Advanced Generation Therapeutics: Biomimetic Nanodelivery System for Tumor Immunotherapy.

Tumor immunotherapy is a safe and effective strategy for precision medicine. However, immunotherapy for most cancer cases still ends in failure, with the root causes of the immunosuppressive and extraordinary heterogeneity of the solid tumors microenvironment. The emerging biomimetic nanodelivery system provides a promising tactic to improve the immunotherapy effect while reducing the adverse reactions on nontarget cells. Herein, we summarize the relationship between tumor occurrence and tumor immune microenvironment, mechanism of tumor immune escape, immunotherapy classification (including adoptive cellular therapy, cytokines, cancer vaccines, and immune checkpoint inhibitors) and recommend target cells for immunotherapy first, and then emphatically introduce the recent advances and applications of the latest biomimetic nanodelivery systems (e.g., immune cells, erythrocytes, tumor cells, platelets, bacteria) in tumor immunotherapy. Meanwhile, we separately summarize the application of tumor vaccines. Finally, the predictable challenges and perspectives in a forward exploration of biomimetic nanodelivery systems for tumor immunotherapy are also discussed.

Contrasting mechanistic susceptibilities of hematopoietic and endothelial stem-progenitor cells in respective pathogeneses of HIV-1 and SARS-CoV-2 infections.

The multitude of cellular types can be expected to behave differently when receiving invading pathogens such as mammalian viruses. The nature-dictated causes for such intrinsic cellular diversity become the criteria for the emergence of specific virus-receptor interactions on that particular host cellular surface, in order to accommodate contact with various other living entities whether desirable to the host or not. At present, we are presented with an example of two contrasting behaviours wherein the well-known HIV-1 and the more recently emergent SARS-CoV-2 cause adverse consequences to the differentiation and functions of progenitor stem cells. These include the two different downstream multipotent CD34+ hematopoietic (HSPC) and CD133+ endothelial (ESPC) stem-progenitor cells of their common pluripotent hemangioblast precursors. The two viruses target the respective endothelial and hematopoietic stem-progenitor cells to thrive upon the relevant host cellular surrounded stromal microenvironments by adopting reciprocally-driven mechanistic routes, which incidentally cause pathogenesis either directly of ESPC (SARS-CoV-2), or indirectly of HSPC (HIV-1). HIV-1 utilizes the CD4+ T-lymphocyte receptor thereby advancing pathogenesis indirectly to the CD34+ HSPC. SARS-CoV-2 directly targets the CD133+ ESPC via ACE2 receptor causing cytokine storms of the CD4+ T-lymphocytes. In this manner, these two viruses cause and extend their damage to the other cellular sub/types coexisting in the host cellular microenvironments. The infected individuals require clinical interventions that are efficacious to prevent cellular dysfunction and ultimate cell depletion or death. We infer from these viruses mediated pathogeneses mechanisms a potential common origin of microRNA molecular therapies to address cellular dysfunctions and prevent cell loss.

SARS-CoV-2 replicates in the human testis with slow kinetics and has no major deleterious effects ex vivo.

IMPORTANCE: SARS-CoV-2 is a new virus responsible for the Covid-19 pandemic. Although SARS-CoV-2 primarily affects the lungs, other organs are infected. Alterations of testosteronemia and spermatozoa motility in infected men have raised questions about testicular infection, along with high level in the testis of ACE2, the main receptor used by SARS-CoV-2 to enter host cells. Using an organotypic culture of human testis, we found that SARS-CoV-2 replicated with slow kinetics in the testis. The virus first targeted testosterone-producing Leydig cells and then germ-cell nursing Sertoli cells. After a peak followed by the upregulation of antiviral effectors, viral replication in the testis decreased and did not induce any major damage to the tissue. Altogether, our data show that SARS-CoV-2 replicates in the human testis to a limited extent and suggest that testicular damages in infected patients are more likely to result from systemic infection and inflammation than from viral replication in the testis.

Phthalates and their effects on human health: Focus on erythrocytes and the reproductive system.

