AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis.
MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model.
RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor.
CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.
METHODS: Electronic database search and hand search with no language limitations were conducted in the Cochrane Library, PubMed, Ovid, Web of Science, Scopus and ClinicalTrials.gov. The selection criteria were set to include studies with patients aged 13 years and above requiring extractions of upper and lower first premolars to treat bimaxillary proclination with high anchorage demand. Risk of bias assessment was undertaken with Cochrane's Risk Of Bias tool 2.0 (ROB 2.0) for randomised controlled trials (RCTs) and ROBINS‑I tool for nonrandomised prospective studies. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used for quality assessment. Results were summarised qualitatively; no meta-analysis was conducted.
RESULTS: Two RCTs and two nonrandomised prospective studies were included. According to the GRADE approach, there is low to very low quality of evidence that treatment using mini-implant anchorage may significantly change nasolabial angle, upper and lower lip procumbence, and facial convexity angle compared to treatment with conventional anchorage. Similarly, very low quality evidence exists showing no differences in treatment duration between treatments with skeletal or conventional anchorage.
CONCLUSIONS: The overall existing evidence regarding the effect of anchorage protocols on soft tissue changes in patients with bimaxillary protrusion and premolar extraction treatment plans is of low quality.
TRIAL REGISTRATION NUMBER: PROSPERO CRD42020216684.
METHODS: A systematic review was conducted across four databases (PubMed, Cochrane Library, Web of Science, and Medline), focusing on studies involving more than four weeks of dance interventions. MeSH terms [dance or dance intervention or dance rehabilitation or dance movement] and [motor function or functional capacity or postural control or functional mobility or mobility or postural balance or balance or flexibility or gait] and [well-being or quality of life or life satisfaction] were utilized in the search. This review was registered in the PROSPERO database (CRD42023422857). Included studies were assessed using the Cochrane Risk of Bias.
RESULTS: The search revealed 885 studies, and 16 met the inclusion criteria. The effects of various dance genres on physical functions and quality of life were compared. Most studies showed that dance intervention improved physical function, balance, postural control and quality of life. Dance intervention showed a high level of adherence compared to physiotherapy, self-care, conventional therapy, and aerobic and resistance exercise.
CONCLUSION: In terms of improving physical function and quality of life, structured dance is a safe and relatively effective alternative to exercise. Note the effect of movement selection and intensity in the dance interventions. Dance with music may increase participants' interest, encouraging more physical activity among middle-aged and older adults.
PURPOSE/OBJECTIVE: To analyze function of new K21 molecule in the invasive process of oral squamous cell carcinoma (OSCC) cell line.
MATERIALS & METHODS: The Fusobacterium (ATCC 23726) streaks were made, and pellets were resuspended in Cal27 (ATCC CRL-2095) OSCC cell line spheroid cell microplate. Cells were seeded and Lysotracker staining performed for CathepsinK red channel. Cell and morphology were evaluated using Transmission Electron microscopy. Thiobarbituric acid assay was performed. OSCC was analyzed for Mic60. Raman spectra were collected from the cancer cell line. L929 dermal fibroblast cells were used for Scratch Assay. ELISA muti arrays were used for cytokines and matrix molecules. Internalization ability of fibroblast cells were also analyzed. Structure of K21 as a surfactant molecule with best docked poses were presented.
RESULTS: Decrease in lysosomal staining was observed after 15 and 30 min of 0.1% treatment. Tumor clusters were associated with cell membrane destruction in K21 primed cells. There was functional silencing of Mic60 via K21, especially with 1% concentration with reduced cell migration and invasiveness. Raman intensity differences were seen at 700 cm-1, 1200 cm-1 and 1600 cm-1 regions. EVs were detected within presence of fibroblast cells amongst K21 groups. Wound area and wound closure showed the progress of wound healing.
CONCLUSION: Over expression of CatK can be reduced by a newly developed targeted K21 based drug delivery system leading to reduced migration and adhesion of oral squamous cell carcinoma cells. The K21 drug formulation can have great potential for cancer therapies due to targeting and cytotoxicity effects.
METHODS: Based on predefined eligibility criteria, the search was conducted following PRISMA-P 2015 guidelines on MEDLINE, EBSCO Host, Scopus, PubMed, and Web of Science databases in 2022 by 2 reviewers. Articles then underwent Cochrane GRADE approach and JBI critical appraisal for certainty of evidence and bias evaluation.
RESULTS: Thirty articles were included following eligibility screening. Both in vitro experiments (20%) and in vivo (80%) devices ranging from electronic axiography, electromyography, optoelectronic and ultrasonic, oral or extra-oral tracking, photogrammetry, sirognathography, digital pressure sensors, electrognathography, and computerised medical-image tracing were documented. 53.53% of the studies were rated below "moderate" certainty of evidence. Critical appraisal showed 80% case-control investigations failed to address confounding variables while 90% of the included non-randomised experimental studies failed to establish control reference.
