Detailed role of mesenchymal stem cell (MSC)-derived exosome therapy in cardiac diseases.

Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality. There are numerous therapeutic reperfusion methods, including thrombolytic therapy, primary percutaneous coronary intervention, and anti-remodeling drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Despite this, there is no pharmacological treatment that can effectively stop cardiomyocyte death brought on by myocardial ischemia/reperfusion (I/R) injury. For the purpose of regenerating cardiac tissue, mesenchymal stem cell (MSC) therapy has recently gained more attention. The pleiotropic effects of MSCs are instead arbitrated by the secretion of soluble paracrine factors and are unrelated to their capacity for differentiation. One of these paracrine mediators is the extracellular vesicle known as an exosome. Exosomes deliver useful cargo to recipient cells from MSCs, including peptides, proteins, cytokines, lipids, miRNA, and mRNA molecules. Exosomes take part in intercellular communication processes and help tissues and organs that have been injured or are ill heal. Exosomes alone were found to be the cause of MSCs' therapeutic effects in a variety of animal models, according to studies. Here, we have focused on the recent development in the therapeutic capabilities of exosomal MSCs in cardiac diseases.

Impact of Doxorubicin and Docetaxel on Immune Checkpoint Expression in Colorectal Cancer: Insights into Chemotherapy Resistance Mechanisms.

After chemotherapy, tumor cells tend to become more aggressive, making it challenging for natural and adaptive immune responses to fight them. This often results in recurrence and metastasis, leading to higher mortality rates. The purpose of this study is to discover the mechanisms that cause chemotherapy resistance, including altered expression of immune checkpoints, in a colorectal cancer cell line. We used conventional methods to culture the SW-1116 colorectal cancer cell line in this study. The MTT assay was used to determine the IC50 and efficacy of Docetaxel and Doxorubicin. After treatment, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze PD-L1, CTLA-4, and VISTA gene expression in the SW-1116 cell line. The upregulation of VISTA expression showed a significant increase (p < 0.0001) in response to both chemotherapy agents. Moreover, the expression of CTLA-4 exhibited a remarkable level of significance (p < 0.0001), and PD-L1 expression also displayed notable significance (p < 0.0001). Chemotherapeutic agents heighten immune checkpoint gene expression, highlighting potential immune response pathway modulation.

New immunotherapy approaches for colorectal cancer: focusing on CAR-T cell, BiTE, and oncolytic viruses.

Colorectal cancer is one of the most common causes of mortality worldwide. There are several potential risk factors responsible for the initiation and progression of colorectal cancer, including age, family history, a history of inflammatory bowel disease, and lifestyle factors such as physical activity and diet. For decades, there has been a vast amount of study on treatment approaches for colorectal cancer, which has led to conventional therapies such as chemotherapy, surgery, etc. Considering the high prevalence and incidence rate, scholars believe there is an urgent need for an alternative, more efficacious treatment with fewer adverse effects than the abovementioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and has become one of the fastest-evolving therapeutic methods. Immunotherapy works by activating or enhancing the immune system's power to identify and attack cancerous cells. This review summarizes the most crucial new immunotherapy methods under investigation for colorectal cancer treatment, including Immune checkpoint inhibitors, CAR-T cell therapy, BiTEs, Tumor-infiltrating lymphocytes, and Oncolytic virus therapy. Furthermore, this study discusses the application of combination therapy, precision medicine, biomarker discovery, overcoming resistance, and immune-related adverse effects. Video Abstract.

Exosome-mediated tumor metastasis: Biology, molecular targets and immuno-therapeutic options.

Small extracellular vesicles called exosomes play a crucial part in promoting intercellular communication. They act as intermediaries for the exchange of bioactive chemicals between cells, released into the extracellular milieu by a variety of cell types. Within the context of cancer progression, metastasis is a complex process that plays a significant role in the spread of malignant cells from their main site of origin to distant anatomical locations. This complex process plays a key role in the domain of cancer-related deaths. In summary, the trajectory of current research in the field of exosome-mediated metastasis is characterized by its unrelenting quest for more profound understanding of the molecular nuances, the development of innovative diagnostic tools and therapeutic approaches, and the unwavering dedication to transforming these discoveries into revolutionary clinical applications. This unrelenting pursuit represents a shared desire to improve the prognosis for individuals suffering from metastatic cancer and to nudge the treatment paradigm in the direction of more effective and customized interventions.

Advances in siRNA delivery approaches in cancer therapy: challenges and opportunities.

