Improving Fertility in Non-obstructive Azoospermia: Results from an Autologous Bone Mar-row-Derived Mesenchymal Stromal/Stem Cell Phase I Clinical Trial.

BACKGROUND: In this phase I clinical trial, our primary objective was to develop an innovative therapeutic approach utilizing autologous bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) for the treatment of nonobstructive azoospermia (NOA). Additionally, we aimed to assess the feasibility and safety of this approach. MATERIALS AND METHODS: We recruited 80 participants in this non-randomized, open-label clinical trial, including patients undergoing NOA treatment using autologous BM-MSCs (n=40) and those receiving hormone therapy as a control group (n=40). Detailed participant characteristics, such as age, baseline hormonal profiles, etiology of NOA, and medical history, were thoroughly documented. Autotransplantation of BM-MSCs into the testicular network was achieved using microsurgical testicular sperm extraction (microTESE). Semen analysis and hormonal assessments were performed both before and six months after treatment. Additionally, we conducted an in-silico analysis to explore potential protein-protein interactions between exosomes secreted from BM-MSCs and receptors present in human seminiferous tubule cells. RESULTS: Our results revealed significant improvements following treatment, including increased testosterone and inhibin B levels, elevated sperm concentration, and reduced levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Notably, in nine patients (22.5%) previously diagnosed with secondary infertility and exhibiting azoospermia before treatment, the proposed approach yielded successful outcomes, as indicated by hormonal profile changes over six months. Importantly, these improvements were achieved without complications. Additionally, our in-silico analysis identified potential binding interactions between the protein content of BM-MSC-derived exosomes and receptors integral to spermatogenesis. CONCLUSION: Autotransplantation of BM-MSCs into the testicular network using microTESE in NOA patients led to the regeneration of seminiferous tubules and the regulation of hormonal profiles governing spermatogenesis. Our findings support the safety and effectiveness of autologous BM-MSCs as a promising treatment modality for NOA, with a particular focus on the achieved outcomes in patients with secondary infertility (registration number: IRCT20190519043634N1).

Proliferating and migrating effects of regenerating sea anemone Aulactinia stella cells-derived exosomes on human skin fibroblasts.

Regenerative effects of sea anemone-derived exosomes on human foreskin fibroblasts (HFFs) were investigated. Water-based extracts from regenerating Aulactinia stella tissue were collected at various time points, and exosomes were extracted after inducing wounds. Both the extract and exosomes were tested on HFF for proliferation and in vitro wound healing. In silico analysis explored protein-protein docking between regenerative exosome proteins and HFF receptors. The MTT (3-(4,5-dimethylthiazol-2yl)-2,5 diphenyltetrazolium bromide proliferation assay and in vitro wound healing test of aquatic extract showed proliferative effects on HFF cell lines, with the 60 µg/mL concentration significantly enhancing cell migration. Exosomes were characterised. Exosomes showed a significantly positive effect on cell proliferation and migration at the 50 µg/mL concentration 48 h post-wound induction. In silico analysis revealed potential binding affinities between exosome proteins and HFF receptors. In conclusion, optimised concentrations of A. stella-derived exosomes exhibited positive effects on HFF regeneration and migration, suggesting their potential in accelerating wound healing.

Comprehensive Overview of Innovative Strategies in Preventing Renal Ischemia-reperfusion Injury: Insights from Bibliometric and In Silico Analyses.

BACKGROUND: Ischemia-Reperfusion Injury (IRI) is a complex pathophysiological process with severe consequences, including irreversible loss of renal function. Various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and kidney reperfusion. AIM: This comprehensive analysis provides an overview of pharmacological agents and intraoperative methods for preventing and treating renal IRI. METHODS: Our analysis revealed that eplerenone exhibited the highest binding affinity to crucial targets, including Aldehyde Dehydrogenase (AD), Estrogen Receptor (ER), Klotho protein, Mineralocorticoid Receptor (MR), and Toll-Like Receptor 4 (TLR4). This finding indicates eplerenone's potential as a potent preventive agent against IRI, surpassing other available therapeutics like Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. In preventing kidney IRI, our comprehensive analysis emphasizes the significance of eplerenone due to its strong binding affinity to key targets involved in the pathogenesis of IRI. RESULTS: This finding positions eplerenone as a promising candidate for further clinical investigation and consideration for future clinical practice. CONCLUSION: The insights provided in this analysis will assist clinicians and researchers in selecting effective preventive approaches for renal IRI in surgical settings, potentially improving patient outcomes.

A Review of the Metal Additive Manufacturing Processes.

