Pro-inflammatory responses after peptide-based cancer immunotherapy.

Therapeutic vaccinations are designed to prevent cancer by inducing immune responses against tumor antigens. in cancer cells, tumor-associated antigens (TAA) or tumor-specific (mutated) derived peptides are presented within the clefts of main histocompatibility complex (MHC) class I or class II molecules, they either activate cytotoxic T-lymphocytes (CTLs), CD4+ T or CD8+ T lymphocytes, which release cytokines that can suppress tumor cells growth. In cancer immunotherapies, CD8+ T lymphocytes are a major mediator of tumor repression. The effect of peptide-based vaccinations on cytokines in the activating CD8+ T cell against targeted tumor antigens is the subject of this review. It is believed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12, secreting CTL line by interacting with dendritic cell (DC), supposed to stimulate immune system. Additionally, mechanisms of CTL activation and dysfunction were also studied. According to most of the data resulted from in vivo and in vitro research works, it is assumed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12.

CAR T therapies in multiple myeloma: unleashing the future.

In recent years, the field of cancer treatment has witnessed remarkable breakthroughs that have revolutionized the landscape of care for cancer patients. While traditional pillars such as surgery, chemotherapy, and radiation therapy have long been available, a cutting-edge therapeutic approach called CAR T-cell therapy has emerged as a game-changer in treating multiple myeloma (MM). This novel treatment method complements options like autologous stem cell transplants and immunomodulatory medications, such as proteasome inhibitors, by utilizing protein complexes or anti-CD38 antibodies with potent complement-dependent cytotoxic effects. Despite the challenges and obstacles associated with these treatments, the recent approval of the second FDA multiple myeloma CAR T-cell therapy has sparked immense promise in the field. Thus far, the results indicate its potential as a highly effective therapeutic solution. Moreover, ongoing preclinical and clinical trials are exploring the capabilities of CAR T-cells in targeting specific antigens on myeloma cells, offering hope for patients with relapsed/refractory MM (RRMM). These advancements have shown the potential for CAR T cell-based medicines or combination therapies to elicit greater treatment responses and minimize side effects. In this context, it is crucial to delve into the history and functions of CAR T-cells while acknowledging their limitations. We can strategize and develop innovative approaches to overcome these barriers by understanding their challenges. This article aims to provide insights into the application of CAR T-cells in treating MM, shedding light on their potential, limitations, and strategies employed to enhance their efficacy.

The role of key biomarkers in lymphatic malformation: An updated review.

The lymphatic system, crucial for tissue fluid balance and immune surveillance, can be severely impacted by disorders that hinder its activities. Lymphatic malformations (LMs) are caused by fluid accumulation in tissues owing to defects in lymphatic channel formation, the obstruction of lymphatic vessels or injury to lymphatic tissues. Somatic mutations, varying in symptoms based on lesions' location and size, provide insights into their molecular pathogenesis by identifying LMs' genetic causes. In this review, we collected the most recent findings about the role of genetic and inflammatory biomarkers in LMs that control the formation of these malformations. A thorough evaluation of the literature from 2000 to the present was conducted using the PubMed and Google Scholar databases. Although it is obvious that the vascular endothelial growth factor receptor 3 mutation accounts for a significant proportion of LM patients, several mutations in other genes thought to be linked to LM have also been discovered. Also, inflammatory mediators like interleukin-6, interleukin-8, tumor necrosis factor-alpha and mammalian target of rapamycin are the most commonly associated biomarkers with LM. Understanding the mutations and genes expression responsible for the abnormalities in lymphatic endothelial cells could lead to novel therapeutic strategies based on molecular pathways.

Evaluating the effect of conditioned medium from mesenchymal stem cells on differentiation of rat spermatogonial stem cells.

