Tooth eruption is a localised event whereby the signals for eruption for a given tooth are synthesised in the dental follicle of that tooth with a possible cross talk of signals coming from the adjacent stellate reticulum. The eruption process requires alveolar bone resorption that is primarily regulated by the dental follicle. This is reflected by the fact that failures of eruption often can be traced to either osteoclast deficiencies or to dental follicle abnormalities. Recent advances in application of molecular techniques to animal models allowed for better understanding of gene regulatory events involved in the physiology of tooth eruption. This article attempts to consolidate and organise the facts that offshoot from animal studies.
Tooth Eruption ; Dental Sac ; Molecular Biology

OBJECTIVE: The aim of this study is to investigate the main active substances of Qilin pills by high performance liquid chromatogre-electrostatic field orbitrap mass spectrometry (HPLC-Q-Orbitrap /MS), and explore the mechanism of its action in the treatment of asthenozoospermia by combining network pharmacology and molecular docking. METHODS: (1) Qilin pills were quantitatively and qualitatively analyzed by HPLC-Q-Orbitrap /MS. (2) The top 100 compounds in Qilin pills were screened by content analysis and SwissADME, and their targets were predicted. The asthenozoospermia targets were searched through the database. And a "protein-protein interaction" (PPI) network was constructed. KEGG and GO analysis was performed using the DAVID database. And a "drug-target-pathway" network was constructed. (3) SailVina was used for molecular docking. RESULTS: (1) A total of 1 275 known components were found and ranked in Qilin pills by HPLC-Q-Orbitrap /MS analysis. (2) The top 100 compounds in Qilin pills predicted a total of 1 053 targets and 184 potential therapeutic targets for asthenozoospermia. KEGG pathway analysis and GO analysis showed that the treatment of asthenozoospermia by Qilin pills may be related to the steroid hormone synthesis pathway, the response to steroid hormones, the chromosomal region of cells and the activity of steroid hydroxylase. The mechanism of Qilin pills in treating asthenozoospermia may be related to regulating the synthesis, metabolism and reaction process of sex hormone in the body. (3) The molecular docking results of its key targets (CYP19A1, ESR1, HSP90AA1, p53, HIF1α and BCL2) showed that the key active ingredients M030, M039, M043, M050, M055 and M073 of Qilin pills had spontaneous binding. It had a binding energy of less than －5 kJ /mol. CONCLUSION The material basis of Qilin pills has been explored by this study. And the mechanism of action of Qilin pills in the treatment of asthenozoospermia is highly bound to the expression and response process of steroid hormones, which provides a theoretical basis for the clinical application of Qilin pills.
Asthenozoospermia/drug therapy* ; Chromatography, High Pressure Liquid ; Molecular Docking Simulation ; Drugs, Chinese Herbal/chemistry* ; Male ; Computational Biology ; Humans ; Mass Spectrometry ; Protein Interaction Maps ; Liquid Chromatography-Mass Spectrometry

OBJECTIVES: To explore the potential of pyrroline-5-carboxylate reductase 1 (PYCR1) as a pan-cancer biomarker and investigate its expression, function, and clinical significance in bladder cancer (BLCA). METHODS: Bioinformatics analysis was conducted to evaluate the associations of PYCR1 with prognosis, immune microenvironment remodeling, tumor mutation burden (TMB), and microsatellite instability (MSI) in cancer patients. Using the TCGA-BLCA dataset, univariate and multivariate regression analyses were performed to assess the potential of PYCR1 as an independent prognostic risk factor for BLCA, and a clinical decision model was constructed. The IMvigor210 cohort was utilized to evaluate the potential of PYCR1 for independently predicting the efficacy of immunotherapy. The pRRophetic was employed to screen candidate chemotherapeutic agents for treating BLCA with high PYCR1 expression. The CMap-XSum algorithm and molecular docking techniques were used to explore and validate small molecule inhibitors of PYCR1. RESULTS: A high expression of PYCR1 was significantly associated with poor prognosis, immune cell infiltration, TMB and MSI in various tumors (r>0.3). PYCR1 was overexpressed in BLCA, and high PYCR1 expression was closely related to poor prognosis in BLCA patients (HR: 1.14, 95% CI: 1.02-1.68, P=0.006). The IC₅₀ of the anti-cancer drugs cetuximab, 5-fluorouracil, and doxorubicin increased significantly in BLCA cell lines with high PYCR1 expressions (P<0.0001). CONCLUSIONS High PYCR1 expression is an independent risk factor for poor prognosis in BLCA patients and can serve as a significant indicator for clinical decision-making as well as a marker for predicting sensitivity to chemotherapeutic agents and the efficacy of immunotherapy.
Humans ; Urinary Bladder Neoplasms/genetics* ; Immunotherapy ; Prognosis ; Pyrroline Carboxylate Reductases/metabolism* ; Biomarkers, Tumor/genetics* ; delta-1-Pyrroline-5-Carboxylate Reductase ; Microsatellite Instability ; Tumor Microenvironment ; Mutation ; Computational Biology ; Molecular Docking Simulation