Plastics, long-chain artificial polymers, are used worldwide with a global production of 350 million tonnes per year. Various degradation processes transform plastics into smaller fragments divided into micro, meso and macroplastics. In various industries, such as construction, certain plastic additives are used to improve flexibility and enhance performance. Plastic additives include phthalates (PAE), dibutyl phthalate (DPB) and diethyl phthalate (DEP). Due to the use of plastics and plastic additives, these small fragments of different shapes and colours are present in all environmental compartments. For their characteristics, PAEs can be introduced particularly by ingestion, inhalation and dermal absorption. They can accumulate in the human body, where they have already been identified in blood, amniotic fluid and urine. The purpose of this review is to gather the effects that these plastic additives have on various systems in the human body. Being endocrine disruptors, the effects they have on erythrocytes and how they can be considered targets for xenobiotics have been analysed. The influence on the reproductive system was also examined. Phthalates are therefore often overused. Due to their properties, they can reach human tissues and have a negative impact on health. The aim of this review is to give an overview of the presence of phthalates and their hazards. Therefore, the use of these plastic additives should be reduced, replaced and their disposal improved.

Single neurons in the human medial temporal lobe flexibly shift representations across spatial and memory tasks.

Investigations into how individual neurons encode behavioral variables of interest have revealed specific representations in single neurons, such as place and object cells, as well as a wide range of cells with conjunctive encodings or mixed selectivity. However, as most experiments examine neural activity within individual tasks, it is currently unclear if and how neural representations change across different task contexts. Within this discussion, the medial temporal lobe is particularly salient, as it is known to be important for multiple behaviors including spatial navigation and memory, however the relationship between these functions is currently unclear. Here, to investigate how representations in single neurons vary across different task contexts in the medial temporal lobe, we collected and analyzed single-neuron activity from human participants as they completed a paired-task session consisting of a passive-viewing visual working memory and a spatial navigation and memory task. Five patients contributed 22 paired-task sessions, which were spike sorted together to allow for the same putative single neurons to be compared between the different tasks. Within each task, we replicated concept-related activations in the working memory task, as well as target-location and serial-position responsive cells in the navigation task. When comparing neuronal activity between tasks, we first established that a significant number of neurons maintained the same kind of representation, responding to stimuli presentations across tasks. Further, we found cells that changed the nature of their representation across tasks, including a significant number of cells that were stimulus responsive in the working memory task that responded to serial position in the spatial task. Overall, our results support a flexible encoding of multiple, distinct aspects of different tasks by single neurons in the human medial temporal lobe, whereby some individual neurons change the nature of their feature coding between task contexts.

Evaluating the impact of three progestin-based hormonal contraceptive methods on immunologic changes in the female genital tract and systemically (CHIME Study): a prospective cohort study protocol.

BACKGROUND: Gonadal hormones can modify immune function, which may impact susceptibility to infectious diseases, including Human Immunodeficiency Virus (HIV). There is limited knowledge about how hormonal contraceptives (HC) influence the immune response during the course of use. The CHIME study aims to evaluate the effect of long-acting progestin-based hormonal contraceptives (depot medroxyprogesterone acetate, etonogestrel implant, and levonorgestrel intrauterine device) on immunologic changes in the female genital tract (FGT) and systemic compartment. METHODS: CHIME is an observational cohort study where participants attend 2 visits prior to initiating the HC method of their choice, and then attend 6 visits over 12 months with biological sampling (vaginal swabs, cervicovaginal lavage, cytobrush and blood) for immunological, bacteriological, and virological analyses at each visit. Immune profiling will be evaluated by multi-color flow cytometry to determine how different T-cell subsets, in particular the CD4 T-cell subsets, change during the course of contraceptive use and whether they have different profiles in the FGT compared to the systemic compartment. The study aims are (1) to characterize the alterations in FGT and systemic immune profiles associated with three long-acting progestin-only HC and (2) to evaluate the vaginal microenvironment, determined by 16 s rRNA sequencing, as an individual-level risk factor and moderator of genital and systemic immune profile changes following exposure to three commonly used HC. Data collection started in March 2019 and is scheduled to be completed in October 2024. DISCUSSION: The CHIME study aims to contribute to the body of research designed to evaluate the comparative impact of three long-acting progestin-only HC on innate and adaptive immune functions to understand how immunologic effects alter STI and HIV susceptibility.

Expression of the highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) in various types of cells in thymic tissues.