CONCLUSION: Mandibular and condylar growth, kinematic dysfunction of the neuromuscular system, shortened dental arches, previous orthodontic treatment, variations in habitual head posture, temporomandibular joint disorders, fricative phonetics, and to a limited extent parafunctional habits and unbalanced occlusal contact were identified confounding variables that shaped jaw movement trajectories but were not highly dependent on age, gender, or diet. Realistic variations in device accuracy were found between 50 and 330 µm across the digital systems with very low interrater reliability for motion tracing from photographs. Forensic and in vitro simulation devices could not accurately recreate variations in jaw motion and muscle contractions.
METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-455-5p expression in breast cancer tissues and cell lines. CCK8 and Transwell assays were conducted to assess the effects of miR-455-5p on breast cancer line proliferation, migration, and invasion. SOCS3 expression level in breast cancer tissues and cell lines was determined by qPCR and western blotting. The targeting relationship between miR-455-5p and SOCS3 was determined by dual luciferase reporter gene assay in different breast cancer cell lines. Finally, the upstream and downstream regulatory association between miR-455-5p and SOCS3 was confirmed in breast cancer cells by CCK8, western blot, and Transwell assays.
RESULTS: MiR-455-5p expression was up-regulated in breast cancer tissues; miR-455-5p regulates TNBC proliferation, migration, and invasion of TNBC. SOCS3 was the direct target of miR-455-5p and was down-regulated in breast cancer. Interference with SOCS3 reversed the inhibitory effect of the miR-455-5p inhibitor on breast cancer cells' malignant potential.
CONCLUSION: MiR-455-5p promotes breast cancer progression by targeting the SOCS3 pathway and may be a potential therapeutic target for breast cancer.
METHODS: Cell counting kit 8(CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell and wound healing assays were conducted to study the influence of ZnC in the proliferating, invading and migrating processes of CRC cell lines (HCT116, LOVO) in vitro. The antitumor activity ZnC as well as its effects on tumor immune microenvironment were then assessed using CRC subcutaneous tumors in the C57BL/6 mouse model.
RESULTS: According to CCK8, EdU, transwell and wound healing assays, ZnC inhibited CRC cell lines in terms of proliferation, invasion and migration. ZnC could inhibit miR-570 for up-regulating PD-L1 expression. In vivo experiments showed that gavage (100 mg/kg, once every day) of ZnC inhibited the tumor growth of CRC, and the combination of ZnC and anti-PD1 therapy significantly improved the efficacy exhibited by anti-PD1 in treating CRC. In addition, mass cytometry results showed that immunosuppressive cells including regulatory T cells (tregs), bone marrow-derived suppressor cells (MDSC), and M2 macrophages decreased whereas CD8+ T cells elevated after adding ZnC.
CONCLUSIONS: The present study reveals that ZnC slows the progression of CRC by inhibiting CRC cells in terms of proliferation, invasion and migration, meanwhile up-regulating PD-L1 expression via inhibiting miR-570. The ZnC-anti-PD1 co-treatment assists in synergically increasing anti-tumor efficacy in CRC therapy.
OBJECTIVE: This study was designed to investigate the therapeutic and anti-metastatic potential of the two newly obtained anti-nNav1.5 antibodies, polyclonal anti-nNav1.5 (pAb-nNav1.5) and monoclonal anti-nNav1.5 (mAb-nNav1.5), on breast cancer invasion and metastasis.
METHODS: MDA-MB-231 and 4T1 cells were used as in vitro models to study the effect of pAb-nNav1.5 (59.2 µg/ml) and mAb-nNav1.5 (10 µg/ml) (24 hours treatment) on cell invasion. 4T1-induced mammary tumours in BALB/c female mice were used as an in vivo model to study the effect of a single dose of intravenous pAb-nNav1.5 (1 mg/ml) and mAb-nNav1.5 (1 mg/ml) on the occurrence of metastasis. Real-time PCR and immunofluorescence staining were conducted to assess the effect of antibody treatment on nNav1.5 mRNA and protein expression, respectively. The animals' body weight, organs, lesions, and tumour mass were also measured and compared.
RESULTS: pAb-nNav1.5 and mAb-nNav1.5 treatments effectively suppressed the invasion of MDA-MB-231 and 4T1 cells in the 3D spheroid invasion assay. Both antibodies significantly reduced nNav1.5 gene and protein expression in these cell lines. Treatment with pAb-nNav1.5 and mAb-nNav1.5 successfully reduced mammary tumour tissue size and mass and prevented lesions in vital organs of the mammary tumour animal model whilst maintaining the animal's healthy weight. mRNA expression of nNav1.5 in mammary tumour tissues was only reduced by mAb-nNav1.5.
CONCLUSION: Overall, this work verifies the uniqueness of targeting nNav1.5 in breast cancer invasion and metastasis prevention, but more importantly, humanised versions of mAb-nNav1.5 may be valuable passive immunotherapeutic agents to target nNav1.5 in breast cancer.