In cancer patients, chemo/radio therapy may cause infertility by damaging the spermatogenesis affecting the self-renewal and differentiation of spermatogonial stem cells (SSCs). In vitro differentiation of stem cells especially mesenchymal stem cells (MSCs) into germ cells has recently been proposed as a new strategy for infertility treatment. The aim of this study was to evaluate the proliferation and differentiation of SSCs using their co-culture with Sertoli cells and conditioned medium (CM) from adipose tissue-derived MSCs (AD-MSCs). Testicular tissues were separated from 2-7 days old neonate Wistar Rats and after mechanical and enzymatic digestion, the SSCs and Sertoli cells were isolated and cultured in Dulbecco's modified eagle medium with 10% fetal bovine serum, 1X antibiotic, basic fibroblast growth factor, and glial cell line-derived neurotrophic factor. The cells were treated with the CM from AD-MSCs for 12 days and then the expression level of differentiation-related genes were measured. Also, the expression level of two major spermatogenic markers of DAZL and DDX4 was calculated. Scp3, Dazl, and Prm1 were significantly increased after treatment compared to the control group, whereas no significant difference was observed in Stra8 expression. The immunocytochemistry images showed that DAZL and DDX4 were positive in experimental group comparing with control. Also, western blotting revealed that both DAZL and DDX4 had higher expression in the treated group than the control group, however, no significant difference was observed. In this study, we concluded that the CM obtained from AD-MSCs can be considered as a suitable biological material to induce the differentiation in SSCs.

Nanoparticles Containing Oxaliplatin and the Treatment of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is a highly widespread malignancy and ranks as the second most common cause of cancer-related mortality. OBJECTIVE: Cancer patients, including those with CRC, who undergo chemotherapy, are often treated with platinum- based anticancer drugs such as oxaliplatin (OXA). Nevertheless, the administration of OXA is associated with a range of gastrointestinal problems, neuropathy, and respiratory tract infections. Hence, it is necessary to devise a potential strategy that can effectively tackle these aforementioned challenges. The use of nanocarriers has shown great potential in cancer treatment due to their ability to minimize side effects, target drugs directly to cancer cells, and improve drug efficacy. Furthermore, numerous studies have been published regarding the therapeutic efficacy of nanoparticles in the management of colorectal cancer. METHODS: In this review, we present the most relevant nanostructures used for OXA encapsulation in recent years, such as solid lipid nanoparticles, liposomes, polysaccharides, proteins, silica nanoparticles, metal nanoparticles, and synthetic polymer-carriers. Additionally, the paper provides a summary of the disadvantages and limits associated with nanoparticles. RESULTS: The use of different carriers for the delivery of oxaliplatin increased the efficiency and reduced the side effects of the drug. It has been observed that the majority of research investigations have focused on liposomes and polysaccharides. CONCLUSION: This potentially auspicious method has the potential to enhance results and enhance the quality of life for cancer patients undergoing chemotherapy. However, additional investigation is required to ascertain the most suitable medium for the transportation of oxaliplatin and to assess its efficacy through clinical trials.

MicroRNAs Regulate Inhibitor of Apoptosis Proteins (IAPs) in Colorectal Cancer.

Colorectal cancer (CRC) is the second most common cause of cancer mortality, with approximately 1.9 million new cases and 0.9 million deaths globally in 2020. One of the potential ways to treat colorectal cancer may be through the use of molecular methods to induce cell apoptosis. Apoptosis is a natural cellular event that regulates the growth and proliferation of body cells and prevents cancer. In this pathway, several molecules are involved; one group promotes this process, and some molecules that are representative of inhibitors of apoptosis proteins (IAPs) inhibit apoptosis. The most important human IAPs include c-IAP1, c-IAP2, NAIP, Survivin, XIAP, Bruce, ILP-2, and Livin. Several studies have shown that the inhibition of IAPs may be useful in cancer treatment. MicroRNAs (miRNAs) may be effective in regulating the expression of various proteins, including those of the IAPs family; they are a large subgroup of non-coding RNAs that are evolutionarily conserved. Therefore, in this review, the miRNAs that may be used to target IAPs in colorectal cancer were discussed.

Promising effects of exosomes from menstrual blood-derived mesenchymal stem cells on endometriosis.

