three programs specifically recruit older volunteers with cognitive impairment and provide intergenerational engagement and individualized volunteer activities. Both strengths and challenges identified in the programs were discussed. Different types of volunteering-based programs are available for engaging older volunteers. For volunteers to remain active during the pandemic or for volunteers who live with cognitive impairment, remote programs can be a valuable alternative. Program effects on older volunteers need to be tested in more rigorously designed studies.


Subject(s)
Cognitive Dysfunction , Volunteers , Humans , Aged , Volunteers/psychology
13.
Surg Endosc ; 37(6): 4681-4688, 2023 06.
Article in English | MEDLINE | ID: mdl-36881188

ABSTRACT

BACKGROUND AND AIMS: Accurate evaluation of intraductal papillary mucinous neoplasm (IPMN) is necessary to inform clinical decision-making. But it is still difficult to distinguish benign and malignant IPMN preoperatively. This study aims to evaluate the utility of EUS to predict the pathology of IPMN. METHODS: Patients with IPMN who underwent endoscopic ultrasound within 3 months before surgery were collected from six centers. Logistic regression model and random forest model were used to determine risk factors associated with malignant IPMN. In both models, 70% and 30% of patients were randomly assigned to the exploratory group and validation group, respectively. Sensitivity, specificity, and ROC were used in model assessment. RESULTS: Of the 115 patients, 56 (48.7%) had low-grade dysplasia (LGD), 25 (21.7%) had high-grade dysplasia (HGD), and 34 (29.6%) had invasive cancer (IC). Smoking history (OR = 6.95, 95%CI: 1.98-24.44, p = 0.002), lymphadenopathy (OR = 7.91, 95%CI: 1.60-39.07, p = 0.011), MPD > 7 mm (OR = 4.75, 95%CI: 1.56-14.47, p = 0.006) and mural nodules > 5 mm (OR = 8.79, 95%CI: 2.40-32.24, p = 0.001) were independent risk factors predicting malignant IPMN according to the logistic regression model. The sensitivity, specificity, and AUC were 0.895, 0.571, and 0.795 in the validation group. In the random forest model, the sensitivity, specificity, and AUC were 0.722, 0.823, and 0.773, respectively. In patients with mural nodules, random forest model could reach a sensitivity of 0.905 and a specificity of 0.900. CONCLUSIONS: Using random forest model based on EUS data is effective to differentiate benign and malignant IPMN in this cohort, especially in patients with mural nodules.


Subject(s)
Adenocarcinoma, Mucinous , Carcinoma, Pancreatic Ductal , Pancreatic Intraductal Neoplasms , Pancreatic Neoplasms , Humans , Endosonography , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/pathology , Pancreatic Intraductal Neoplasms/diagnostic imaging , Adenocarcinoma, Mucinous/diagnostic imaging , Adenocarcinoma, Mucinous/surgery , Adenocarcinoma, Mucinous/pathology , Retrospective Studies , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology
14.
Eur J Med Chem ; 251: 115253, 2023 May 05.
Article in English | MEDLINE | ID: mdl-36921526

ABSTRACT

Accumulation of evidences suggested that excessive amounts of AChE and BuChE in the brain of AD patients at the different stage of AD, which could hydrolyze ACh and accelerated Aß aggregation. To develop new "hidden" multifunctional agents through AChE/BuChE would be a promising strategy to treat AD. To this end, firstly, a series of chalcone derivatives with chelating property was designed and synthesized. The in vitro results showed that compound 3f indicated significant selective MAO-B inhibitory activity (IC50 = 0.67 µM) and remarkable anti-inflammatory property. It also significantly inhibited self-induced Aß1-42 aggregation and showed remarkable neuroprotective effects on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f was a selective metal chelator and could inhibit Cu2+-induced Aß1-42 aggregation. Based on this, the carbamate fragment was introduced to compound 3f to obtain carbamate derivatives. The biological activity results exhibited that compound 4b showed good BBB permeability, good AChE inhibitory potency (IC50 = 5.3 µM), moderate BuChE inhibitory potency (IC50 = 12.4 µM), significant MAO-B inhibitory potency, anti-inflammation potency on LPS-induced BV-2 cells and neuroprotective effects on Aß25-35-induced PC12 cell injury. Compared with 3f, compound 4b did not show obvious chelation property. Significantly, compound 4b could be activated by AChE/BuChE following inhibition of AChE/BuChE to liberate an active multifunctional chelator 3f, which was consistent with our original intention. More importantly, compounds 3f and 4b presented favorable ADME properties and good stability in artificial gastrointestinal fluid, blood plasma and rat liver microsomes. The in vivo results suggested that compound 4b (0.0195 µg/mL) could significantly improve dyskinesia and reaction capacity of the AlCl3-induced zebrafish AD model by increasing the level of ACh. Together our data suggest that compound 4b was a promising "hidden" multifunctional agent by AChE/BuChE, and this strategy deserved further development for the treatment of AD.


