International Journal of Molecular and Cellular Medicine最新文献

Pulmonary fibrosis (PF) is a lethal inflammatory disease and there has been no effective medication for this progressive disease up to now. Paraquat is commonly used in agricultural settings to control weed growth and is one of the important risk factors for PF. Additionally, emerging evidence has demonstrated Capparis spinosa (C. spinose) fruit extract has anti-fibrotic, anti-inflammatory, and antioxidant properties. We aimed to evaluate whether C. spinose fruit hydroalcoholic extract has a positive effect against Paraquat-induced PF in rats. 30 male Wistar rats were randomly divided into 5 groups, which included: a control group, a Paraquat control group, a C. spinose group with a dose of 20 mg/kg, a C. spinose group with a dose of 30 mg/kg, a C. spinose group with a dose of 50 mg/kg. After 21 days of the treatment, levels of hydroxyproline and malondialdehyde (MDA) in lung tissue were assessed and lung indices and semi-quantitative histopathological changes were determined. The results showed that treatment with C. spinose, led to increased weight gain, whereas reduced lung weight. C. spinose demonstrated a decreasing effect on levels of MDA, and hydroxyproline in lung tissue. Moreover, histopathological data and the number of lung indices indicated the preventive role of C. spinose Paraquat-induced PF in rats.

Gaucher's disease (GD) is the most frequent lysosomal storage disorder resulting from a deficiency of the enzyme glucocerebrosidase (GBA) which causes the accumulation of glucocerebroside. More than 500 mutations have been reported on the GBA gene so far. In this study, we aimed to investigate more on the genotype of less known mutations through haplotype analysis to explain their disease-causing inheritance. Eight patients and three carriers from nine different families were enrolled in the study. DNA sequencing of all GBA gene's exons was performed and pathogenicity of the mutations was investigated. Using GBA gene-linked STR markers, allele segregations were determined in some families. A total of six different mutations were determined. Five and three patients were identified to carry mutations in homozygous and compound heterozygote patterns respectively, three participants also were identified as carriers. The most prevalent mutations were c.1448 T>C and RecNcil, however, three less common mutations were identified (i.e., c.1223 C>T, c.1315 A>G, and c.1214 G>C). In conclusion, we evaluated six different mutations in Iranian patients and elucidated the inheritance of the three less-known mutations by linkage analysis.

Leukemia is a type of cancer that affects the blood and bone marrow. Acute lymphoid leukaemia, also known as ALL, is regarded as one of the deadliest forms of cancer. Due to the rapid increase in various cancer cases and the development of resistance in cancer cells, it is necessary to identify novel lead molecules with more potent anticancer properties. There is a growing interest in using herbal products/analogs as multi-component agents (as anticancer agents and immunomodulators) for cancer treatment. In the present investigation, an attempt has been made to explore the anticancer and immunomodulatory activity of P19, an analog of parthenin in ALL. P19 was reported to exhibit anticancer efficacy by triggering apoptotic signaling events in human leukaemia HL-60 cells by significant NO production. In contrast to this finding, ROS and NO were not required for P19-mediated apoptosis in Raji cells. The mechanism of action of P19 was observed to be cancer cell lineage dependent. P19 demonstrated very effective anticancer properties against ALL (IC₅₀ 3µM). Molecular investigations revealed that P19 induced mitochondrion mediated apoptosis by Bax localization to mitochondria and enhanced cytosolic calcium in the cytoplasm. Further activation of the caspase 3, caspase 8 and PARP cleavage suggested the involvement of the caspase-mediated apoptosis. Anti-proliferative activity revealed the telomerase inhibition and cell cycle arrest in G0/G1 phase after P19 treatment. Immunomodulatory effects of the P19 revealed the enhanced INFɣ and NO production in Jurkat and THP cells. Owing to its antiproliferative and immunomodulatory potential against leukemia cells P19 can further be explored as effective therapeutics against leukemia.