Advancements in the clinical applications of small interfering RNA (siRNA) in cancer therapy have opened up new possibilities for precision medicine. siRNAs, as powerful genetic tools, have shown potential in targeting and suppressing the expression of specific genes associated with cancer progression. Their effectiveness has been further enhanced by incorporating them into nanoparticles, which protect siRNAs from degradation and enable targeted delivery. However, despite these promising developments, several challenges persist in the clinical translation of siRNA-based cancer therapy. This comprehensive review explores the progress and challenges associated with the clinical applications of siRNA in cancer therapy. This review highlights the use of siRNA-loaded nanoparticles as an effective delivery system for optimizing siRNA efficacy in various types of carcinomas and the potential of siRNA-based therapy as a genetic approach to overcome limitations associated with conventional chemotherapeutic agents, including severe drug toxicities and organ damage. Moreover, it emphasizes on the key challenges, including off-target effects, enzymatic degradation of siRNAs in serum, low tumor localization, stability issues, and rapid clearance from circulation that need to be addressed for successful clinical development of siRNA-based cancer therapy. Despite these challenges, the review identifies significant avenues for advancing siRNA technology from the laboratory to clinical settings. The ongoing progress in siRNA-loaded nanoparticles for cancer treatment demonstrates potential antitumor activities and safety profiles. By understanding the current state of siRNA-based therapy and addressing the existing challenges, we aim to pave the way for translating siRNA technology into effective oncologic clinics as an improved treatment options for cancer patients.

Cancer immunotherapy focusing on the role of interleukins: A comprehensive and updated study.

Cytokines bind to specific receptors on target cells to activate intracellular signaling pathways that control diverse cellular functions, such as proliferation, differentiation, migration, and death. They are essential for the growth, activation, and operation of immune cells and the control of immunological reactions to pathogens, cancer cells, and other dangers. Based on their structural and functional properties, cytokines can be roughly categorized into different families, such as the tumor necrosis factor (TNF) family, interleukins, interferons, and chemokines. Leukocytes produce interleukins, a class of cytokines that have essential functions in coordinating and communicating with immune cells. Cancer, inflammation, and autoimmunity are immune-related disorders brought on by dysregulation of cytokine production or signaling. Understanding cytokines' biology to create novel diagnostic, prognostic, and therapeutic methods for various immune-related illnesses is crucial. Different immune cells, including T cells, B cells, macrophages, and dendritic cells, and other cells in the body, including epithelial cells and fibroblasts, generate and secrete interleukins. The present study's main aim is to fully understand interleukins' roles in cancer development and identify new therapeutic targets and strategies for cancer treatment.

Pattern-recognition receptors (PRRs) in SARS-CoV-2.

Pattern recognition receptors (PRRs) are specific sensors that directly recognize various molecules derived from viral or bacterial pathogens, senescent cells, damaged cells, and apoptotic cells. These sensors act as a bridge between nonspecific and specific immunity in humans. PRRs in human innate immunity were classified into six types: toll-like receptors (TLR), C-type lectin receptors (CLRs), nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and cyclic GMP-AMP (cGAMP) synthase (cGAS). Numerous types of PRRs are responsible for recognizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is immensely effective in prompting interferon responses. Detection of SARS-CoV-2 infection by PRRs causes the initiation of an intracellular signaling cascade and subsequently the activation of various transcription factors that stimulate the production of cytokines, chemokines, and other immune-related factors. Therefore, it seems that PRRs are a promising potential therapeutic approach for combating SARS-CoV-2 infection and other microbial infections. In this review, we have introduced the current knowledge of various PRRs and related signaling pathways in response to SARS-CoV-2.

An updated review of a novel method for examining P53 mutations in different forms of cancer.

In the past fifteen years, it has been clear that tumor-associated p53 mutations can cause behaviors distinct from those brought on by a simple loss of p53's tumor-suppressive function in its wild-type form. Many of these mutant p53 proteins develop oncogenic characteristics that allow them to encourage cell survival, invasion, and metastasis. But it is now understood that the immune response is also significantly influenced by the cancer cell's p53 status. The recruitment and activity of myeloid and T cells can be impacted by p53 loss or mutation in malignancies, allowing immune evasion and accelerating cancer growth. Additionally, p53 can work in immune cells, which can have various effects that either hinder or assist the growth of tumors. In this review article, we examined different mutations of P53 in some significant cancers, such as liver, colorectal, and prostate, and reviewed some new therapeutic approaches.

