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1.
Fa Yi Xue Za Zhi ; 40(2): 135-142, 2024 Apr 25.
Article En, Zh | MEDLINE | ID: mdl-38847027

OBJECTIVES: To investigate the application value of combining the Demirjian's method with machine learning algorithms for dental age estimation in northern Chinese Han children and adolescents. METHODS: Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected. The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method. Various machine learning algorithms, including support vector regression (SVR), gradient boosting regression (GBR), linear regression (LR), random forest regression (RFR), and decision tree regression (DTR) were employed. Age estimation models were constructed based on total, female, and male samples respectively using these algorithms. The fitting performance of different machine learning algorithms in these three groups was evaluated. RESULTS: SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples, while GBR showed the best performance in male samples. The mean absolute error (MAE) of the optimal age estimation model was 1.246 3, 1.281 8 and 1.153 8 years in the total, female and male samples, respectively. The optimal age estimation model exhibited varying levels of accuracy across different age ranges, which provided relatively accurate age estimations in individuals under 18 years old. CONCLUSIONS: The machine learning model developed in this study exhibits good age estimation efficiency in northern Chinese Han children and adolescents. However, its performance is not ideal when applied to adult population. To improve the accuracy in age estimation, the other variables can be considered.


Age Determination by Teeth , Algorithms , Asian People , Machine Learning , Radiography, Panoramic , Humans , Adolescent , Child , Male , Female , Age Determination by Teeth/methods , Radiography, Panoramic/methods , China/ethnology , Child, Preschool , Young Adult , Mandible , Tooth/diagnostic imaging , Tooth/growth & development , Support Vector Machine , Decision Trees , Ethnicity , East Asian People
2.
Front Bioeng Biotechnol ; 12: 1414005, 2024.
Article En | MEDLINE | ID: mdl-38863494

Introduction: Our objective in this study was to prepare a novel type of polymethyl methacrylate (PMMA) bone cement, analyze its material properties, and evaluate its safety and antibacterial efficacy. Methods: A halamine compound methacrylate antibacterial PMMA bone cement containing an N-Cl bond structure was formulated, and its material characterization was determined with Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR. The antibacterial properties of the material were studied using contact bacteriostasis and releasing-type bacteriostasis experiments. Finally, in vitro and in vivo biocompatibility experiments were performed to analyze the toxic effects of the material on mice and embryonic osteoblast precursor cells (MC3T3-E1). Results: Incorporation of the antibacterial methacrylate monomer with the N-halamine compound in the new antibacterial PMMA bone cement significantly increased its contact and releasing-type bacteriostatic performance against Staphylococcus aureus. Notably, at 20% and 25% additions of N-halamine compound, the contact and releasing-type bacteriostasis rates of bone cement samples reached 100% (p < 0.001). Furthermore, the new antibacterial bone cement containing 5%, 10%, and 15% N-halamine compounds showed good biocompatibility in vitro and in vivo. Conclusion: In this study, we found that the novel antibacterial PMMA bone cement with N-halamine compound methacrylate demonstrated good contact and releasing-type bacteriostatic properties against S. aureus. In particular, bone cement containing a 15% N-halamine monomer exhibited strong antibacterial properties and good in vitro and in vivo biocompatibility.

3.
Int J Legal Med ; 2024 May 18.
Article En | MEDLINE | ID: mdl-38760564

BACKGROUND & OBJECTIVE: Sex estimation is a critical aspect of forensic expertise. Some special anatomical structures, such as the maxillary sinus, can still maintain integrity in harsh environmental conditions and may be served as a basis for sex estimation. Due to the complex nature of sex estimation, several studies have been conducted using different machine learning algorithms to improve the accuracy of sex prediction from anatomical measurements. MATERIAL & METHODS: In this study, linear data of the maxillary sinus in the population of northwest China by using Cone-Beam Computed Tomography (CBCT) were collected and utilized to develop logistic, K-Nearest Neighbor (KNN), Support Vector Machine (SVM) and random forest (RF) models for sex estimation with R 4.3.1. CBCT images from 477 samples of Han population (75 males and 81 females, aged 5-17 years; 162 males and 159 females, aged 18-72) were used to establish and verify the model. Length (MSL), width (MSW), height (MSH) of both the left and right maxillary sinuses and distance of lateral wall between two maxillary sinuses (distance) were measured. 80% of the data were randomly picked as the training set and others were testing set. Besides, these samples were grouped by age bracket and fitted models as an attempt. RESULTS: Overall, the accuracy of the sex estimation for individuals over 18 years old on the testing set was 77.78%, with a slightly higher accuracy rate for males at 78.12% compared to females at 77.42%. However, accuracy of sex estimation for individuals under 18 was challenging. In comparison to logistic, KNN and SVM, RF exhibited higher accuracy rates. Moreover, incorporating age as a variable improved the accuracy of sex estimation, particularly in the 18-27 age group, where the accuracy rate increased to 88.46%. Meanwhile, all variables showed a linear correlation with age. CONCLUSION: The linear measurements of the maxillary sinus could be a valuable tool for sex estimation in individuals aged 18 and over. A robust RF model has been developed for sex estimation within the Han population residing in the northwestern region of China. The accuracy of sex estimation could be higher when age is used as a predictive variable.

