The mechanisms behind the dual role of long non-coding RNA (lncRNA) metastasis suppressor-1 in human tumors: Shedding light on the molecular mechanisms.

When the expression levels of metastasis suppressor-1 (MTSS1) were discovered to be downregulated in a metastatic cancer cell line in 2002, it was proposed that MTSS1 functioned as a suppressor of metastasis. The 755 amino acid long protein MTSS1 connects to actin and organizes the cytoskeleton. Its gene is located on human chromosome 8q24. The suppressor of metastasis in metastatic cancer was first found to be MTSS1. Subsequent reports revealed that MTSS1 is linked to the prevention of metastasis in a variety of cancer types, including hematopoietic cancers like diffuse large B cell lymphoma and esophageal, pancreatic, and stomach cancers. Remarkably, conflicting results have also been documented. For instance, it has been reported that MTSS1 expression levels are elevated in a subset of melanomas, hepatocellular carcinoma associated with hepatitis B, head and neck squamous cell carcinoma, and lung squamous cell carcinoma. This article provides an overview of the pathological effects of lncRNA MTSS1 dysregulation in cancer. In order to facilitate the development of MTSS1-based therapeutic targeting, we also shed light on the current understanding of MTS1.

The interaction between lncRNAs and transcription factors regulating autophagy in human cancers: A comprehensive and therapeutical survey.

Autophagy, as a highly conserved cellular process, participates in cellular homeostasis by degradation and recycling of damaged organelles and proteins. Besides, autophagy has been evidenced to play a dual role through cancer initiation and progression. In the early stage, it may have a tumor-suppressive function through inducing apoptosis and removing damaged cells and organelles. However, late stages promote tumor progression by maintaining stemness features and induction of chemoresistance. Therefore, identifying and targeting molecular mechanisms involved in autophagy is a potential therapeutic strategy for human cancers. Multiple transcription factors (TFs) are involved in the regulation of autophagy by modulating the expression of autophagy-related genes (ATGs). In addition, a wide array of long noncoding RNAs (lncRNAs), a group of regulatory ncRNAs, have been evidenced to regulate the function of these autophagy-related TFs through tumorigenesis. Subsequently, the lncRNAs/TFs/ATGs axis shows great potential as a therapeutic target for human cancers. Therefore, this review aimed to summarize new findings about the role of lncRNAs in regulating autophagy-related TFs with therapeutic perspectives.

Evaluation of telomere length, reactive oxygen species, and apoptosis in spermatozoa of patients with oligospermia.

50% of cases of infertility are caused by male factor, which acquired or congenital problems may bring on. Male infertility can be caused by oligospermia and asthenozoospermia, which are common. Since the same mutations that cause azoospermia in some people also cause oligozoospermia in others, oligozoospermia may be thought of as a less severe form of azoospermia. Studies have demonstrated telomere length, catalase activity, super oxide dismutase (SOD), and DNA fragmentation can be influential factors for male infertility. The amount of apoptosis, oxidative stress factors, telomere length, and DNA fragmentation were some aspects of healthy sperm that we chose to look into in this study and compare to oligospermia individuals. Oligospermia patients (n = 24) and fertile men (n = 27) semen samples were collected, and the apoptosis rate of sperms in both groups was analyzed (Flow cytometry). Also, gene expression of apoptotic and antiapoptotic markers and telomere length were examined (real-time polymerase chain reaction). The sperm DNA fragmentation kit was used to determine DNA fragmentation and to evaluate catalase and SOD activity; the specific kits and methods were utilized. Higher expression levels of caspase3 (p = .0042), caspase8 (p = .0145), caspase9 (p = .0275), and BAX (p = .0202) mRNA were observed in patients who had oligospermia. In contrast, lower mRNA expression of BCL-2 (p = .0009) was detected in this group. In addition, telomere length was decreased in the oligospermia group (p < .0001) compared to the health group. Moreover, the frequency of apoptosis is induced in patients (p = .0026). The catalase activity is low (p = .0008), but the SOD activity is high (p = .0015) in the patient group. As a result of our findings, we may list the sperm cell apoptosis rate, telomere length, the degree of sperm DNA fragmentation, and lastly, the measurement of significant and efficient oxidative stress markers like SOD and catalase in semen plasma among the principal diagnostic characteristics for oligospermia. Future studies will be better able to treat oligospermia by showing whether these indicators are rising or falling.

Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms.