Thymus, an important central immune organ in pigs, is the site of T lymphocyte development and maturation and an important target organ for infection and replication of various pathogens. Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection results in severe thymic atrophy in piglets. This study aimed to explore the effects of HP-PRRSV on the thymic structure of piglets to elucidate the pathogenesis of thymic atrophy induced by HP-PRRSV. In this study, histopathological techniques and immunofluorescence double staining techniques were used to analyze thymic tissues infected by HP-PRRSV to explore the structural changes of thymus caused by the viral infection and its target cell types. An antibody of cluster of differentiation (CD) 3 (CD3), CD20, CD80, or calgranulin + calprotectin was applied to identify T cells, B cells, dendritic cells (DCs), and macrophages, respectively. The results indicated that a variety of cell components in the thymic tissue were diffusely damaged after viral infection. In the infected thymic tissue, CD80- or calgranulin + calprotectin- -labeled cells supported the HP-PRRSV infection, whereas CD3-labeled T cells and CD20- -labeled B cells did not support the viral infection. The results showed that HP-PRRSV caused the reduction of visible cell components in the thymic tissue, and the virus attacked CD80- and calgranulin + calprotectin-positive cells (such as DCs and macrophages) in the thymic tissue, which played an important role in the pathogenesis of thymus atrophy. These results lay the foundation for elucidating the immunosuppression of piglets after infection with HP-PRRSV.

Research progress of whole-cell-SELEX selection and the application of cell-targeting aptamer.

BACKGROUND: Aptamers refer to the artificially synthesized nucleic acid sequences (DNA/RNA) that can bind to a wide range of targets with high affinity and specificity, which are generally generated from systematic evolution of ligands by exponential enrichment (SELEX). As a novel method of aptamers screening, whole-cell-SELEX (WC-SELEX) has gained more and more attention in many fields such as biomedicine, analytical chemistry, and molecular diagnostics due to its ability to screen multiple potential aptamers without knowing the detailed structural information of target molecules. METHODS AND RESULTS: In recent years, with the deepening of research on application of aptamers, the traditional WC-SELEX cannot meet the practical application because of long experimental period, complicated operation process and low specificity, etc. Therefore, the development of more efficient methods for screening aptamer is always on the road. This paper summarizes the current research status of WC-SELEX for bacteria, parasites and animal cells, and reviews the latest advances of WC-SELEX techniques that are dependent on novel instruments, materials and microelectronics, including fluorescence-activated cell sorting-assisted SELEX, three-dimensional assisted WC-SELEX, and microfluidic chip system-assisted WC-SELEX. In addition, the application of aptamers targeting cells was discussed. CONCLUSION: Taken together, this review is aimed at providing a reference for WC-SELEX selection and application of aptamer targeting cells.

Marine toxin domoic acid induces moderate toxicological response in non-target HepG2 cells.

Domoic acid (DA) is a marine neurotoxin produced as a defence compound by diatom Pseudo-nitzschia. Although its toxicity is well known in marine mammals and fish, data on DA cyto/genotoxicity in human non-target cells is still limited. Hence, we aimed to study the effect of DA (0.001-10 µg/mL) on cell viability and proliferation kinetics of human hepatocellular carcinoma (HepG2) cells as well as DNA damage induction after 4, 24 and 72 h of exposure. The results revealed that DA up to 10 µg/mL did not elicit significant changes in HepG2 cell viability, proliferation and cell cycle at applied conditions. DA did not generate DNA double-strand breaks, while it exhibited significant dose- and time-dependent increase of DNA damage in the form of either DNA single-strand breaks or alkali labile sites. Additionally, increased malondialdehyde level after DA treatment indicated oxidative damage to lipids. Altogether, the results showed that neurotoxin DA induced only minor adverse genotoxic effects in non-target HepG2 cells that most probably occurred resulting from the oxidative stress. However, additional research is needed to further elucidate the mechanisms of DA toxicity, particularly in terms of chronic exposure, as well as to understand its potential influence on human non-target cells.

Persistent, Asymptomatic Colonization with Candida is Associated with Elevated Frequencies of Highly Activated Cervical Th17-Like Cells and Related Cytokines in the Reproductive Tract of South African Adolescents.

