فهرست مطالب farhad jadidi niaragh

An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into  Tregs from patients with COVID-19. Exosomes were isolated from adipose tissue–derived MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127-  Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-β1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo–treated PBMCs. The concentration of IL‐10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-β was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of  Tregs, potentiating its therapeutic effects in COVID-19.

Natural killer (NK) cells play a role in the pathogenesis of rheumatoid arthritis (RA). Upregulated levels of programmed cell death protein 1 (PD-1) is a sign of exhausted NK cells that could be regulated by microRNAs (miRNAs). In this investigation, we determined PD‑1 expression on NK cells (as a representation of NK cell exhaustion) in RA patients and evaluated if miRNAs are involved in the modulation of PD-1 expression in NK cells. Peripheral blood specimens were obtained from 40 RA patients and 20 healthy subjects. NK cells were isolated by negative selection from a pool of peripheral blood mononuclear cells. The frequency of PD-1–expressing NK cells and the expression of PD-1 on NK cells were analyzed by flow cytometry. Real-time PCR was used to measure the expression levels of PD-1 mRNA and miRNAs in the NK cells. The percentage of the PD-1–expressing NK cells and Mean fluorescence intensity (MFI) of PD-1 expression on the NK cells were significantly higher in the RA cases compared to the controls. The mRNA expression of PD-1 was significantly upregulated in NK cells from RA patients compared to healthy subjects. The expression levels of miR-28, miR-138, and miR-4717 were significantly downregulated in the NK cells from RA patients compared to the healthy group. In RA, miRNAs probably regulate the NK cell exhaustion process through driving PD-1 expression.

Colorectal cancer (CRC) continues to be a leading cause of cancer related death in the world and approximately 70 to 75 % of patients with metastatic colorectal cancer survive for up to 1 year after diagnosis. Curcumin (CUR) is a potential chemotherapeutic agent used to treat cancer. There is ample evidence of the inhibitory effects of Hypericum perforatum L. extract (HPE) on cell proliferation and its effects on the induction of apoptosis in various human cancer cell lines.

The purpose of this study was to investigate the proapoptotic effect of HPE and its nanoliposomes (HPE-Lip) and to scrutinize the synergistic and therapeutic potential of HPE/CUR-loaded nanoliposome (HPE/CUR-Lip).

In the present in vitro study, SW1116 and SW48 cell lines were cultured and then treated with different doses of HPE, CUR, bare liposome solely (Lip-Sol), and nanoliposomes loaded with HPE (HPE-Lip), CUR (CUR-Lip) and CUR/HPE (HPE/CUR-Lip) for 24, 48 and 72 hours. Cytotoxicity was measured by MTT assay and apoptosis rate by an annexin-V FITC/propidium iodide double-staining method using flow cytometry.

The results showed that cell viability was inhibited in a dose-dependent and time-dependent manner in all groups compared to the control group. The use of nanoliposomes improved the outcomes. HPE/CUR-Lip exhibited higher in vitro cytotoxic and proapoptotic activity against SW1116 and SW48 cell lines (P < 0.05).

The findings of this study suggest that the HPE/CUR-Lip complex could provide a potential strategy to achieve a synergistic effect of HPE and CUR in the treatment of colorectal cancer.

Herbal products are beneficial compounds with many applications in human life. In this study the chemical composition and cytotoxic activity of the essential oil of the aerial parts of Dorema aucheri were assessed.

The essential oil was extracted by hydrodistillation after drying the aerial parts of D. aucheri, collected from the mountains around Yasuj city in the South-West of Iran. The oil composition was determined by GC/MS. To evaluate in vitro cytotoxic activity, the apoptotic effects of the essential oil were investigated against SW48 and SW1116 colorectal cancer cell lines by (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium) bromide (MTT) assay and flow cytometry.

The essential oil yield was obtained 0.02% (W/W). Twenty-five compounds were identified in the oil, and the main constituents were caryophyllene (E) (31.29%), Phytol (14.92%), gurjunene (β-) (9.84%), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (8.7%), and n-hexadecanoic acid (8.09%). The MTT assay showed that the IC50 values of the essential oil for SW48 and SW1116 cell lines were 1.4 and 1.2 mg/mL, respectively. The results of flow cytometry showed that the essential oil significantly increased the apoptosis in SW48 cell line compared with the vincristine (P < 0.05). It also increased the apoptosis in SW1116 cells compared with the vincristine, but this difference is not significant.