BACKGROUND: Gemfibrozil (Gem) is a drug that has been shown to activate PPAR-α, a nuclear receptor that plays a key role in regulating lipid metabolism. Gem is used to lower the levels of triglycerides and reduce the risk of coronary heart disease in patients. Experimental studies in vitro and in vivo have shown that Gem can prevent or slow the progression of neurological disorders (NDs), including cerebral ischemia (CI), Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Neuroinflammation is known to play a significant role in these disorders. METHOD: The literature review for this study was conducted by searching Scopus, Science Direct, PubMed, and Google Scholar databases. RESULT: The results of this study show that Gem has neuroprotective effects through several cellular and molecular mechanisms such as: (1) Gem has the ability to upregulate pro-survival factors (PGC-1α and TFAM), promoting the survival and function of mitochondria in the brain, (2) Gem strongly inhibits the activation of NF-κB, AP-1, and C/EBPß in cytokine-stimulated astroglial cells, which are known to increase the expression of iNOS and the production of NO in response to proinflammatory cytokines, (3) Gem protects dopamine neurons in the MPTP mouse model of PD by increasing the expression of PPARα, which in turn stimulates the production of GDNF in astrocytes, (4) Gem reduces amyloid plaque pathology, reduces the activity of glial cells, and improves memory, (5) Gem increases myelin genes expression (MBP and CNPase) via PPAR-ß, and (6) Gem increases hippocampal BDNF to counteract depression. CONCLUSION: According to the study, Gem was investigated for its potential therapeutic effect in NDs. Further research is needed to fully understand the therapeutic potential of Gem in NDs.

miR-221 and Parkinson's disease: A biomarker with therapeutic potential.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to various motor and non-motor symptoms. Several cellular and molecular mechanisms such as alpha-synuclein (α-syn) accumulation, mitochondrial dysfunction, oxidative stress and neuroinflammation are involved in the pathogenesis of this disease. MicroRNAs (miRNAs) play important roles in post-transcriptional gene regulation. They are typically about 21-25 nucleotides in length and are involved in the regulation of gene expression by binding to the messenger RNA (mRNA) molecules. miRNAs like miR-221 play important roles in various biological processes, including development, cell proliferation, differentiation and apoptosis. miR-221 promotes neuronal survival against oxidative stress and neurite outgrowth and neuronal differentiation. Additionally, the role of miR-221 in PD has been investigated in several studies. According to the results of these studies, (1) miR-221 protects PC12 cells against oxidative stress induced by 6-hydroxydopamine; (2) miR-221 prevents Bax/caspase-3 signalling activation by stopping Bim; (3) miR-221 has moderate predictive power for PD; (4) miR-221 directly targets PTEN, and PTEN over-expression eliminates the protective action of miR-221 on p-AKT expression in PC12 cells; and (5) miRNA-221 controls cell viability and apoptosis by manipulating the Akt signalling pathway in PD. This review study suggested that miR-221 has the potential to be used as a clinical biomarker for PD diagnosis and stage assignment.

Detailed role of microRNA-mediated regulation of PI3K/AKT axis in human tumors.

The regulation of signal transmission and biological processes, such as cell proliferation, apoptosis, metabolism, migration, and angiogenesis are greatly influenced by the PI3K/AKT signaling pathway. Highly conserved endogenous non-protein-coding RNAs known as microRNAs (miRNAs) have the ability to regulate gene expression by inhibiting mRNA translation or mRNA degradation. MiRNAs serve key role in PI3K/AKT pathway as upstream or downstream target, and aberrant activation of this pathway contributes to the development of cancers. A growing body of research shows that miRNAs can control the PI3K/AKT pathway to control the biological processes within cells. The expression of genes linked to cancers can be controlled by the miRNA/PI3K/AKT axis, which in turn controls the development of cancer. There is also a strong correlation between the expression of miRNAs linked to the PI3K/AKT pathway and numerous clinical traits. Moreover, PI3K/AKT pathway-associated miRNAs are potential biomarkers for cancer diagnosis, therapy, and prognostic evaluation. The role and clinical applications of the PI3K/AKT pathway and miRNA/PI3K/AKT axis in the emergence of cancers are reviewed in this article.

Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis.

