International Journal of Molecular and Cellular Medicine最新文献

Laryngeal squamous cell carcinoma (LSCC) remains a significant global health challenge despite advances in treatment. This study investigated the involvement of LINC01980, a long non-coding RNA, in LSCC pathogenesis. We conducted an integrative analysis of transcriptomic data sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases to identify genes that are differentially expressed in LSCC. LINC01980 expression was evaluated in 32 matched pairs of advanced-stage LSCC and adjacent normal tissues using quantitative real-time PCR (qRT-PCR). The potential competing endogenous RNA (ceRNA) network involving LINC01980 was explored through bioinformatics analyses. Findings revealed significant upregulation of LINC01980 in LSCC tissues compared to normal adjacent tissues (p < 0.0001), with elevated expression in 78.125% of tumor samples. Receiver Operating Characteristic (ROC) curve analysis demonstrated LINC01980's potential as a diagnostic biomarker (AUC = 0.7666, p = 0.0002). While no significant correlations were found between LINC01980 expression and clinicopathological features, bioinformatics analyses identified potential LINC01980/ miRNA/ mRNA regulatory network involving hsa-let-7e-5p and hub gene MMP9. This study provides insights into LINC01980's role in LSCC and suggests its potential as a diagnostic biomarker and therapeutic target. Further research is warranted to elucidate the precise molecular mechanisms of LINC01980 in LSCC progression.

Diabetic nephropathy is a leading cause of end-stage renal disease globally, with limited treatment options to prevent its progression. Gambogic acid (GA), a xanthone isolated from Garcinia hanburyi, has shown notable anti-oxidative, anti-inflammatory, and anti-proliferative properties. This study aimed to assess GA's renoprotective effects in a model of diabetic nephropathy mediated by low dose streptozotocin (STZ) combined with a high-fat diet, focusing on its potential to reduce oxidative stress and inflammation. Control-treated vehicle and STZ/high-fat diet-mediated diabetic rats were administered either the vehicle or 3 or 6 mg/kg of GA to assess its effects on renal inflammation, fibrosis, and oxidative stress. Renal histological changes were assessed, and markers for inflammation and oxidative stress, including I-κBα, p-p38/MAPK, and p-p65NF-κB pathways, were measured to explore the mechanisms of GA. Diabetic rats showed significant renal dysfunction, structural damage, and increased inflammation and fibrosis. Treatment with GA markedly improved renal structure and function. GA also reduced oxidative stress, increased I-κBα expression, and inhibited key signaling pathways, specifically p-p38/MAPK and p-p65NF-κB, involved in cellular inflammation. GA exhibits promising renoprotective effects in diabetic nephropathy by reducing oxidative stress and inflammation, supporting its potential as a natural therapeutic agent for diabetic renal disease.

By 2040 the burden of colorectal cancer will increase to 3.2 million new cases per year and 1.6 million deaths per year. This highlights the importance of improving preventive measures and treatment strategies. This piece concisely overviews the latest therapeutic and diagnostic approaches for colorectal cancer. In 2019, factors such as low milk intake, smoking, insufficient calcium consumption, and alcohol use had a significant impact on colorectal cancer DALYs worldwide. A comprehensive search was conducted in December 2023 using keywords related to drugs, therapeutic agents, colorectal cancer, diagnostic methods, epidemiology, and novel therapeutic approaches in the PubMed and Scopus databases. Initially, 325 articles were identified based on titles, abstracts, and publication dates. After removing duplicates, 170 unique articles were included. Medications like Nimotuzumab, Cetuximab, and Panitumumab target the Epidermal Growth Factor Receptor (EGFR), which EGF activates. HER2, activated by ligands, is the focus of drugs like Trastuzumab and Pertuzumab. The PD-1/PD-L1 and CTLA-4 pathways, as the immune checkpoints, which involve T cells, are targeted by medications like Ipilimumab. Adoptive cell therapy, including CAR-T cell therapy, TCR modification, and enhancing T cell activity through tumor-infiltrating lymphocytes, is used to combat cancer cell growth. In medical advancements, adoptive cell transfer therapy (ACT) and exosomes in the tumor immune microenvironment (TME) are notable treatment methods that boost the immune system. HIF1A-AS1, CRNDE-h, NEAT1, ZFAS1, and GAS5, along with IGFBP-2, have demonstrated significant CRC diagnostic capacity. Compared to CRC patients with low HIF1A-AS1 expression, individuals with high expression levels were linked to a worse 5-year survival rate.

