The Role of Paxillin Aberrant Expression in Cancer and Its Potential as a Target for Cancer Therapy.

Paxillin is a multi-domain adaptor protein. As an important member of focal adhesion (FA) and a participant in regulating cell movement, paxillin plays an important role in physiological processes such as nervous system development, embryonic development, and vascular development. However, increasing evidence suggests that paxillin is aberrantly expressed in many cancers. Many scholars have also recognized that the abnormal expression of paxillin is related to the prognosis, metastases, invasion, survival, angiogenesis, and other aspects of malignant tumors, suggesting that paxillin may be a potential cancer therapeutic target. Therefore, the study of how aberrant paxillin expression affects the process of tumorigenesis and metastasis will help to develop more efficacious antitumor drugs. Herein, we review the structure of paxillin and its function and expression in tumors, paying special attention to the multifaceted effects of paxillin on tumors, the mechanism of tumorigenesis and progression, and its potential role in tumor therapy. We also hope to provide a reference for the clinical prognosis and development of new tumor therapeutic targets.

The long noncoding RNA MALAT1/microRNA-598-3p axis regulates the proliferation and apoptosis of retinoblastoma cells through the PI3K/AKT pathway.

Purpose: This study was designed to dissect the role of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in retinoblastoma (RB) and its underlying mechanism. Methods: Gain- and loss-of-function experiments were adopted to explore the effects of MALAT1 and microRNA (miR)-598-3p on the biologic behaviors of RB cells. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of MALAT1 and miR-598-3p in Y79 and HXO-RB44 cells. The proliferation of RB cells was determined with the cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) staining. Flow cytometry was employed for the measurement of the apoptotic rate, western blotting for examination of the expression of apoptosis-related proteins (Bax and Bcl-2) and phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) pathway-related factors (PI3K, AKT, p-PI3K, and p-AKT), and the luciferase reporter assay for assessment of the interaction between MALAT1 and miR-598-3p. Results: High expression of MALAT1 and low expression of miR-598-3p were noticed in Y79 and HXO-RB44 cells. MALAT1 upregulation or miR-598-3p downregulation facilitated RB cell proliferation and inhibited cell apoptosis, as evidenced by the increased proliferation rate and Bcl-2 expression, as well as diminished Bax expression and apoptotic rate, in the RB cells after transfection with pcDNA3.1-MALAT1 or miR-598-3p inhibitor. MALAT1 bound to and negatively regulated miR-598-3p. The PI3K/AKT pathway activation occurred with MALAT1 overexpression. MALAT1 promoted RB cell proliferation and repressed cell apoptosis by repressing miR-598-3p to activate the PI3K/AKT pathway. Conclusions: MALAT1 repressed miR-598-3p to activate the PI3K/AKT pathway, thus facilitating cell proliferation and inhibiting cell apoptosis in RB.

MicroRNA-199a-3p inhibits angiogenesis by targeting the VEGF/PI3K/AKT signalling pathway in an in vitro model of diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a major inducer of blindness and visual impairment. As a critical cause for DR, hyperglycaemia is able to trigger multiple biochemical alterations. MiRNAs, which contain various functions, can effectively regulate blood glucose levels. This research aims to confirm the roles of miRNA-199a-3p in the progression of angiogenesis in an in vitro model of DR. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried to determine the expression levels of miR-199a-3p and VEGF in both hRMECs and APRE-19 cells. The luciferase reporter assay was used to study the interaction between miR-199a-3p and VEGF. Western blot assay was conducted to examine the expression levels of VEGF and the PI3K/AKT signalling pathway. The cell proliferation capacity was detected via the CCK-8 test. The impact of miR-199a-3p on migration was determined using Transwell and wound healing assays. A Matrigel tube formation assay was employed to determine the vascular formation of hRMECs. Flow cytometry was used to determine cell apoptosis in the presence of LY294002 as a PI3K inhibitor. RESULTS: Our results showed that high glucose (HG) decreased the relative expression level of miR-199a-3p but increased VEGF expression in hRMECs and APRE-19 cells. MiR-199a-3p inhibitor augmented cell growth, migration and angiogenesis of hRMECs. Moreover, upregulation of miR-199a-3p evidently alleviated the increases in cell proliferation, migration and angiogenesis caused by HG. In addition, the luciferase reporter assay indicated that miR-199a-3p directly targeted VEGF. The overexpression of miR-199a-3p obviously restrained the HG-stimulated PI3K/AKT signalling pathway and angiogenesis, which could be further inhibited by LY294002. Moreover, LY294002 could slightly ameliorate the miR-199a-3p inhibitor-stimulated PI3K/AKT signalling pathway and angiogenesis. CONCLUSION: MiR-199a-3p upregulation ameliorated HG-stimulated angiogenesis of hRMECs by modulating the PI3K/AKT pathway through inhibiting VEGF. Although retinal neovascularization in vivo has not been studied, these in vitro findings provide more evidence for the role of miR-199a-3p upregulation against HG-induced angiogenesis.