4.
J Mater Chem B ; 12(18): 4389-4397, 2024 May 08.
Article En | MEDLINE | ID: mdl-38623831

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.


Bone Cements , Hydrazones , Isoniazid , Isoniazid/chemistry , Isoniazid/pharmacology , Bone Cements/chemistry , Animals , Hydrazones/chemistry , Hydrazones/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Antitubercular Agents/administration & dosage , Mice , Drug Liberation , Polymethyl Methacrylate/chemistry , Materials Testing , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
5.
J Orthop Surg Res ; 19(1): 169, 2024 Mar 06.
Article En | MEDLINE | ID: mdl-38448971

OBJECTIVE: The objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC). METHODS: Based on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials. RESULTS: The combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P < 0.05). Except for the groups containing tannic acid, cells in all other groups showed good proliferation across varying time intervals without displaying significant cytotoxicity (P < 0.05). CONCLUSION: In this study, aloe-emodin, quercetin, curcumin, and tannic acid were capable of enhancing the in vitro antibacterial performance of gentamicin-loaded bone cement against S. aureus. While the groups containing tannic acid displayed moderate cytotoxicity in in vitro cell culture, all other groups showed no discernible cytotoxic effects.


Anthraquinones , Biological Products , Curcumin , Emodin , Polyphenols , Gentamicins/pharmacology , Bone Cements/pharmacology , Curcumin/pharmacology , Quercetin , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Biological Products/pharmacology
6.
BMC Oral Health ; 24(1): 253, 2024 Feb 19.
Article En | MEDLINE | ID: mdl-38374033

BACKGROUND: Sex estimate is a key stage in forensic science for identifying individuals. Some anatomical structures may be useful for sex estimation since they retain their integrity even after highly severe events. However, few studies are focusing on the Chinese population. Some researchers used teeth for sex estimation, but comparison with maxillary sinus were lack. As a result, the objective of this research is to develop a sex estimation formula for the northwestern Chinese population by the volume of the maxillary sinus and compare with the accuracy of sex estimation based on teeth through cone-beam computed tomography (CBCT). METHODS: CBCT images from 349 samples were used to establish and verify the formula. The volume of both the left and right maxillary sinuses was measured and examined for appropriate formula coefficients. To create the formula, we randomly picked 80% of the data as the training set and 20% of the samples as the testing set. Another set of samples, including 20 males and 20 females, were used to compare the accuracy of maxillary sinuses and teeth. RESULTS: Overall, sex estimation accuracy by volume of the left maxillary sinus can reach 78.57%, while by the volume of the right maxillary sinus can reach 74.29%. The accuracy for females, which can reach 91.43% using the left maxillary sinus, was significantly higher than that for males, which was 65.71%. The result also shows that maxillary sinus volume was higher in males. The comparison with the available results using measurements of teeth for sex estimation performed by our group showed that the accuracy of sex estimation using canines volume was higher than the one using maxillary sinus volume, the accuracies based on mesiodistal diameter of canine and first molar were the same or lower than the volume of maxillary sinus. CONCLUSIONS: The study demonstrates that measurement of maxillary sinus volume based on CBCT scans was an available and alternative method for sex estimation. And we established a method to accurately assess the sex of the northwest Chinese population. The comparison with the results of teeth measurements made the conclusion more reliable.


