International Journal of Molecular and Cellular Medicine最新文献

Colorectal cancer (CRC) is a popular type of cancer, characterized by high mortality and a notable impression on the well-being of individuals. The success of adoptive chimeric antigen receptor T (CAR-T) cell therapy in treating hematological malignancies has been remarkable in recent years; however, its application in solid tumors like CRC has many challenges. These obstacles encompass the immunosuppressive microenvironment of the tumor, the insufficient targeting of CAR-T cells, the limited lifespan of CAR-T cells within the body, and the constrained capacity for proliferation. Additionally, CAR-T cells face hurdles in effectively infiltrating the tumor site, which further complicates treatment outcomes. Diverse innovative strategies have been suggested to surmount these barriers in the context of CRC. This comprehensive review endeavors to meticulously elucidate an exhaustive and detailed evaluation of the prevailing and contemporary landscape concerning CAR-T cell therapy as it pertains to the intricate management of CRC, while simultaneously offering a thorough indication of the various risk factors and the associated prevalence that are intricately linked with the manifestation and progression of CRC.

The worldwide spread of COVID-19, triggered by SARS-CoV-2, has highlighted how viral accessory proteins contribute significantly to bypassing host immune defenses and increasing illness severity. This study investigates the relationship between the levels of SARS-CoV-2 subgenomic RNA (sgRNA) for ORF7a and ORF7b and host interferon-beta (IFN-β) expression in hospitalized COVID-19 patients with different prognoses. Upper respiratory tract samples from 89 patients (49 with poor prognosis and 40 with good prognosis) were analyzed using quantitative real-time PCR to measure ORF7a, ORF7b, and IFN-β expression levels. The results revealed significantly higher expression of ORF7a and ORF7b in patients with poor prognosis compared to those with favorable outcomes (P < 0.001). Conversely, IFN-β expression was significantly reduced in the poor prognosis group (P < 0.001), suggesting a potential mechanism of immune suppression. Older age, underlying health conditions, and elevated levels of inflammatory biomarkers, such as CRP and D-dimer, were also associated with poorer outcomes. These findings underscore the potential role of ORF7 proteins in suppressing IFN-β signaling, contributing to disease severity. Targeting these viral proteins may offer promising therapeutic avenues to enhance antiviral responses and improve patient outcomes. The study was conducted from August 2022 to February 2022. Further research is warranted to better understand the interplay between viral immune evasion mechanisms and host responses across diverse patient populations.

This study aimed to evaluate the osteogenic response of human dermal fibroblasts (hDFs) and human dental pulp stem cells (hDPSCs) when exposed to hydroxyapatite nanoparticles (HA-NPs), which are commonly employed biomaterials in the field of bone regeneration. The sol-gel method was employed to synthesize HA-NPs. Cell viability was assessed using the MTT assay after 24 and 72 hours of exposure to HA-NPs. Osteogenic differentiation was assessed through Alizarin red S staining (ARS), alkaline phosphatase (ALP) activity assay, and quantitative real-time PCR (qPCR) to evaluate the expression levels of osteogenic markers, including BMP-2, VEGF-A, RUNX2, and IL-6. The HA-NPs had a nanorod shape, with dimensions of 17-29 nm in width and 62-89 nm in length. Both hDPSCs and hDFs demonstrated enhanced osteogenic potential when exposed to HA-NPs, as indicated by increased ARS staining for calcium deposition and elevated ALP activity. Gene expression analysis showed up-regulation of BMP-2 and VEGF-A and down-regulation of RUNX2 in both cell types. IL-6 expression markedly increased in hDFs but did not show significant changes in hDPSCs compared to the control group. The findings of this study suggest that HA-NPs may enhance the osteogenic capability of hDPSCs and hDFs. The results demonstrate that while fibroblasts exhibit some mineralization potential, hDPSCs are the most suitable cell type for bone regenerative applications.

Stroke is the major cause of disability and mortality worldwide. Identification of molecular biomarkers in the early hours after stroke is important in terms of both diagnostic and therapeutic applications. miR-34a, a highly expressed miRNA, is involved in many pathological mechanisms in the central nervous system. This miRNA targets sirtuin 1 (SIRT1) gene. Here, the efficacy of miR-34a/SIRT1 axis as a potential biomarker in the acute phase of ischemic stroke has been evaluated. 100 patients (in the first 12 hours after ischemic stroke) and 100 healthy subjects were examined. miR-34a expression level was assessed using real-time polymerase chain reaction and SIRT1 level was measured using Enzyme-linked immunosorbent assay. Stroke etiology and infarct size were investigated in the patients. The National Institutes of Health Stroke Scale (NIHSS) was also evaluated. Compared to the healthy controls, ischemic stroke patients showed increased miR-34a expression (P < 0.0001) and decreased SIRT1 levels (P < 0.0001). The levels of miR-34a and SIRT1 showed significant differences among various subtypes of stroke etiology and infarct size. The baseline NIHSS values were correlated negatively with SIRT1 (r=-0.89) and positively with miR-34a (r=0.81). Our results suggested that dysregulation in miR-34a/SIRT1 may be a potential biomarker in occurrence and severity of ischemic stroke.