One of the important stimulating molecules for the function of T lymphocytes is tumor necrosis factor receptor OX40 (CD134), activated by its cognate ligand OX40L (CD134L, CD252). OX40L interactions have been proposed as a potential therapeutic target for treating infectious and non-infectious diseases. The main purpose of this study was to determine the potency of two novel resins MBI and MEP for the purification of OX40L-IgG fusion protein and the biological activities of this OX40L-IgG fusion protein. The biological activity of the OX40L-IgG purified by these resins compared with protein A sepharose resin. Mice treated with the same doses of the OX40L purified by the three resins showed a significant delay in tumor growth compared to the controls injected with PBS. Mice treated with the OX40L purified by MBI resin showed a significant delay in tumor cell (CT26) growth compared with mice injected with OX40L purified by other resins.

Abnormal miRNA expression has been associated with breast cancer. Knowing miRNA and its target genes gives a better understanding of the biological mechanism behind the development of breast cancer. Here, we evaluated the potential prognostic and predictive values of miRNAs in breast cancer development by analyzing Malay women with breast cancer expression profiles. Seven differentially expressed miRNAs (DEMs) were subjected to miRNA‒target interaction network analysis (MTIN). A comprehensive MTIN was developed by integrating the information on miRNA and target gene interactions from five independent databases, including DIANA-TarBase, miRTarBase, miRNet, miRDB, and DIANA-microT. To understand the role of miRNAs in the progress of breast cancer, functional enrichment analysis of the miRNA target genes was conducted, followed by survival analysis to assess the prognostic values of the miRNAs and their target genes. In total, 1416 interactions were discovered among seven DEMs and 1274 target genes with a confidence score (CS) > 0.8. The overall survival analysis of the three most DEMs revealed a significant association of miR-27b-3p with poor prognosis in the TCGA breast cancer patient cohort. Further functional analysis of 606 miR-27b-3p target genes revealed their involvement in cancer-related processes and pathways, including the progesterone receptor signaling pathway, PI3K-Akt pathway, and EGFR transactivation. Notably, six high-confidence target genes (BTG2, DNAJC13, GRB2, GSK3B, KRAS, and UBR5) were discovered to be associated with worse overall survival in breast cancer patients, underscoring their essential roles in breast cancer development. Thus, we suggest that miR-27b-3p has significant potential as a biomarker for detecting breast cancer and can provide valuable understanding regarding the molecular mechanisms of the disease.

Venetoclax, a specific inhibitor of the BCL2 protein, is administered for the treatment of acute lymphoblastic leukemia. However, despite being utilized in conjunction with chemotherapy, the drug exhibits instances of resistance. The exact mechanisms responsible for this resistance remain relatively obscure. Within the context of this investigation, the study aimed to explore the involvement of anti- and pro-apoptotic proteins as one of the potential mechanisms underlying this resistance phenomenon. Blast cells were extracted from patients diagnosed with B&T acute lymphoid leukemia. Subsequently, these cells were subjected to a cultivation process. Following the cultivation, treatment with the Venetoclax drug was administered to both groups of B&T cells. Additionally, one group from each cell type was designated as a control. The relative expression levels of genes BCL-2, MCL-1, and BIM were assessed in comparison to the control group. Annexin V-fluorescein isothiocyanate and propidium iodide staining was done to check cell apoptosis. The results showed a significant increase in the expression of BIM gene and a significant decrease in BCL-2 gene compared to the control group, but the change in the expression of MCL-1 gene was not significant. Also, an increase in apoptosis was observed in the treatment groups compared to the control. Although it was shown that changes in the expression of pro- and anti-apoptotic genes can lead to an increase in cell apoptosis and a decrease in the number of blast cells, more studies are needed to investigate the simultaneous effect of Venetoclax drug with other drugs and also in the form of a clinical trial.

