International Journal of Molecular and Cellular Medicine最新文献

As a leading non-fermentative opportunistic bacterium, Pseudomonas aeruginosa (P. aeruginosa) plays a major role in healthcare-associated infections. The emergence of carbapenem-resistant strains is a serious clinical threat, often associated with integrons and carbapenemases such as blaIMP. The present study aimed to assess the distribution of class 1 and 2 integrons and the blaIMP gene among clinical isolates of carbapenem-resistant P. aeruginosa from hospitals in Shiraz. Seventy clinical isolates of P. aeruginosa were collected from different hospital wards. The identification of the isolates was performed using common microbiology methods. The disk diffusion method was used to evaluate the antimicrobial susceptibility. Minimum inhibitory concentration (MIC) values for imipenem in carbapenem-resistant strains were obtained using E-test strips. Polymerase chain reaction (PCR) was used to identify the resistance determinants including intI1, intI2, and blaIMP. Of the 70 clinical isolates, 35 (50%) isolates were imipenem-resistant. MIC testing showed that 34 isolates had a resistant MIC (MIC ≥ 8 μg/mL). PCR results showed that 33 (94.3%) isolates carried the intI1 gene and 17 (48.6%) isolates carried the blaIMP gene. Co-existence of intI1 and blaIMP genes was observed in 17 (48.6%) isolates. The intI2 gene was not detected in any of the samples. The prevalence of the intI1 and blaIMP genes was higher among the isolates obtained from intensive care units (ICU) and internal medicine wards. The high prevalence of class 1 integrons and the blaIMP gene among carbapenem-resistant isolates suggests the key function of mobile genetic elements in the horizontal spread of resistance factors.

This study investigated the anti-tumor properties of Lactobacillus delbrueckii, a probiotic bacterium, against HT-29 human colorectal cancer cells. The primary objective was to evaluate the effects of Lactobacillus delbrueckii supernatant on gene expression, cell viability, apoptosis, and cell cycle progression in HT-29 cells. In Gilan Province, Iran, a native strain of Lactobacillus delbrueckii was identified from the supernatant of local yogurt. After treating HT-29 cells with different doses of the supernatant, the MTT test was used to calculate the IC50 value 24 hours later. Annexin V/PI staining and flow cytometry were used to evaluate the induction of apoptosis, and real-time PCR was used to measure changes in gene expression. The results showed that the supernatant of Lactobacillus delbrueckii strongly and dose-dependently reduced the growth of HT-29 cells. In addition to causing apoptosis and stopping the cell cycle in the G0/G1 phase, the therapy also increased the number of Sub-G1 cells, which is a sign of cell death. According to gene expression study, anti-apoptotic genes (AKT, Bcl-2) were downregulated while pro-apoptotic genes (PTEN, p53, and Bax) were upregulated. Interestingly, the natural isolate outperformed a conventional strain in terms of anticancer efficacy. These results demonstrate Lactobacillus delbrueckii's potential as a colorectal cancer treatment.

Cardiotoxicity represents a significant adverse effect associated with 5-fluorouracil (5-FU), a widely used chemotherapeutic agent. Melatonin (MLT), a powerful antioxidant and agent that prevents apoptosis, has shown promise in mitigating various toxicities. This study evaluated the cardioprotective effect of MLT on 5-FU-induced cardiotoxicity (5-FU-IC) in the H9c2 cardiomyoblast cell line. The cells were grown in DMEM + FBS and divided into four groups: control (untreated), 5-FU-treated (varying concentrations for 48 hours), MLT-treated (varying concentrations), and 5-FU plus MLT-treated (combined treatment for 48 hours). The cell viability was evaluated using the MTT assay, while apoptosis was analyzed through flow cytometry following Annexin V staining and caspase-3/7 (Cas-3/7) activity assays. Treatment with 5-FU led to a significant decrease in the viability of H9c2 cells in a dose-dependent fashion, with an estimated IC50 value of 400 μM. Co-treatment with MLT at 100 and 200 μM significantly enhanced cell viability and reduced apoptosis induced by 5-FU, as demonstrated by flow Cytometry and reduced Cas-3/7 activity. These results emphasize the protective effects of MLT against 5-FU-IC, primarily through its anti-apoptotic mechanisms. These findings underscore the importance of MLT to protect against 5-FU-IC through its anti-apoptotic properties. MLT shows promise as a cardioprotective agent in mitigating 5-FU-IC, providing perspectives on its potential therapeutic application in mitigating cardiac risks linked to chemotherapy.