Cervicovaginal inflammation, nonoptimal microbiota, T-cell activation, and hormonal contraceptives may increase HIV risk, yet associations between these factors and subclinical Candida colonization or hyphae are unknown. We collected cervicovaginal samples from 94 South African adolescents, aged 15 to 19 years, who were randomized to injectable norethisterone enanthate (Net-En), an etonorgesterol/ethinyl estradiol vaginal ring (NuvaRing), or oral contraceptives in the UChoose trial (NCT02404038) at baseline and 16 weeks post-randomization. We assessed cervicovaginal samples for subclinical Candida colonization (by quantitative PCR [qPCR]), hyphae (by Gram stain), microbiota composition (by 16S rRNA gene sequencing), cytokine concentrations (by Luminex), and cervical T-cell phenotypes and activation (by multiparameter flow cytometry). While hormonal contraceptive type did not influence incidence of Candida colonization or hyphae, hyphae presence was associated with significantly elevated concentrations of IL-22, IL-17A and IL-17F, all produced by Th17 cells, but not of other cytokines, such as IL-1ß or IL-6, after adjustment for confounders. Subclinical Candida colonization was associated with reduced frequencies of Th17-like cells and elevated frequencies of CCR6-CCR10 T cells. Women with Candida hyphae were less likely to have bacterial vaginosis (BV). Persistent, subclinical colonization with Candida over 16 weeks was associated with significant increases in Th17-related cytokine concentrations and highly activated Th17-like and CCR6-CCR10 T-cell frequencies. These data suggest that vaginal Candida colonization and hyphae increase Th17-related cytokines, but not overall female genital tract inflammation in Sub-Saharan African adolescents. Persistent Candida colonization, even when asymptomatic, may increase Th17 cell frequencies and related cytokines and thereby could subsequently increase HIV risk, although the causal relationship requires confirmation. IMPORTANCE Sub-Saharan African female adolescents are globally at the highest risk of HIV acquisition, and genital inflammation, microbial dysbiosis, and cervical HIV target cell activation are thought to contribute to this risk. Previously, the relationship between these mucosal factors and subclinical vaginal Candida colonization or hyphae has not been described, and the role of HIV-susceptible Th17 cells in mediating anti-Candida immunity in the human female genital tract has not been clearly established. We show that presence of yeast hyphae was associated with increases in Th17 cell-related cytokines and the absence of microbial dysbiosis, and that persistent Candida colonization resulted in significant increases in Th17-related cytokines and highly activated Th17-like cell frequencies. Our results suggest that Th17 cells are important for anti-Candida immunity in the human female genital tract and that prolonged vaginal Candida colonization may contribute to increased HIV risk in Sub-Saharan African adolescents by increasing HIV target cell frequencies and activation.

Regular Use of Depot Medroxyprogesterone Acetate Causes Thinning of the Superficial Lining and Apical Distribution of Human Immunodeficiency Virus Target Cells in the Human Ectocervix.

BACKGROUND: The hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may be associated with an increased risk of acquiring human immunodeficiency virus (HIV). We hypothesize that DMPA use influences the ectocervical tissue architecture and HIV target cell localization. METHODS: Quantitative image analysis workflows were developed to assess ectocervical tissue samples collected from DMPA users and control subjects not using hormonal contraception. RESULTS: Compared to controls, the DMPA group exhibited a significantly thinner apical ectocervical epithelial layer and a higher proportion of CD4+CCR5+ cells with a more superficial location. This localization corresponded to an area with a nonintact E-cadherin net structure. CD4+Langerin+ cells were also more superficially located in the DMPA group, although fewer in number compared to the controls. Natural plasma progesterone levels did not correlate with any of these parameters, whereas estradiol levels were positively correlated with E-cadherin expression and a more basal location for HIV target cells of the control group. CONCLUSIONS: DMPA users have a less robust epithelial layer and a more apical distribution of HIV target cells in the human ectocervix, which could confer a higher risk of HIV infection. Our results highlight the importance of assessing intact genital tissue samples to gain insights into HIV susceptibility factors.

Utilizing the codon adaptation index to evaluate the susceptibility to HIV-1 and SARS-CoV-2 related coronaviruses in possible target cells in humans.