The essential oil of D. aucheri consisted of high amounts of caryophyllene and showed significant cytotoxic effects against SW48 and SW1116 cancerous cell lines.

In 2019, the world has witnessed the emergence of a virus that caused acute respiratory distress syndrome in human with high mortality rates (approximately 3.7%). So far, no effective treatment has been proven against COVID-19. This study aimed at designing a multi-epitope vaccine combining several T-cell and B-cell epitopes of the SARS-CoV-2.

Based on immunoinformatics strategies, B-cell and T-cell epitopes were predicted using immune Epitope Database and Analysis Resource (IEDB). Then, the appropriate predicted epitopes were joined to each other by suitable linkers, and the multi-epitope vaccine constructed was suggested as a vaccine candidate against SARS-CoV-2.

In this study, 28 B-cell epitopes and 33 T-cell epitopes were predicted. Then, to design the multi epitope vaccine, 5 epitopes were used from the virion surface of spike protein and one epitope was used from intravirion region of the Envelope, Membrane, and Nucleocapsid proteins that later on were joined with flexible glycine linker.

Based on the immunoinformatics results obtained, it seems that different epitopes from SARS-CoV-2 structural proteins have high ability to stimulate humoral and cellular immune responses, so the multi-epitope vaccine designed with these epitopes, can help to accelerate the production of effective vaccines against COVID-19.

Previous studies have demonstrated that maturation of dendritic cells (DCs) by pathogenic components through pathogen-associated molecular patterns (PAMPs) such as Listeria monocytogenes lysate (LML) or CpG DNA can improve cancer vaccination in experimental models. In this study, a mathematical model based on an artificial neural network (ANN) was used to predict several patterns and dosage of matured DC administration for improved vaccination. The ANN model predicted that repeated co-injection of tumor antigen (TA)-loaded DCs matured with CpG (CpG-DC) and LML (List-DC) results in improved antitumor immune response as well as a reduction of immunosuppression in the tumor microenvironment. In the present study, we evaluated the ANN prediction accuracy about DC-based cancer vaccines pattern in the treatment of Wehi164 fibrosarcoma cancer-bearing mice. Our results showed that the administration of the DC vaccine according to ANN predicted pattern, leads to a decrease in the rate of tumor growth and size and augments CTL effector function. Furthermore, gene expression analysis confirmed an augmented immune response in the tumor microenvironment. Experimentations justified the validity of the ANN model forecast in the tumor growth and novel optimal dosage that led to more effective treatment.

Apoptosis is a crucial process in the failure of cancer progression. However, the occurrence of resistance to chemotherapy in cancer cells may prevent apoptosis via induction of the expression of the anti-apoptotic genes (Bcl-2) and/or reduction of the expression of the apoptotic caspases.

The current study aimed at investigating the apoptotic effects of targeted co-delivery of docetaxel and cMet siRNA (siMet) through mucin1 aptamer-conjugated chitosan nanoparticles on mucin1 + metastatic breast cancer cells (SKBR3).

Characterization of nano-drugs,Western blotting assay, annexin V/ propidium iodide staining assay, and gene expression studies were evaluated based on metastatic breast cancer cells.

Characterization showed the appropriate size (110.5  3.9 nm), zeta potential (11.6  0.8 mV), and spherical shape of nanoparticles. Loading efficiency of 90.7% and 88.3% were gained for siRNA and docetaxel, respectively. The siRNA entrapment onto nanoparticles and conjugation of aptamers to nanoparticles were confirmed by gel electrophoresis. Gene knockdown assay represented the effectiveness of siMet on cMet gene silencing. According to the flow cytometry results, targeted co-delivery was successful in leading tumor cells to apoptosis (94.9%). Also, targeted co-delivery could reduce the expression of Bcl-2 gene (P < 0.0001) and increase the expression of caspase-8 and caspase-9 genes (P < 0.0001).

Combination treatment of metastatic breast cancer cells with aptamer-conjugated nanoparticles containing docetaxel and cMet siRNA significantly increased apoptosis.