جستجوی مقالات مرتبط با کلیدواژه "t cells" در نشریات گروه "پزشکی"

The use of cryoablation for colorectal liver metastases (CLM) remains limited and controversial. This study aimed to investigate the antitumor immune response following cryoablation combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment in a CLM mouse model.

A CLM mouse model was established using BALB/c mice. The tumor-bearing mice were randomly divided into Control group, GM-CSF group, cryoablation group, and cryoablation + GM-CSF group. Tumor size, survival time, dendritic cells (DCs) count, serum cytokine levels (IL-4, IFN-γ), and the Th1/Th2 ratio (IFN-γ/IL-4) were compared among the four groups.

The combination of cryoablation and GM-CSF demonstrated synergistic effects, resulting in the smallest tumor lesion, longest mean survival time, and highest DC count on day 21 post-treatment compared to other groups. Both cryoablation alone and combined with GM-CSF significantly increased serum IFN-γ levels and suppressed IL-4 levels on day 21 compared to pre-treatment levels (P<0.05). Notably, the combination of cryoablation and GM-CSF significantly elevated the Th1/Th2 ratio (P<0.05).

Combining cryoablation with GM-CSF treatment holds promise for CLM management. It exhibits increased DC infiltration within the tumor microenvironment, enhanced immune responses, and prolonged survival in tumor-bearing mice.

Hepatocellular carcinoma (HCC) is one of the lethal malignancies with a poor prognosis due to metastatic complications. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have an important role in metastasis. MicroRNA-21 (miR-21) is significantly overexpressed in nearly all types of human cancers, including HCC. Targeting miR-21 pharmacologically could be a promising therapeutic approach for HCC. 3,4-dihydroxyphenylethanol (DHPE), a phenolic phytochemical compound found in olive, has potent antioxidant and anticancer properties. This study aimed to investigate the effect of DHPE on the expression of miR-21 with genes associated with metastasis (MMP-2, MMP-9, TIMP-1, and TIMP-2) and their correlation with miR-21 in HepG2 cells.

This experimental study had four groups, including a control, and three groups of treatment with different concentrations of DHPE (50, 100, and 150 µM) for 24 hours. The expression levels of genes were determined by RT-qPCR.

The results showed that the treatment of cells with DHPE significantly reduced the expression of miR-21, MMP-2, MMP-9, and TIMP-1 but increased TIMP-2 compared to the control group; additionally, there was a negative correlation between miR-21 and TIMP-2 but a positive correlation between miR-21 with MMP-2, MMP-9, and TIMP-1.

The results showed that DHPE, likely by reducing the expression of miR-21, can increase TIMP-2 and reduce MMP-2, MMP-9, and TIMP-1 gene expression and may play a role in inhibiting cell migration in HepG2 cells.

Extracellular vesicles (EVs) are cell-derived vesicles that play a critical role in host-pathogen interactions, facilitating intercellular communication and transporting both pathogen- and host-derived molecules during infection spread. To regulate their environment, for instance, by modulating innate and adaptive inflammatory immune responses, pathogens may alter the composition of EVs produced by infected cells. Gastric cancer is one of the leading causes of cancer-related deaths worldwide, and Helicobacter pylori infection is considered a significant risk factor for its development. This cancer is characterized by significant inflammation mediated by EVs generated from infected host cells. H. pylori contributes substantially to inflammation, promoting disease progression. Moreover, H. pylori produces and releases vesicles known as outer membrane vesicles (H. pylori-OMVs), which contribute to the shrinkage and cellular transformation of the gastric epithelium. Although the vacuolating cytotoxin A (VacA) plays a critical role in pathogenesis, its association with EVs in H. pylori has not been previously addressed. Understanding the roles of extracellular vesicles and VacA during H. pylori infection—whether they benefit the host or the pathogen—could pave the way for new treatment approaches. This review briefly discusses the role of VacA and extracellular vesicles in the growth and pathogenesis of H. pylori.

Background and purpose:

Intracellular delivery is crucial in biological and medical studies. Although many molecular tools have been created for cell-based gene therapies, it remains challenging to introduce external molecules into cells. As one of the most popular non-viral transfection methods, electroporation induces transient pores in the cell membrane by applying an external electric field. Unsatisfactory transfection efficiency and low cell viability are the major drawbacks of electroporation. To overcome these issues, the current study investigated the effect of urea on electroporation-mediated transfection efficiency.

Experimental approach:

Three voltages of electroporation, including 100, 120, and 140 V, and 3 concentrations of urea buffer, including 0.25%, 0.5%, and 1% W/V, were considered as variables in this study. The HEK-293 cell line was used for transfection, and green fluorescent protein (GFP) expression was evaluated using flow cytometry and fluorescence microscopy.

