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

Background and Objectives: Type 2 diabetes mellitus (T2DM) is a global health concern affecting more than 400 million people worldwide. Diabetic neuropathy, nephropathy, retinopathy, and cardiovascular complications lead to debilitating effects to patients. To prevent these, the treatment goal is to lower the blood sugar levels and maintain at a normal range which is achieved through conventional treatments like insulin and oral hypoglycemic agents. However, the high cost of these medications implicates patient treatment outcomes. Hence, alternatives are sought for including the use of herbal medicines. Momordica charantia (MC) and Lagerstroemia speciosa (LS) are common herbal medicines used to manage T2DM. In the Philippines, these herbal preparations are validated for their glucose lowering effects and are commonly found in combination in food supplements. The study aims to screen the possible mechanisms of compounds present in these herbal medicines which can offer possible explanations for their synergistic effects and rationalization of their combination in preparations. Methods: Network pharmacology was employed to determine pivotal proteins that are targeted by MC and LS compounds. Molecular docking was then done to evaluate the favorability of the binding of these compounds toward their target proteins. Results: Our results showed that TNF, HSP90AA1, MAPK3, ALDH2, GCK, AKR1B1, TTR and RBP4 are the possible pivotal targets of MC and LS compounds in T2DM. Conclusion Terpenoids from MC and decanoic acid from LS are the compounds which showed favorable binding towards pivotal protein targets in T2DM. By binding towards the different key proteins in T2DM, they may exhibit their synergistic effects. However, the results of this study are bound to the limitations of computational methods and experimental validation are needed to verify our findings.
Molecular Docking Simulation ; Network Pharmacology ; Momordica charantia

Objectives: This study aims to assess the drug-likeness and binding of nucleobase-substituted ponatinib analogues towards wild-type and T315I mutant BCR-ABL tyrosine kinases. Methodology: A total of 415 ponatinib analogues, encompassing single and combinatorial modifications on five parts of the drug were generated, profiled in SwissADME, and subjected to molecular docking using AutoDock4. Complexes formed by the top analogues then underwent a 100-ns molecular dynamics simulation with GROMACS. Results: Analogues featuring the replacement of the imidazo[1,2b]pyridazine with adenine and cytosine exhibited promising binding free energies, attributed to the presence of primary amines that facilitate crucial hydrogen bond interactions in the hinge region. RMSD, RMSF, and atomic distance analyses of the MD trajectories revealed that the six top analogues formed stable complexes in their inactive DFG-out conformations. Changes in the MMPBSA and MMGBSA-calculated free energies were mainly driven by changes in hydrogen bonds. Furthermore, drug-likeness predictions supported the formulation of most analogues for oral administration. Conclusion Among the top analogues, VP10004 and VP81014 exhibited the most favorable binding free energies and interactions with the target models, while VP10312 was identified as the most feasible candidate for synthesis.
Hydrogen Bonding ; Molecular Dynamics Simulation ; Molecular Docking Simulation

Artemisia argyi (A. argyi), a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia, has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties. Despite its widespread use, scientific evidence validating the antifungal efficacy of A. argyi water extract (AAWE) against dermatophytes, particularly Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, remains limited. This study aimed to substantiate the scientific basis of the folkloric use of A. argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes. The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species. The subfraction AAWE6, isolated using D101 macroporous resin, emerged as the most potent subfraction. The minimum inhibitory concentrations (MICs) of AAWE6 against T. rubrum, M. gypseum, and T. mentagrophytes were 312.5, 312.5, and 625 μg·mL^-1, respectively. Transmission electron microscopy (TEM) results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T. rubrum, creating breaches ("small holes"), and disrupt the internal mitochondrial structure ("granary"). Furthermore, transcriptome data, quantitative real-time PCR (RT-qPCR), and biochemical assays corroborated the severe disruption of mitochondrial function, evidenced by inhibited tricarboxylic acid (TCA) cycle and energy metabolism. Additionally, chemical characterization and molecular docking analyses identified flavonoids, primarily eupatilin (131.16 ± 4.52 mg·g^-1) and jaceosidin (4.17 ± 0.18 mg·g^-1), as the active components of AAWE6. In conclusion, the subfraction AAWE6 from A. argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function. This research validates the traditional use of A. argyi and provides scientific support for its anti-dermatophytic applications, as recognized in the Chinese patent (No. ZL202111161301.9).
Antifungal Agents/chemistry* ; Arthrodermataceae ; Artemisia/chemistry* ; Molecular Docking Simulation ; Mitochondria ; Microbial Sensitivity Tests

