Dual Checkpoint Inhibition in M2 Macrophages via Anti-PD-L1 and siRNA-Loaded M1-Exosomes: Enhancing Tumor Immunity through RNA-Targeting Strategies.

The interaction between a cluster of differentiation 47 (CD47) on cancer cells and signal regulatory protein alpha (SIRPα) on macrophages is thought to hinder macrophage phagocytic activity, which can be blocked by combining siRNAs targeting SIRPα (siSIRPα) with simultaneous involvement of activating receptors like FcRs (Fc receptors) anti-programmed death-ligand 1 (anti-PD-L1). For this study, M1 macrophage-derived exosomes were used to deliver the siRNAs, isolated from lipopolysaccharide (LPS)-stimulated RAW264.7 cells and electroporated with siSIRPα.

Enhancing the anti-tumor activity and reprogramming M2 macrophages by delivering siRNAs against SIRPα and STAT6 via M1 exosomes and combining with anti-PD-L1.

Background: The invasive property of breast cancer and the complex composition of the tumor microenvironment (TME) antibodies like anti-PD-L1, can inhibit tumor growth by promoting macrophage phagocytosis. In this research, we used anti-PD-L1 antibody and siRNAs targeting SIRPα (siSIRPα) and STAT6 (siSTAT6). The siRNAs were transported to macrophages using M1-derived exosomes.

The differential effects of blocking retinal orexin receptors on the expression of retinal c-fos and hypothalamic Vip, PACAP, Bmal1, and c-fos in Male Wistar Rats.

Orexin A and B (OXA and OXB) and their receptors are expressed in the majority of retinal neurons in humans, rats, and mice. Orexins modulate signal transmission between the different layers of the retina. The suprachiasmatic nucleus (SCN) and the retina are central and peripheral components of the body's biological clocks; respectively.

7SK small nuclear RNA (Rn7SK) induces apoptosis through intrinsic and extrinsic pathways in human embryonic kidney cell line.

Background: Rn7SK, a highly conserved small nuclear non-coding RNA, controls Polymerase II transcription machinery by activating of the Positive Transcriptional Elongation Factor b (P-TEFb). Apart from its role in transcriptional regulation, the potential functions of Rn7SK in cell apoptosis are poorly understood. In a previous study, we demonstrated that overexpression of 7SK induces apoptosis in HEK cells.

Engineering chimeric autoantibody receptor T cells for targeted B cell depletion in multiple sclerosis model: An study.

Background: Recent evidence suggests that B cells and autoantibodies have a substantial role in the pathogenesis of Multiple sclerosis. T cells could be engineered to express chimeric autoantibody receptors (CAARs), which have an epitope of autoantigens in their extracellular domain acting as bait for trapping autoreactive B cells. This study aims to assess the function of designed CAAR T cells against B cell clones reactive to the myelin basic protein (MBP) autoantigen.

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view.

Autophagy is a highly conserved, lysosome-dependent biological mechanism involved in the degradation and recycling of cellular components. There is growing evidence that autophagy is related to male reproductive biology, particularly spermatogenic and endocrinologic processes closely associated with male sexual and reproductive health. In recent decades, problems such as decreasing sperm count, erectile dysfunction, and infertility have worsened.

In vitro naive CD4 T cell differentiation upon treatment with miR-29b-loaded exosomes from mesenchymal stem cells.

Background: Gene regulation by microRNA (miRNA) is central in T lymphocytes differentiation processes. Here, we investigate miRNA-29b (miR-29b) roles in the reprogramming of T cell differentiation, which can be a promising therapeutic avenue for various types of inflammatory disorders such as rheumatoid arthritis and multiple sclerosis.

Methods And Results: Adipose Mesenchymal Stem Cell-derived exosomes (AMSC-Exo) enriched with miR-29b were delivered into naive CD4 T (nCD4) cells.

Effect of miR-18a-5p, miR-19a-3p, and miR-20a-5p on Cardiomyocyte Differentiation of Human Endometrium Tissue-Derived Stem Cells Through Regulation of Smad4 Expression.

Background: Smad4 regulates the expression of the genes required for heart homeostasis. Regarding the central role of microRNAs in cardiac biology, we investigated the expression of the three Smad4-targeting miRNAs, namely miR-18a-5p, miR-19a-3p, and miR-20a-5p, as well as Smad4 during differentiation of human endometrium-derived mesenchymal stem cells (hEMSCs) into cardiomyocytes (CMs).

Methods: To evaluate mesenchymal phenotype and multi-lineage differentiation ability of hEMSCs, immunophenotyping by flow cytometry and differentiation into osteoblasts and adipocytes were performed, respectively.