Findings/Results:

The results showed that the combination of electroporation and urea increased electroporation efficacy, but the effect depended on voltage and urea concentration. When different concentrations of urea were added to HEK-293 cells at a voltage of 100 V, the number of cells transfected by pEGFP-N1 increased (from 12.3 ± 0.2% in untreated cells to 17.35 ± 0.55%, 23.3 ± 0.3%, and 14 ± 0.1% at urea concentrations of 0.25%, 0.5%, and 1% W/V, respectively). The electroporation buffer containing 0.5% W/V urea showed the highest EGFP expression (23.3 ± 0.3%) and high cell viability (over 90%).

Conclusion and implications:

This research offers a new perspective for improving gene transfection efficiency once electroporation is utilized.

Cell-based therapy has shown promising outcomes in the treatment of cerebral palsy (CP). However, there is noconsensus on a standard therapeutic protocol regarding the source of cells, optimal cell dose, timing and frequencyof cell injections, route of administration, or the use of combination therapy. This lack of consensus necessitates acomprehensive investigation to clarify these crucial yet undefined factors in cell-based therapy for CP patients. In thiscommentary, we discuss and compare the trends in Gross Motor Function Measure-66 following intrathecal injectionof umbilical cord blood mononuclear cells (UCB-MNCs) and umbilical cord tissue mesenchymal stromal cells (UCTMSCs)in children with CP. Our study revealed that MNC injections led to earlier improvements in gross motor function,whereas MSC applications resulted in more sustainable changes. These findings provide key insights into the efficacyof different cell types, which will be beneficial for future studies and for refining cell-based therapy protocols for CPtreatment.

Chronic lymphocytic leukemia (CLL) is the most prevalent hematological cancer, with various medical interventions. In the recent decade, cold physical plasma has become an interesting agent for future cancer therapy. The goal of this study was to see whether cold physical plasma or cold physical plasma-treated liquid (PTL) affected integrin beta 3 (ITGB3) expression, which is hypothesized to mediate an interaction between cancer stem cells and the bone marrow microenvironment, in CLL patients' blood cells. The metabolic activity, cell death pattern, lipid oxidation and ITGB3 gene expression of these treatments was evaluated. Both direct cold physical plasma and PTL exposure enhanced lipid peroxidation in cells of CLL patients, but to a lesser extent in healthy participants. Furthermore, following 48h of cold physical plasma or PTL exposure, the metabolic activity of leukocytes was preferentially reduced in CLL patient leukocytes. In addition, cold physical plasma and PTL treatment elevated ITGB3 mRNA expression in CLL patients' leukocytes compared to untreated and healthy controls. Collectively, our study suggests selective effects of direct cold physical plasma and PTL exposure on blood leukocytes from leukemia patients, but further and more detailed studies are needed to provide additional rationales for such treatment options as future therapy.

Endothelial cells (ECs), as the main cell types in the micro- and macro-vascular structure, are crucial to many vital physiological processes occurring in human body among which are both physiologic and pathologic angiogenesis. Due to their great heterogeneity, it is recommended that the ECs of each tissue should be studied separately. Recently, targeting angiogenesis in cancer has become one of the main strategies for cancer management. Accordingly, this study aimed to introduce a simple, costeffective, and practical model for studying tumor angiogenesis, which can contribute to studies focused on antiangiogenic-based treatments for cancer.

In this original study, the explants of both normal and tumor tissues of mouse lung and 4T1 mouse cancer model were cultured separately in a collagen type 1 bed. Sprouting ECs formed a network of vessel-liked structures that were photographed as a model for investigating cancerous and normal angiogenesis. These ECs were then isolated from the collagen matrix using collagenase to confirm their endothelial nature.

The results showed that the cells invading the collagen matrix and forming a vessel-liked network were of endothelial nature. They were also found to have EC-specific characteristics and express EC-specific markers. These embedded cells may have been treated with the desired drug or further isolated from the collagen matrix and investigated in a genome or protein level.

In sum, this modeling had the potential to become a suitable model for studying the pathological angiogenesis such as tumors in human and animal tissues.

Peripheral nerve injury (PNI) is a critical clinical issue primarily caused by trauma. Tissue engineering approaches using nanofiber scaffolds have been extensively explored to improve material quality and create an environment resembling the natural extracellular matrix (ECM). 

In this study, we employed electrospinning technique to fabricate a composite scaffold comprising poly(ɛ-caprolactone) (PCL) and collagen (Col) loaded with all-trans retinoic acid (RA), a neural patterning and signaling chemical known to promote nerve regeneration. 