Cone-Beam Computed Tomography , Maxillary Sinus , Male , Female , Humans , Maxillary Sinus/diagnostic imaging , Cone-Beam Computed Tomography/methods , Molar , Maxilla/diagnostic imaging , China
7.
Article En | MEDLINE | ID: mdl-37217281

Rodent models of breast cancer have played critical roles in our understanding of breast cancer development and progression as well as preclinical testing of cancer prevention and therapeutics. In this article, we first review the values and challenges of conventional genetically engineered mouse (GEM) models and newer iterations of these models, especially those with inducible or conditional regulation of oncogenes and tumor suppressors. Then, we discuss nongermline (somatic) GEM models of breast cancer with temporospatial control, made possible by intraductal injection of viral vectors to deliver oncogenes or to manipulate the genome of mammary epithelial cells. Next, we introduce the latest development in precision editing of endogenous genes using in vivo CRISPR-Cas9 technology. We conclude with the recent development in generating somatic rat models for modeling estrogen receptor-positive breast cancer, something that has been difficult to accomplish in mice.


Neoplasms , Mice , Rats , Animals , Disease Models, Animal , Oncogenes , Epithelial Cells
8.
Arch Insect Biochem Physiol ; 114(2): 1-9, 2023 Oct.
Article En | MEDLINE | ID: mdl-37672308

The mitochondrial genome (mitogenome) has been widely used as a powerful marker in phylogenetic and evolutionary studies of various Dipteran groups. However, only a few mitogenomes from the Thienemanniella genus have been reported till now. Furthermore, there is still indeterminacy in the phylogenetic relationships of the genus Thienemanniella. In this study, mitogenomes of five Thienemanniella species were sequenced and analyzed newly. Combined with the published mitogenome of Thienemanniella nipponica, the obtained results showed that mitogenomes of Thienemanniella were conserved in structure, and all genes were observed to be arranged in the same gene order as the ancestral mitogenome. Nucleotide composition varied significantly among different genes, and the control region displayed the highest A + T content. All protein coding genes are subjected to purification selection, and the fastest evolving gene is ATP8. Maximum likelihood and Bayesian inference analyses showed the phylogeny of Thienemanniella which was supported in five topologies. Our present study provides valuable insight into the phylogenetic relationships of Thienemanniella species.


Chironomidae , Genome, Mitochondrial , Animals , Chironomidae/genetics , Bayes Theorem , Phylogeny , Biological Evolution
9.
Cancer Cell ; 41(9): 1586-1605.e15, 2023 09 11.
Article En | MEDLINE | ID: mdl-37567170

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of ß-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.


Endometrial Neoplasms , Metformin , Proteogenomics , Female , Humans , Proto-Oncogene Proteins c-akt/genetics , Prospective Studies , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , beta Catenin/genetics , beta Catenin/metabolism , Metformin/pharmacology
10.
Br J Pharmacol ; 180(23): 3008-3023, 2023 12.
Article En | MEDLINE | ID: mdl-37428102

BACKGROUND AND PURPOSE: Nitazoxanide is a therapeutic anthelmintic drug. Our previous studies found that nitazoxanide and its metabolite tizoxanide activated adenosine 5'-monophosphate-activated protein kinase (AMPK) and inhibited signal transducer and activator of transcription 3 (STAT3) signals. As AMPK activation and/or STAT3 inhibition are targets for treating pulmonary fibrosis, we hypothesized that nitazoxanide would be effective in experimental pulmonary fibrosis. EXPERIMENTAL APPROACH: The mitochondrial oxygen consumption rate of cells was measured by using the high-resolution respirometry system Oxygraph-2K. The mitochondrial membrane potential of cells was evaluated by tetramethyl rhodamine methyl ester (TMRM) staining. The target protein levels were measured by using western blotting. The mice pulmonary fibrosis model was established through intratracheal instillation of bleomycin. The examination of the lung tissues changes were carried out using haematoxylin and eosin (H&E), and Masson staining. KEY RESULTS: Nitazoxanide and tizoxanide activated AMPK and inhibited STAT3 signalling in human lung fibroblast cells (MRC-5 cells). Nitazoxanide and tizoxanide inhibited transforming growth factor-ß1 (TGF-ß1)-induced proliferation and migration of MRC-5 cells, collagen-I and α-smooth muscle cell actin (α-SMA) expression, and collagen-I secretion from MRC-5 cells. Nitazoxanide and tizoxanide inhibited epithelial-mesenchymal transition (EMT) and inhibited TGF-ß1-induced Smad2/3 activation in mouse lung epithelial cells (MLE-12 cells). Oral administration of nitazoxanide reduced the bleomycin-induced mice pulmonary fibrosis and, in the established bleomycin-induced mice, pulmonary fibrosis. Delayed nitazoxanide treatment attenuated the fibrosis progression. CONCLUSIONS AND IMPLICATIONS: Nitazoxanide improves the bleomycin-induced pulmonary fibrosis in mice, suggesting a potential application of nitazoxanide for pulmonary fibrosis treatment in the clinic.


