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.

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.

Role of SARS-COV-2 and ACE2 in the pathophysiology of peripheral vascular diseases.

The occurrence of a novel coronavirus known as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), created a serious challenge worldwide. SARS-CoV-2 has high infectivity, the ability to be transmitted even during the asymptomatic phase, and relatively low virulence, which has resulted in rapid transmission. SARS-CoV-2 can invade epithelial cells, hence, many patients infected with SARS-CoV-2 have suffered from vascular diseases (VDs) in addition to pulmonary manifestations. Accordingly, SARS-CoV-2 may can worsen the clinical condition of the patients with pre-existing VDs. Endothelial cells express angiotensin-converting enzyme 2 (ACE2). ACE2 is a biological enzyme that converts angiotensin (Ang)- 2 to Ang-(1-7). SARS-CoV-2 uses ACE2 as a cell receptor for viral entry. Thus, the SARS-CoV-2 virus promotes downregulation of ACE2, Ang-(1-7), and anti-inflammatory cytokines, as well as, an increase in Ang-2, resulting in pro-inflammatory cytokines. SARS-CoV-2 infection can cause hypertension, and endothelial damage, which can lead to intravascular thrombosis. In this review, we have concentrated on the effect of SARS-CoV-2 in peripheral vascular diseases (PVDs) and ACE2 as an enzyme in Renin-angiotensin aldosterone system (RAAS). A comprehensive search was performed on PubMed, Google Scholar, Scopus, using related keywords. Articles focusing on ("SARS-CoV-2", OR "COVID-19"), AND ("Vascular disease", OR "Peripheral vascular disease", OR interested disease name) with regard to MeSH terms, were selected. According to the studies, it is supposed that vascular diseases may increase susceptibility to severe SARS-CoV-2 infection due to increased thrombotic burden and endothelial dysfunction. Understanding SARS-CoV-2 infection mechanism and vascular system pathogenesis is crucial for effective management and treatment in pre-existing vascular diseases.

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.

Dual role of Exosome in neurodegenerative diseases: a review study.

INTRODUCTION: Extracellular vesicles (EVs) are one of the crucial means of intercellular communication, which takes many different forms. They are heterogeneous, secreted by a range of cell types, and can be generally classified into microvesicles and exosomes depending on their location and function. Exosomes are small EVs with diameters of about 30-150 nm and diverse cell sources. METHODS: The MEDLINE/PubMed database was reviewed for papers written in English and publication dates of recent years, using the search string "Exosome" and "Neurodegenerative diseases." RESULTS: The exosomes have attracted interest as a significant biomarker for a better understanding of disease development, gene silencing delivery, and alternatives to stem cell-based therapy because of their low-invasive therapeutic approach, repeatable distribution in the central nervous system (CNS), and high efficiency. Also, they are nanovesicles that carry various substances, which can have an impact on neural plasticity and cognitive functioning in both healthy and pathological circumstances. Therefore, exosomes are conceived as nanovesicles containing proteins, lipids, and nucleic acids. However, their composition varies considerably depending on the cells from which they are produced. CONCLUSION: In the present review, we discuss several techniques for the isolation of exosomes from different cell sources. Furthermore, reviewing research on exosomes' possible functions as carriers of bioactive substances implicated in the etiology of neurodegenerative illnesses, we further examine them. We also analyze the preclinical and clinical research that shows exosomes to have therapeutic potential.

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.

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.

Dendritic Cells - Winning the Fight against HIV.

HIV is a virus that targets and hijacks the immune cells of the host. It multiplies by attacking the helper T-lymphocytes. HIV has remained one of the most difficult and dangerous infections in the world due to the inability to find a successful treatment and a lack of access to medical care. When the virus reaches the body, dendritic cells are the first cells it encounters. DCs have been identified as one of the most effective mediators of immune responses, implying a promising strategy against viral infection. The current state of knowledge about the function of dendritic cells and their subsets is critical for using their full potential as a candidate for the development of an HIV vaccine. Despite extensive efforts, a reliable vaccine with the fewest side effects has yet to be found, and further research is needed to find a dependable and efficient vaccine. The extent to which dendritic cell-based therapy is used to treat HIV was investigated in this study. As the virus attacks the host immune system, the dendritic cells can trigger an immune response against HIV-1 infection.

Retraction Note to: Evaluation of the Ability of Natural and Synthetic Scaffolds in Providing an Appropriate Environment for Growth and Chondrogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells.

[This retracts the article DOI: 10.4103/0019-5413.164043.].

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.

Neuroprotective effects of coenzyme Q10-loaded exosomes obtained from adipose-derived stem cells in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative disease that causes memory and learning impairments as well as dementia. Coenzyme Q10 (CoQ10) is an anti-inflammatory and anti-oxidative stress supplement that can improve inflammation and oxidative stress associated with AD. This study investigated the effects of drug delivery of COQ10 by exosomes derived from adipose-derived stem cells (ADSCs-Exo) on cognition, memory, and neuronal proliferation in a rat model of Streptozotocin (STZ)-induced AD. Since the establishment of the AD model, the rats have received intraperitoneal injections of CoQ10, Exo, or CoQ10-loaded ADSCs-Exo (Exo+ CoQ10). The passive avoidance test and the Morris water maze (MWM) were used to assess memory and cognition changes. Cell density was determined using histological methods. The expression of BDNF was measured using an ELISA kit. SOX2 expression was determined using immunohistochemistry. According to the results of the MWM and passive avoidance task, Exo+CoQ10 significantly improved STZ-induced memory impairment compared to CoQ10 and Exo groups alone. Furthermore, BDNF expression increased in the STZ-induced rats after Exo+ CoQ10, when compared to the CoQ10 and Exo groups. In addition, Exo+CoQ10 had the highest cell density and SOX2 gene expression, when compared to the CoQ10 and Exo groups. According to the findings of this study, Exo+ COQ10 enhanced cognition and memory deficiency in Alzheimer's disease by boosting BDNF and SOX2 levels in the hippocampus. Hence, the use of exosomes derived from adipose-derived stem cells as the carrier of CoQ10 may increase the therapeutic effect of CoQ10, which can possibly be due to the regenerative properties of the exosomes.

New Insights into Cartilage Tissue Engineering: Improvement of Tissue-Scaffold Integration to Enhance Cartilage Regeneration.

Distinctive characteristics of articular cartilage such as avascularity and low chondrocyte conversion rate present numerous challenges for orthopedists. Tissue engineering is a novel approach that ameliorates the regeneration process by exploiting the potential of cells, biodegradable materials, and growth factors. However, problems exist with the use of tissue-engineered construct, the most important of which is scaffold-cartilage integration. Recently, many attempts have been made to address this challenge via manipulation of cellular, material, and biomolecular composition of engineered tissue. Hence, in this review, we highlight strategies that facilitate cartilage-scaffold integration. Recent advances in where efficient integration between a scaffold and native cartilage could be achieved are emphasized, in addition to the positive aspects and remaining problems that will drive future research.

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.