The synthesized nanofiber scaffold exhibited a diameter of 391±79 nm and a tensile strength of 250±13 MPa, providing sufficient support for native peripheral nerve regeneration. The inclusion of Col enhanced the scaffold’s hydrophilic behavior (contact angle: 43±6°), ensuring stability in an aqueous solution. Moreover, the results demonstrated the proliferation and adhesion of nerve cells on the scaffold, aligning with the directions of the warp and weft of the nanofiber mat. Importantly, the scaffolds demonstrated non-toxicity, making them a promising substitute for the native ECM for enhanced cell attachment and proliferation. Finally, immune-histochemistry analyses further confirmed that the scaffolds supported the release and growth of neurites, promoting cell differentiation toward nerve repair. 

The RA-loaded scaffolds demonstrated the enhanced biocompatibility, supported neurite growth, and showed potential as a capable candidate for nerve regeneration.

Scientists have focused on the development of new drug delivery systems including pH-sensitive nanomaterials adaptive to tumor microenvironments. We aimed to fabricate a microfluidic system to synthesize and characterize curcumin (Cur)-containing PCL and Chitosan (CSN) polymeric nanoparticles against MCF7 breast cancer cells.

The microfluidic chip was fabricated by photolithography and polydimethylsiloxane (PDMS) molding procedure. The chip was Y-shaped and equipped with two inlets and one outlet. PCL and Chitosan (CSN) were dissolved in acetic acid overnight and mixed with Cur for three hours. The prepared solution was injected from one inlet and a solution of tween 80 in distilled water was injected from the other inlet. The nanoparticles were characterized in size, electrical charge, structure, drug loading, and drug release efficiency. Finally, the cytotoxicity was assessed using the MTT assay at specific concentrations after 24 and 48 hr. 

The mean diameter/zeta potentials of spherical-shaped nanoparticles with and without Cur were 209 ±2 nm / +15 and 219 ± 4 nm /+3 , respectively. FTIR results confirmed the presence of all components in the nanoparticles. The Cur loading rate was 1.5%, and Cur represented a sustained release manner. Also, the release profile showed faster release in a low-pH medium. MTT assay results showed that Cur-containing nanoparticles exerted a significant effect on cell viability. 

It can be concluded that microfluidic systems can pave the way for nanoparticle synthesis easily rapidly and cost-effectively for cancer agent delivery. Based on our observations, PCL-CSN-loaded Cur nanoparticles represent appropriate characteristics and suitable anti-cancer effects.

This study explored the link between clinical features, immune markers, and asthma-chronic obstructive pulmonary disease overlap (ACO), aiming to enhance diagnostic precision and tailor treatment. The study included 60 patients per group: COPD patients, ACO patients, and healthy controls. Biological indicators such as fractional exhaled nitric oxide (FeNO), eosinophils, immunoglobulin E (IgE), T helper (Th) 17 cell counts, regulatory T-cell (Treg) counts, and cytokine levels of interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured using standard enzyme-linked immunosorbent assay and flow cytometry techniques. Elevated Th17 cells, IL-17, and Th17/Treg ratio, alongside reduced IL-10 and Treg levels, were observed in COPD and ACO patients. ACO patients showed worse lung function, with a negative correlation between FeNO, Th17 cells, Th17/Treg ratio, IL-17, and lung function indices, and a positive correlation with residual volume/total lung capacity (RV/TLC) ratio. The study suggests that Th17/Treg imbalance, FeNO, eosinophils, and IgE could be key in ACO pathogenesis, potentially aiding early diagnosis and targeted treatment. Future research may utilize these findings to develop preventative and therapeutic strategies for ACO.

Context: 

Adoptive T-cell therapy with chimeric antigen receptor (CAR) has shown tremendous progress in hematological cancers. However, some obstacles, such as high price tag, cytokine release syndrome, inability to penetrate solid tumors, and manufacturing complexity limit the wide application of this therapy. Natural killer (NK) cells can kill target cells via mechanisms similar to those of CD8+ cytotoxic T cells; therefore, CAR-NK cell therapy is a promising strategy for cancer treatment.

Evidence Acquisition:

 In this manuscript, all articles published in English regarding CAR-NKs and their application for the treatment of different types of cancers were collected from several databases, including PubMed, Scopus, and Google Scholar, using related keywords such as "Cancer, CAR construction, NK cells, and CAR-NK cells".

Compared with CAR-T cells, CAR-NK cells have several advantages, including less toxicity, a high potential opportunity for universal off-the-shelf manufacturing, increased infiltration into solid tumors, overcoming resistant tumor microenvironment, and absence of graft-versus-host disease (GVHD).