Subject(s)
Alzheimer Disease , Neuroprotective Agents , Rats , Animals , Alzheimer Disease/drug therapy , Amyloid beta-Peptides , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Zebrafish , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Drug Design , Monoamine Oxidase , Chelating Agents/pharmacology , Chelating Agents/therapeutic use , Pain , Ligands , Carbamates/therapeutic use , Acetylcholinesterase/therapeutic use
15.
J Enzyme Inhib Med Chem ; 38(1): 2169682, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36688444

ABSTRACT

A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC50 values of 1.3 µM and 0.81 µM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1ß and NO. In addition, compound 3f presented significant neuroprotective effect on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes in vitro and plasma. Furthermore, compound 3f could improve AlCl3-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.


Subject(s)
Alzheimer Disease , Hydroxyquinolines , Neuroprotective Agents , Quinolines , Animals , Alzheimer Disease/drug therapy , Amyloid beta-Peptides , Carbamates/pharmacology , Zebrafish , Cholinesterase Inhibitors/pharmacology , Quinolines/pharmacology , Drug Design , Acetylcholinesterase/metabolism , Structure-Activity Relationship , Molecular Structure
16.
Appl Biochem Biotechnol ; 195(10): 5792-5801, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36708490

ABSTRACT

This study is to identify the pathogenic mutation of a child with Sots syndrome and provide prenatal diagnosis for his pregnant mother. Chromosome microarray technology was used to detect whether there were minor deletions/duplication in patients' chromosomes. The gene mutation of patients was screened by next-generation sequencing technology, and it was verified by Sanger sequencing. Prenatal diagnosis of the fetus was conducted according to the selected pathogenic sites, and genetic counseling was conducted for her parents. Chromosome microarray results showed that there was no minor deletion in a chromosome 5q35 region, and the second-generation sequencing results showed that there was a c.4138delG heterozygous mutation in the patient's NSD1 gene, and the pathogenic of this mutation was not reported in related databases. Sanger sequencing found that there was a c.4138delG heterozygous mutation in the NSD1 gene of the patient and her parents' genotype at this locus was wild type. The prenatal gene test results indicated that there was heterozygous mutation of NSD1 gene c.4138delG in the fetus, so it was suggested to terminate the pregnancy. Gentling results indicated that the fetus and the patient inherited the same maternal chromosome 5. The heterozygous mutation of NSD1 gene c.4138delG is the pathogenic mutation of this Sots syndrome patient, and the mother may be germinal mosaicism.


Subject(s)
Sotos Syndrome , Humans , Child , Female , Sotos Syndrome/diagnosis , Sotos Syndrome/genetics , Sotos Syndrome/pathology , Histone-Lysine N-Methyltransferase/genetics , Histone Methyltransferases/genetics , Mothers , Mosaicism , Phenotype
17.
J Appl Toxicol ; 43(3): 373-386, 2023 03.
Article in English | MEDLINE | ID: mdl-36062847