Metal additive manufacturing (AM) is a layer-by-layer process that makes the direct manufacturing of various industrial parts possible. This method facilitates the design and fabrication of complex industrial, advanced, and fine parts that are used in different industry sectors, such as aerospace, medicine, turbines, and jewelry, where the utilization of other fabrication techniques is difficult or impossible. This method is advantageous in terms of dimensional accuracy and fabrication speed. However, the parts fabricated by this method may suffer from faults such as anisotropy, micro-porosity, and defective joints. Metals like titanium, aluminum, stainless steels, superalloys, etc., have been used-in the form of powder or wire-as feed materials in the additive manufacturing of various parts. The main criterion that distinguishes different additive manufacturing processes from each other is the deposition method. With regard to this criterion, AM processes can be divided into four classes: local melting, sintering, sheet forming, and electrochemical methods. Parameters affecting the properties of the additive-manufactured part and the defects associated with an AM process determine the method by which a certain part should be manufactured. This study is a survey of different additive manufacturing processes, their mechanisms, capabilities, shortcomings, and the general properties of the parts manufactured by them.

Genetic and epigenetic factors of arterial hypertension: a bibliometric- and in-silico-based analyses.

Introduction: Arterial hypertension (AH) is a pervasive global health concern with multifaceted origins encompassing both genetic and environmental components. Previous research has firmly established the association between AH and diverse genetic factors. Consequently, scientists have conducted extensive genetic investigations in recent years to unravel the intricate pathophysiology of AH. Methods: In this study, we conducted a comprehensive bibliometric analysis employing VOSviewer software to identify the most noteworthy genetic factors that have been the focal point of numerous investigations within the AH field in recent years. Our analysis revealed genes and microRNAs intricately linked to AH, underscoring their pivotal roles in this condition. Additionally, we performed molecular docking analyses to ascertain microRNAs with the highest binding affinity to these identified genes. Furthermore, we constructed a network to elucidate the in-silico-based functional interactions between the identified microRNAs and genes, shedding light on their potential roles in AH pathogenesis. Results: Notably, this pioneering in silico examination of genetic factors associated with AH promises novel insights into our understanding of this complex condition. Our findings prominently highlight miR-7110-5p, miR-7110-3p, miR-663, miR-328-3p, and miR-140-5p as microRNAs exhibiting a remarkable affinity for target genes. These microRNAs hold promise as valuable diagnostic and therapeutic factors, offering new avenues for the diagnosis and treatment of AH in the foreseeable future. Conclusion: In summary, this research underscores the critical importance of genetic factors in AH and, through in silico analyses, identifies specific microRNAs with significant potential for further investigation and clinical applications in AH management.

MRI Tracking of Marine Proliferating Cells In Vivo Using Anti-Oct4 Antibody-Conjugated Iron Nanoparticles for Precision in Regenerative Medicine.

Marine invertebrates are multicellular organisms consisting of a wide range of marine environmental species. Unlike vertebrates, including humans, one of the challenges in identifying and tracking invertebrate stem cells is the lack of a specific marker. Labeling stem cells with magnetic particles provides a non-invasive, in vivo tracking method using MRI. This study suggests antibody-conjugated iron nanoparticles (NPs), which are detectable with MRI for in vivo tracking, to detect stem cell proliferation using the Oct4 receptor as a marker of stem cells. In the first phase, iron NPs were fabricated, and their successful synthesis was confirmed using FTIR spectroscopy. Next, the Alexa Fluor anti-Oct4 antibody was conjugated with as-synthesized NPs. Their affinity to the cell surface marker in fresh and saltwater conditions was confirmed using two types of cells, murine mesenchymal stromal/stem cell culture and sea anemone stem cells. For this purpose, 106 cells of each type were exposed to NP-conjugated antibodies and their affinity to antibodies was confirmed by an epi-fluorescent microscope. The presence of iron-NPs imaged with the light microscope was confirmed by iron staining using Prussian blue stain. Next, anti-Oct4 antibodies conjugated with iron NPs were injected into a brittle star, and proliferating cells were tracked by MRI. To sum up, anti-Oct4 antibodies conjugated with iron NPs not only have the potential for identifying proliferating stem cells in different cell culture conditions of sea anemone and mouse cell cultures but also has the potential to be used for in vivo MRI tracking of marine proliferating cells.

Application of bioactive glasses in various dental fields.