It is predicted with near certainty that an estimated 310,720 women will be diagnosed with invasive breast carcinoma in 2024, while the number of men will be significantly lower at around 2,800, highlighting the alarming prevalence of this cancer across the sexes. The Solute Carrier Family 7 Member 11(SLC7A11) gene is vital for the exchange of extracellular cystine for glutamate at a 1:1 ratio and its expression is significantly increased in various tumors. Numerous research studies have shown that SLC7A11 expression is fine-tuned at several levels, contributing to its pharmacological functions in tumors, such as maintaining cellular redox balance, promoting cell proliferation, and influencing ferroptosis. Many studies suggest that reducing SLC7A11 expression and activity may be beneficial for cancer treatment, making it a promising target for therapy. However, recent findings also suggest that inhibiting SLC7A11 in certain scenarios may increase the survival of cancer cells and promote drug resistance. This review begins with a brief overview of the properties of SLC7A11, including its structural features and physiological functions, followed by a summary of its potential regulators. We then delve deeper into its role in cancer, particularly breast cancer, and explore the relationships between SLC7A11 and ferroptosis, proliferation, metastasis, and therapeutic resistance. Consequently, more customized therapeutic approaches should be considered when targeting SLC7A11 in the context of breast cancer. Thus, high expression of SLC7A11 is associated with poor prognosis in breast cancer, and various inhibitors have been identified that can effectively target this transporter. Innovative therapeutic strategies, including immunotherapies targeting SLC7A11, can potentially reduce tumor growth and metastasis in breast cancer models.

Breast cancer encompasses a diverse array of conditions classified as hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative breast cancer subtypes, dictating treatment approaches. The therapeutic strategies commonly involve addressing estrogen receptors (ER) and HER2, which have exhibited efficacy in managing cancer. Nevertheless, the prevalence of resistance to these therapies, whether inherent or acquired, persists despite the introduction of novel treatment modalities. Progress in comprehending the biology of tumors has facilitated the identification of fresh targets, such as inhibitors targeting different pathways like phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR), cell-cycle regulation, heat shock protein, and epigenetic pathways, demonstrating encouraging outcomes in clinical experiments. For example, the mTOR inhibitor everolimus has been sanctioned for ER+ breast cancer and resistance to aromatase inhibitors in the advanced or metastatic phase. Triple-negative breast cancer, characterized by the absence of estrogen receptors, progesterone receptors, and HER2, currently lacks established targeted therapies. While poly (ADP-ribose) polymerase inhibitors exhibit effectiveness in BRCA-related cancers, their efficiency in addressing triple-negative breast cancer residues is uncertain. This paper furnishes a comprehensive outline of the principal targeted therapies presently employed or under exploration for breast cancer treatment within the three clinical subsets.

For almost 40 years, human T-lymphotropic virus type 1 (HTLV-1) has posed a persistent challenge in managing the major diseases associated with HTLV-1. Intracellular inhibitors are critical regulators of T cell activation, and their function can be influenced by viruses. Because of less studied aspects of HTLV-1 in T cell activation, we evaluated three suppressor genes in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic carriers (ACs). Thirty samples were collected from three groups from 10/09/2022 to 03/27/2024. To confirm all the samples, ELISA and PCR tests were done. The isolation of peripheral blood mononuclear cells (PBMCs), RNA extraction, and cDNA synthesis were conducted. Subsequently, the expression of Tax trans-activator, HTLV-1 bZIP factor (HBZ), protein phosphatase 2 A (PP2A), and two E3 ligases, including Casitas B lymphoma-b (Cbl-b) and itchy E3 Ubiquitin protein ligase (ITCH), was measured via Real-time PCR. This survey showed a significant increase in ITCH among individuals with HAM/TSP and ACs compared to the healthy group. The PP2A mRNA expression level was upregulated in the ACs; in contrast, the expression levels were approximately similar in the HAM/TSP and healthy groups. Also, the mean expression level of Cbl-b was higher in the ACs than in the other groups; however, it was not statistically significant. Our findings demonstrated that the intercellular suppressor genes could be dysregulated during the HTLV-1 infection, probably as part of the virus's strategic goals. The findings can be helpful for future investigation in the diagnosis and treatment area.

