Multi-Drug Resistance and Breast Cancer Progression via Toll-Like Receptors (TLRs) Signaling.

Toll-like receptors (TLRs) are essential receptors involved in inflammation and innate immunity. Various types of cancer cells, as well as innate immune cells, express TLRs. There is mounting proof that TLRs are critical to the development and spread of cancer as well as metabolism. In breast cancer, up-regulated levels of TLRs have been linked to the aggressiveness of the diseases, worse treatment outcomes, and the emergence of therapeutic resistance. Patients with advanced non-resectable, recurring, and metastatic breast cancer currently have few available treatment choices. An intriguing new strategy is an innate immunity-mediated anticancer immunotherapy, either used alone or in conjunction with existing treatments. In fact, several TLR agonists and antagonists have been used in clinical studies for anti-cancer immunotherapy. Consequently, TLRs serve as critical targets for controlling the course of breast cancer and treatment resistance in addition to being implicated in immune responses against pathogen infection and cancer immunology. In this review, we deliver an overview of the most current findings on TLR involvement in the development of breast cancer and treatment resistance.

Application of mesenchymal stem cells derived from the umbilical cord or Wharton's jelly and their extracellular vesicles in the treatment of various diseases.

Mesenchymal stem cells (MSCs) originating from the umbilical cord (UC) or Wharton's jelly (WJ) have attracted substantial interest due to their potential to augment therapeutic approaches for a wide range of disorders. These cells demonstrate a wide range of capabilities in the process of differentiating into a multitude of cell types. Additionally, they possess a significant capacity for proliferation and are conveniently accessible. Furthermore, they possess a status of being immune-privileged, exhibit minimal tumorigenic characteristics, and raise minimal ethical concerns. Consequently, they are well-suited candidates for tissue regeneration and the treatment of diseases. Additionally, UC-derived MSCs offer a substantial yield compared to other sources. The therapeutic effects of these MSCs are closely associated with the release of nanosized extracellular vesicles (EVs), including exosomes and microvesicles (MVs), containing lipids, microRNAs, and proteins that facilitate intercellular communication. Due to their reduced tumorigenic and immunogenic characteristics, in addition to their convenient manipulability, EVs have arisen as a viable alternative for the management of disorders. The favorable characteristics of UC-MSCs or WJ-MSCs and their EVs have generated significant attention in clinical investigations encompassing diverse pathologies. Therefore, we present a review encompassing current preclinical and clinical investigations, examining the implications of UC-MSCs in diverse diseases, including those affecting bone, cartilage, skin, liver, kidney, neural, lung, cardiovascular, muscle, and retinal tissues, as well as conditions like cancer, diabetes, sepsis, and others.

Detailed role of SR-A1 and SR-E3 in tumor biology, progression, and therapy.

The first host defense systems are the innate immune response and the inflammatory response. Among innate immune cells, macrophages, are crucial because they preserve tissue homeostasis and eradicate infections by phagocytosis, or the ingestion of particles. Macrophages exhibit phenotypic variability contingent on their stimulation state and tissue environment and may be detected in several tissues. Meanwhile, critical inflammatory functions are played by macrophage scavenger receptors, in particular, SR-A1 (CD204) and SR-E3 (CD206), in a variety of pathophysiologic events. Such receptors, which are mainly found on the surface of multiple types of macrophages, have different effects on processes, including atherosclerosis, innate and adaptive immunity, liver and lung diseases, and, more recently, cancer. Although macrophage scavenger receptors have been demonstrated to be active across the disease spectrum, conflicting experimental findings and insufficient signaling pathways have hindered our comprehension of the molecular processes underlying its array of roles. Herein, as SR-A1 and SR-E3 functions are often binary, either protecting the host or impairing the pathophysiology of cancers has been reviewed. We will look into their function in malignancies, with an emphasis on their recently discovered function in macrophages and the possible therapeutic benefits of SR-A1 and SR-E3 targeting.

Advancing therapeutic efficacy: nanovesicular delivery systems for medicinal plant-based therapeutics.

The utilization of medicinal plant extracts in therapeutics has been hindered by various challenges, including poor bioavailability and stability issues. Nanovesicular delivery systems have emerged as promising tools to overcome these limitations by enhancing the solubility, bioavailability, and targeted delivery of bioactive compounds from medicinal plants. This review explores the applications of nanovesicular delivery systems in antibacterial and anticancer therapeutics using medicinal plant extracts. We provide an overview of the bioactive compounds present in medicinal plants and their therapeutic properties, emphasizing the challenges associated with their utilization. Various types of nanovesicular delivery systems, including liposomes, niosomes, ethosomes, and solid lipid nanoparticles, among others, are discussed in detail, along with their potential applications in combating bacterial infections and cancer. The review highlights specific examples of antibacterial and anticancer activities demonstrated by these delivery systems against a range of pathogens and cancer types. Furthermore, we address the challenges and limitations associated with the scale-up, stability, toxicity, and regulatory considerations of nanovesicular delivery systems. Finally, future perspectives are outlined, focusing on emerging technologies, integration with personalized medicine, and potential collaborations to drive forward research in this field. Overall, this review underscores the potential of nanovesicular delivery systems for enhancing the therapeutic efficacy of medicinal plant extracts in antibacterial and anticancer applications, while identifying avenues for further research and development.