This research investigates the roles of microRNAs (miR-138, miR-195-5p) and the long non-coding RNA (lncRNA) H19 in orthodontic tooth movement (OTM). A literature review using databases such as PubMed and Scopus identified 148 articles, which were subsequently narrowed down to 61 unique studies after duplicate removal. The findings underscore the significance of mechanical stimulation in bone metabolism and the complex biological mechanisms of OTM, with a focus on the functions of osteoblasts and osteoclasts. The study aimed to elucidate the expression patterns of non-coding RNA and microRNA in response to orthodontic force, potentially revealing new clinical methods to enhance the safety of orthodontic treatment. Additionally, it examines the therapeutic roles of miRNAs in orthodontics, specifically their influence on inflammation and bone regeneration. Notably, recent evidence has suggested miR-138 may inhibit osteogenesis, indicating its potential role in regulating bone remodeling during OTM, as mechanical forces affect both alveolar bone and periodontal tissues. Furthermore, miR-195-5p has been shown to directly interact with crucial osteogenic proteins, such as Wingless/Integrated 3 A (WNT3A), fibroblast growth factor 2 (FGF2), and bone morphogenetic protein receptor type 1A (BMPR1A). By downregulating these proteins, miR-195-5p negatively impacts essential osteogenic pathways related to bone formation and stability. The cyclic strain was found to upregulate lncRNA H19 while downregulating miR-138, promoting osteogenic differentiation of MSCs. This review outlines the complex regulatory networks involving these molecules, contributing to an understanding of OTM in dental and skeletal health, and aims to enhance treatment outcomes for malocclusion.

Colorectal cancer (CRC) is a malignancy with a significant global disease burden.Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been implicated in tumorigenesis. The oncogenic long non-coding RNA highly upregulated in liver cancer (HULC) plays a pivotal role in CRC progression. However, the exact molecular mechanism of HULC and its correlation with TMAO in CRC pathogenesis has remained unclear. This study tested whether TMAO regulates HULC and whether HULC mediates changes in selected miRNAs relevant to CRC. Caco-2 cells were treated with TMAO (300 µM, 24 h) and HULC expression was quantified by RT-qPCR. HULC was transiently silenced using CRISPR/Cas13 (CasRx) and the expression of candidate downstream miRNAs (miR-21-5p, miR-200a-3p and miR-34a-5p) was measured by stem-loop RT-qPCR. Data are presented as mean ± SD of at least three independent biological replicates. Group differences were analyzed by ANOVA with appropriate post-hoc testing. TMAO treatment significantly increased HULC expression in Caco-2 cells. TMAO also elevated miR-21-5p and miR-200a-3p levels; these increases were attenuated when HULC was silenced. miR-34a-5p expression was not significantly affected by TMAO or by HULC knockdown. This study demonstrates that TMAO upregulates the oncogenic lncRNA HULC, and this upregulation is associated with increases the expression of miR-21-5p and miR-200a-3p. These findings reveal a TMAO-HULC signaling axis that positively influences the levels of oncogenic miRNAs. However, since a single cell line model was used in this study, it needs for further investigation across diverse CRC cell lines to confirm its generalizability.

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent malignancy associated with considerable morbidity and mortality. This article offers a comprehensive overview of its major risk factors, molecular characteristics, and emerging therapeutic approaches. Key risk factors include tobacco use, alcohol consumption, and environmental exposures such as air pollution. Viral infections, particularly with Epstein-Barr Virus (EBV) and high-risk genotypes of Human Papillomaviruses (HPV), are also implicated in OCSCC pathogenesis. At the molecular level, OCSCC is characterized by aberrant expression of growth factors, especially transforming growth factor α (TGF-α) and epidermal growth factor receptor (EGFR). EGFR overexpression, often due to gene amplification, is closely associated with tumor progression and poor clinical outcomes. These insights into molecular pathways are guiding the development of targeted therapies. Innovative treatments are being explored, including combination therapies such as metformin with 4SC-202, which show promise in reducing tumor cell migration and enhancing chemotherapy sensitivity. Additionally, nanoengineered formulations of cisplatin aim to improve drug delivery specificity and minimize systemic toxicity, offering a more patient-friendly approach. The article emphasizes the need for continued investigation into novel therapeutic strategies and a deeper understanding of the molecular basis of OCSCC to improve treatment outcomes. Future research priorities include the identification of new risk factors, refinement of induction chemotherapy protocols, and incorporation of personalized treatment strategies. Addressing these areas is crucial for advancing prevention, enabling early diagnosis, and improving survival and quality of life for patients with OCSCC. This work supports ongoing progress in oral cancer research and clinical care.

