Iranian Biomedical Journal最新文献

Background: : The role of Toxascaris leonina in visceral larva migrans is controversial. This study aimed to investigate the migratory behavior of T. leonina larvae across different organs in mice.

Methods: Six-week-old Swiss albino mice (n = 26) were randomly allocated into six experimental groups and one control group. Each mouse in the experimental groups was orally inoculated with 1,000 embryonated T. leonina eggs. The animals were euthanized at 2, 5, 10, 15, 20 and 30 dpi (days post-infection). Tissue samples were examined for larval presence and associated pathological changes using digestive and histopathological methods. The squash method was used for brain tissue analysis.

Results: T. leonina larvae were recovered from the small intestinal wall, lungs, liver, and striated muscles. No larvae were detected in the kidneys, heart, spleen, and brain using digestive or squash methods. Histological examination revealed granulomatous reactions, inflammatory cell accumulation, and larval presence in the isolated tissues. Larval concentration in the striated muscles increased over time, demonstrating the potential of Swiss albino mice to serve as paratenic hosts in toxocariasis.

Conclusion: Our study exhibits that Swiss albino mice are susceptible to T. leonina infection, with larvae localizing primarily in the small intestinal wall, liver, lungs, and striated muscles.

Background: Chemoresistance, the primary cause of disease relapse and treatment failure, poses a significant challenge in the treatment of colorectal cancer (CRC). Understanding the molecular mechanisms that underlie the pathogenesis and chemoresistance of colorectal tumor cells, as well as identifying novel therapeutic strategies, would be crucial. This study aimed to evaluate the role of hsa_Circ_0001821 in response to 5-fluorouracil (5-FU) in CRC, a topic that has not been examined to date.

Methods: The current study investigated the effect of hsa_Circ_0001821 suppression using interfering RNAs on the response of colorectal tumor cells to 5-FU. The expression levels of hsa_Circ_0001821, hsa-miR-203a-3p, BAX, BCL-2, and FGF-2 were determined via quantitative RT-PCR. Cell survival, migration rate, and apoptosis induction of colorectal tumor cells subjected to 5-FU treatment were assessed using the MTT test, scratch assay, and flow cytometry analysis, respectively.

Results: Knockdown of hsa_Circ_0001821 with siRNA increased the expression level of hsa-miR-203a-3p and decreased the expression level of FGF-2. Additionally, the knockdown of hsa_Circ_0001821 enhanced the sensitivity of colorectal tumor cells to 5-FU. This circRNA significantly affected the viability, apoptosis, and migration of tumor cells.

Conclusion: Our study reveals the potential role of hsa_Circ_0001821 in controlling the tumor cell viability and response to 5-FU by targeting the hsa-miR-203a-3p/FGF-2 axis. These findings enhance our understanding of the molecular mechanisms that influence chemotherapy response in CRC, paving the way for the identification of more effective treatments for this disease.

Background: Brucella is a type of bacteria that causes a disease known as brucellosis in both humans and animals. Many different vaccine formulations are available for this disease; however, vaccines based on epitopes have shown to be effective, especially in combating this pathogen. In the present study, we designed a multi-epitope vaccine against brucellosis using a chimeric protein that combines segments from various Brucella proteins known to contain both B- and T-cell epitopes.

Methods: In this study, a vaccine candidate was developed using multiple epitopes derived from various proteins, including OMP31, TF, BLS, SOD, BP26, and L9. These epitopes were selected based on their high density of both B-cell and T-cell epitopes. The construct of the vaccine candidate was inserted into a pEGFP-N1 vector and introduced into HEK-293T cells. Subsequently, the vaccine was tested on different groups of mice; some received the expressed protein in E. coli, while others received the DNA vaccine candidate. An ELISA assay was employed to evaluate the humoral immune response.

Results: Both the MEB protein (Pro/Pro) and pCI-MEB plasmid/MEB protein (DNA/Pro) groups showed a specific humoral response. The anti-DNA vaccine antibody titer did not rise as high as that of the protein groups; however, the observed protection indicated the efficiency of the DNA vaccine in activating the immune system.

Conclusion: While the chimeric DNA vaccine candidate induced a weaker humoral response, it remained effective in protecting against virulent strains of B. abortus and B. melitensis in the challenge route.

Background: Natural compounds can regulate the growth and progression of cancer cells with low toxicity to normal cell; therefore, these compounds are unique targets for cancer treatment. Recently, extracts from Salvia species have shown promising antiproliferative potential. This study aimed to isolate and characterize bioactive compounds from Salvia aegyptiaca and evaluate their antioxidant, cytotoxic, and protease-inhibitory activities.

Methods: In this study, various extracts of S. aegyptiaca were prepared, and several compounds, including ursolic acid, oleanolic acid, luteolin-7-O-glucoside, quercetin-3-O-rutoside, and rosmarinic acid, were isolated and characterized using different spectroscopic methods. Finally, the antioxidant activity, protease inhibitory activity, and cytotoxicity of the crude extract, multiple fractions, and isolated compounds were examined.