Background: An increasing number of studies have suggested the relationship between single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes and gastric cancer (GC) susceptibility; however, the available evidence is contradictory. This meta-analysis aimed to comprehensively evaluate whether the SNPs within the TLR family are related to GC development. Methods: PubMed, Scopus, and China National Knowledge Infrastructure (CNKI) were systematically searched up to May 2023 to obtain the pertinent publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were applied to examine the associations using the random-effects model. Results: A total of 45 studies with 25,831 participants (cases: 11,308; controls: 14,523) examining the relation of 18 different SNPs in the TLR family to GC were analyzed. Variations in TLR-4 rs4986790, TLR-4 rs4986791, TLR-5 rs5744174, and TLR-9 rs187084 were significantly associated with increased risk of GC in different genetic models. No significant association was detected for TLR-2-196 to -174de (Delta22), TLR-2 rs3804100, TLR-4 rs11536889, TLR-4 rs11536878, TLR-4 rs2770150, TLR-4 rs10116253, TLR-4 rs1927911, TLR-4 rs10983755, TLR-4 rs10759932, TLR-4 rs1927914, and TLR-10 rs10004195. Conclusion: These findings indicate that variations in TLR-4, TLR-5, and TLR-9 genes were found to be potential risk factors for GC.

A comprehension of signaling pathways and drug resistance; an insight into the correlation between microRNAs and cancer.

Despite the development of numerous therapies, cancer remains an incurable disease due to various factors, including drug resistance produced by cancer cells. MicroRNAs (miRNAs) regulate different target genes involved in biological and pathological processes, including cancer, through post-transcriptional mechanisms. The development of drug resistance in cancer treatment is a significant barrier because it decreases drug uptake, cellular transport, and changes in proteins involved in cell proliferation, survival, and apoptotic pathways. Numerous studies have found a connection between miRNAs and the development of drug resistance in cancer cells. This paper provides a broad overview of how miRNAs regulate signaling pathways and influence treatment resistance in different cancers.

Involving stemness factors to improve CAR T-cell-based cancer immunotherapy.

Treatment with chimeric antigen receptor (CAR) T cells indicated remarkable clinical responses with liquid cancers such as hematological malignancies; however, their therapeutic efficacy faced with many challenges in solid tumors due to severe toxicities, antigen evasion, restricted and limited tumor tissue trafficking and infiltration, and, more importantly, immunosuppressive tumor microenvironment (TME) factors that impair the CAR T-cell function adds support survival of cancer stem cells (CSCs), responsible for tumor recurrence and resistance to current cancer therapies. Therefore, in-depth identification of TME and development of more potent CAR platform targeting CSCs may overcome the raised challenges, as presented in this review. We also discuss recent stemness-based innovations in CAR T-cell production and engineering to improve their efficacy in vivo, and finally, we propose solutions and strategies such as oncolytic virus-based therapy and combination therapy to revive the function of CAR T-cell therapy, especially in TME of solid tumors in future.

Synthesis of novel antibacterial and biocompatible polymer nanocomposite based on polysaccharide gum hydrogels.

According to recent studies on the benefits of natural polymer-based hydrogels in biomedical applications, gellan gum (GG)/acacia gum (AG) hydrogel was prepared in this study. In order to regulate the mechanical behavior of the hydrogel, graphite carbon nitride (g-C3N4) was included in the hydrogel matrix. In addition, metal oxide nanoparticles ZnCuFe2O4 were added to the composite for antibacterial activity. The prepared GG-AG hydrogel/g-C3N4/ZnCuFe2O4 nanobiocomposite was characterized by using FE-SEM, FTIR, EDX, XRD and TGA. The nanobiocomposite exhibited spherical morphology, which was related to the incorporation of the metal oxide nanoparticles. GG-AG hydrogel/g-C3N4/ZnCuFe2O4 nanobiocomposite showed 95.11%, 92.73% and 88.97% biocompatibility toward HEK293T cell lines within 24 h, 48 h and 72 h incubation, respectively, which indicates that this nanobiocomposite is completely biocompatible with healthy cells. Also, the nanobiocomposite was able to inhibit Pseudomonas aeruginosa biofilm growth on its surface up to 87%. Rheological studies showed that the nanobiocomposite has a viscoelastic structure and has a water uptake ratio of 93.2%. In comparison with other similar studies, this nanobiocomposite has exhibited superior antibacterial activity complete biocompatibility and proper mechanical properties, high swelling and water absorption capability. These results indicate that GG-AG hydrogel/g-C3N4/ZnCuFe2O4 nanocomposite can be considered as a potential candidate for biomedical applications such as tissue engineering and wound healing.

