Cell Journal最新文献

Given the critical role of human papillomavirus (HPV) in the cause of cervical cancer and other malignancies, there is a need for innovative approaches to preventing this infection. It has been shown that immunoinformatics is an important strategy in computational vaccinology. It is used to design new multi-epitope vaccines against different types of HPV and subsequent cervical cancer. This paper reviews the scope of the entire computational pipeline of HPV vaccine design, starting from data analysis at the genomic and proteomic levels and continuing to epitope predictions of the innate and adaptive immune systems. The search strategy was based on investigating original articles published in "Google Scholar" and "PubMed" from 2015 to 2023-2024. The terms "Immunoinformatics", "Bioinformatics", "Human papillomavirus (HPV)", "Vaccine design", "In silico vaccine design", "Multi-epitope vaccine design", "Vaccinology" and "HPV vaccine" were used to for this purpose. We discussed various essential tools involved in the computational design of the vaccine process, e.g., sequence analysis, epitope prediction, conservancy analysis, tertiary structure modeling, refinement, molecular docking, molecular dynamics (MD) simulation, and in silico cloning. This review article describes immunoinformatics methods that facilitate the design of a multi-epitope vaccine against HPV. However, this pipeline can also be used to design novel chimeric vaccines for other pathogens.

Objective: Head and neck squamous cell carcinoma (HNSCC) with a high mortality rate is among the most common types of cancer in the world. Human epidermal growth factor receptor 2 (HER2) is expressed higher than normal level in the most HNSCC tumors, making them resistant to chemotherapy and radiotherapy. Therefore, HER2 has been introduced as a suitable target for anticancer drugs. The aim of this study is to examine the efficacy of a treatment protocol involving targeted delivery of idarubicin encapsulated in trastuzumab-decorated liposomes to HNSCC cells.

Materials and methods: In the current experimental study, efficacies of idarubicin, prepared liposomal idarubicin, and constructed immunoliposomal idarubicin (trastuzumab-decorated) were investigated in killing HN5 cells, a HER2- overexpressing HNSCC-originating cell line. Liposomal content of idarubicin and trastuzumab were qualified by UVVisible spectroscopy and preparations were characterized for shape and size by atomic force microscopy (AFM) and dynamic light scattering (DLS). To clarify role of the missing parts of the available crystal structure (PDB ID: 1n8z) within trastuzumab-HER2 interactions, we used a 40 ns molecular dynamic simulation approach.

Results: Based on the obtained results, liposomal idarubicin showed higher toxicity of the encapsulated drug on HN5 cells compared to the traditional free drug formulations. The immunoliposomal form of idarubicin was more effective than the liposomal formulation, in killing of HN5 cells. In addition, simulation of interactions between trastuzumab and HER2 revealed that the missing parts (in the crystal structure) of HER2 have critical interaction with trastuzumab, through salt-bridges and hydrogen bonds.

Conclusion: It seems that the prepared immunoliposomes could attach more efficiently to HER2 overexpressing cells, which consequently leads to increasing cellular uptake of idarubicin through a receptor-mediated endocytosis mechanism. Moreover, simulation of the interaction between HER2 and trastuzumab suggested considerable possibilities for increasing trastuzumab affinity to HER2.

Damaged articular cartilage has limited self-healing potential and often leads to osteoarthritis (OA), pain, and dysfunction of the affected joint. Autologous and allogenic transplants cannot fully meet the needs of clinical treatment. Two dimensional (2D) and three-dimensional (3D) cell cultures can help to study growth modeling and physiological characteristics of the human body. Among the problems that 2D and single-layer cultures have the lack of proper and accurate tissue modeling and the lack of tissue complications similar is to the original tissue. With organoid models, cellular and tissue structural studies and functional and physiological studies of tissues have been revolutionized and more accurate. Organoids are useful for studying repair and drug efficacy. Physiological and pathological investigations by combining in vitro and in vivo methods have become more effective today. The purpose of this study is to investigate the factors involved in the formation of cartilage organoids so that we can introduce the best method of organoid production for the healing of cartilage damage by using cell types and organoid model.

Objective: Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with atherosclerosis serving as a primary factor in their development. Platelets, leukocytes, and their interactions play a crucial role in initiating and amplifying atherosclerosis. This study aims to evaluate the levels of platelet-monocyte aggregates (PMA) and specific integrins involved in leukocyte recruitment, including macrophage-1 antigen (Mac-1) and lymphocyte functionassociated antigen-1 (Lfa-1), in patients with acute coronary syndrome (ACS).

Materials and methods: In this case-control study, thirty-two subjects with ACS and 30 healthy individuals participated. It aimed to evaluate PMA expression and the median fluorescence intensity (MFI) of Mac-1 and Lfa-1 using flow cytometry. Dot plots and Pearson correlation coefficient were employed to examine the relationship between PMA, Mac-1, and Lfa-1. Multilevel model analysis was used to explore the effects and relationships of various parameters, including Mac-1 and Lfa-1, on PMA. Finally, receiver operating characteristic (ROC) curves were utilized to assess the diagnostic accuracy of PMA, Mac-1, and Lfa-1 markers.