Anthelmintics , Nitro Compounds , Pulmonary Fibrosis , Thiazoles , Humans , Mice , Animals , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Transforming Growth Factor beta1/metabolism , AMP-Activated Protein Kinases , Bleomycin , Collagen Type I , Disease Models, Animal , Anthelmintics/adverse effects , Mice, Inbred C57BL
11.
Sci Adv ; 9(19): eade0059, 2023 05 12.
Article En | MEDLINE | ID: mdl-37172086

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either Kras or Pik3ca in both normal and hyperplastic mammary glands led to swift tumorigenesis. The resulting tumors shared some histological, transcriptome, and proteome features with tumors induced by lentivirus-mediated expression of the respective oncogenes, but they also exhibited some distinct characteristics, particularly showing less intertumor variation, thus potentially offering more consistent models for cancer studies and therapeutic development. Therefore, this technological advance fills a critical gap between the power of CRISPR technology and high-fidelity mouse models for studying human tumor evolution and preclinical drug testing.


Gene Editing , Neoplasms , Animals , Mice , Humans , Gene Editing/methods , CRISPR-Cas Systems/genetics , Neoplasms/genetics , Neoplasms/therapy , Recombinational DNA Repair , Disease Models, Animal
12.
Forensic Sci Int ; 348: 111704, 2023 Jul.
Article En | MEDLINE | ID: mdl-37094502

Sex estimation is very important in forensic applications as part of individual identification. Morphological sex estimation methods predominantly focus on anatomical measurements. Based on the close relationship between sex chromosome genes and facial characterization, craniofacial hard tissues morphology shows sex dimorphism. In order to establish a more labor-saving, rapid, and accurate reference for sex estimation, the study investigated a deep learning network-based artificial intelligence (AI) model using orthopantomograms (OPG) to estimate sex in northern Chinese subjects. In total, 10703 OPG images were divided into training (80%), validation (10%), and test sets (10%). At the same time, different age thresholds were selected to compare the accuracy differences between adults and minors. The accuracy of sex estimation using CNN (convolutional neural network) model was higher for adults (90.97%) compared with minors (82.64%). This work demonstrated that the proposed model trained with a large dataset could be used in automatic morphological sex-related identification with favorable performance and practical significance in forensic science for adults in northern China, while also providing a reference for minors to some extent.


Artificial Intelligence , Neural Networks, Computer , Adult , Humans , Forensic Sciences , Forensic Medicine , China
13.
J Vis Exp ; (192)2023 02 10.
Article En | MEDLINE | ID: mdl-36847377

Mouse mammary glands comprise ductal trees, which are lined by epithelial cells and have one opening at the tip of each nipple. The epithelial cells play a major role in mammary gland function and are the origin of most mammary tumors. Introducing genes of interest into mouse mammary epithelial cells is a critical step in evaluating gene function in epithelial cells and generating mouse mammary tumor models. This goal can be accomplished through the intraductal injection of a viral vector carrying the genes of interest into the mouse mammary ductal tree. The injected virus subsequently infects mammary epithelial cells, bringing in the genes of interest. The viral vector can be lentiviral, retroviral, adenoviral, or adenovirus-associated viral (AAV). This study demonstrates how a gene of interest is delivered into mammary epithelial cells through mouse mammary intraductal injection of a viral vector. A lentivirus carrying GFP is used to show stable expression of a delivered gene, and a retrovirus carrying Erbb2 (HER2/Neu) is used to demonstrate oncogene-induced atypical hyperplastic lesions and mammary tumors.