Dishevelled: An emerging therapeutic oncogene in human cancers.

Cancer is a multifaceted and complex disorder characterized by uncontrolled rates of cell proliferation and its ability to spread and attack other organs. Emerging data indicated several pathways and molecular targets are engaged in cancer progression. Among them, the Wnt signaling pathway was shown to have a crucial role in cancer onset and progression. Dishevelled (DVL) acts in a branch point of canonical and non-canonical Wnt pathway. DVL not only acts in the cytoplasm to inactivate the destruction complex of ß-catenin but is also transported into the nucleus to affect the transcription of target genes. Available data revealed that the expression levels of DVL increased in cell and clinical specimens of various cancers, proposing that it may have an oncogenic role. DVL promoted cell invasion, migration, cell cycle, survival, proliferation, 3D-spheroid formation, stemness, and epithelial mesenchymal transition (EMT) and it suppressed cell apoptosis. The higher levels of DVL is associated with the clinicopathological characteristic of cancer-affected patients, including lymph node metastasis, tumor grade, histological type, and age. In addition, the higher levels of DVL could be a promising diagnostic and prognostic biomarker in cancer as well as it could be a mediator in cancer chemoresistance to Methotrexate, paclitaxel, and 5-fluorouracil. This study aimed to investigate the underlying molecular mechanism of DVL in cancer pathogenesis as well as to explore its importance in cancer diagnosis and prognosis as well as its role as a mediator in cancer chemotherapy.

A thorough and current study of miR-214-related targets in cancer.

Cancer is a complex genetic anomaly involving coding and non-coding transcript structural and expressive irregularities. A class of tiny non-coding RNAs known as microRNAs (miRNAs) regulates gene expression at the post-transcriptional level by binding only to messenger RNAs (mRNAs). Due to their capacity to target numerous genes, miRNAs have the potential to play a significant role in the development of tumors by controlling several biological processes, including angiogenesis, drug resistance, metastasis, apoptosis, proliferation, and drug resistance. According to several recent studies, miRNA-214 has been linked to the emergence and spread of tumors. The human genome's q24.3 arm contains the DNM3 gene, which is about 6 kb away and includes the microRNA-214. Its primary purpose was the induction of apoptosis in cancerous cells. The multifaceted and complex functions of miR-214 as a modulator in neoplastic conditions have been outlined in the current review.

Advances in preparation, biomedical, and pharmaceutical applications of chitosan-based gold, silver, and magnetic nanoparticles: A review.

During the last decades, the ever-increasing incidence of various diseases, like cancer, has led to a high rate of death worldwide. On the other hand, conventional modalities (such as chemotherapy and radiotherapy) have not indicated enough efficiency in the diagnosis and treatment of diseases. Thus, potential novel approaches should be taken into consideration to pave the way for the suppression of diseases. Among novel approaches, biomaterials, like chitosan nanoparticles (CS NPs, N-acetyl-glucosamine and D-glucosamine), have been approved by the FDA for some efficient pharmaceutical applications. These NPs owing to their physicochemical properties, modification with different molecules, biocompatibility, serum stability, less immune response, suitable pharmacokinetics and pharmacodynamics, etc. have received deep attention among researchers and clinicians. More importantly, the impact of CS polysaccharide in the synthesis, preparation, and delivery of metallic NPs (like gold, silver, and magnetic NPs), and combination of CS with these metallic NPs can further facilitate the diagnosis and treatment of diseases. Metallic NPs possess some features, like converting NIR photon energy into thermal energy and anti-microorganism capability, and can be a potential candidate for the diagnosis and treatment of diseases in combination with CS NPs. These combined NPs would be efficient pharmaceuticals in the future.

Breast cancer vaccines; A comprehensive and updated review.

According to the International Agency for Research on Cancer, breast cancer is more common than lung cancer globally. By 2040, mortality from breast cancer will rise by 50% and 40%, respectively. Despite advances in chemotherapy, endocrine therapy, and HER2-targeted therapy, breast cancer metastases and recurrences remain challenging to treat. Cancer vaccines are an effective treatment option because they stimulate a long-lasting immune response that will eliminate tumor cells. In studies on the breast cancer vaccine, no appreciable advantages were discovered. A recent study claims that immune checkpoint inhibitors or anti-HER2 monoclonal antibodies may be used in vaccinations. This vaccination strengthens the immune system to fight off breast cancer cells. Clinical trials have been conducted on DNA, dendritic cells, and peptide-based breast cancer vaccines. Studies on the breast cancer vaccine have employed subcutaneous, intramuscular, and intradermal injections. Clinical studies have shown that these efforts have not been successful. Several factors might have slowed the development of a breast cancer vaccine. The complexity of the immune system makes it challenging to create cancer vaccines. Given the heterogeneity of breast cancer, there may be a need for different vaccination strategies. Despite these obstacles, research into breast cancer vaccines continues. Effective methods for creating vaccines include immune checkpoint inhibition and anti-HER2 monoclonal antibodies. Research is also being done on specialized tumor vaccinations.