Results: It was observed that patients had higher PMA levels compared to the control group (58.99 ± 16.27 vs. 29.99 ± 4.19 in controls, P<0.001), which correlated with PLT (ρ=0.512, P=0.035). Additionally, CD18 and CD11b expression on monocytes were significantly elevated in patients (P<0.001) and were positively associated with PMA (β=19.09, P<0.001; β=6.90, P=0.022), but no significant relationship between CD11a and PMA was observed (β=5.06, P=0.315). PMA and Mac-1 were identified as better markers for differentiating patients from healthy individuals. (respectively, AUC=0.94, Sensitivity= 0.84, specificity=0.98; AUC=0.84, Sensitivity= 0.93, specificity=0.70).

Conclusion: The study results indicated an increase in both Mac-1 and PMA levels in patients with ACS. Additionally, the significant association observed between Mac-1 and PMA in the patient group suggests a potential relationship between these markers and ACS.

Objective: The purpose of this study was to investigate the effects of 8 weeks of high-intensity interval training (HIIT) and vitamin D3 supplementation on Chemokine (C-C motif) Ligand 5 (CCL-5) and C-C motif chemokine receptor 5 (CCR5) in the white adipose tissue (WAT) of male rats with type 2 diabetes (T2DM).

Materials and methods: The experimental study involved 40 male Wistar rats divided into 5 groups (n=8). These groups were healthy control (HC), diabetic control (DC), diabetic+HIIT (DHIIT), diabetic+vitamin D3 (DD3), and diabetic+HIIT+vitamin D3 (DHIITD3). The rats completed 8 weeks of HIIT, consisting of 12 sessions lasting 1 minute each at an intensity of 90-95% of their maximum running speed. Additionally, the rats were administered a weekly dose of 10,000 IU/kg of vitamin D3 for 8 weeks.

Results: The levels of CCL-5 (P<0.001) and CCR5 (P=0.003) were found to be higher in the DC group as compared to the HC group. However, when HIIT training and vitamin D3 were administered together, there was a decrease in CCL-5 (P=0.001) and CCR5 (P<0.001) in the DHIITD3 group (P=0.001). Similarly, vitamin D3 alone reduced CCR5 levels in the DD3 group (P< 0.001). Also, the decrease of CCR5 in the DD3 group was higher than in the DHIIT group (P=0.022), and the DHIITD3 group was higher than in the DHIIT group (P<0.001), but there was no difference between the DD3 and DHIITD3 groups (P≥0.05).

Conclusion: The results indicate that combining HIIT training with vitamin D3 has a greater effect on reducing the expression of CCL-5 and CCR5 in the white adipose tissue of rats with type 2 diabetes induced by streptozotocin (STZ) and a high-fat diet (HFD), compared to the effects of each one alone. It is recommended that the study be conducted by measuring the variables involved in the mechanisms and the changes in CCL-5 and CCR5.

Objective: Kienböck disease is a rare condition characterized by severe pain and restricted wrist movement. Various palliative methods have been proposed as therapeutic strategies for alleviating symptoms. Mesenchymal stromal cell transplantation has been suggested as an innovative and promising approach due to its potential for inducing regeneration and immunomodulation in the necrotic tissue. This study aims to evaluate the safety of autologous bone marrow derived mesenchymal stromal cells (BM-MSCs) transplantation after core decompression in Kienböck disease.

Materials and methods: In this phase I of an open-label clinical trial, three patients (one female and two males) with stage 2 Kienböck disease underwent autologous BM-MSCs transplantation following lunate core decompression. The patients were followed up for six months to assess safety as well as secondary clinical outcomes, including pain level, range of motion (ROM), and functional disability.

Results: Safety of BM-MSCs injection following the core decompression was evaluated by recording post-treatment complications during the six-month follow-up. No adverse events (AEs) or severe AEs (SAEs) were reported, indicating that BM-MSCs injection after core decompression is a safe intervention. All patients showed a remarkable reduction in visual analog scale (VAS) scores and "Disabilities of the Arm, Shoulder, and Hand" (DASH) questionnaire scores, suggesting the therapeutic potential of this intervention. Moreover, an increase in the ROM indicated that BM-MSCs transplantation can improve wrist functionality. Additionally, radiographic assessments before and after cell infusion demonstrated a reduction in lunate sclerosis after six months of follow-up.

Conclusion: The transplantation of autologous BM-MSCs following lunate core decompression seems to be a safe clinical intervention and may lead to pain relief in patients with Kienböck disease. Furthermore, this procedure may help prevent disease progression during the follow-up period (registration number: NCT02646007).

Objective: Bisphenols are a type of phenolic chemical frequently used in producing various consumer products. Owing to their widespread exposure, these compounds can cause multiple toxic effects in humans. This study aimed to assess the protective effects of zinc oxide nanoparticles (ZnONPs) against bisphenol S (BPS)-induced cytotoxicity in the human testicular embryonic carcinoma cell line (NT2/D1).