In this review, we discuss NK cell biology, the source of CAR-NK cells, CAR structure, advances, challenges, and ways to overcome these challenges in CAR-NK cell therapy. Furthermore, we have summarized and highlighted some preclinical and clinical studies in this field.

Dendritic cell-based cancer immunotherapy is considered an innovative and promising approach aimed at enhancing the host's immune response to combat tumors. Additionally, IPI-549 has been identified as a first-line therapeutic option for breast cancer treatment. The objective of this research was to develop and formulate a novel therapeutic supplement by combining dendritic cells with IPI-549 (Eganelisib) for breast cancer treatment. The concurrent administration of dendritic cells and IPI-549 (DC-IPI) was utilized to treat mice and elicit immunological responses triggered by vaccination. Tumor regression and overall survival rates were evaluated across five distinct experimental groups. The administration of tumor cell lysate alongside DC-IPI resulted in a significant reduction in tumor growth and a two- to three-fold increase in the survival duration of treated mice. DC-IPI, whether decorated with mannan or not, elicited stronger responses in terms of delayed-type hypersensitivity, lymphocyte proliferation, and CD107a expression. Moreover, our findings demonstrated a reduction in IL-4 production in the supernatants of splenocyte cultures. A significant reduction in BRCA1 mRNA levels was also observed following treatment with DC-IPI. In conclusion, our results suggest that the DC-IPI antigen delivery system exhibited substantial anti-tumor efficacy in a breast cancer mouse model, representing a potential advancement in immunotherapy for human breast cancer.

Levels of the human epidermal growth factor receptor 2 (HER2) gene are low in normal breast tissue, but half of the patients with breast cancer exhibit higher levels of this receptor. The differential expression of the HER2 gene in normal and malignant cells makes it an excellent biomarker for therapeutic purposes. In this study, we evaluated the degree of HER2 overexpression in patients and its relationship with age and the occurrence of metastases.

In this retrospective, registry-based, two-center cohort study, information on 1500 breast cancer patients recruited from Shahid Mostafa Khomeini Hospital in Ilam Province was collected from 2020 to 2023.

 The likelihood of metastasis in cancer patients with HER2 gene expression was three times higher (adjusted OR: 2.82; 95% CI: 1.79–3.29; P=0.001). Additionally, the involvement of lymph nodes (adjusted OR: 2.01; 95% CI: 0.87–3.79; P=0.03) was significantly associated with increased metastasis.

 This study demonstrates that HER2 gene expression and the number of involved lymph nodes are significant prognostic factors that increase the risk of metastasis. Therefore, implementing comprehensive breast cancer screenings can play an important role in the treatment and prevention of metastasis in breast cancer patients.

Dendritic cells (DCs) are remarkable professional antigen-presenting cells (APCs) that are pivotal in bridging the gap between innate and adaptive immunity (1). Given this unique ability, these cells are a promising target for immunotherapy of various diseases (2). Monocytes serve as a valuable resourcefor generating DCs in vitro. To generate monocyte-derived DCs and investigate morphological changes during the differentiation phenomenon, following the reception of written informed consent, peripheral blood samples were obtained from healthy donors using falcon tubes containing heparin. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll solution with a density of 1.077 g/ml and density gradient centrifugation. Monocytes were subsequently extracted from PBMCs through the magnetic-activated cell sorting method (MACS) following the instructions provided with the kit. The culture of monocytes was carried out in a concentration of 1.5 × 106/mLin a 6-well plate using complete culture media (RPMI-1640 supplemented with 15% FBS, 100 μg/mL streptomycin, 100 IU/mL penicillin, and 2 mM L-glutamine), in conjunction with 50 μM 2-mercaptoethanol solution and recombinant human GM-CSF and IL-4 cytokines at concentrations of 40 and 25 ng/mL, respectively. The plate was incubated at 37°C with 5% CO2 and humidification. After three days, half of the culture media was substituted with a new mixture containing GM-CSF and IL-4 cytokines. Immature DC (iDCs) cells were collected on the fifth day. Following this, iDCs were treated with 100 ng/mL of lipopolysaccharide (LPS) and incubated for 24 hours to induce the maturation of iDCs. On the sixth day, mature DCs were harvested. Monocytes and DCs were examined for their morphology, with images captured utilizing an inverted light microscope. In this regard, microscopic analysis revealed morphological alterations between monocytes derived from PBMCs at the initiation of culture and differentiated mature DCs acquired on day 6. Monocytes appeared as round cells with no visible dendrites, in contrast to DCs whichwere distinguishable by their visible dendrites (Figure1).