Mammary Neoplasms, Experimental , Neoplasms , Mice , Animals , Mammary Glands, Animal/pathology , Epithelial Cells/metabolism , Gene Transfer Techniques , Oncogenes , Retroviridae/genetics , Adenoviridae , Neoplasms/pathology , Mammary Neoplasms, Experimental/pathology , Mice, Transgenic
14.
Br J Pharmacol ; 180(14): 1862-1877, 2023 07.
Article En | MEDLINE | ID: mdl-36740831

BACKGROUND AND PURPOSE: Piezo1 channels are mechanosensitive cationic channels that are activated by mechanical stretch or shear stress. Endothelial Piezo1 activation by shear stress caused by blood flow induces ATP release from endothelial cells; however, the link between shear stress and endothelial ATP production is unclear. EXPERIMENTAL APPROACH: The mitochondrial respiratory function of cells was measured by using high-resolution respirometry system Oxygraph-2k. The intracellular Ca2+ concentration was evaluated by using Fluo-4/AM and mitochondrial Ca2+ concentration by Rhod-2/AM. KEY RESULTS: The specific Piezo1 channel activator Yoda1 or its analogue Dooku1 increased [Ca2+ ]i in human umbilical vein endothelial cells (HUVECs), and both Yoda1 and Dooku1 increased mitochondrial oxygen consumption rates (OCRs) and mitochondrial ATP production in HUVECs and primary cultured rat aortic endothelial cells (RAECs). Knockdown of Piezo1 inhibited Yoda1- and Dooku1-induced increases of mitochondrial OCRs and mitochondrial ATP production in HUVECs. The shear stress mimetics, Yoda1 and Dooku1, and the Piezo1 knock-down technique also demonstrated that Piezo1 activation increased glycolysis in HUVECs. Chelating extracellular Ca2+ with EGTA or chelating cytosolic Ca2+ with BAPTA-AM did not affect Yoda1- and Dooku1-induced increases of mitochondrial OCRs and ATP production, but chelating cytosolic Ca2+ inhibited Yoda1- and Dooku1-induced increase of glycolysis. Confocal microscopy showed that Piezo1 channels are present in mitochondria of endothelial cells, and Yoda1 and Dooku1 increased mitochondrial Ca2+ in endothelial cells. CONCLUSION AND IMPLICATIONS: Piezo1 channel activation stimulates ATP production through enhancing mitochondrial respiration and glycolysis in vascular endothelial cells, suggesting a novel role of Piezo1 channel in endothelial ATP production.


Ion Channels , Mitochondria , Animals , Humans , Rats , Adenosine Triphosphate , Glycolysis , Human Umbilical Vein Endothelial Cells/metabolism , Ion Channels/metabolism , Mitochondria/metabolism , Respiration
15.
Br J Pharmacol ; 180(1): 62-79, 2023 Jan.
Article En | MEDLINE | ID: mdl-36082580

BACKGROUND AND PURPOSE: The anthelmintic drug nitazoxanide has a mitochondrial uncoupling effect. Mitochondrial uncouplers have been proven to inhibit smooth muscle cell proliferation and migration, inhibit NLRP3 inflammasome activation of macrophages and improve dyslipidaemia. Therefore, we aimed to demonstrate that nitazoxanide would protect against atherosclerosis. EXPERIMENTAL APPROACH: The mitochondrial oxygen consumption of cells was measured by using the high-resolution respirometry system, Oxygraph-2K. The proliferation and migration of A10 cells were measured by using Edu immunofluorescence staining, wound-induced migration and the Boyden chamber assay. Protein levels were measured by using the western blot technique. ApoE (-/-) mice were fed with a Western diet to establish an atherosclerotic model in vivo. KEY RESULTS: The in vitro experiments showed that nitazoxanide and tizoxanide had a mitochondrial uncoupling effect and activated cellular AMPK. Nitazoxanide and tizoxanide inhibited serum- and PDGF-induced proliferation and migration of A10 cells. Nitazoxanide and tizoxanide inhibited NLRP3 inflammasome activation in RAW264.7 macrophages, the mechanism by which involved the AMPK/IκBα/NF-κB pathway. Nitazoxanide and tizoxanide also induced autophagy in A10 cells and RAW264.7 macrophages. The in vivo experiments demonstrated that oral administration of nitazoxanide reduced the increase in serum IL-1ß and IL-6 levels and suppressed atherosclerosis in Western diet-fed ApoE (-/-) mice. CONCLUSION AND IMPLICATIONS: Nitazoxanide inhibits the formation of atherosclerotic plaques in ApoE (-/-) mice fed on a Western diet. In view of nitazoxanide being an antiprotozoal drug already approved by the FDA, we propose it as a novel anti-atherosclerotic drug with clinical translational potential.