An inverse association of Helicobacter pylori infection with oral squamous cell carcinoma.

BACKGROUND: Few studies have focused on the relationship between Helicobacter pylori (H. pylori) infection and oral diseases. In this study, we explored the correlation between H. pylori infection and oral squamous cell carcinoma (OSCC). METHODS: A total of 68 patients with OSCC and 104 age- and sex- matched healthy control subjects were retrospectively enrolled in this study. The H. pylori immunoglobin (Ig) G antibodies in serum were detected by enzyme-linked immunosorbent assay (ELISA) method to assess the status of H. pylori infection of our study sample. Polymerase chain reaction (PCR) was also employed using H. pylori genus-specific 16S rRNA primers in fasting blood, and OSCC specimens were analyzed by histochemical stain of each enrolled subject. The strength of correlation between H. pylori and the development of OSCC was estimated by Spearman's correlation coefficient. RESULTS: According to the three methods for detecting prevalence of H. pylori infection in the patients with OSCC, it was statistically lower than that in the healthy controls (35.3% vs. 54.8%, P = 0.012). An inverse correlation was observed between H. pylori infection and OSCC development (Spearman's correlation coefficient = -0.191, P = 0.012). In stratification analysis, we also found a statistical association between H. pylori infection and OSCC in the subpopulation with age ≥ 60 years (P = 0.037). CONCLUSION: Our findings suggested that H. pylori infection may be negatively related to OSCC. A reverse association of H. pylori infection with OSCC risk in the subpopulation with age ≥ 60 years was also found.

WITHDRAWN: Lentiviral Mediated Overexpression of Sema3A in Oral Cancer Cells Decreases Tumor Growth by Inhibiting Angiogenesis.

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Chaperonin containing TCP1 subunit 6A may activate Notch and Wnt pathways to facilitate the malignant behaviors and cancer stemness in oral squamous cell carcinoma.

Chaperonin containing TCP1 subunit 6A (CCT6A) was recently discovered to be involved in cancer pathogenesis and stemness; however, its role in oral squamous cell carcinoma (OSCC) has not been reported. The current study aimed to investigate the impact of CCT6A on OSCC cell malignant behaviors and stemness and to explore its potentially interreacted pathways. SCC-15 and HSC-3 cells were transfected with the plasmid loading control overexpression, CCT6A overexpression, control knockout, or CCT6A knockout. Wnt4 overexpression or Notch1 overexpression plasmids were transfected into CCT6A-knockout SCC-15 cells. Cell proliferation, apoptosis, invasion, stemness, Notch, and Wnt pathways were detected in both cell lines, whereas RNA sequencing was only performed in SCC-15 cells. CCT6A was upregulated in five OSCC cell lines, including SCC-15, HSC-3, SAT, SCC-9, and KON, compared to that in the control cell line. In SCC-15 and HSC-3 cells, CCT6A overexpression increased cell proliferation, invasion, sphere formation, CD133, and Sox2 expression, but decreased cell apoptosis; on the contrary, CCT6A knockout exhibited an opposite effect on the above indexes. RNA-sequencing data revealed that the Wnt and Notch pathways were involved in the CCT6A'effect on SCC-15 cell functions. CCT6A positively regulates the Wnt and Notch pathways in SCC-15 and HSC-3 cells. Importantly, it was shown that activation of the Wnt or Notch pathways attenuated the effect of CCT6A knockout on SCC-15 cell survival, invasion, and stemness. CCT6A may promote OSCC malignant behavior and stemness by activating the Wnt and Notch pathways.