Comprehensive identification of possible target cells for viruses is crucial for understanding the pathological mechanism of virosis. The susceptibility of cells to viruses depends on many factors. Besides the existence of receptors at the cell surface, effective expression of viral genes is also pivotal for viral infection. The regulation of viral gene expression is a multilevel process including transcription, translational initiation and translational elongation. At the translational elongation level, the translational efficiency of viral mRNAs mainly depends on the match between their codon composition and cellular translational machinery (usually referred to as codon adaptation). Thus, codon adaptation for viral ORFs in different cell types may be related to their susceptibility to viruses. In this study, we selected the codon adaptation index (CAI) which is a common codon adaptation-based indicator for assessing the translational efficiency at the translational elongation level to evaluate the susceptibility to two-pandemic viruses (HIV-1 and SARS-CoV-2) of different human cell types. Compared with previous studies that evaluated the infectivity of viruses based on codon adaptation, the main advantage of our study is that our analysis is refined to the cell-type level. At first, we verified the positive correlation between CAI and translational efficiency and strengthened the rationality of our research method. Then we calculated CAI for ORFs of two viruses in various human cell types. We found that compared to high-expression endogenous genes, the CAIs of viral ORFs are relatively low. This phenomenon implied that two kinds of viruses have not been well adapted to translational regulatory machinery in human cells. Also, we indicated that presumptive susceptibility to viruses according to CAI is usually consistent with the results of experimental research. However, there are still some exceptions. Finally, we found that two viruses have different effects on cellular translational mechanisms. HIV-1 decouples CAI and translational efficiency of endogenous genes in host cells and SARS-CoV-2 exhibits increased CAI for its ORFs in infected cells. Our results implied that at least in cases of HIV-1 and SARS-CoV-2, CAI can be regarded as an auxiliary index to assess cells' susceptibility to viruses but cannot be used as the only evidence to identify viral target cells.

Determining ADCC Activity of Antibody-Based Therapeutic Molecules using Two Bioluminescent Reporter-Based Bioassays.

Antibody Fc effector function is one of the main mechanisms of action (MoA) for therapeutic monoclonal antibodies. Measurement of antibody-dependent cellular cytotoxicity (ADCC) is critical for understanding the Fc effector function during monoclonal antibody development. This article covers two cell-based ADCC bioassays which can quantitatively measure the antibody potency in ADCC. Basic Protocol 1 describes the ADCC reporter bioassay using engineered ADCC effector cells which measures the FcγRIIIa-mediated luciferase reporter activation upon the binding of antibody-coated target cells. Basic Protocol 2 describes the PBMC ADCC bioassay using primary peripheral blood mononuclear cells (PBMC) as effector cells and engineered HiBiT target cells in an assay that measures the release of HiBiT from target cells upon antibody-mediated target lysis. Optimization of several key assay parameters including cell handling, effector:target (E:T) ratios, assay plate, and plate reader requirement, and how these parameters impact assay performance are discussed. © 2021 Promega Corporation. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: ADCC reporter bioassay using engineered ADCC bioassay effector cells Basic Protocol 2: PBMC ADCC bioassay using primary PBMC and engineered HiBiT target cells.

[In the search of mobile target for acupuncture: why is mast cell?]

Both clinical practice and basic research of acupuncture have pointed out that acupuncture treatment has specific tissue and cellular targets. In addition to the known fixed tissue targets such as nerves and blood vessels, the author analyzes the biological characteristics of other skin resident cells in the skin and concludes that cutaneous mast cells are the most suitable candidate for the cellular target of acupuncture. A hypothesis of the bionic acupuncture is proposed to explain the biological principles by which the innate immunity and healing system respond to acupuncture. The distribution of mast cells in the human skin is characterized by "approaching to the terminals and gathering at the orifices", and the cell density is highly correlated with the density of acupoints and the micro-acupuncture systems. These evidences all support that mast cells are the mobile target cells for acupuncture, which can explain some clinical phenomena and principles of acupuncture, and suggest mast cells as one of the tissue markers for acupoints.

Antigen-Specific In Vivo Killing Assay.

The in vivo killing assay allows the quantification of the antigen-specific killing capacity of Cytotoxic CD8+ T Lymphocytes (CTLs) in mice. CTLs are indeed known for the lysis of cells expressing foreign or modified antigen peptides on their MHC class I molecules. Here we describe the detailed protocol used for the in vivo specific lysis of cells expressing the H-2 Kb immunodominant CD8+ T-cell epitope of the OVA protein: an 8 amino acid peptide corresponding to the 257-264 region of OVA (SIINFEKL).

Reproductive tract immune cells from pregnant women or those using depot medroxyprogesterone acetate show no excess susceptibility to HIV-1: Results of an ex vivo fusion assay.

INTRODUCTION: Ex vivo fusion assays offer an efficient method for studying HIV-1 entry associated with contraceptive use and pregnancy outside of cohort studies of HIV-1 incidence. METHODS: We measured ex vivo HIV-1 fusion to cervical or endometrial immune cells from three groups of women: pregnant, non-pregnant not using hormonal or intrauterine contraception, and using depot medroxyprogesterone acetate (DMPA). RESULTS AND CONCLUSIONS: There was no excess susceptibility to HIV-1 fusion of cells from pregnant women or DMPA users compared to controls. Although the number of target cells in endometrium was higher in DMPA users compared to controls, HIV-1 fusion was lower. IMPLICATIONS: In ex vivo assays, HIV-1 showed no enhanced fusion to cervical immune cells from pregnant women or DMPA users compared to controls, and lower fusion to endometrial immune cells from DMPA users. This assay is useful for studying hormonal and contraceptive effects on HIV-1 entry into reproductive tract immune cells.