Humans ; Parathyroid Neoplasms/genetics* ; Molecular Biology ; Parathyroid Glands

This study aims to investigate the effect of Linggui Zhugan Decoction(LGZGD) on autophagy in the mouse model of chronic heart failure(CHF) induced by myocardial infarction(MI), as well as the regulatory effect of LGZGD on the hypoxia-inducible factor-1α(HIF-1α)/heme oxygenase-1(HO-1) signaling pathway, based on bioinformatics and animal experiments. The active ingredients and corresponding targets of LGZGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database, and GEO, GeneCards, and DisGeNET were searched for the disease targets. Cytoscape was used to establish a "drug-component-target" network. The protein-protein interaction(PPI) network analysis was performed on STRING. R language was used for Gene Ontology(GO) and Kyoto Encycloperfia of Genes and Genomes(KEGG) enrichment analyses. Molecular docking was adopted to validate the core targets. The mouse model of MI-induced CHF was established by surgical ligation of the left anterior descending coronary artery. The modeled mice were assigned into the sham, model, low-, medium-, and high-dose(2.34, 4.68, and 9.36 g·kg~(-1), respectively) LGZGD, and captopril(3.25 mg·kg~(-1)) groups. After continuous administration for 6 weeks, a Doppler ultrasound imaging system was used to examine the heart function indicators: left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), left ventricular end-systolic dimension(LVIDs), and left ventricular end-diastolic dimension(LVIDd). The myocardial tissue was stained with hematoxylin-eosin for the observation of morphological changes. The mRNA levels of microtubule-associated protein 1 light chain 3 beta(LC3B), Beclin1, p62, HIF-1α, and HO-1 in the myocardial tissue were determined by RT-qPCR. The protein levels of LC3B, beclin1, p62, autophagy-related protein 5(ATG5), HIF-1α, and HO-1 were determined by Western blot. The results showed that 103 active components of LGZGD, corresponding to 224 targets, were obtained. A total of 3 485 and 6 165 targets related to MI and CHF, respectively, were retrieved. The GSE16499 dataset obtained 3 263 differentially expressed genes. There were 31 common targets. The top 3 core active components were quercetin, naringenin, and 1-methoxyphaseollidin. The topology analysis results showed that the core targets were MAPK3, HMOX1(HO-1), MYC, ADRB2, PPARD, and HIF1A(HIF-1α). The molecular docking results showed strong binding between the core targets and the main active components of LGZGD. LGZGD significantly improved the heart function and alleviated the pathological changes in the myocardial tissue of mice. Western blot and RT-qPCR results showed that the HIF-1α/HO-1 signaling pathway and autophagy were activated in the model group. LGZGD up-regulated the levels of LC3B, Beclin1, ATG5, HIF-1α, and HO-1 while down-regulating the mRNA and protein levels of p62. In summary, LGZGD can enhance autophagy and improve the heart function in the mouse model of CHF after MI by upregulating the HIF-1α/HO-1 signaling pathway.
Animals ; Drugs, Chinese Herbal/chemistry* ; Myocardial Infarction/drug therapy* ; Heart Failure/physiopathology* ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Signal Transduction/drug effects* ; Male ; Computational Biology ; Heme Oxygenase-1/genetics* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Mice, Inbred C57BL ; Humans ; Chronic Disease ; Disease Models, Animal

This article aims to analyze the therapeutic effect and probe into the mechanism of Sanhuang Hushen Fangshuai Decoction in treating chronic kidney disease(CKD) based on metabolomics and bioinformatics. The patients with stage 3-4 CKD diagnosed and treated in the Changzhou Hospital of Traditional Chinese Medicine from June 2023 to March 2024 were enrolled in this study. The patients were treated with Sanhuang Hushen Fangshuai Decoction, and the therapeutic effect was evaluated. The serum samples were collected before and after treatment. Ultra-performance liquid chromatography was employed to detect metabolites in the serum, and multivariate statistical analysis was performed. Bioinformatics was employed to screen the active components and targets of the decoction and the potential targets of CKD. The protein-protein interaction(PPI) network of the common targets shared by the decoction and CKD and the drug-component-target network were constructed. The core components and targets were screened according to the correlation degree of the network. The binding between core components and targets was verified by molecular docking. The results showed that Sanhuang Hushen Fangshuai Decoction improved the renal function and reduced proteinuria. Compared with the healthy population, the post-treatment population showed recovery of 54 up-regulated metabolites and 43 down-regulated metabolites. Enrichment analysis results showed that the key pathways included adenosine triphosphate binding cassette(ABC) transport, tryptophan metabolism, and tyrosine metabolism. The results of bioinformatics analysis showed that the core components of Sanhuang Hushen Fangshuai Decoction in treating CKD included kaempferol, β-sitosterol, luteolin, 7-O-methylisolingol, and tanshinone Ⅱ_A. The core targets included TP53, PTGS2, JUN, AKT1, and TNF. Molecular docking results showed that the core components bound well to the target genes. The results of joint pathway analysis suggested that both differential metabolites and key targets were involved in galactose metabolism, nicotinamide metabolism, and other pathways. This study suggests that Sanhuang Hushen Fangshuai Decoction is effective for CKD, and it can regulate multiple abnormal metabolites and participates in multiple metabolic pathways involving amino acids and sugars. The active components such as kaempferol in the decoction may regulate related targets such as TP53 and PTGS2. This study provides a basis for the prevention and treatment of CKD with traditional Chinese medicine.
Drugs, Chinese Herbal/administration & dosage* ; Renal Insufficiency, Chronic/genetics* ; Humans ; Computational Biology ; Male ; Metabolomics ; Protein Interaction Maps/drug effects* ; Middle Aged ; Molecular Docking Simulation ; Female ; Adult ; Aged