Mesenchymal stem cell-released oncolytic virus: an innovative strategy for cancer treatment.

Oncolytic viruses (OVs) infect, multiply, and finally remove tumor cells selectively, causing no damage to normal cells in the process. Because of their specific features, such as, the ability to induce immunogenic cell death and to contain curative transgenes in their genomes, OVs have attracted attention as candidates to be utilized in cooperation with immunotherapies for cancer treatment. This treatment takes advantage of most tumor cells' inherent tendency to be infected by certain OVs and both innate and adaptive immune responses are elicited by OV infection and oncolysis. OVs can also modulate tumor microenvironment and boost anti-tumor immune responses. Mesenchymal stem cells (MSC) are gathering interest as promising anti-cancer treatments with the ability to address a wide range of cancers. MSCs exhibit tumor-trophic migration characteristics, allowing them to be used as delivery vehicles for successful, targeted treatment of isolated tumors and metastatic malignancies. Preclinical and clinical research were reviewed in this study to discuss using MSC-released OVs as a novel method for the treatment of cancer. Video Abstract.

CAR-T cell combination therapy: the next revolution in cancer treatment.

In recent decades, the advent of immune-based therapies, most notably Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment. The promising results of numerous studies indicate that CAR-T cell therapy has had a remarkable ability and successful performance in treating blood cancers. However, the heterogeneity and immunosuppressive tumor microenvironment (TME) of solid tumors have challenged the effectiveness of these anti-tumor fighters by creating various barriers. Despite the promising results of this therapeutic approach, including tumor degradation and patient improvement, there are some concerns about the efficacy and safety of the widespread use of this treatment in the clinic. Complex and suppressing tumor microenvironment, tumor antigen heterogeneity, the difficulty of cell trafficking, CAR-T cell exhaustion, and reduced cytotoxicity in the tumor site limit the applicability of CAR-T cell therapy and highlights the requiring to improve the performance of this treatment. With this in mind, in the last decade, many efforts have been made to use other treatments for cancer in combination with tuberculosis to increase the effectiveness of CAR-T cell therapy, especially in solid tumors. The combination therapy results have promising consequences for tumor regression and better cancer control compared to single therapies. Therefore, this study aimed to comprehensively discuss different cancer treatment methods in combination with CAR-T cell therapy and their therapeutic outcomes, which can be a helpful perspective for improving cancer treatment in the near future.

Effect of a diet based on Iranian traditional medicine on inflammatory markers and clinical outcomes in COVID-19 patients: A double-blind, randomized, controlled trial.

Introduction: SARS-CoV-2 causes severe acute respiratory syndrome prompting worldwide demand for new antiviral treatments and supportive care for organ failure caused by this life-threatening virus. This study aimed to help develop a new Traditional Persian Medicine (TPM) -based drug and assess its efficacy and safety in COVID-19 patients with major symptoms. Methods: In February 2022, a randomized clinical trial was conducted among 160 patients with a confirmed diagnosis of COVID-19 admitted to Emam Reza (AJA) Hospital in Tehran, Iran. During their hospitalization, the intervention group received a treatment protocol approved by Iran's Ministry of Health and Medical Education (MOHME), consisting of an Iranian regimen, Ficus carica; Vitis vinifera, Safflower, Cicer arietinum, Descurainiasophia seeds, Ziziphus jujuba, chicken soup, barley soup, rose water, saffron, and cinnamon spices. All patients were compared in terms of demographics, clinical, and laboratory variables. Results: One hundred and sixty COVID-19 patients were divided into two groups: intervention and control. In baseline characteristics, there was no significant difference between the intervention and control groups (p>0.05). Using SPSS software version 22, statistical analysis revealed a significant difference in four symptoms: myalgia, weakness, headache, and cough (p<0.05). During the 5-day treatment period, the control group had significantly lower C-reactive protein (p<0.05). Conclusion: While more research with a larger sample size is needed, the proposed combination appears to be effective in the treatment of symptoms as well as inflammatory biomarkers such as C-reactive protein in COVID-19 patients.Iranian registry of clinical trials (IRCT) IRCT20220227054140N1.

Osteoporosis treatment by mesenchymal stromal/stem cells and their exosomes: Emphasis on signaling pathways and mechanisms.

Osteoporosis is the loss of bone density, which is one of the main problems in developed and developing countries and is more common in the elderly. Because this disease is often not diagnosed until a bone fracture, it can become a life-threatening disease and cause hospitalization. With the increase of older people in a population, this disease's personal and social costs increase year by year and affect different communities. Most current treatments focus on pain relief and usually do not lead to bone tissue recovery and regeneration. But today, the use of stem cell therapy is recommended to treat and improve this disease recovery, which helps restore bone tissue by improving the imbalance in the osteoblast-osteoclast axis. Due to mesenchymal stromal/stem cells (MSCs) characteristics and their exosomes, these cells and vesicles are excellent sources for treating and preventing the progression and improvement of osteoporosis. Due to the ability of MSCs to differentiate into different cells and migrate to the site of injury, these cells are used in tissue regenerative medicine. Also, due to their contents, the exosomes of these cells help regenerate and treat various tissue injuries by affecting the injury site's cells. In this article, we attempted to review new studies in which MSCs and their exosomes were used to treat osteoporosis.