Existing therapeutic interventions for controlling cancer are limited and associated with side effects. Furthermore, the recurrence of cancer poses a significant challenge to the cure of cancer. Therefore, avenues are wanted to find novel therapies for cancer treatment and cancer recurrence. In this review, we have highlighted that lactoferrin (LF) and activated protein C (APC) carry enormous potential in cancer treatment. Studies have shown that the decreased level of APC and impaired function of APC are associated with cancer progression and cancer-related mortality. Moreover, APC plays an important role in preventing prothrombotic state-mediated cancer progression and deaths. LF can also inhibit the progression of cancer by controlling the generation of reactive oxygen species, triggering the apoptosis of cancer cells, arresting the cell cycle and hindering the angiogenesis process. Additionally, APC and LF could have the potential to inhibit neutrophil extracellular traps (NETs) formations which are involved in cancer progression and the reawakening of dormant cancer cells. Hence, in this review, the anticancer potential and mechanism of APC and LF along with their potential to mitigate inflammation and NETs-mediated cancer progression and recurrence has been discussed. Additionally, possible future strategies to develop effective and safe anticancer treatment using LF and APC have also been discussed in this review.

Surface proteins containing leucine-rich repeat (LRR) are essential for the formation of synapses. Therefore, proteins containing aberrant LRR regions are speculated to cause synaptic dysfunction, an abnormality often associated with Autism spectrum disorder (ASD). LRR transmembrane 3 (LRRTM3) genetic variants showed association with ASD in the Caucasoid probands. We for the first time, analyzed two LRRTM3 genetic variants, rs1925575, and rs1925608, in Indian subjects (N=1048), including ASD probands (N=270), their parents (N=428), and healthy controls (N=350). ASD severity was assessed by the Childhood Autism Rating Scale2-standard test (CARS2-ST). Peripheral blood was collected after obtaining informed written consent for participation, and target sites were amplified by polymerase chain reaction using genomic DNA. Amplicons generated were subjected to differential digestion using a restriction enzyme, and the genotype data were analyzed for association with ASD by both population and family-based methods. Frequencies of rs1925608 and rs1925575 "CC" genotypes and C-C haplotype were higher in the probands (P=0.001). Analysis of parental data revealed a higher frequency of rs1925575 "T" in the fathers (P=0.01) and biased paternal transmission of rs1925575 "C" allele (P=0.03). The "Activity level" was higher in the ASD probands having rs1925608 "CC". Additionally, the score for "Relating to people" was higher in the presence of rs1925575 "TC" genotypes. The gender-based stratified analysis revealed the influence of the variants on a higher number of traits of the female probands. This pilot investigation indicated an influence of LRRTM3 genetic variants on the trait severity of Indian ASD probands.

To investigate the efficacy of Wharton's jelly mesenchymal stem cells (WJSCs) and their conditioned medium (CM) for corneal nerve regeneration in rats with diabetic keratopathy. Streptozotocin (STZ)-induced male diabetic (DM) rats (250-300 g) were divided into four groups (n=7/group): Control, DM, DM with WJSCs (DM+WJ), and DM with CM treatment (DM+CM). DM+WJ and DM+CM group received WJSCs or CM, respectively, topically with eye drops. Corneal sensibility, corneal epithelial layer integrity, histology, expression of GAP-43 and TUBB3 on mRNA level and their immunohistochemical expression were examined after two weeks of treatment. There were changes in corneal sensibility and corneal integrity between normal control and diabetic groups with/without WJSC or CM injection. Total central corneal thickness was significantly higher in DM+CM (249.81 ± 43.85 μm) than in control (174.72 ± 44.12 μm, P=0.004) and DM groups (190.15 ± 9.63 μm, P=0.03). GAP-43 mRNA expression levels of DM+WJ and DM+CM groups were higher compared with DM and control groups. TUBB3 mRNA level was increased after CM (P=0.047), but not after WJSCs treatment (P=1.00). GAP-43 and TUBB3 immunohistochemical expression of nerve fibers along the epithelial layer significantly increased in DM+WJ and DM+CM compared with DM group. Our findings showed that WJSCs and their CM improved corneal nerve regeneration in rats with diabetic keratopathy.

The mRNA vaccines replace our conventional vaccines (live-attenuated and inactivated vaccines) due to their high safety, efficacy, potency and low cost for their manufacturing. Since these many years, the use of these mRNA vaccines has been restricted as they are unstable and their low efficiency in in-vivo delivery. But now, these problems have been solved by recent technological advances. Many studies conducted in animal models and humans demonstrated the good results for the mRNA vaccines. This review provides you a detailed overview of mRNA viral vaccines and considers the current perspectives and future prospects.