The success of endodontic treatments can be significantly impaired by persistent microbial pathogens, especially Enterococcus faecalis (E. faecalis) and Candida albicans (C. albicans). The aim of this study was to investigate how the incorporation of chitosan nanoparticles (CsNPs) and arginine (Arg) can enhance the antimicrobial and antibiofilm efficacy of AH Plus, a widely used epoxy resin-based root canal sealer. The CsNPs were synthesized by ionotropic gelation and assessed for their size, morphology, chemical structure, and cytotoxicity. The antimicrobial effectiveness of the modified sealers was evaluated against E. faecalis and C. albicans by determining the minimum inhibitory concentration, minimum bactericidal concentration, minimum fungicidal concentration, and agar diffusion method. Additionally, antibiofilm activity was assessed using a microtiter plate assay. Characterization of the CsNPs revealed an average size of 144 ± 12.8 nm by scanning electron microscopy and 182.4 nm by dynamic light scattering with a zeta capacitance of +49.2 mV. CsNPs maintained more than 68% cell viability at 625 μg/mL after 24 and 48 hours. Adding CsNPs and Arg significantly enhanced the impact of AH Plus sealer on antimicrobial and antibiofilm, especially at elevated additive concentrations. This study suggests that AH Plus sealers containing CsNPs and Arg may offer a promising approach to enhance endodontic treatment outcomes by efficiently combating resistant root canal infections.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor response to the limited treatment options currently available. Hence, there is a need to identify new agents that could enhance the efficacy of existing treatments. This study investigated a combination therapy using gemcitabine (GEM) and SCH772984, an extracellular signal-regulated kinase (ERK) inhibitor, in both free form and nanoparticle-encapsulated form for PDAC treatment. Cell viability and Matrigel growth assays were used to determine the anti-proliferative and cytotoxic effects of GEM and SCH772984 on PDAC cells. Additionally, western blotting was used to determine the degree to which SCH772984 engaged ERK in PDAC cells. Lastly, immunohistochemistry and hematoxylin and eosin (H&E) staining were used to determine how GEM and SCH772984 affected expression of Ki-67 cell proliferation marker in PDX (patient derived xenograft) PDAC tissues. PDAC cell lines (MIA PaCa-2 and PANC-1) treated with the combination of free GEM and SCH772984 showed reduction in cell viability compared to cells treated with free GEM or SCH772984 administered as a single agent. Encapsulated forms of GEM and SCH772984 caused a greater reduction in cell viability than the free forms. Interestingly, co-administration of GEM and SCH772984 in separate nanoparticle (NP) systems exhibited the highest reduction in cell viability. Western blotting analysis confirmed ERK signaling was inhibited by both free and encapsulated SCH772984. Importantly, GEM did not interfere with the inhibitory effect of SCH772984 on phosphorylated ERK (pERK). Collectively, our studies suggest that combination therapy with GEM and SCH772984 effectively reduced PDAC cell viability and growth, and co-administration of NP encapsulated GEM and SCH772984 in separate NP systems is an effective treatment strategy for PDAC.

Gallic acid (GA) is a powerful antioxidant extracted from plants of the Brazilian Cerrado. Oxidative stress plays an important role in the occurrence of radiation-induced osteonecrosis in patients treated for head and neck cancer. There is a need to develop research aimed at developing complementary therapies to prevent or reverse bone damage. The aim of the present study was to investigate the effect of GA in preosteoblasts exposed to therapeutic ionizing radiation. MC3T3-E1 preosteoblast cells were treated with 10 µM GA and exposed to 6 Gy ionizing radiation. We performed in vitro assays of cell proliferation, oxidative stress analysis by detection of reactive oxygen species, and alkaline phosphatase assay. GA at lower concentrations was able to significantly increase proliferation and inhibit radiation-induced generation of reactive oxygen species in osteoblast precursor cells, despite ionizing radiation-induced injury. Furthermore, GA significantly increased alkaline phosphatase at a dose of 6 Gy. The findings suggested that GA could attenuate ionizing radiation-induced injuries in osteoblast precursor cells. Moreover, in vivo studies are needed to better investigate the role of GA in osteonecrosis, especially in cancer patients undergoing radiotherapy or taking antiresorptive drugs.

CDX1 and CDX2 are homeobox-type transcription factors that are potential biomarkers and are associated with prognostic significance in intestinal-type gastric cancer early disease before lymph node metastasis is associated with better prognosis. In addition, the genes IDH 1 and IDH 2 previously known to be involved in brain cancer are implicated in cancer-related molecular signatures as a result new targeted personalized therapies may be possible. Our retrospective study determined the correlation between CDX markers and clinicopathologic data including survival in patients with gastric cancer. This study included studies from 1997 to December 2022 a meta-analysis to provide odds ratios (ORs) and relative risks (RRs). We discussed in detail the impact of IDH 1/2 on the prognosis of gastric cancer outcomes and potential therapeutic strategies. Our meta-analysis included 20 studies identifying 11,163 patients with gastric cancer. We found that CDX 1 overexpression was associated with better overall survival (pooled HR: 1.28) and CDX 2 expression and better 3-year survival (pooled HR: 1.64) and 5-year survival was the pooled HR was correlated 1 94 with both showing statistical correlation. Evidence suggests that IDH 1/2 mutations and CDX 1/2 overexpression are closely associated with metabolic abnormalities epigenetic changes and mutations evidence suggests the potential for novel targeted therapies in gastric cancer. CDX 1/2 overexpression is associated with a favorable prognosis in gastric cancer cases. Further studies are needed to explore the clinical significance of IDH 1/2 mutations and CDX 1/2 expression.