Dysregulation of P53 in breast cancer: Causative factors and treatment strategies.

One of the most prevalent cancers impacting women worldwide is breast cancer. Although there are several risk factors for breast cancer, the p53 gene's function has recently received much attention. The "gatekeeper" gene, or p53, is sometimes referred to as such since it is crucial in controlling cell proliferation and preventing the development of malignant cells. By identifying DNA damage and initiating cellular repair processes, p53 usually functions as a tumor-suppressor. But p53 gene alterations can result in a lack of function, allowing cells to divide out of control and perhaps triggering the onset of cancer. Various factors, such as mutation genes, signaling pathways, and hormones, can dysregulate P53 proteins and cause breast cancer. A promising strategy for individualized cancer treatment involves focusing on p53 mutations in breast cancer. While numerous techniques, including gene therapy and small compounds, have shown promise, further study is required to create safe and efficient treatments to target p53 mutations in breast cancer successfully.

SARS-CoV-2-associated gut microbiome alteration; A new contributor to colorectal cancer pathogenesis.

The emergence of a novel coronavirus, COVID-19, in December 2019 led to a global pandemic with more than 170 million confirmed infections and more than 6 million deaths (by July 2022). Studies have shown that infection with SARS-CoV-2 in cancer patients has a higher mortality rate than in people without cancer. Here, we have reviewed the evidence showing that gut microbiota plays an important role in health and is linked to colorectal cancer development. Studies have shown that SARS-CoV-2 infection leads to a change in gut microbiota, which modify intestinal inflammation and barrier permeability and affects tumor-suppressor or oncogene genes, proposing SARS-CoV-2 as a potential contributor to CRC pathogenesis.

Development and characterization of polyclonal antibody against human kappa light chain in rabbit.

Polyclonal antibodies against kappa light chain are used to diagnose diseases producing free light chain. The kappa and lambda light chains are products of immunoglobulin synthesis and released into the circulation in minor amounts such as serum, cerebrospinal fluid, urine and synovial fluid in normal condition. The purpose of this study was the production and purification of polyclonal immunoglobulin G (IgG) against human kappa light chains. In this study, early human IgG was purified by ion-exchange chromatography, reduced with Dithiothreitol and heavy and light chains were separated with size-exclusion chromatography. Afterward, affinity chromatography with protein L Sepharose at pH 2.00 was displayed to be a dominant condition for the separation and purification of the kappa light chain of immunoglobulins from human serum. Eventually, the rabbit was immunized by human kappa light chains. The rabbit IgG was purified and labeled with horseradish peroxidase (HRP). Direct enzyme-linked immunosorbent assay was planned to determine the titer of HRP conjugated rabbit IgG against the human kappa light chain. The optimum titer of anti-kappa IgG was 1:16000. At the result, purified polyclonal anti-kappa is useful tool in biomedical and biochemical researches and diagnostic kits.

Which source and level of dietary sodium is appropriate for broiler chickens reared in a high-altitude area?

This study investigated effect of increasing level of dietary sodium using sodium bicarbonate or sodium chloride on growth performance, mortality, characteristics of carcass, organs and tibia, calcium and phosphorus of serum in broilers reared in a high-altitude area (1,700 m above sea level). A total of 588 Ross 308 male broiler chicks were used in seven treatments, six replicates per treatment of 14 birds per each from 1 to 38 d of age. Seven dietary treatments consisted of a basal diet (with 0.16% sodium and 0.23% chloride), top-dressed for six diets to give three supplementary levels of sodium (0.07%, 0.14% and 0.21%) from sodium bicarbonate (respectively by 0.26%, 0.52% and 0.78%) or sodium chloride (respectively by 0.18%, 0.36% and 0.54%), resulting in seven diets with total sodium and chloride levels of 0.16% and 0.23%, 0.23% and 0.23%, 0.30% and 0.23%, 0.37% and 0.23%, 0.23% and 0.33%, 0.30% and 0.44%, 0.37% and 0.55% respectively. Increasing sodium level improved feed conversion ratio (FCR) linearly and quadratically. However, when FCR was calculated without adjusting for feed intake of mortalities, the enhanced sodium level did not improve this parameter. Increasing sodium level via sodium chloride enhanced ascites mortality, total mortality, relative weight of heart and right ventricle linearly. Increasing sodium level reduced serum calcium and enhanced serum phosphorus linearly; however, there was a linear tendency to increase tibia ash when sodium level was enhanced by sodium bicarbonate (p = 0.08) or sodium chloride (p = 0.07). Increasing sodium level via sodium bicarbonate tended (p = 0.08) to reduce tibia strength linearly. In conclusion, a diet with 0.16% sodium and 0.23% chloride is enough for broiler chicken reared in a high-altitude area, and increasing dietary sodium level via sodium chloride has detrimental effect on survivability of broiler in such condition.