Serum cell division control 42 reflects treatment response and survival profiles in recurrent or metastatic oral squamous cell carcinoma patients who receive programmed death-1 inhibitors.

OBJECTIVES: Cell division control 42 (CDC42) facilitates tumor growth, migration, and immune escape to accelerate the pathogenesis and progression of oral squamous cell carcinoma (OSCC). This study intended to explore the optimal cut-value of serum CDC42 for predicting treatment response to programmed death-1 (PD-1) inhibitors and survival in recurrent or metastatic (R/M) OSCC patients. METHODS: CDC42 was detected from serum by enzyme-linked immunosorbent assay in 45 R/M OSCC patients before initiating PD-1 inhibitors with or without chemotherapy. Different cutoff values (500, 600, 700, and 800 pg/mL) of CDC42 were selected for further analyses. RESULTS: The median (interquartile range) value of CDC42 was 604.0 (477.5-867.5) pg/mL in R/M OSCC patients. Generally, objective response rate (ORR) and disease control rate (DCR) were 37.8 % and 62.2 %. Additionally, ORR (P = 0.030) and DCR (P = 0.004) were decreased in patients with CDC42 ≥ 700 pg/mL versus those with CDC42 < 700 pg/mL; meanwhile, DCR was also reduced in patients with CDC42 ≥ 800 pg/mL versus those with CDC42 < 800 pg/mL (P = 0.014). Interestingly, CDC42 ≥ 600 (P = 0.023), 700 (P = 0.007), and 800 (P = 0.039) pg/mL were related to shorter progression-free survival (PFS). While only CDC42 ≥ 700 (P = 0.004) and 800 (P = 0.046) pg/mL were correlated with worse overall survival (OS). After adjustment, only CDC42 ≥ 700 pg/mL (yes vs. no) independently estimated poor PFS (hazard ratio (HR) = 2.637, P = 0.005) and OS (HR = 5.824, P < 0.001). CONCLUSION: CDC42 ≥ 700 pg/mL exerts the optimal prognostic ability to reflect poor treatment response and survival profiles in R/M OSCC patients who receive PD-1 inhibitors.

Progerin Inhibits the Proliferation and Migration of Melanoma Cells by Regulating the Expression of Paxillin.

Objective: Progerin, the underlying cause of Hutchinson-Gilford Progeria Syndrome (HGPS), has been extensively studied for its impact on normal cells and premature aging patients. However, there is a lack of research on its specific effects on tumor cells. Melanoma is one of the most common malignant tumors with high morbidity and mortality. This study aimed to elucidate the potential therapeutic role of progerin in melanoma. Materials and Methods: We constructed the melanoma A375 cell line and M14 cell line with stable expression of progerin. The expression of progerin, paxillin, and epithelial-mesenchymal transition (EMT) marker proteins in each cell group was measured using Western blot. The migration, proliferation, and cell cycle of cancer cells were assessed using the transwell assay, wound healing assay, colony formation assay, CCK 8 assay, and flow cytometry. RT-qPCR technology was used to examine the impact of progerin overexpression on microRNA expression. Finally, we transfected paxillin into the progerin overexpression cell group to verify whether progerin regulates the phenotype of tumor cells through paxillin. Results: Our study demonstrated that overexpression of progerin leads to decreased expression of paxillin and inhibits cancer cell migration, proliferation, EMT process and cell cycle progression. Additionally, rescue experiments revealed that the migration, proliferation ability, and EMT marker protein expression in progerin overexpressing cancer cells could be partially restored by transfecting a plasmid containing the paxillin gene. Mechanistic investigations further revealed that progerin achieves this inhibition of paxillin expression by upregulating miR-212. Conclusion: This study reveals that progerin may inhibit the migration and proliferation of melanoma cells through the miR-212/paxillin axis, which provides a new approach for the future treatment of this disease.

Expression of overall survival-EMT-immune cell infiltration genes predict the prognosis of glioma.