Early detection is crucial for improving survival rates in colorectal cancer (CRC). This study evaluates the non-invasive diagnosis of polyps by assessing the methylation status of the TFPI2 and SDC2 genes in plasma. This study enrolled 27 individuals with low-risk polyps (LRP), 27 with high-risk polyps (HRP), and 27 healthy controls. The quantitative methylation levels of TFPI2 and SDC2 genes were analyzed in plasma cell-free DNA (cfDNA) using the methylation-quantification endonuclease-resistant DNA (MethyQESD) method. Increased methylation percentages of both TFPI2 (TFPI2_1 and TFPI2_2) and SDC2 (SDC2_2) were observed in individuals with LRP and HRP. The combination of SDC2 and TFPI2 yielded an Area Under the Curve (AUC) of 0.732 (95% CI 0.78 to 0.96, p=0.001) with a sensitivity of 66% (95% CI 46% - 82%) and specificity of 77% (95 CI 56% - 91%) for LRP. For HRP, the AUC was 0.890 (95% CI 0.596 to 0.843, p<0.001) with a sensitivity of 70% (95% CI 51% - 84%) and specificity of 92% (95 CI 75% - 99%). The combined assessment of SDC2 and TFPI2 methylation presents a potential approach for the early non-invasive detection of CRC and its associated precancerous lesions.

Cancer stem cells (CSCs) are a subset of cells within tumors that exhibit stem cell-like characteristics, including the ability to self-renew and differentiate. CSCs are the cause of carcinogenesis and tumorigenesis. The expression of cell surface markers, which varies linked to the kind of tumor, is utilized to recognize CSCs. An essential part of tumor invasion and metastasis is played by CSCs. Numerous investigations have been carried out to find distinguished markers and different phenotypes of CSCs, which are especially crucial for identifying and separating this subset of cells. It was discovered that the regulation of CSCs involves a multitude of signaling pathways. These cells are determined by their ability to self-renewal pathways such as Wnt/β-catenin, JAK/STAT3, PTEN/PI3-K/Akt, and Hedgehog, their surface biomarkers, and their resistance to many drugs. Aberrant activation of these signaling pathways is associated with cell growth. Thus, focusing on CSCs is seen to be a viable anti-cancer treatment approach. It is encouraging that CSCs' self-renewal pathways present a viable target for changing their survival tactics and limiting their capacity to proliferate tumors. This study highlights the characterization and investigation of CSC self-renewal pathways, also discusses potential targeted therapy for CSC, and gives a summary of the significant factors and pathways that adjust CSC formation.

N-Methyl-D-Aspartate (NMDA) receptors are involved in synaptic plasticity and neuronal communication. They have various responses to oxidative stress based on the dosage of agonists or antagonists that may be applied. This study focuses on modulation of NMDA receptors in primary hippocampal neurons in oxidative stress condition to understand the effects of NMDA receptor activation and inhibition. In our experiments, primary hippocampal neurons were treated with NMDA and MK-801 to assess their effect on cell viability and apoptosis. Oxidative stress was induced at different concentrations, to evaluate NMDA receptor activity and the neuroprotective effects of MK-801. Apoptosis rates were specified by applying flow cytometry, and assaying caspase-3 activity. Intracellular calcium levels were monitored using fluorescent dye Fura-2 AM. NMDA at 200 μM significantly prevented the cytotoxic effect induced by H₂O₂ (P<0.001). MK-801 with concentrations of 5 to 20 μM, could reverse the cytotoxic effect of H₂O₂. As a result, it significantly inhibited the toxicity of H₂O₂ on neuronal cells (P<0.001), while 40 μM could not reverse its effects. NMDA (200 μM) increased neuronal survival to 88.3% in the presence of H₂O₂ and prevented apoptosis. MK-801 (5 μM) also elevated cell survival to 87.2%. Treatment with NMDA (200 µM) + H₂O₂ also did not show any changes in the Fura-2AM fluorescence compared to the H₂O₂ group (P>0.05). However, MK-801+ H₂O₂ reduced the effects of H₂O₂ on the fluorescence ratio and calcium influx considerably in comparison with the H₂O₂ group (P<0.01). Treatment with MK-801 (5 μM) effectively mitigated the effects of H₂O₂ on caspase-3 activity compared to the H₂O₂ group (P<0.001). Importantly, the dose-dependent effects of NMDA receptors offer a new path into finding therapeutic strategies for neurodegenerative diseases .