Endometriosis as a non-malignant gynecological disease leads to dysregulation of numerous cellular functions including apoptosis, angiogenesis, migration, proliferation, and inflammation. Accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. According to the fact that the therapeutic benefits of mesenchymal stem cells are provided through paracrine functions, we used exosomes from menstrual blood-derived stem cells (MenSCs) for treating endometriotic stem cells to inhibit their lesion formation tendency. Menstrual blood samples from healthy and endometriosis women were collected. Isolated MenSCs by the density-gradient centrifugation method were characterized by flow cytometry. Secreted exosomes were isolated from healthy MenSCs (NE-MenSCs) and used to treat endometriotic cells (E-MenSCs). 72 h after treatment, different mechanisms and pathways including inflammation, proliferation, apoptosis, migration, and angiogenesis were analyzed using Real-Time PCR, ELISA, immunocytochemistry, annexin V/PI, and scratching assay. Exosome treatment significantly reduce the expression level of markers related to inflammation, proliferation, migration, and angiogenesis in E-MenSCs which are aberrantly expressed in endometriosis. Moreover, apoptosis was induced in E-MenSCs after treatment which was evaluated in both gene and protein levels. In this study, we give preliminary evidence for the potential of MenSCs-Exo in ameliorating endometriosis. Regarding our results, we suggest that after relevant clinical trial, MenSCs-derived exosomes can be considered as a better treatment option to improve endometriosis compared to common and conventional treatments and show their potential as a cell-free product in endometriosis repair.

Crosstalk between long non-coding RNAs and p53 signaling pathway in colorectal cancer: A review study.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and the third leading cause of cancer-related fatalities. Long non-coding RNAs (lncRNAs) are key regulators of diverse physiological processes and are dysregulated in a wide range of pathophysiological circumstances such as CRC. Studies revealed that aberrant expressions of lncRNAs clearly modulate the expression level of p53 gene in CRC, thereby transactivating multiple downstream pathways. P53 is regarded as a crucial tumor suppressor gene which promotes cell-cycle arrest, DNA repair, senescence or apoptosis in response to cellular stresses. P53 is also mutated in CRC as well as various types of human malignancies. Therefore, lncRNAs interact with the p53 signaling pathway in numerus ways and significantly influence CRC-related processes. The current findings in the investigation of the crosstalk between lncRNAs and the P53 pathway in controlling CRC carcinogenesis, tumor progression, and therapeutic resistance are summarized in the this review. A deeper knowledge of CRC carcinogenesis may also have implications in CRC prevention and treatment through more research.

The emerging role of LncRNA AWPPH in multiple cancers: a review study.

Long non-coding RNAs (lncRNAs) are transcribed RNA molecules longer than 200 nucleotides in length that have no protein-coding potential. They are able to react with DNA, RNA, and protein. Hence they involve in regulating gene expression at the epigenetic, transcriptional, post-transcriptional, and translational levels. LncRNAs have been proven to play an important role in human malignancies and prognostic outcomes. In this review, we will comprehensively and functionally discuss the role of a novel identified lncRNA, namely lncRNA WAPPH located on human chromosome 2q13, in various cancers. Increasing research studies have shown that lncRNA AWPPH is deregulated in different malignancies, including breast cancer, gastric cancer, colorectal cancer, ovarian cancer, bladder cancer, leukemia, and others. LncRNA WAPPH serves as an oncogene in tumorigenesis and the development of cancer. Moreover, lncRNA AWPPH is involved in numerous biological processes of solid and blood cancers. Taken together, based on our scrutiny analysis, lncRNA AWPPH can be regarded as a putative biomarker for diagnosis or therapeutic target in human malignancies.

Use of Mesenchymal Stem Cells in Crohn's Disease and Perianal Fistulas: A Narrative Review.