Atherosclerosis , Mice , Animals , Pharmaceutical Preparations/metabolism , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Mitochondria/metabolism , Nitro Compounds/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/metabolism
16.
Cancer Prev Res (Phila) ; 16(2): 65-73, 2023 02 06.
Article En | MEDLINE | ID: mdl-36343340

Antiestrogen medication is the only chemoprevention currently available for women at a high risk of developing breast cancer; however, antiestrogen therapy requires years to achieve efficacy and has adverse side effects. Therefore, it is important to develop an efficacious chemoprevention strategy that requires only a short course of treatment. PIK3CA is commonly activated in breast atypical hyperplasia, the known precancerous precursor of breast cancer. Targeting PI3K signaling in these precancerous lesions may offer a new strategy for chemoprevention. Here, we first established a mouse model that mimics the progression from precancerous lesions to breast cancer. Next, we demonstrated that a short-course prophylactic treatment with the clinically approved PI3K inhibitor alpelisib slowed early lesion expansion and prevented cancer formation in this model. Furthermore, we showed that alpelisib suppressed ex vivo expansion of patient-derived atypical hyperplasia. Together, these data indicate that the progression of precancerous breast lesions heavily depends on the PI3K signaling, and that prophylactic targeting of PI3K activity can prevent breast cancer. PREVENTION RELEVANCE: PI3K protein is abnormally high in breast precancerous lesions. This preclinical study demonstrates that the FDA-approved anti-PI3K inhibitor alpelisib can prevent breast cancer and thus warrant future clinical trials in high-risk women.


Precancerous Conditions , Thiazoles , Animals , Mice , Female , Hyperplasia/drug therapy , Thiazoles/therapeutic use , Phosphoinositide-3 Kinase Inhibitors , Precancerous Conditions/drug therapy , Estrogen Receptor Modulators , Class I Phosphatidylinositol 3-Kinases
17.
Zootaxa ; 5382(1): 55-61, 2023 Dec 07.
Article En | MEDLINE | ID: mdl-38221276

Heissophila Schuh, 2006, a monotypic genus of Heissophilinae (Hemiptera: Plokiophilidae), is newly recorded from Oriental China based on Heissophila macrotheleae Schuh, 2006 collected from Yunnan Province, China. The diagnosis of the species is expanded based on the newly collected materials. In addition, a DNA barcode of H. macrotheleae and host spider are provided. Photographs of the co-existing web-loving bugs and the natural habitat are also present.


Hemiptera , Heteroptera , Spiders , Animals , Heteroptera/genetics , China , Animal Distribution
18.
Clin Transl Med ; 12(11): e1075, 2022 11.
Article En | MEDLINE | ID: mdl-36324258

BACKGROUND: A number of studies have demonstrated that N6-methyladenosine (m6A) plays a vital role in the pathological process of various tumours. Recently, it was found that m6A writers or erasers affect the tumourigenesis of melanoma. However, the relationship between m6A readers such as YTH domain family (YTHDF) proteins and melanoma was still elusive. METHODS: RT-qPCR, Western blot and immunohistochemistry were conducted to measure the expression level of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and lysyl oxidase-like 3 (LOXL3) in melanoma tissues and cells. The effects of YTHDF3 and LOXL3 on melanoma were verified in vitro and in vivo. Multi-omics analysis including RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses was performed to identify the target. The interaction between YTHDF3 and LOXL3 was verified by RT-PCR, Western blot, MeRIP-qPCR, RIP-qPCR and CRISPR-Cas13b-based epitranscriptome engineering. RESULTS: In this study, we found that m6A reader YTHDF3 could affect the metastasis of melanoma both in vitro and in vivo. The downstream targets of YTHDF3, such as LOXL3, phosphodiesterase 3A (PDE3A) and chromodomain helicase DNA-binding protein 7 (CHD7) were identified by means of RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses. Besides, RT-qPCR, Western blot, RIP-qPCR and MeRIP-qPCR were performed for subsequent validation. Among various targets of YTHDF3, LOXL3 was found to be the optimal target of YTHDF3. With the application of CRISPR-Cas13b-based epitranscriptome engineering, we further confirmed that the transcript of LOXL3 was captured and regulated by YTHDF3 via m6A binding sites. YTHDF3 augmented the protein expression of LOXL3 without affecting its mRNA level via the enrichment of eukaryotic translation initiation factor 3 subunit A (eIF3A) on the transcript of LOXL3. LOXL3 downregulation inhibited the metastatic ability of melanoma cells, and overexpression of LOXL3 ameliorated the inhibition of melanoma metastasis caused by YTHDF3 downregulation. CONCLUSIONS: The YTHDF3-LOXL3 axis could serve as a promising target to be interfered with to inhibit the metastasis of melanoma.