Review on mechanistic strategy of gene therapy in the treatment of disease.

Gene therapy has become a revolution and its breakthrough is a corner stone in modern science. This treatment has rising advantages with limited negative aspects. Gene therapy is a therapeutic method in which, transfer of DNA to an individual to manipulate a defective gene is performed and to mitigate a disease which is not responding to pharmacological therapy. The gene therapy strategies are divided into two main categories such as direct in-vivo gene delivery of manipulated viral vector vehicle into the host and ex-vivo genetically engineered stem cells. In this review, we tried to cover all aspects of gene therapy studies; starting with the concept of gene, its treatment, gene delivery system and types, clinical trial either by vitro or In-Vivo -Clinical Trials and Clinical Intoxication of Gene Therapy. Therefore, the promise of successful treatment with gene therapy could positively affect millions of lives. The main aim of this review is to address the principles of gene therapy, various methods involved in the gene therapy, clinical applications and its merits and demerits.

In the search of mobile target for acupuncture: why is mast cell? / 中国针灸

Both clinical practice and basic research of acupuncture have pointed out that acupuncture treatment has specific tissue and cellular targets. In addition to the known fixed tissue targets such as nerves and blood vessels, the author analyzes the biological characteristics of other skin resident cells in the skin and concludes that cutaneous mast cells are the most suitable candidate for the cellular target of acupuncture. A hypothesis of the bionic acupuncture is proposed to explain the biological principles by which the innate immunity and healing system respond to acupuncture. The distribution of mast cells in the human skin is characterized by "approaching to the terminals and gathering at the orifices", and the cell density is highly correlated with the density of acupoints and the micro-acupuncture systems. These evidences all support that mast cells are the mobile target cells for acupuncture, which can explain some clinical phenomena and principles of acupuncture, and suggest mast cells as one of the tissue markers for acupoints.

Marine toxin domoic acid induces in vitro genomic alterations in human peripheral blood cells.

Domoic acid (DA) is an excitatory marine neurotoxin produced by diatoms Pseudo-nitzschia spp. as a defence compound that accumulates in the food web and is associated with amnesic shellfish poisoning in humans. Although its toxicity has been well established in marine species, there is limited data on DA cytogenotoxicity in human non-target cells. Therefore, we aimed to investigate the cytogenotoxic potential of DA (0.01-10 µg/mL) in human peripheral blood cells (HPBCs) using a battery of bioassays in vitro. In addition, the influence of DA on oxidative stress parameters as a possible mechanism of action was assessed. Results revealed that DA induced dose- and time-dependent cytotoxic effects. DA significantly affected genomic instability by increasing the frequency of micronuclei and nuclear buds. Furthermore, a slight induction of primary DNA strand breaks was detected after 24 h of exposure accompanied by a significant increase in the number of abnormal size tailed nuclei. No induction of hOGG1 (human 8-oxoguanine DNA glycosylase) sensitive sites was determined upon exposure to DA. Additionally, DA induced oxidative stress by increased production of reactive oxygen species accompanied by changes in glutathione, superoxide dismutase, malondialdehyde and protein carbonyl levels. Overall, the obtained results showed adverse genotoxic effects of DA in non-target HPBCs.

Extracellular Vesicles: The Next Frontier in Regenerative Medicine and Drug Delivery.

Extracellular vesicles (EVs) are nanosized membrane particles secreted by cells to convey intercellular information. In recent years, EVs have enticed scientists owing to their prevalent distribution, enormous possibility as therapeutic aspirants, and probable roles as disease biomarkers. As natural transporters in the endogenous communication system, they play a role in protein, lipid, miRNA, mRNA, and DNA transport. In this chapter, we recapitulate the roles of EVs in the vast field of regenerative medicine. This summary mainly describes the potential roles of EVs in the regeneration of extensively studied organs or tissues, such as the heart, kidney, lung, liver, skin, and hair. Furthermore, EV can also transport drugs and corroborate their uptake by target cells through endocytosis; therefore, this chapter also highlights the use of EVs in the field of drug delivery.