Crohn's Disease (CD), which usually leads to anal fistulas among patients, is the most important inflammatory bowel disease that causes morbidity in many people around the world. This review article proposes using MSCs as a hopeful therapeutic strategy for CD and anal fistula treatment in both preclinical and clinical conditions. Finally, darvadstrocel, a cell-based medication to treat complex anal fistulas in adults, as the only European Medicines Agency (EMA)-approved product for the treatment of anal fistulas in CD is addressed. Although several common therapies, such as surgery and anti-tumor necrosis factor-alpha (TNF-α) drugs as well as a combination of these methods is used to improve this disease, however, due to the low effectiveness of these treatments, the use of new strategies with higher efficiency is still recommended. Cell therapy is among the new emerging therapeutic strategies that have attracted great attention from clinicians due to its unique capabilities. One of the most widely used cell sources administrated in cell therapy is mesenchymal stem cell (MSC). This review article will discuss preclinical and clinical studies about MSCs as a potent and promising therapeutic option in the treatment of CD and anal fistula.

The Emerging Role of LncRNA FENDRR in Multiple Cancers: A Review.

Long noncoding RNAs (lncRNAs) are prominent as crucial regulators of tumor establishment and are repeatedly dysregulated in multiple cancers. Therefore, lncRNAs have been identified to play an essential function in carcinogenesis and progression of cancer at genetic and epigenetic levels. FENDRR (fetal-lethal noncoding developmental regulatory RNA) as a LncRNA is a hallmark of various malignancies. FENDRR is crucial for multiple organs' development, such as the lung and heart. The effects of FENDRR under signaling pathways in different cancers have been identified. In addition, it has been verified that FENDRR can affect the development and progression of various cancers. In addition, FENDRR expression has been associated with epigenetic regulation of target genes participating in tumor immunity. Furthermore, FENDRR downregulation was observed in various types of cancers, including colorectal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, liver cancer, gallbladder cancer, lung cancer, breast cancer, endometrial cancer, prostate cancer, chronic myeloid leukemia, osteosarcoma, and cutaneous malignant melanoma cells. Here, we review the biological functions and molecular mechanisms of FENDRR in several cancers, and we will discuss its potential as a cancer biomarker and as a probable option for cancer treatment.

Bone marrow mesenchymal stem cell treatment improves post-stroke cerebral function recovery by regulating gut microbiota in rats.

Early intervention with bone marrow mesenchymal stem cells to change the form and function of the gut microbiota may help rats regain neurological function after a stroke.

Competing Endogenous RNAs (ceRNAs) in Colorectal Cancer: A Review.

Colorectal cancer (CRC) is a common type of cancer and the second leading cause of cancer-related deaths worldwide. Competing endogenous RNAs (ceRNAs) that contain microRNA response elements (MREs) are involved in CRC progression. They can compete with microRNAs (miRNAs) via their MREs, which can combine non-coding and coding RNAs via complex ceRNA networks. This molecular interaction has the potential to affect a wide variety of biological processes, and many cancers can occur as a result of an imbalanced ceRNA network. Recent research indicates that numerous dysregulated RNAs in CRC may function as ceRNAs, regulating multiple biological functions of the tumour, including proliferation, apoptosis, metastasis, invasion and migration. In this review, we discuss the role of protein-coding and non-coding RNAs, such as long non-coding RNAs, circular RNAs and pseudogenes, in the occurrence of ceRNA networks in CRC, and their function in cancer-related pathways, such as Wnt/ß-catenin, mitogen-activated protein kinase and transforming growth factor-ß signalling pathways. Additionally, we discuss validated ceRNAs associated with CRC biological functions and their potential role as novel prognostic and diagnostic biomarkers. Examining the role of ceRNAs in CRC sheds new light on cancer treatment and pathogenesis.

The Promise of CAR T-Cell Therapy for the Treatment of Cancer Stem Cells: A Short Review.