Rapid identification of bacteria by the pattern of redox reactions rate using 2',7'-dichlorodihydrofluorescein diacetate.

Bacterial infection is a life-threatening situation, and its rapid diagnosis is essential for treatment. Apart from medical applications, rapid identification of bacteria is vital in the food industry or the public health system. There are various bacterial identification techniques, including molecular-based methods, immunological approaches, and biosensor-based procedures.

Exosomal delivery of 7SK long non-coding RNA suppresses viability, proliferation, aggressiveness and tumorigenicity in triple negative breast cancer cells.

Aims: RN7SK (7SK), a highly conserved non-coding RNA, serves as a transcription regulator via interaction with a few proteins. Despite increasing evidences which support the cancer-promoting roles of 7SK-interacting proteins, limited reports address the direct link between 7SK and cancer. To test the hypothetic suppression of cancer by overexpression of 7SK, the effects of exosomal 7SK delivery on cancer phenotypes were studied.

Repairing rat calvarial defects by adipose mesenchymal stem cells and novel freeze-dried three-dimensional nanofibrous scaffolds.

Treatment of critical-sized bone defects is challenging. Tissue engineering as a state-of-the-art method has been concerned with treating these non-self-healing bone defects. Here, we studied the potentials of new three-dimensional nanofibrous scaffolds (3DNS) with and without human adipose mesenchymal stem cells (ADSCs) for reconstructing rat critical-sized calvarial defects (CSCD).

Inhibition of the retinal orexin receptors affects the hypothalamic-pituitary-gonadal axis through retinal pituitary adenylate cyclase activating polypeptide (PACAP) in male Wistar rats.

Orexins A and B (OXA and OXB) and their receptors are expressed in the retina of both human and rodents and play a vital role in regulating signal transmission circuits in the retina. There is an anatomical-physiological relationship between the retinal ganglion cells and suprachiasmatic nucleus (SCN) through glutamate as a neurotransmitter and retinal pituitary adenylate cyclase-activating polypeptide (PACAP) as a co-transmitter. SCN is the main brain center for regulating the circadian rhythm, which governs the reproductive axis.

RNAa-mediated epigenetic attenuation of the cell senescence via locus specific induction of endogenous SIRT1.

SIRT1, a known regulator of cellular senescence, is a therapeutic target for age related disorders and its upregulation is a strategy to improve the cell therapeutic potentials of human mesenchymal stem cell (MSCs). Knockdown of natural antisense transcripts via small activating RNAs (RNAa) is an emerging approach for safe and locus specific gene regulation. We have recently identified a natural antisense transcript at human SIRT1 locus (SIRT1-NAT), the expression of which shows a negative correlation with that of SIRT1.

Investigating the Effects of Maternal Separation on Hypothalamic-Pituitary-Adrenal Axis and Glucose Homeostasis under Chronic Social Defeat Stress in Young Adult Male Rat Offspring.

Introduction: Given the suggested metabolic regulatory effects of stress-responsive genes and based on the impacts of early-life stress on HPA axis development, this study aimed to characterize the maternal separation (MS) impact on the communication between glucose metabolism and HPA axis dysregulations under chronic social defeat stress (CSDS).

Methods: During the first 2 weeks of life, male Wistar rats were either exposed to MS or left undisturbed with their mothers (Std). Starting on postnatal day 50, the animals of each group were either left undisturbed in the standard group housing (Con) or underwent CSDS for 3 weeks.

Oxidative and endoplasmic reticulum stress develop adverse metabolic effects due to the high-fat high-fructose diet consumption from birth to young adulthood.

Aims: The early postnatal dietary intake has been considered a crucial factor affecting the offspring later life metabolic status. Consistently, this study investigated the oxidative and endoplasmic reticulum (ER) stress interventions in the induction of adverse metabolic effects due to the high-fat high-fructose diet (HFHFD) consumption from birth to young adulthood in rat offspring.

Materials And Methods: After delivery, the dams with their pups were randomly allocated into the normal diet (ND) and HFHFD groups.

Maternal stress induced endoplasmic reticulum stress and impaired pancreatic islets' insulin secretion via glucocorticoid receptor upregulation in adult male rat offspring.