This study investigates the crucial role of immune- and epithelial-mesenchymal transition (EMT)-associated genes and non-coding RNAs in glioma development and diagnosis, given the challenging 5-year survival rates associated with this prevalent CNS malignant tumor. Clinical and RNA data from glioma patients were meticulously gathered from CGGA databases, and EMT-related genes were sourced from dbEMT2.0, while immune-related genes were obtained from MSigDB. Employing consensus clustering, novel molecular subgroups were identified. Subsequent analyses, including ESTIMATE, TIMER, and MCP counter, provided insights into the tumor microenvironment (TIME) and immune status. Functional studies, embracing GO, KEGG, GSVA, and GSEA analyses, unraveled the underlying mechanisms governing these molecular subgroups. Utilizing the LASSO algorithm and multivariate Cox regression, a prognostic risk model was crafted. The study unveiled two distinct molecular subgroups with significantly disparate survival outcomes. A more favorable prognosis was linked to low immune scores, high tumor purity, and an abundance of immune infiltrating cells with differential expression of non-coding RNAs, including miRNAs. Functional analyses illuminated enrichment of immune- and EMT-associated pathways in differentially expressed genes and non-coding RNAs between these subgroups. GSVA and GSEA analyses hinted at abnormal EMT status potentially contributing to glioma-associated immune disorders. The risk model, centered on OS-EMT-ICI genes, exhibited promise in accurately predicting survival in glioma. Additionally, a nomogram integrating the risk model with clinical characteristics demonstrated notable accuracy in prognostic predictions for glioma patients. In conclusion, OS-EMT-ICI gene and non-coding RNA expression emerges as a valuable indicator intricately linked to immune microenvironment dysregulation, offering a robust tool for precise prognosis prediction in glioma patients within the OBMRC framework.

NEDD4L inhibits glycolysis and proliferation of cancer cells in oral squamous cell carcinoma by inducing ENO1 ubiquitination and degradation.

Glycolysis contributes to cell metabolism and facilitates cell proliferation of oral squamous cell carcinoma (OSCC), the most common type of oral cancer. Understanding the regulatory mechanisms involved in the glycolysis of OSCC cells may provide important therapeutic inspirations. Immunohistochemistry was used to examine protein localization patterns in human OSCC tissues and Western blot was conducted to gauge protein level. Lentivirus transduction was used to overexpress or silence genes of interest. Cell proliferation was assessed by Cell Counting Kit (CCK)-8 assay while glycolysis was examined via measurement of extracellular acidification rate, oxygen consumption rate, and lactate and ATP production. In vivo cancer development was evaluated with a mouse tumor growth model. OSCC tissues displayed reduced expression of NEDD4L compared with normal tissues. NEDD4L expression positively correlated with 5-year patient survival rate, indicating that NEDD4L may be a prognosis marker for OSCC. NEDD4L overexpression suppressed proliferation, cell cycle transition, and glycolysis in OSCC cells, and inhibited in vivo tumor growth. UbiBrowser identified ENO1, an enzyme that catalyzes glycolysis, as a substrate of NEDD4L. Overexpression of NEDD4L resulted in the ubiquitination and subsequent degradation of ENO1 whereas overexpression of ENO1 reversed the functional effects of NEDD4L overexpression, restoring proliferation, cell cycle transition, and glycolysis in OSCC cells. NEDD4L elicits tumor-suppressive functions via inhibition of OSCC cell proliferation, cell cycle transition, and glycolysis by stimulating ENO1 ubiquitination and degradation. Our results unraveled a signaling axis important for OSCC cell survival and metabolism, which can serve as a potential therapeutic target.

Vascular endothelial growth factor-165b protects the blood-retinal barrier from damage after acute high intraocular pressure in rats.