Materials and methods: In this experimental study, cytotoxic concentrations of ZnONPs and BPS on NT2/D1 cells were optimized using the MTT assay. Thereafter, the effects of ZnONPs (50 and 500 μM), BPS (300 and 600 μM), and pre-treatment with ZnONPs (50 μM) followed by exposure to BPS (600 μM) on the expression of SOX2 and OCT4 genes and apoptosis-related proteins (i.e. Bax and Bcl-2) were evaluated, using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively.

Results: Both BPS and ZnONPs reduced the viability of NT2/D1 cells in a time- and dose-dependent manner. Pretreatment with 50 μM of ZnONPs increased mRNA levels of SOX2 and OCT4 and improved the reduction of cell viability caused by exposure to half-maximal inhibitory concentration (IC₅₀) of BPS (P<0.001). In addition, pre-treatment with ZnONPs was able to suppress BPS-induced apoptosis, as evidenced by increased Bcl-2 (P<0.05) and decreased Bax (P<0.001) protein levels.

Conclusion: Although our findings indicate that short-term treatment with a low concentration of ZnONPs could have beneficial effects in preventing the cytotoxic effects of BPS by modulating the expression of apoptosis-related proteins and pluripotent genes in the NT2/D1 cells, further studies are recommended to confirm these results.

Objective: Chronic inflammation is a common feature in diabetes, especially when blood sugar levels are poorly controlled. This chronic low-grade inflammation can affect various organs, including the kidneys. Podocyte damage play a key role in the development of diabetic nephropathy (DN). The aim of the study was to evaluate the nephroprotective effect of Boeravinone B (BB) against streptozotocin (STZ) induced DN in rats and explore the underlying mechanism.

Materials and methods: In this experimental study, the rats received intraperitoneal injections of STZ (60 mg/kg) to induce DN. Various doses of BB (2.5, 5, and 7.5 mg/kg) were administered orally. Glucose levels, body weights, and organ weights (hepatic and renal) were assessed. Renal, histomorphological, antioxidant, hepatic, and cytokine levels were determined, as were the mRNA expression levels of JAK2 and STAT3. At end of the experimental study, the rats were sacrificed and their renal tissues were removed for histopathological assessment.

Results: BB treatment decreased glucose levels and increased body weights. This treatment suppressed hepatic weights, increased renal tissue weights, and also decreased renal parameters like uric acid, urea, bilirubin, creatinine (Cr) and, albumin. There was a decrease (P<0.001) in histomorphological parameters such as kidney hypertrophy index (KHI), mean glomerular volume (MGV), foot process fusion ratio (FPFR), and glomerular basement membrane thickness (GBMT) after treatment with BB. In addition, this treatment improved the levels of renal podocin, renal CD2- associated protein (CD2AP) and suppressed hepatic parameter levels. BB treatment (P<0.001) altered antioxidant parameters and cytokine levels, and suppressed mRNA expressions of JAK2, STAT3, RAGE, KIM-1, NAGL, and S100A8.

Conclusion: Administration of BB showed renal protective effects against STZ-induced DN in rats via the reduction of oxidative stress and inflammatory reactions.

The 24^th and 19^th International Congresses on Reproduction and Stem Cell Biology in the Islamic Republic of Iran brought together experts and researchers worldwide to explore the latest advancements in these fields. Different topics were discussed, including such as reproductive health, infertility treatments, stem cell research, and regenerative medicine. This report provides a summary of the congress's key findings by emphasizing pioneer research and technologies that can influence the future of reproduction and stem cell biology programs. The presence of keynote speakers such as Professor Nicolas Rivron, Mohammad Ebrahim Parsanezhad, Ashraf Moini, Abbas Aflatoonian, Hadi Shafiee, Anna Brini, Omid Camron Farokhzad, and Jeffrey Schweitzer added value to the event, which had over 1100 participants from around the world. While foreign speakers were from various countries Iranian speakers mainly came from Tabriz, Isfahan, Shiraz, Babol, and Tehran that all discussed cutting-edge science and successful disease treatments. To ensure a more comprehensive representation, it is suggested that a wider geographic distribution of national and foreign speakers should be considered in future plan.

This study delves into Usher syndrome type 2 (USH2), an uncommon genetic disorder characterized by sensorineural hearing loss (HL) and retinitis pigmentosa (RP), often associated with the USH2A gene. Focusing on an Iranian family exhibiting USH2 symptoms, exome-sequencing was employed for a comprehensive genome analysis in a 30-yearold patient. The investigation unveiled a novel variation (NM_206933.4: c.9389G>A; p.Trp3130*) within exon 48 of the USH2A gene, a previously unreported variant emphasizing the genetic diversity in USH2. Sanger sequencing was then utilized to assess variation segregation within the family, offering insights into the inheritance pattern. This discovery not only advances our understanding of the genetic basis of USH2 but also holds significant implications for genetic counseling, early management, and informed decision-making regarding prenatal options. By adopting an integrated approach, this study aims to empower affected families, facilitating a nuanced understanding of the disorder's complexities and ultimately improving patient outcomes and family well-being through informed decisionmaking and proactive management strategies.