A key component of the Hippo signaling pathway (HSP) is a kinase cascade that connects the tumor suppressor Hippo to the oncoprotein Yki (YAP and TAZ). This oncoprotein functions as a transcriptional coactivator for target genes that play critical roles in cell proliferation and survival. The objective of this study is to evaluate the interaction between TGF-β proteins and key components of the Hippo signaling pathway in regulating hepatocellular carcinoma (HCC) cell behavior. One important achievement of this study was to reveal the significant inhibitory role of the HSP in the growth of HCC cells through TGF-β proteins. In the present study, we examined the expression of key proteins of the Hippo pathway in HCC cells treated with TGF-β proteins and their correlation with the Hippo signaling pathway (HSP) by immunofluorescent staining, immunoblotting method, and Real-time PCR. Both Yes‑associated protein (YAP) and large tumor suppressor 1 (LATS1) were correlated with HCC cells. In the HSP, LATS1 plays as an upstream inhibitory agent of YAP. Nucleus-cytoplasm translocation of YAP1 and overexpression of LATS1 occurred in HCC cells treated with TGF-β. The nucleocytoplasmic distribution of YAP1 and overexpression of LATS1 have anti-oncogenetic roles in the incidence and progression of HCC. TGF-β in 5 ng/mL treatment resulted in a 2.5-fold increase in LATS1 expression and significant YAP1 translocation from the nucleus to the cytoplasm. We concluded that the Hippo signaling pathway mediates TGF-β/TBR-induced effects on HCC progression.

Pediatric acute myeloid leukemia (AML) is biologically heterogeneous, necessitating integrated genetic and immunophenotypic profiling for precise diagnosis and risk stratification. We analyzed 74 pediatric AML patients diagnosed between 2012 and 2023 at Ali-Asghar Children's Hospital, Tehran, Iran, via blood counts, bone marrow morphology, cytogenetic karyotyping, flow cytometry, and nested PCR for common fusion genes. In this study, the median age was 5.9 years (range, 0.5-17 years). Clinical presentations vary by cytogenetic subtype: t(15;17) is associated with bleeding, bruising, and fever; t(8;21) is associated with moderate fever and fatigue; inv(16) is associated with fatigue and minimal bleeding; trisomy 19 and duplication 5q often lack systemic symptoms; and cytogenetically normal cases present diverse symptoms, including fever, fatigue, weakness, and weight loss. The most frequent rearrangements were t (8;21) (n=9, 12.16%), t(15;17) (n=8, 10.81%), and t(9;11) (n=8, 10.81%), whereas t(1;22) (n=2, 2.70%) and inv(16) (n=1, 1.35%) were rare. Immunophenotyping revealed universal CD33 and CD45 expression (>90%), frequent CD34 positivity, the absence of HLA-DR and CD11b at t (15;17), and characteristic CD34/CD33 patterns at t(8;21). Our findings underscore the genetic and immunophenotypic complexity of pediatric AML and highlight the value of integrated diagnostics for risk-adapted therapy. Personalized treatment strategies may improve outcomes. However, multicenter studies are needed to validate these findings and identify novel therapeutic targets.

Previous researches revealed that Jianpi-Qinghua Formula (JPQH) exhibited anti-cancer activity. However, the pharmacological effect of JPQH on HBV-positive hepatocellular carcinoma (HCC) remains unknown. Cisplatin chemotherapy serves as a major treatment for HCC. Therefore, the aim of this study was to investigate whether JPQH or in combination with cisplatin therapy could inhibit the proliferation of HepG2.2.15 cells and elucidate the underlying mechanisms associated with the effect of cisplatin on HepG2.2.15 cells. We found that JPQH alleviated carbon tetrachloride (CCl4)-induced liver fibrosis and hepatitis in vivo. In vitro expriements, cisplatin effectively enhanced the suppression of HepG2.2.15 HCC cell proliferation and decreased their migration capacity. Moreover, JPQH could reduce CCl4-induced AST and ALT levels, as well as serum markers for liver fibrosis (including PⅢNP, C-Ⅳ, LN, HA levels) and hepatitis markers (including TBIL, IL6, and IL-1β levels). JPQH also induced cellular apoptosis by downregulating the expression levels of proteins such as Bcl-2 and IL-6. Additionally, JPQH could downregulate HBV expression. These findings collectively demonstrate that JPQH may inhibit the proliferation of HepG2.2.15 cells through suppression of HBV replication.