Bioactive glasses are a group of bioceramic materials that have extensive clinical applications. Their properties such as high biocompatibility, antimicrobial features, and bioactivity in the internal environment of the body have made them useful biomaterials in various fields of medicine and dentistry. There is a great variation in the main composition of these glasses and some of them whose medical usage has been approved by the US Food and Drug Administration (FDA) are called Bioglass. Bioactive glasses have appropriate biocompatibility with the body and they are similar to bone hydroxyapatite in terms of calcium and phosphate contents. Bioactive glasses are applied in different branches of dentistry like periodontics, orthodontics, endodontics, oral and maxillofacial surgery, esthetic and restorative dentistry. Also, some dental and oral care products have bioactive glasses in their compositions. Bioactive glasses have been used as dental implants in the human body in order to repair and replace damaged bones. Other applications of bioactive glasses in dentistry include their usage in periodontal disease, root canal treatments, maxillofacial surgeries, dental restorations, air abrasions, dental adhesives, enamel remineralization, and dentin hypersensitivity. Since the use of bioactive glasses in dentistry is widespread, there is a need to find methods and extensive resources to supply the required bioactive glasses. Various techniques have been identified for the production of bioactive glasses, and marine sponges have recently been considered as a rich source of it. Marine sponges are widely available and many species have been identified around the world, including the Persian Gulf. Marine sponges, as the simplest group of animals, produce different bioactive compounds that are used in a wide range of medical sciences. Numerous studies have shown the anti-tumor, anti-viral, anti-inflammatory, and antibiotic effects of these compounds. Furthermore, some species of marine sponges due to the mineral contents of their structural skeletons, which are made of biosilica, have been used for extracting bioactive glasses.

Mesenchymal Stromal/Stem Cells-Derived Exosomes as an Antimicrobial Weapon for Orodental Infections.

The oral cavity as the second most various microbial community in the body contains a broad spectrum of microorganisms which are known as the oral microbiome. The oral microbiome includes different types of microbes such as bacteria, fungi, viruses, and protozoa. Numerous factors can affect the equilibrium of the oral microbiome community which can eventually lead to orodental infectious diseases. Periodontitis, dental caries, oral leukoplakia, oral squamous cell carcinoma are some multifactorial infectious diseases in the oral cavity. In defending against infection, the immune system has an essential role. Depending on the speed and specificity of the reaction, immunity is divided into two different types which are named the innate and the adaptive responses but also there is much interaction between them. In these responses, different types of immune cells are present and recent evidence demonstrates that these cell types both within the innate and adaptive immune systems are capable of secreting some extracellular vesicles named exosomes which are involved in the response to infection. Exosomes are 30-150 nm lipid bilayer vesicles that consist of variant molecules, including proteins, lipids, and genetic materials and they have been associated with cell-to-cell communications. However, some kinds of exosomes can be effective on the pathogenicity of various microorganisms and promoting infections, and some other ones have antimicrobial and anti-infective functions in microbial diseases. These discrepancies in performance are due to the origin of the exosome. Exosomes can modulate the innate and specific immune responses of host cells by participating in antigen presentation for activation of immune cells and stimulating the release of inflammatory factors and the expression of immune molecules. Also, mesenchymal stromal/stem cells (MSCs)-derived exosomes participate in immunomodulation by different mechanisms. Ease of expansion and immunotherapeutic capabilities of MSCs, develop their applications in hundreds of clinical trials. Recently, it has been shown that cell-free therapies, like exosome therapies, by having more advantages than previous treatment methods are emerging as a promising strategy for the treatment of several diseases, in particular inflammatory conditions. In orodental infectious disease, exosomes can also play an important role by modulating immunoinflammatory responses. Therefore, MSCs-derived exosomes may have potential therapeutic effects to be a choice for controlling and treatment of orodental infectious diseases.

An Inference Attack on Genomic Data Using Kinship, Complex Correlations, and Phenotype Information.

Individuals (and their family members) share (partial) genomic data on public platforms. However, using special characteristics of genomic data, background knowledge that can be obtained from the Web, and family relationship between the individuals, it is possible to infer the hidden parts of shared (and unshared) genomes. Existing work in this field considers simple correlations in the genome (as well as Mendel's law and partial genomes of a victim and his family members). In this paper, we improve the existing work on inference attacks on genomic privacy. We mainly consider complex correlations in the genome by using an observable Markov model and recombination model between the haplotypes. We also utilize the phenotype information about the victims. We propose an efficient message passing algorithm to consider all aforementioned background information for the inference. We show that the proposed framework improves inference with significantly less information compared to existing work.

Evaluation of Effects of Intraperitoneal CO2 Pressure in Laparoscopic Operations on Kidney, Pancreas, Liver and Spleen in Dogs.

BACKGROUND: During laparoscopy, insufflation of an inert gas in the peritoneal cavity creates a working space to facilitate surgery. The space should be large enough to facilitate surgery without increasing intra-abdominal pressure (IAP) over a threshold limit (usually 15 mm Hg). OBJECTIVES: This experimental study was performed to evaluate the effects of increasing in intra-abdominal pressure on internal organs. MATERIALS AND METHODS: Twenty female mixed breed dogs (20 ± 3 kg, 18 ± 1.2 months) were selected. They were randomly divided to two groups (n = 10). The intra-abdominal pressure was maintained 12 mm Hg and 20 mm Hg during the operation in control group and in test group respectively. RESULTS: Histopathologic evaluations revealed more pathological changes at the kidney of all the dogs in test group in comparison to control group. CONCLUSIONS: Our findings revealed that organs that their blood supplies are related to one single or two arteries and their blood drainage are related to one or two veins are more sensitive to increased intra-abdominal pressure.