Double-edged sword role of miRNA-633 and miRNA-181 in human cancers.

Understanding the function and mode of operation of microRNAs (miRNAs) in cancer is of growing interest. The short non-coding RNAs known as miRNAs, which target mRNA in multicellular organisms, are described as controlling essential cellular processes. The miR-181 family and miR-633 are well-known miRNAs that play a key role in the development and metastasis of tumor cells. They may facilitate either tumor-suppressive or oncogenic function in malignant cells, according to mounting evidence. Metastatic cells that are closely linked to cancer cell migration, invasion, and angiogenesis can be identified by abnormal levels of miR-181 and miR-633. Numerous studies have demonstrated their capacity to control drug resistance, cell growth, apoptosis, and the epithelial-mesenchymal transition (EMT) and metastasis process. Interestingly, the levels of miR-181 and miR-633 and their potential target genes in the basic cellular process can vary depending on the type of cancer cells and their gene expression profile. Such miRNAs' interactions with other non-coding RNAs such as long non-coding RNAs and circular RNAs can influence tumor behaviors. Herein, we concentrated on the multifaceted roles of miR-181 and miR-633 and potential targets in human tumorigenesis, ranging from cell growth and metastasis to drug resistance.

The mechanisms, functions and clinical applications of miR-542-3p in human cancers.

MicroRNAs, as a major type of noncoding RNAs, have crucial roles in various functions during development. Available data have shown that miR-542-3p decreased in various types of cancers. MiR-542-3p is engaged in various cancer-related behaviors like glycolysis, metastasis, epithelial-to-mesenchymal transition (EMT), cell cycle, apoptosis, and proliferation via targeting at least 18 genes and some important signaling pathways like Wnt/ß-catenin, Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Janus kinase 2 (JAK2) signaling, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling. Current studies have proposed that the level of miR-542-3p could be modulated by several upstream regulators like transcription factors, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). In addition, the level of miR-542-3p or its related lncRNAs/circRNAs are correlated with poor prognosis and clinicopathological features of cancer-affected patients. Here, we have discussed the biogenesis, function, and regulation of miR-542-3p as well as its aberrant expression in various types of neoplastic cells. Moreover, we have discussed the prognostic value of miR-542-3p in cancer. Finally, we have added the underlying molecular mechanism of miR-542-3p in cancer pathogenesis.

The cross-talk between LncRNAs and JAK-STAT signaling pathway in cancer.

Long non-coding RNAs (lncRNAs) are non-coding RNAs that were transcribed from the human genome and have become important regulators in a number of cellular activities, mostly via controlling gene expression. A growing body of evidence shows that lncRNAs regulate various factors to impact various biological activities that are related to tumorigenesis, including the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. lncRNAs influence the JAK-STAT signaling pathway either by directly targeting or via indirectly modulating other upstream or downstream pathways' components like members of the suppressor of cytokine signaling (SOCS) family, and other genes that regulate cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition. Furthermore, lncRNAs can act as downstream effectors of the JAK-STAT pathway and mediates tumorigenesis. The relationship between JAK-STAT signaling and lncRNAs differs among various types of cancers. Besides, lncRNAs, as biological molecules, have been shown to play a dual role in either tumorigenesis or tumor suppression in various cancers. In this review, we focus on the reciprocated regulation and functions of lncRNAs and the JAK-STAT signaling pathway in cancer, as well as narrate the latest research progress on this association. A deeper understanding of this correlation may simplify the recognition of potential targets for clinical therapeutics.

Anti-HSP70 alleviates cell migration and proliferation in colorectal cancer cells (CRC) by targeting CXCR4 (in vitro study).