Chimeric antigen receptor (CAR) T-cell therapy is a type of sophisticated tailored immunotherapy used to treat a variety of tumors. Immunotherapy works by utilizing the body's own immune system to discover and destroy malignant cells. In CAR-T therapy, a patient's own immune cells are genetically engineered to recognize and attack cancer. Treatments employing CAR T-cells are currently showing promising therapeutic results in patients with hematologic malignancies, and their safety and feasibility in solid tumors have been verified. In this review, we will discuss in detail the likelihood that CAR Tcells inhibit cancer stem cells (CSCs) by selectively targeting their cell surface markers will ultimately improve the therapeutic response for patients with various forms of cancer. This review addresses the major components of cancer stem cell (CSC)-targeted CAR T-cells against malignancies, from bench to bedside.

Use of CAR T-cell for acute lymphoblastic leukemia (ALL) treatment: a review study.

Acute lymphoblastic leukemia (ALL) is a cancer-specific lymphoid cell. Induction and consolidation chemotherapy alone or in combination with different therapeutic approaches remain the main treatment. Although complete or partial remission of the disease can be achieved, the risk of relapse or refractory leukemia is still high. More effective and safe therapy options are yet unmet needs. In recent years' new therapeutic approaches have been widely used. Hematopoietic Stem Cell Transplantation (HSCT) presents significant limitations and the outcome of the consolidation treatment is patient dependent. Side effects such as Graft versus Host Disease (GvHD) in allogeneic hematopoietic stem cell transplantation are extremely common, therefore, using alternative methods to address these challenges for treatment seems crucial. In the last decade, T cells genetically engineered with Chimeric Antigen Receptor (CAR) treatment for the ALL are largely studied and represent the new era of strategy. According to the Phase I/II clinical trials, this technology results seem very promising and can be used in the next future as an effective and safe treatment for ALL treatment. In this review different generations, challenges, and clinical studies related to chimeric antigen receptor (CAR) T-cells for ALL treatment are discussed.

Therapeutic roles of CAR T cells in infectious diseases: Clinical lessons learnt from cancer.

Cancer immunotherapy has made improvements due to the advances in chimaeric antigen receptor (CAR) T cell development, offering a promising treatment option for patients who have failed to respond to traditional treatments. In light of the successful use of adoptive CAR T cell therapy for cancer, researchers have been inspired to develop CARs for the treatment of other diseases beyond cancers such as viral infectious diseases. Nonetheless, various obstacles limit the efficacy of CAR T cell therapies and prevent their widespread usage. Severe toxicities, poor in vivo persistence, antigen escape, and heterogeneity, as well as off-target effect, are key challenges that must all be addressed to broaden the application of CAR T cells to a wider spectrum of diseases. The key advances in CAR T cell treatment for cancer and viral infections are reviewed in this article. We will also discuss revolutionary CAR T cell products developed to improve and enhance the therapeutic advantages of these treatments.

A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women.

BACKGROUND: Research into the pathogenesis of endometriosis would substantially promote its effective treatment and early diagnosis. Currently, accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. OBJECTIVES: We aimed to identify the differences in some genes' expression between menstrual blood-derived mesenchymal stem cells (MenSCs) isolated from endometriosis patients (E-MenSCs) and MenSCs from healthy women (NE-MenSCs). METHODS: Menstrual blood samples (2-3 mL) from healthy and endometriosis women in the age range of 22-35 years were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation method were characterized by flow cytometry. MenSCs were evaluated for key related endometriosis genes by real-time-PCR. RESULTS: E-MenSCs were morphologically different from NE-MenSCs and showed, respectively, higher and lower expression of CD10 and CD9. Furthermore, E-MenSCs had higher expression of Cyclin D1 (a cell cycle-related gene) and MMP-2 and MMP-9 (migration- and invasion-related genes) genes compared with NE-MenSCs. Despite higher cell proliferation in E-MenSCs, the BAX/BCL-2 ratio was significantly lower in E-MenSCs compared to NE-MenSCs. Also, the level of inflammatory genes such as IL1ß, IL6, IL8, and NF-κB and stemness genes including SOX2 and SALL4 was increased in E-MenSCs compared with NE-MenSCs. Further, VEGF, as a potent angiogenic factor, showed a significant increase in E-MenSCs rather than NE-MenSCs. However, NE-MenSCs showed increased ER-α and ß-catenin when compared with E-MenSCs. CONCLUSION: Here, we showed that there are gene expression differences between E-MenSCs and NE-MenSCs. These findings propose that MenSCs could play key role in the pathogenesis of endometriosis and further support the menstrual blood retrograde theory of endometriosis formation. This could be of great importance in exploiting promising therapeutic targets and new biomarkers for endometriosis treatment and prognosis.