AIM: To elucidate the role of vascular endothelial growth factor-165b (VEGF-165b) in blood-retinal barrier (BRB) injury in the rat acute glaucoma model. METHODS: In this study, the rat acute high intraocular pressure (HIOP) model was established before and after intravitreous injection of anti-VEGF-165b antibody. The expression of VEGF-165b and zonula occludens-1 (ZO-1) in rat retina was detected by double immunofluorescence staining and Western blotting, and the breakdown of BRB was detected by Evans blue (EB) dye. RESULTS: The intact retina of rats expressed VEGF-165b and ZO-1 protein, which were mainly located in the retinal ganglion cell layer and the inner nuclear layer and were both co-expressed with vascular endothelial cell markers CD31. After acute HIOP, the expression of VEGF-165b was up-regulated; the expression of ZO-1 was down-regulated at 12h and then recovered at 3d; EB leakage increased, peaking at 12h. After intravitreous injection of anti-VEGF-165b antibody, the expression of VEGF-165b protein was no significantly changed; and the down-regulation of the expression of ZO-1 was more obvious; EB leakage became more serious, peaking at 3d. EB analysis also showed that EB leakage in the peripheral retina was greater than that in the central retina. CONCLUSION: The endogenous VEGF-165b protein may protect the BRB from acute HIOP by regulating the expression of ZO-1. The differential destruction of BRB after acute HIOP may be related to the selective loss of retinal ganglion cells.

QTL identification of flowering time at three different latitudes reveals homeologous genomic regions that control flowering in soybean.

Since the genetic control of flowering time is very important in photoperiod-sensitive soybean (Glycine max (L.) Merr.), genes affecting flowering under different environment conditions have been identified and described. The objectives were to identify quantitative trait loci (QTLs) for flowering time in different latitudinal and climatic regions, and to understand how chromosomal rearrangement and genome organization contribute to flowering time in soybean. Recombinant inbred lines from a cross between late-flowering 'Jinpumkong 2' and early-flowering 'SS2-2' were used to evaluate the phenotypic data for days to flowering (DF) collected from Kamphaeng Saen, Thailand (14°01'N), Suwon, Korea (37°15'N), and Longjing, China (42°46'N). A weakly positive phenotypic correlation (r = 0.36) was found between DF in Korea and Thailand; however, a strong correlation (r = 0.74) was shown between Korea and China. After 178 simple sequence repeat (SSR) markers were placed on a genetic map spanning 2,551.7 cM, four independent DF QTLs were identified on different chromosomes (Chrs). Among them, three QTLs on Chrs 9, 13 and 16 were either Thailand- or Korea-specific. The DF QTL on Chr 6 was identified in both Korea and China, suggesting it is less environment-sensitive. Comparative analysis of four DF QTL regions revealed a syntenic relationship between two QTLs on Chrs 6 and 13. All five duplicated gene pairs clustered in the homeologous genomic regions were found to be involved in the flowering. Identification and comparative analysis of multiple DF QTLs from different environments will facilitate the significant improvement in soybean breeding programs with respect to control of flowering time.

High SQLE Expression and Gene Amplification Correlates with Poor Prognosis in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: Squalene epoxidase (SQLE) is considered a metabolic oncogene, but its biological function and prognostic value in head and neck squamous cell carcinoma (HNSCC) remain unclear. We aimed to evaluate the role of SQLE in the occurrence and development of HNSCC through bioinformatics analysis, and validation experiments. METHODS: Transcriptomic, genomic, and clinical data from The Cancer Genome Atlas were used for pan-cancer analysis. SQLE expression in HNSCC was evaluated using Gene Expression Omnibus datasets and immunohistochemistry. The biological significance of SQLE in the tumor microenvironment (TME) of HNSCC was determined using TISCH, HuRI, LinkedOmics, and TIMER 2.0. The prognostic value of SQLE in HNSCC was analyzed using univariate Cox regression and Kaplan-Meier survival curves. Effect of SQLE on the Cal27 HNSCC cell line was evaluated using cell counting kit 8, wound healing, and EdU assays. RESULTS: SQLE was overexpressed and amplified in various cancers, including HNSCC. High SQLE expression promoted cell proliferation, associated with T stage in HNSCC patients. Copy number amplification and DNA demethylation contributed to high SQLE expression in HNSCC, which was associated with poor prognosis. SQLE was related to HNSCC TME, and its mRNA expression/copy number alterations were negatively correlated with the infiltration of CD8+ T cells, follicular helper T cells, and regulatory T cell infiltration and mast cell activation and positively correlated with the infiltration of M0 macrophages and resting mast cells in HNSCC. CONCLUSION: SQLE was identified as a prognostic biomarker and a potential pharmaceutical target for HNSCC.

The influence of comprehensive nursing intervention on the compliance of glaucoma patients with their doctors' advice.