The resistance of tumor cells to ABT-737 can be attributed to alterations in the equilibrium of Bcl-2 family proteins. In this study, the effect of curcumin on the Mcl-1expression and the sensitivity of glioblastoma cells to ABT-737 were examined. Trypan blue assay and colony formation assay were performed to explore the effects of treatments on cell proliferation. MTT assay was performed to measure cytotoxicity. Cell migration was determined using a wound healing assay. Cell apoptosis was measured by Hoechst 33342 staining, ELISA cell death, and caspase-3 activity assay. The expression levels of Mcl-1 mRNA were also tested by qRT-PCR. Our results revealed that combination therapy significantly lowered the IC₅₀ value and synergistically decreased the colony formation and migration, cell survival and growth of glioblastoma cells compared with curcumin or ABT-737 alone. Treatment with curcumin clearly inhibited the expression of Mcl-1 mRNA. Moreover, suppression of Mcl-1 mRNA by curcumin was associated with enhancement of apoptosis induced by ABT-737. In conclusion, curcumin has the ability to inhibit the cell proliferation and migration, and activate the intrinsic pathway of apoptosis. Moreover, it can enhance the sensitivity of glioblastoma cells to ABT-737 by suppressing the expression of Mcl-1.

Colorectal cancer (CRC), which is among the most prevalent cancers worldwide, is caused by environmental and genetic factors. It has been shown that the p53 gene is associated with CRC pathogenesis; moreover, Zyxin (ZYX) may play a role in p53 level and activity. Therefore, the present research aimed to investigate the levels of P53 and ZYX genes and proteins in CRC tumor samples. Cancerous tissues (n=31) and matched non-cancerous tissues (n=31) were randomly obtained from 31 patients with CRC. Total RNA was extracted using RNXplus, and gene expressions were assessed by Real-time PCR. Furthermore, the Western blot technique was used to investigate the expression of ZYX and P53 proteins. The obtained results revealed that the expression of ZYX and p53 genes in cancerous tissues showed no significant difference compared to matched non-cancerous tissues. On the other hand, measuring protein expression using the Western blotting technique indicated that the ZYX (P=0.0081) and p53 (P=0.0065) expression in tumor tissues significantly decreased compared to those in matched non-cancerous tissues. Correlation analysis indicated a significant correlation between ZYX and P53 proteins (r=0.746, P=0.013). Based on our findings, ZYX might have a suppressive function in CRC and is associated with P53.

Multi-drug-resistant (MDR) Acinetobacter baumannii has become a major global healthcare concern due to its opportunistic infections and high antibiotic resistance. This investigation is intended to investigate curcumin's potential anti-bacterial and antibiofilm impacts on MDR A. baumannii and to present a promising strategy for fighting against infections caused by this pathogen. This cross-sectional investigation comprised 34 MDR A. baumannii clinical isolates. The Kirby-Bauer disc diffusion method evaluated the sensitivity of isolates to multifaceted anti-bacterial agents. The microdilution broth method quantified curcumin's minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). The efficacy of curcumin in inhibiting MDR A. baumannii biofilm was assessed via 96-well microtiter plates. The expression of the biofilm-associated protein (bap) gene was evaluated by employing quantitative real-time PCR (qRT-PCR). Within the 34 MDR A. baumannii isolates, the highest resistance was noted for trimethoprim/sulfamethoxazole and ciprofloxacin, with all 34 isolates (100%) indicating resistance. The lowest resistance was noted for ampicillin/sulbactam, with 22 isolates (64.7%) exhibiting resistance. The MICs of curcumin ranged from 0.625 to 2.5 mg/ml, while the MBCs varied between 1.25 to 5 mg/ml. Curcumin reduced biofilm formation by 25% to 91%, depending on the concentration. In contrast to the untreated control, the average relative activity of the bap gene in MDR A. baumannii isolates declined by 62.07%. The findings indicate that curcumin demonstrates antimicrobial and anti-biofilm activities against MDR A. baumannii. The downregulation noted in the bap gene further supports the curcumin's anti-biofilm impact.