Results: According to the results obtained, rosmarinic acid demonstrated the highest antioxidant performance, as indicated by the following assays: DPPH (IC50: 28.39 ± 0.75 µg/mL), ABTS (39.52 ± 0.72 µg/mL), FRAP (31.87 ± 0.67 µg/mL), NO scavenging (71.44 ± 1.04 µg/mL), and ORAC values (0.6 TE/mg). Furthermore, both cynaroside and rosmarinic acid exhibited the most potent antiproliferative effects against the Hep G2 cell line, with IC50 value of 34.4 ± 2.34 and 47.84 ± 5.87 µg/mL, respectively. The EtOAc fraction and rosmarinic acid also showed higher protease inhibitory activity, with IC50 of 17.6 ± 0.10 and 17.0 ± 0.30 µg/mL, respectively, as compared to other compounds.

Conclusion: Our findings suggest that the identified compounds may be responsible for the antiproliferative effects of S. aegyptiaca. Overall, S. aegyptiaca could serve as a valuable natural antioxidant and anticancer agent in both pharmaceutical and food industries

Background: Ovarian cancer (OC) remains the leading cause of mortality among gynecological cancers, mainly because of resistance to platinum-based chemotherapy, particularly cisplatin. This study investigated the potential of quercetin (QU)-loaded solid lipid nanoparticles (SLNs) to address cisplatin resistance in OC cells.

Methods: The efficacy of QU-SLN was assessed in vitro on the cisplatin-resistant SK-OV-3 and cisplatin-sensitive A2780s human OC cell lines. Various assays, including cytotoxicity, cell viability, clonogenicity, flow cytometry, quantitative RT-PCR, and wound healing assays, evaluated the combined effects of QU and QU-SLN with cisplatin on cell viability, apoptosis, gene expression levels related to cisplatin resistance, and cell migration.

Results: Combining QU-SLN with cisplatin resulted in significantly reduced cell viability and colony formation, accompanied by increased apoptotic rates compared to each treatment alone. Moreover, there was a notable reduction in the expression level of genes associated with cisplatin resistance, particularly ABCG2, MT-2A, GST-pi, and XIAP, in the combined treatment. Wound healing assays indicated that the QU-SLN and cisplatin combination severely impaired OC cell motility compared to cisplatin monotherapy.

Conclusion: QU-SLN and cisplatin combination enhances the therapeutic response in cisplatin-resistant OC cells. By reducing cell proliferation, promoting apoptosis, and downregulating drug resistance genes, QU-SLN might present a promising strategy to improve treatment outcomes for OC patients resistant to cisplatin.

Background: In non-small cell lung cancer (NSCLC), miR-200a plays a significant role in apoptosis. One of the genes involved in this pathway is XIAP, which has been shown anti-apoptotic activity. Research has indicated a significant association between miR-200a and the XIAP gene in this pathway. The present study investigated the expression profiles of miR-200a and the XIAP gene in NSCLC patients compared to normal individuals, as well as cancer cells compared to normal and apoptosis-inducing conditions.

Methods: In this study, 40 blood specimens were collected from NSCLC patients and 40 from healthy individuals. After isolating plasma and peripheral blood mononuclear cells from these samples, we analyzed the miR-200a and XIAP gene expression levels using real-time PCR. Subsequently, normal and lung cancer cells were treated with paclitaxel as a model of apoptosis. The antiproliferative effects and induction of apoptosis were then evaluated using the MTT and flow cytometry assays, respectively. Finally, the expression patterns of miR-200a and the XIAP gene were investigated through a real-time PCR method.

Results: Results indicated that the miR-200a expression level was lower in NSCLC patients than in healthy ones, while the expression level of XIAP gene increased in the NSCLC Patients’ blood. The MTT and flow cytometry results demonstrated a decreased proliferation and increased apoptosis rates in two lung line cells (A549 and MRC5) treated with paclitaxel. XIAP expression level also decreased in A549 cells treated with paclitaxel compared to untreated A549 cells.

Conclusion: MiR-200a may be associated with the XIAP gene expression and the induction of the apoptosis pathway in NSCLC.

Background: Despite existing treatments, advanced solid tumors, such as prostate cancer (PCa), require the development of novel anticancer therapies. Oncolytic viruses (OVs) present a potential treatment option for solid tumors. Newcastle disease virus (NDV) is one of the most promising OVs that can replicate within and destroys human cancer cells. This study aimed to evaluate the cytotoxic and apoptotic effects of the NDV strain on human PCa cells in vitro. Additionally, We examined a novel treatment for PCa by combining Lenalidomide (Len) with NDV.

Methods: NDV strains La Sota, B1, and I2 were tested for cytotoxicity against several cell lines. A safety assessment was conducted in primary cells using peripheral blood mononuclear cells (PBMCs). Also, apoptosis induction was measured using annexin V/7AAD staining. Finally, the cytotoxic effects of NDV alone and in combination with Len, were assessed using MTT.