ABSTRACT

Borneol is an example of traditional Chinese medicine widely used in Asia. There are different isomers of chiral borneol in the market, but its toxicity and effects need further study. In this study, we used zebrafish embryos to examine the effects of exposure to three isomers of borneol [(-)-borneol, (+)-borneol, and isoborneol] on heart development and the association with Na+ /K+ -ATPase from 4 h post-fertilization (4 hpf). The results showed that the three isomers of borneol increased mortality and decreased hatching rate when the zebrafish embryo developed to 72 hpf. All three isomers of borneol (0.01-1.0 mM) significantly reduced heart rate from 48 to 120 hpf and reduced the expression of genes related to Ca2+ -ATPase (cacna1ab and cacna1da) and Na+ /K+ -ATPase (atp1b2b, atp1a3b, and atp1a2). At the same time, the three isomers of borneol significantly reduced the activities of Ca2+ -ATPase and Na+ /K+ -ATPase at 0.1 to 1.0 mM. (+)-Borneol caused the most significant reduction (p < 0.05), followed by isoborneol and (-)-borneol. Na+ /K+ -ATPase was mainly expressed in otic vesicles and protonephridium. All three isomers of borneol reduced Na+ /K+ -ATPase mRNA expression, but isoborneol was the most significant (p < 0.01). Our results indicated that (+)-borneol was the least toxic of the three isomers while the isoborneol showed the most substantial toxic effect, closely related to effects on Na+ /K+ -ATPase.


Subject(s)
Cardiotoxicity , Zebrafish , Animals , Zebrafish/metabolism , Camphanes/toxicity , Sodium-Potassium-Exchanging ATPase/genetics , Sodium-Potassium-Exchanging ATPase/metabolism
18.
STOMATOLOGY ; (12): 233-236, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-979360

ABSTRACT

Objective@#To study the effect of a space stabilizing device on the capacity for osteogenesis in the bone-grafted area. @*Methods@#Patients with anterior teeth defects as well as labial alveolar ridge defects were randomly divided into two groups: the experimental group was treated using a space stabilization device after guided bone regeneration whereas the control group received regular guided bone regeneration. The CBCT data was analyzed prior to, immediately and 6 months after procedure to compare the osteogenesis with or without the device.@*Results@#Seventeen bone-grafted sites were examined(7 in the experimental group and 10 in the control group). At 2 mm and 4 mm below the alveolar ridge, the horizontal bone resorption rate in the experimental group was significantly lower than the corresponding level in the control group(P=0.001). The horizontal bone resorption rate at 2 mm below the alveolar ridge of each group was significantly higher than that at 4 mm below the alveolar ridge in corresponding groups(P=0.003). @*Conclusion@#The space stabilizing device used in this study has a positive clinical impact on preserving space stability and minimizing bone resorption.

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-986053

ABSTRACT

At present, there are disadvantages with the detection for occupational hazard factors, such as insufficient monitoring data, poor timeliness, weak representativeness, long detection cycles, and inability to continuously monitor. Taking advantages of internet of things technology, an online monitoring platform for occupational hazard factors has been designed. The platform collects the concentration (intensity) of hazard factors through sensors, transmits the occupational hazards data collected online in realtime. The online monitoring cloud center for occupational hazard factors processes and analyzes online monitoring data in realtime, stores the hazard factors data to form database management, and provides user application services to form an intelligent online monitoring service model for occupational hazard factors. Based on the online monitoring platform of occupational hazard factors, multi-level government health supervision departments and employers can grasp the status of hazard factors in real time, which is conducive to improving the level of occupational hazard supervision.


Subject(s)
Internet of Things , Internet
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-986018

ABSTRACT

Objective: To explore the sound insulation, sound absorption and other noise reduction transformation methods in a noise workshop handover control room. Methods: In December 2021, through the occupational health investigation and on-site testing of the handover control room of a noise workshop, the causes of excessive noise were analyzed, and the transformation design scheme to reduce noise was proposed and the effect was analyzed. Results: Before the transformation, the peak frequency band noise intensity of the noise workshop handover control room was 112.8 dB (A), and the peak frequency was 1000 Hz. After noise reduction, the theoretical calculated control value was 61.0 dB (A), and the measured noise intensity was 59.8 dB (A) . Conclusion: The noise intensity of the handover control room is reduced after noise reduction, which is in line with the contact limit requirements of the control room in GBZ 1-2010 "Hygienic Standards for the Design of Industrial Enterprises", and has reference significance for noise control engineering.


Subject(s)
Noise/prevention & control , Occupational Health , Industry , Reference Standards , Hygiene , Noise, Occupational/prevention & control
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