OBJECTIVE: To determine the effect of targeted comprehensive nursing on the compliance of glaucoma patients with their doctors' advice. METHODS: A total of 78 patients with glaucoma admitted to the Ophthalmology Department of the First Affiliated Hospital of Hainan Medical University were retrospectively enrolled and assigned to a routine nursing group and a comprehensive nursing group according to the different nursing modes each patient underwent. The routine nursing group underwent routine nursing, and the comprehensive nursing group underwent comprehensive nursing intervention. The causes of not following their doctor's advice among the two groups were evaluated, and the two groups were compared in terms of their compliance rates after the intervention and quality of life and psychological state before and after the intervention. RESULTS: The causes of not following the doctor's advice were mainly classified into three categories: physiological, psychological, and comprehensive factors. Before the nursing intervention, the two groups were not significantly different in their quality of life scores or their psychological states (both P>0.05). After the nursing intervention, the intraocular pressure values (IOP), the visual field pattern standard deviations (PSD), the cup/disk area ratios (C/D AR), the mean retinal nerve fiber layer thicknesses (mRNFLT), and the other indexes in the comprehensive nursing group were significantly better than they were in the routine nursing group, and the comprehensive nursing group showed notably better quality of life and psychological states and a notably higher compliance rate than the routine nursing group (all P<0.05). CONCLUSION: Targeted comprehensive nursing can help glaucoma patients correct bad behaviors, improve their compliance rates and quality of life, and alleviate their negative emotions.

The effects of HBXIP on the biological functions of tongue squamous cell carcinoma cells and correlation with PI3K/Akt.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is the most malignant oral cancer, having a high mortality rate. METHODS: The effects of hepatitis B X-interacting protein (HBXIP) overexpression on the proliferation, migration, and invasion of TSCC cells were measured by micro-culture tetrazolium assay (MTT) assay, transwell assay and scratch test, respectively, and the effects of HBXIP mRNA overexpression on the protein expression levels of AKT, p-AKT, PI3K, p-PI3K and S100A4 were detected by western blotting. RESULTS: MTT assay showed that there were significantly more proliferating cells than in the experimental group. In the scratch test and transwell assay, the migration rate and the number of invading cells were remarkably greater in the experimental group. The expression levels of p-AKT, p-PI3K and S100A4 were increased in the experimental group after HBXIP overexpression. CONCLUSIONS: HBXIP mRNA overexpression can influence the proliferation, invasion, and migration of TSCC cells and promote their proliferation and migration by increasing the protein expression levels of p-AKT, p-PI3K and S100A4.

USP13 serves as a tumor suppressor via the PTEN/AKT pathway in oral squamous cell carcinoma.

BACKGROUND: : Recent studies have shown that USP13 a deubiquitinase, serves as an important regulator of tumorigenesis. However, the biological role of USP13 in oral squamous cell carcinoma (OSCC) remains enigmatic. MATERIALS AND METHODS: : We examined USP13 expression in OSCC and adjacent normal tissues by immunohistochemical staining. The biological functions of USP13 in OSCC cells and the possible underlying mechanisms were investigated. RESULTS: : In this study, we showed that USP13 expression was frequently reduced in human OSCC specimens and that the reduction was correlated with the clinical stage. Functional studies demonstrated that overexpression of USP13 suppressed OSCC cell proliferation, glucose uptake and lactate production in vitro and inhibited tumor growth in vivo. Furthermore, USP13 overexpression induced phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression and repressed the activation of AKT as well as the expression of the downstream effectors glucose transporter-1 (GLUT1) and hexokinase-2 (HK2). Overexpression of PTEN reversed the USP13-knockdown-induced glucose uptake, lactate production, AKT activation, and expression of GLUT1 and HK2. CONCLUSION: : Our findings suggest that USP13 serves as a tumor suppressor by regulating the PTEN/AKT signaling pathway in OSCC cells, improving our understanding of OSCC progression and providing a clue for the development of a novel cancer therapy.

An approach to revolutionize cataract treatment by enhancing drug probing through intraocular cell line.