The development of new agricultural science is a new idea and a new measure that aims to deepen the reform of higher education in agriculture and forestry for the development of new agriculture, new countryside, new farmers and new ecosystem. It is therefore essential for the current undergraduate experimental teaching reform to timely introduce new technologies and new methods used in the development of agriculture and forestry industry into the experimental course teaching, and promote the integration of professional education with innovation and entrepreneurship education, according to the requirements of the new agricultural science. In view of this, the exploration and practice of molecular biology experiment course was carried out from the perspective of experimental projects, teaching modes and evaluation methods, according to the teaching requirements and characteristics of molecular biology experiment and teachers' scientific research achievements. The results showed that this reform greatly improved the students' comprehensive quality and innovation ability and may facilitate the innovation experiment teaching of other courses.
Humans ; Ecosystem ; Students ; Curriculum ; Molecular Biology

Birth defects are an important factor for the quality of newborn population. With the development of molecular genetic technology, an increasing number of genetic disorders leading to birth defects can now be detected. The lack of the knowledge for the basics and clinical applications of molecular genetic techniques have emerged as a shortcoming for primary care physicians who have formed the first tier prevention for birth defects. Currently, government has paid more attention to the above problems and formulated more training programs for primary obstetricians and gynecologists, e.g., "Prenatal Screening and Prenatal Diagnosis Post Training Program", "National Birth Defects Training Program", "National Primary Obstetrician Training Program". To some extent, such programs have met the urgent need for birth defect prevention in primary hospitals. But at the same time, some problems have also emerged. For instance, the knowledge for birth defects among primary obstetricians and gynecologists is poor, and there is lack of young personnel. This article has aimed to discuss the strategies to systematically improve the ability for preventing birth defects among primary care physicians by analyzing the obstacles and challenges for primary obstetricians and gynecologists in the era of molecular genetic testing.
Female ; Pregnancy ; Infant, Newborn ; Humans ; Gynecology ; Obstetrics ; Gynecologists ; Obstetricians ; Molecular Biology

Humans ; Hemangiosarcoma/pathology* ; Colonic Neoplasms ; Molecular Biology

Objective: To investigate the clinicopathological and molecular features of primary cardiac angiosarcoma (PCAS), and to analyze the correlation between KDR mutation and the clinicopathological features of PCAS. Methods: Thirteen cases of PCAS were collected at Beijing Anzhen Hospital, Capital Medical University from January 2007 to December 2021. The clinicopathological features, diagnosis, differential diagnosis and outcome were retrospectively analyzed. KDR mutation was detected by next-generation sequencing (NGS) and then the expression of KDR (VEGFR2) was determined by immunohistochemistry (IHC), with review of relevant literatures. Results: There were eight males and five females with a mean age of 45 years. The primary tumor was in the right atrium in 10 cases, left atrium in two cases and right ventricle in one case. The histomorphology was mainly poorly differentiated angiosarcoma (11 cases), with highly pleomorphic spindle or round cells in solid sheets, brisk mitotic activity and extensive necrosis. Vascular lumen formation was observed in two cases of high to moderate differentiation, and biphenotypic differentiation was seen in five cases. IHC staining showed CD34, CD31, Fli1, ERG and vimentin were diffusely positive, pan-cytokeratin was positive, Ki-67 index ranged from 3% to 90%, which was positively correlated with the differentiation degree and grade of the PCASs (P<0.05). At the end of follow-up period, one patient was alive, two patients were lost to follow-up, and the remaining 10 patients had an average survival time of 4.6 months. Finally, NGS sequencing was performed on seven samples after screening, and the results showed that KDR and NF1 mutations were both present in three cases. VEGFR2 expression had no significant correlation with the differentiation degree and grade of PCAS (P>0.05), and it was not related to KDR mutation. Conclusions: PCASs mainly occur in the right atrium, and are mainly poorly differentiated. Ki-67 index is helpful to assess the degree and grade of tumor differentiation. The occurrence and development of PCAS may be related to the pathway involved in KDR mutation, but KDR mutation has no clear correlation with clinicopathological characteristics of PCAS, and immunohistochemical staining can not replace gene detection to determine whether the tumor had KDR mutation.
Male ; Female ; Humans ; Middle Aged ; Hemangiosarcoma/genetics* ; Retrospective Studies ; Ki-67 Antigen ; Immunohistochemistry ; Molecular Biology ; Biomarkers, Tumor/analysis*