Colorectal cancer (CRC), the third most common cancer in men and women, accounts for 8% of new cancer cases in the US and 8 to 9% of the nation's anticipated cancer mortality in 2014. In the pathophysiology of colon cancer, heat shock protein 70 (HSP70) and CXCR4 are essential. In this research, we concentrated on the connection between CXCR4 expression and HSP70 inhibitor activity in the development of colorectal cancer. The HSP70 inhibitor's effect on cell proliferation was also evaluated. Samples were obtained from patients with CRC; the surrounding marginal tissues were considered healthy. The One CRC cell lines (HCA-7) were divided into two groups based on untreated and treated with anti-HSP70. HSP70 and CXCR4 mRNA expression and migration (Wound healing assay) were measured in these groups. Also, we evaluated the expression levels of HSP70 and CXCR4 in thirty CRC and healthy non-cancerous samples (Using Real-time PCR and Western Blotting). Moreover, we examined the viability of CRC cells in untreated and treated groups with anti-HSP70. Higher expression levels of CXCR4 (p < 0.0001) and HSP70 (p = 0.002) mRNA were observed in patients who had CRC. In contrast, lower mRNA expressions of HSP70 (p < 0.0001) and CXCR4 (P < 0.0001) were detected in the CRC cell line (HCA-7) after being treated with anti-HSP70. Moreover, the viability and migration of cancer cells were remarkably reduced in CRC cells treated with anti-HSP70. Our study's innovation was the in vitro demonstration of inhibiting HSP70 in the CRC cancer cell line drastically reduced CXCR4 expression, viability, and cancer cell migration. These findings may pave the way for additional studies on CRC cancer treatment and be examined in vivo in studies, given that the primary goal of therapy is to decrease the viability and spread of cancer cells.

Hyperbaric Oxygen in Combination with Epigallocatechin-3-Gallate Synergistically Enhance Recovery from Spinal Cord Injury in Rats.

Spinal cord injury (SCI) following trauma is a devastating neurological event that can lead to loss of sensory and motor functions. However, the most effective measures to prevent the spread of damage are treatment measures in the early stages. Currently, we investigated the combined effects of hyperbaric oxygen (HBO) along with epigallocatechin-3-gallate (EGCG) in the recovery of SCI in rats. Ninety male mature Sprague-Dawley rats were randomly planned into five equal groups (n = 18). In addition to sham group that only underwent laminectomy, SCI rats were allocated into 4 groups as follows: control group; HBO group; EGCG group; and HBO + EGCG group. Tissue samples at the lesion site were obtained for stereological, immunohistochemical, biochemical, and molecular evaluation. In addition, behavioral tests were performed to assess of neurological functions. The finding indicated that the stereological parameters, antioxidant factors (CAT, GSH, and SOD), IL-10 gene expression levels and neurological functions were considerably increased in the treatment groups in comparison with control group, and these changes were more obvious in the HBO + EGCG group (P < 0.05). On the other hand, we observed that the density of apoptotic cells and gliosis, the biochemical levels of MDA and the expression levels of inflammatory genes (TNF-α and IL-1ß) in the treatment groups, especially the HBO + EGCG group, were considerably reduced in comparison with control group (P < 0.05). We conclude that co-administration of HBO and EGCG has a synergistic neuroprotective effects in animals undergoing SCI.

VAV3 in human cancers: Mechanism and clinical implication.

Guanine nucleotide exchange factors (GEFs) are primarily involved in signal transmission between cell membrane receptors and intracellular mediators. Upon replacing GDP with GTP, GEFs can alter their conformation, resulting in their binding to downstream effectors, such as GTPases like Ras homologous (Rho). VAV GEF family are versatile proteins working as an adaptor mediator and GEF for Rho GTPase. They act as a phosphorylation-dependent molecular switcher, fluctuating between active (tyrosine phosphorylated) and inactive (non-phosphorylated) conformation in cell signaling. Accumulating data showed that VAV3 is implicated in cancer progression. The higher levels of VAV3 in human cancers proposed that it may have an oncogenic role in cancer progression. Available studies demonstrated that VAV3 promoted cell proliferation, epithelial-mesenchymal transition (EMT), colony formation, cell cycle, survival, migration and invasion, and suppressed cell apoptosis. In addition, other studies indicated that VAV3 may have a prognostic value in cancer as well as it may act as a mediator in cancer chemoresistance. Here, we aimed to investigate the underlying molecular mechanism of VAV3 in cancer progression as well as to review its value as a prognostic biomarker and chemoresistance mediator in human cancers.