FLVCR1-AS1 and FBXL19-AS1: Two Putative lncRNA Candidates in Multiple Human Cancers.

(1) Background: Mounting evidence supports the idea that one of the most critical agents in controlling gene expression could be long non-coding RNAs (lncRNAs). Upregulation of lncRNA is observed in the different processes related to pathologies, such as tumor occurrence and development. Among the crescent number of lncRNAs discovered, FLVCR1-AS1 and FBXL19-AS1 have been identified as oncogenes in many cancer progression and prognosis types, including cholangiocarcinoma, gastric cancer, glioma and glioblastoma, hepatocellular carcinoma, lung cancer, ovarian cancer, breast cancer, colorectal cancer, and osteosarcoma. Therefore, abnormal FBXL19-AS1 and FLVCR1-AS1 expression affect a variety of cellular activities, including metastasis, aggressiveness, and proliferation; (2) Methods: This study was searched via PubMed and Google Scholar databases until May 2022; (3) Results: FLVCR1-AS1 and FBXL19-AS1 participate in tumorigenesis and have an active role in impacting several signaling pathways that regulate cell proliferation, migration, invasion, metastasis, and EMT; (4) Conclusions: Our review focuses on the possible molecular mechanisms in a variety of cancers regulated by FLVCR1-AS1 and FBXL19-AS1. It is not surprising that there has been significant interest in the possibility that these lncRNAs might be used as biomarkers for diagnosis or as a target to improve a broader range of cancers in the future.

DLX6-AS1: a putative lncRNA candidate in multiple human cancers.

Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.

A Comparative Study on the Effect of Exosomes Secreted by Mesenchymal Stem Cells Derived from Adipose and Bone Marrow Tissues in the Treatment of Osteoarthritis-Induced Mouse Model.

BACKGROUND: Exosomes as extracellular vesicles (EVs) are nanoscale intercellular messengers secreted from cells to deliver biological signals. Today, exosomes have become a new field of research in regenerative medicine and are considered as potential therapies to control inflammation and wound healing and enhance and improve healing in many diseases. Given the global burden of osteoarthritis (OA) as the fastest-growing health condition and one of the major causes of physical disability in the aging population, research to establish EVs as therapeutic products can meet the basic clinical needs in the management of osteoarthritis and provide a therapeutic solution. OBJECTIVES: The present study is aimed at evaluating the regenerative potentials of the exosomes secreted from adipose and bone marrow tissue-derived mesenchymal stem cells (AD- and BM-MSCs) in ameliorating the symptoms of OA. METHOD: In this experimental study, AD- and BM-MSCs were isolated and cultured in the laboratory until passage 3. Finally, these cells' secreted exosomes were isolated from their conditioned medium. Ciprofloxacin-induced OA mouse models underwent intra-articular injection of exosomes from AD-MSCs and BM-MSCs. Finally, the expression levels of collagen I and II, sox9, and aggrecan genes using real-time PCR, histological analysis, and immunohistochemical (IHC) studies were performed. RESULTS: Real-time PCR data showed that although the expression level of collagen type II was lower in both exosome-treated groups than the normal, but it was significantly increased in comparison with the sham and OA, with higher expression in BM-Exo rather than AD-Exo group. Similarly, the histological staining and IHC results have provided almost identical data, emphasizing on better therapeutic effect of BM-MSCs-exosome than AD-MSCs-exosome. CONCLUSION: BM-MSCs secreted exosomes in comparison with AD-MSCs could be considered as a better therapeutic option to improve osteoarthritis and exhibit potential as a disease-modifying osteoarthritis cell-free product.