Exposure to perinatal (prenatal and/or postnatal) stress is considered as a risk factor for metabolic disorders in later life. Accordingly, this study aimed to investigate the perinatal stress effects on the pancreatic endoplasmic reticulum (ER) stress induction, insulin secretion impairment and WFS1 (wolframin ER transmembrane Glycoprotein, which is involved in ER homeostasis and insulin secretion) expression changes, in rat offspring. According to the dams' period of exposure to variable stress, their male offspring were divided into, control (CTRL); pre-pregnancy, pregnancy, lactation stress (PPPLS); pre-pregnancy stress (PPS); pregnancy stress (PS); lactation stress (LS); pre-pregnancy, pregnancy stress (PPPS); pregnancy, lactation stress (PLS); pre-pregnancy, lactation stress (PPLS) groups.

The Use of Trichostatin A during Pluripotent Stem Cell Generation Does Not Affect MHC Expression Level.

Pluripotent stem cells (PSCs) are considered as a potent tool for use in regenerative medicine. Highly efficient generation of PSCs through chromatin modulators such as trichostatin A (TSA) might change their MHC molecule expression profile. The efficiency of PSC generation and their immunogenicity is major obstacles for clinical use.

Optimization of Topography and Surface Properties of Polyacrylonitrile-Based Electrospun Scaffolds via Nonoclay Concentrations and its Effect on Osteogenic Differentiation of Human Mesenchymal Stem Cells.

Nowadays, mesenchymal stem cells (MSCs) are the most widely used cell sources for bone regenerative medicine. Electrospun polyacrylonitrile (PAN)-based scaffolds play an important role in bone tissue engineering due to their good mechanical properties, which could be enhanced by the presence of nanoparticles such as nanoclay. This study evaluated the effect of different concentrations of nanoclay in surface characteristic properties of PAN-based electrospun nanofiber scaffolds and the osteogenic differentiation ability of adipose-derived mesenchymal stem cells (AD-MSCs).

miR-146b-5p and miR-520h Expressions Are Upregulated in Serum of Women with Recurrent Spontaneous Abortion.

Unexplained recurrent spontaneous abortion (URSA) is characterized by two or more consecutive pregnancy losses before the 20th week of gestation with unknown etiology. Dysregulation of microRNAs (miRNAs) expression has been reported in reproductive diseases. This study aimed to compare differentially expressed miRNAs in the serum samples between URSA patients and healthy individuals.

Dendritic cell immunotherapy with miR-155 enriched tumor-derived exosome suppressed cancer growth and induced antitumor immune responses in murine model of colorectal cancer induced by CT26 cell line.

Nowadays, various strategies are considered to prime Dendritic cells (DCs) with tumor antigens. The tumor cell-derived exosomes are recognized as one of the most efficient strategies for achieving this purpose. In this regard, MicroRNA 155 (miR-155) is employed as one of the most prominent miRNAs, which play substantial roles in DCs maturation and IL-12 production.

MicroRNAs and exosomes: Cardiac stem cells in heart diseases.

Treating cardiovascular diseases with cardiac stem cells (CSCs) is a valid treatment among various stem cell-based therapies. With supplying the physiological need for cardiovascular cells as their main function, under pathological circumstances, CSCs can also reproduce the myocardial cells. Although studies have identified many of CSCs' functions, our knowledge of molecular pathways that regulate these functions is not complete enough.

Evaluating the influence of Human Umbilical Cord Mesenchymal Stem Cells-derived exosomes loaded with miR-3182 on metastatic performance of Triple Negative Breast Cancer cells.

Aims: Deregulation of microRNA (miRNA) function has been linked to numerous human cancers, such as Triple Negative Breast Cancer (TNBC). Exosomes, a subgroup of extracellular vehicles (EVs), can efficiently deliver many different cargo types to the target cell and have an extensive role in delivering therapeutic cargo for treatment. The present study intended to interrogate the effects of exosomal delivery of miR-3182 on TNBC cellular processes.

MicroRNA Targeting.

MicroRNAs (miRNAs) are small noncoding elements that play essential roles in the posttranscriptional regulation of biochemical processes. miRNAs recognize and target multiple mRNAs; therefore, investigating miRNA dysregulation is an indispensable strategy to understand pathological conditions and to design innovative drugs. Targeting miRNAs in diseases improve outcomes of several therapeutic strategies thus, this present study highlights miRNA targeting methods through experimental assays and bioinformatics tools.

Antimicrobial peptides as potential therapeutics for breast cancer.

Breast cancer is the most common and deadliest cancer in women worldwide. Although notable advances have been achieved in the treatment of breast cancer, the overall survival rate of metastatic breast cancer patients is still considerably low due to the development of resistance to breast cancer chemotherapeutic agents and the non-optimal specificity of the current generation of cancer medications. Hence, there is a growing interest in the search for alternative therapeutics with novel anticancer mechanisms.