The purpose of this study is to prepare and characterize solid lipid nanoparticles (SLN) of N-Acetyl Carnosine (NAC) to treat cataract since surgery necessitates equipments and professional help. Cataract is believed to be formed by the biochemical approach where the crystalline eye proteins lose solubility and forms high molecular weight masses. Added advantages of SLN of NAC (henceforth referred as SLN-NAC) in the study are reduced size, sustained release and better corneal penetration of drug. The method of preparation of SLN-NAC by Mill's method is unique in itself. The size of the SLN-NAC was 75 ± 10 nm in the range of ideal for penetration. The in-vitro release study and the SLN-NAC formulations prepared with Mill's method demonstrated sustained release up to 24 h following an initial burst after 1 h. The zeta potential of the prepared formulation was -22.1 ± 1 mV. Corneal permeation studies using goat corneas indicate that SLN-NAC penetration rate was higher than those from NAC eye drops. Corneal hydration studies indicated that the formulation caused no harm to the corneal cells. Therefore it may be concluded that SLN-NAC may revolutionize cataract treatment and reversal by improving drug permeation, reducing toxicity and no damage to corneal tissue.

Tbx2 confers poor prognosis in glioblastoma and promotes temozolomide resistance with change of mitochondrial dynamics.

Tbx2 is a cancer-related protein that was found to be overexpressed in several human malignancies. The present study aims to investigate the clinical significance and biological role of Tbx2 in human astrocytoma. We examined its protein expression in 102 cases of astrocytoma tissues using immunohistochemical staining. Negative Tbx2 staining was observed in normal astrocytes, and positive nuclear staining was found in 41 out of 102 astrocytoma specimens. The rate of Tbx2 overexpression in pylocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma multiform (GBM) were 0%, 26.1%, 40%, and 52%, respectively. Tbx2 overexpression correlated with poor prognosis in patients with astrocytoma or GBM. Tbx2 plasmid transfection was performed in A172 cells, and Tbx2 siRNA knockdown was carried out in U251 cells. Cell Counting Kit-8, cell cycle analysis, and matrigel invasion assay showed that Tbx2 overexpression upregulated cell proliferation, G1-S transition, and invasion, with corresponding change of cyclin D1, p21, and MMP 2 and 9. Importantly, we demonstrated that Tbx2 reduced apoptosis and conferred resistance to temozolomide in GBM cell lines. Further experiments showed that Tbx2 could regulate mitochondrial fission/fusion balance. Western blot showed that Tbx2 overexpression reduced caspase 3 cleavage, while it induced Bcl-2 and p-Drp1 upregulation. In conclusion, our results indicated that Tbx2 might serve as an indicator for poor prognosis and also be useful as an important therapeutic in human GBM, which inhibits apoptosis through regulation of mitochondrial function.

Sema3A drastically suppresses tumor growth in oral cancer Xenograft model of mice.

BACKGROUND: Multiple studies suggest anti-angiogenesis to be a promising and rational option in cancer treatment. Interestingly, the axonal sprouting inhibitor semaphorin 3A (Sema3A), a potent suppressor of tumor angiogenesis in various cancer models, is lowly expressed in human oral cancer. Thus, we hypothesized that overexpression of Sema3A in human oral cancer cells may have potential therapeutic effects. METHODS: The LentiSema3A-EGFP was first constructed and transduced to the tongue squamous cell carcinoma cell line SSC-9. Angiogenesis assay was performed with endothelial cell tube formation assay and chorioallantoic membrane (CAM) assay. Tumor xenografts model was used to evaluate the effect of Sema3a on the tumor growth. Finally, western blot was performed to study the mechanisms of inhibiting angiogenesis by Sema3A. RESULTS: In vitro and in vivo approaches revealed that Sema3A significantly inhibited tube formation of endothelial cells and reduced angiogenesis in CAM assay. In addition, overexpression of Sema3A in the tongue squamous cell carcinoma cell line SSC-9 resulted in significantly reduced angiogenesis and drastically suppressed tumor growth in mice. Mechanistically, Sema3A inhibited the phosphorylation of VEGFR2, as well as Src and FAK, downstream of the VEGF/VEGFR2 pathway. CONCLUSION: Our results demonstrated that overexpression of Sema3A in oral cancer cells drastically suppressed tumor growth by inhibiting angiogenesis. Our findings provide a basis for the development of novel therapeutics in the management of oral cancer.