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

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

BACKGROUND: The thoracic small biopsy sampling procedure including transbronchial forceps lung biopsy (TBLB) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) can be accompanied by rapid on-site evaluation (ROSE) of sample material to provide immediate feedback for the proceduralist. The present study aims to investigate the supplemental effect of ROSE smear samples for lung cancer molecular test. METHODS: In a retrospective study, 308 patients admitted to our hospital from August 2020 to December 2022 undergoing diagnostic TBLB and EBUS-TBNA with ROSE and subsequently diagnosed as non-small cell lung cancer (NSCLC) were analyzed. The matched formalin-fixed paraffin-embedding (FFPE) tissue section and ROSE smears for tumor cellularity were compared. DNA yields of smears were determined. Real-time polymerase chain reaction (PCR) and next-generation sequencing (NGS) were performed on adequate smear samples. RESULTS: ROSE smear samples were enriched in tumor cells. Among 308 biopsy samples, 78 cases (25.3%) exhibited inadequate FFPE tissue sections, whereas 44 cases (14.3%) yielded adequate smear samples. Somatic mutations detected in the FFPE tissue section samples were also detected in the matching adequate smear sample. CONCLUSIONS ROSE smear samples of the thoracic small biopsies are beneficial supplemental materials for ancillary testing of lung cancer. Combined use of cytology smear samples with traditional FFPE section samples can enhance the detection rate of informative mutations in patients with advanced NSCLC. We recommend that the laboratory could further evaluate the ROSE cell smears of the patient when FFPE tissue sections are inadequate, and that adequate cell smears can be used as a supplemental source for the molecular testing of NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Rapid On-site Evaluation ; Retrospective Studies ; Molecular Diagnostic Techniques ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods*

So far, the monoclonal hypothesis of tumor occurrence and development cannot be justified. The genetic diversity selection hypothesis for the occurrence and development of lung cancer links Mendelian genetics with Darwin's theory of evolution, suggesting that the genetic diversity of tumor cell populations with polyclonal origins-monoclonal selection-subclonal expansion is the result of selection pressure. Normal cells acquire mutations in oncogenic driver genes and have a selective advantage over other cells, becoming tumor initiating cells; In the interaction with the tumor microenvironment (TME), the vast majority of initiating cells are recognized and killed by the human immune system. If immune escape occurs, the incidence of malignant tumors will greatly increase, and subclonal expansion, intratumour heterogeneity, etc. will occur. This article proposed the hypothesis of genetic diversity selection and analyzed its clinical significance.
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Humans ; Lung Neoplasms/genetics* ; Clinical Relevance ; Evolution, Molecular ; Mutation ; Tumor Microenvironment

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Background and Objective: Epidemiological studies have shown that Filipinos have a higher prevalence of welldifferentiated thyroid cancer and a higher rate of recurrence. The BRAF V600E mutation has been proposed as a potential prognostic marker in aggressive papillary thyroid cancers. In this study, we determined whether this mutation is a risk factor for tumor recurrence in papillary thyroid cancer among Filipinos. Methods: We conducted an age and sex-matched case-control study of patients with papillary thyroid cancer; we had two groups – with and without tumor recurrence – of 14 patients each, with at least a 5-year follow-up. We extracted the DNA samples from the patients’ (paraffin-embedded) tumor biopsy tissue blocks from thyroidectomy specimens, then detected the BRAF V600E mutation using polymerase chain reaction. The McNemar’s test for difference of proportions in paired data was used to determine the association of BRAF V600E mutation with recurrence. Results: The BRAF V600E mutation was found in 57.14% of all cases. We found a prevalence of 64.29% among those with recurrence and 50.00% among those without recurrence, with no significant difference between the two groups (p = 0.688). Conclusion Our study showed the BRAF V600E mutation was not associated with recurrence. We encountered several limitations: we had limited data regarding molecular methodologies in the Philippine setting, we had a small sample size, and therefore we could not study other parameters (e.g., tumor characteristics, lymph node metastasis, stage of disease). We hope that this paves the way for future studies and collaborations to establish the role of BRAF V600E in Filipinos with papillary thyroid tumor recurrence.
papillary thyroid cancer ; molecular diagnostics ; tumor recurrence