Production and characterization of anti-human IgG F(ab')2 antibody fragment.

In present study an optimized protocol for the separation of antibodies into antigen-binding fragments F(ab')2 using pepsin digestion was investigated. The production of these fragments is a consequential step in the development of medical research, treatment and diagnosis. For production of polyclonal antibody rabbit received antigen in four steps. The rabbit serum at 1/128000 dilution showed high absorbance in reaction with human IgG at the designed ELISA method. Rabbit IgG was purified by Ion-Exchange Chromatography (IEC) method. Purity was assessed by SDS-PAGE method. In non-reduced condition only one band was seen in about 150 kDa MW position and in reduced form, two bands were seen in 50 and 25 kDa MW positions. Rabbit IgG was digested by pepsin enzyme. The antibody fragments solution was applied to Gel filtration column to isolate the F(ab')2. Non-reduced SDS-PAGE for determining the purity of F(ab')2 fragment resulted in one band in 100 kDa corresponds to F(ab')2 fragment and a band in 150 kDa MW position corresponds to undigested IgG antibodies. The activities of FITC conjugated F(ab')2 fragment and commercial ones were compared using flowcytometry method. The activity results implied that the FITC conjugated- anti human F(ab')2 fragment worked as efficiently as the commercial one.

Antibody-drug conjugates: Promising and efficient tools for targeted cancer therapy.

Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR).

Antibody-cytokine fusion proteins for improving efficacy and safety of cancer therapy.

Cytokines are key players in the regulation of immune responses both in physiological and pathological states. A number of cytokines have been evaluated in clinical trials and shown promising results in the treatment of different malignancies. Despite this, the clinical application of these molecules may be plagued by undesirable side effects The development of recombinant antibody-cytokine fusion proteins, which offer a means for target delivery of cytokines toward the tumor site, has significantly improved the therapeutic index of these immunomodulatory molecules. Selective tumor localization is provided by the monoclonal antibody component of the fusion protein that binds to the molecules present on the surface of tumor cells or accumulated preferentially in the diseased site. In this manner, the cytokine element is specifically located at the tumor site and can stimulate immune cells with appropriate cytokine receptors. Over the recent years, several antibody-cytokine fusion proteins have been developed with the capacity to target a wide variety of cancers whose application, in some cases, has led to complete rejection of the tumor. These findings support the notion that antibody-cytokine fusion proteins represent huge potential for cancer therapy. This review presents an overview of the advances made in the field of targeted cytokine delivery, which is made possible by genetically engineering antibody-cytokine fusion proteins.

Production and purification of polyclonal antibody against F(ab')2 fragment of human immunoglobulin G.

Antibodies are essential tools of biomedical and biochemical researches. Polyclonal antibodies are produced against different epitopes of antigens. Purified F(ab')2 can be used for animal's immunization to produce polyclonal antibodies. Human immunoglobulin G (IgG) was purified by ion exchange chromatography method. In all stages verification method of the purified antibodies was sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Purified IgG was digested by pepsin enzyme and F(ab')2 fragment was purified by gel filtration separation method. For production of polyclonal antibody, rabbit was immunized by purified F(ab')2 and antibody production was investigated by enzyme-linked immunosorbent assay. Purified anti-IgG F(ab')2 was conjugated with fluorescein isothiocyanate. Ion exchange chromatography purification yielded 38 mg of human IgG antibody. The results of SDS-PAGE in reduced and non-reduced conditions showed bands with 25-30 kDa molecular weight (MW) and 50-kDa respectively and a distinct band with 150 kDa MW. The results of non-reduced SDS-PAGE for determining the purity of F(ab')2 fragment showed one band in 90 kDa and a band in 150 kDa MW position. Purification by Ion exchange chromatography method resulted about 12 mg rabbit polyclonal antibody. Flow cytometry showed generated polyclonal antibody had an acceptable activity compared to commercial antibody. Taking together, purified IgG F(ab')2 and polyclonal anti-IgG F(ab')2 are useful tools in biomedical and biochemical researches and diagnostic kits.