Results: The NDV showed cytotoxic effects on tumor cell lines and induced apoptosis in infected prostate cells compared to control cells. The NDV La Sota strain exhibited significant oncolytic capacity, reducing the viability of LNCaP and DU145 cells to less than 40% at specific concentrations, while showing no cytotoxic effects on primary PBMCs. Also, NDV induced apoptosis in the prostate cell line by 60%. Furthermore, Len enhanced the cytotoxicity of PCa cells when combined with NDV.

Conclusion: Our study confirms the efficacy of oncolytic NDV treatment for PCa, particularly utilizing the La Sota strain. When combined with Len, NDV indicates an enhanced effectiveness in destroying tumor cells. These findings suggest a prospective treatment approach that needs more preclinical and clinical studies to improve outcomes in PCa treatment.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant global health problem, mainly due to the increasing prevalence of obesity and metabolic syndrome. The gut microbiota plays an essential role in the development of NAFLD through the gut-liver axis. Dysbiosis of. the gut microbiota (GM) is associated with the pathogenesis of NAFLD. Dietary choices and other lifestyle factors influence the composition of the GM and contribute to the development of NAFLD. At the phylum level, individuals with NAFLD show an increased level in Actinobacteria and Firmicutes, while Verrucomicrobia, Thermus, Proteobacteria, Lentiphaerae, and Fusobacteria are found to be decreased. Several genera, including Faecalibacterium and Akkermansia, exhibit alterations in NAFLD and are linked to disease progression. Modulating the GM through prebiotics, probiotics, or fecal microbiota transplantation represents a promising therapeutic strategy for NAFLD. This review summarizes the current understanding of GM changes in NAFLD, focusing on findings from both human and animal studies.

Background: Metacyclogenesis is a critical developmental process in the life cycle of Leishmania parasites, particularly in their transition from non-infective procyclic to infective metacyclic promastigotes. This transformation is closely linked to the metabolic adaptation of the parasite, optimizing its survival and study, we integrated metabolomics and transcriptomics data to gain deeper molecular mechanisms of Leishmania major metacyclogenesis.

Methods: The metabolic profiles of procyclic and metacyclic promastigotes were first identified using ¹H-NMR spectroscopy. Multivariate statistical analysis conducted to distinguish different metabolites between the two forms. Metabolic pathway analysis was performed using the KEGG database to identify the metabolic pathways that significantly altered and overrepresented in the metabolomic profile. Finally, the differential gene expression and pathway enrichment analyses were conducted on transcriptomic data retrieved from public repositories.

Result: Multivariate statistical analysis revealed that 44 metabolites and ten pathways were significantly different between the two forms. Transcriptome genes during metacyclogenesis. These genes underwent GO and KEGG pathway analyses, revealing upregulated GO categories in the metacyclic phase, including protein phosphorylation, ion transport, signal transduction, and phosphorylation reactions, as well as several downregulated GO categories. Integrating metabolomic and transcriptomic data demonstrated seven significantly different KEGG pathways between procyclic and metacyclic forms, including fructose and mannose, galactose, ascorbate and aldarate, arginine and proline, histidine, inositol phosphate, and pyruvate metabolism.

Conclusion: Our findings suggest distinct metabolic profiles and changes in gene expression associated with the transition from procyclic to metacyclic promastigotes. By integrating diverse omics data, we could identify more reliable altered pathways and biomarkers.

Background: Urinary tract infection caused by uropathogenic E. coli (UPEC) is a common infectious disease. The growing frequency of antibiotic resistance highlights the need for alternative strategies, such as vaccines, to combat UTIs. This study aimed to evaluate the immunogenicity of a novel vaccine candidate targeting UPEC.

Methods: Different bioinformatics servers were used to design a vaccine candidate composed of PapG II and FimH antigens from UPEC, along with the N- (1-173) and C-terminal (401-495) domains of FliC from Salmonella typhimurium. The final construct was cloned into the pET28a vector, expressed, purified, and confirmed using SDS-PAGE and Western blotting. Mice were immunized with the recombinant protein, both with and without alum adjuvant, and antibody responses were measured using ELISA.

Results: The final vaccine construct included one domain of PapG II (81 aa) and FimH (83 aa). The conserved domains of FliC were incorporated into the construct. SDS-PAGE and Western blot confirmed the purification of the protein, with a size of 53 kDa. Immunization of mice with PapG.FimH.FliC protein induced significantly higher levels of serum IgG, IgG isotypes, IgA, as well as mucosal IgA and IgG responses compared to the controls (p < 0.05). The addition of alum to the protein significantly enhanced serum IgG1 and IgA and mucosal IgG, compared to the protein without alum (p < 0.05).

Conclusion: The vaccine construct induced significant humoral responses in the mouse model, suggesting its potential as a promising candidate against UPEC. However, additional experimental analyses are required to validate the efficacy of the vaccine construct.