Melanoma , RNA-Binding Proteins , Humans , RNA-Binding Proteins/genetics , Adenosine/metabolism , Melanoma/genetics , RNA, Messenger/genetics , Amino Acid Oxidoreductases/metabolism
19.
BMC Oral Health ; 22(1): 320, 2022 08 01.
Article En | MEDLINE | ID: mdl-35915494

OBJECTIVE: This study aimed to investigate whether the subjects with mouth breathing (MB) or nasal breathing (NB) with different sagittal skeletal patterns showed different maxillary arch and pharyngeal airway characteristics. METHODS: Cone-beam computed tomography scans from 70 children aged 10 to 12 years with sagittal skeletal Classes I and II were used to measure the pharyngeal airway, maxillary width, palatal area, and height. The independent t-test and the Mann-Whitney U test were used for the intragroup analysis of pharyngeal airway and maxillary arch parameters. RESULTS: In the Skeletal Class I group, nasopharyngeal airway volume (P < 0.01), oropharyngeal airway volume (OPV), and total pharyngeal airway volume (TPV) (all P < 0.001) were significantly greater in subjects with NB than in those with MB. Furthermore, intermolar width, maxillary width at the molars, intercanine width, maxillary width at the canines, and palatal area were significantly larger in subjects with NB than in those with MB (all P < 0.001). In the Skeletal Class II group, OPV, TPV (both P < 0.05) were significantly greater in subjects with NB than in those with MB. No significant differences in pharyngeal airway parameters in the MB group between subjects with Skeletal Class I and those with Skeletal Class II. CONCLUSION: Regardless of sagittal Skeletal Class I or II, the pharyngeal airway and maxillary arch in children with MB differ from those with NB. However, the pharyngeal airway was not significantly different between Skeletal Class I and II in children with MB.


Imaging, Three-Dimensional , Maxilla , Mouth Breathing , Pharynx , Cephalometry/methods , Cone-Beam Computed Tomography/methods , Humans , Imaging, Three-Dimensional/methods , Mandible , Maxilla/diagnostic imaging , Palate , Pharynx/diagnostic imaging
20.
BMC Pediatr ; 22(1): 506, 2022 08 25.
Article En | MEDLINE | ID: mdl-36008795

OBJECTIVES: This study aimed to examine the clinical effects of myofunctional treatment on children with functional mouth breathing by cephalometric radiographs and study models. METHODS: A total of 224 children (6-10 years old; 114 males and 110 females; SNA°: 82.24 ± 1.67°; ANB°: 2.79 ± 0.80°, 28° < SN-GoGn° < 37°) formed three groups: MB-M group (mouth breathers with myofunctional treatment,n = 75); MB-N group (mouth breathers with no treatment,n = 70); NB group (nasal breathers with no treatment, n = 79). A blind evaluation of cephalometric radiographs and study models was conducted at T1(pre-study) and T2 (post-study), respectively. RESULTS: Two hundred four children (MB-M:66, MB-N:68, NB:70) completed the present study. At T1, MB-M and MB-N groups, compared to their NB counterpart, had greater anterior lower facial height(P < 0.01) and overjet(P < 0.001) but shorter overbite and maxillary canines width (P < 0.001). At T2, the MB-N group exhibited a higher ANB angle, anterior lower facial height, and overjet, but shorter overbite and maxillary canines width (P < 0.001). From T1 to T2, the anterior lower facial height increased, overbite and the maxillary canines width further decreased in the MB-N group (P < 0.001). However, in the MB-M group, the incisors were retracted, overbite increased (P < 0.001), anterior lower facial height increased insignificantly (P > 0.05), and maxillary canines width increased slightly (P < 0.05). In the NB and MB-M groups, the mandible showed a normal tendency to grow forward, whereas, in the MB-N group, the mandible showed a tendency to grow downward (P < 0.001). CONCLUSIONS: Mouth breathers demonstrated increased anterior facial height and overjet but reduced overbite and maxillary arch width, which improved significantly following myofunctional treatment. TRIAL REGISTRATION: TCTR: TCTR20220401001 . Registered 1stApril 2022-Retrospectively registered.


Mouth Breathing , Overbite , Cephalometry , Dentition, Mixed , Female , Humans , Male , Mandible , Mouth Breathing/therapy
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