Comparative Analysis of Stromal Vascular Fraction and Alternative Mechanisms in Bone Fracture Stimulation to Bridge the Gap between Nature and Technological Advancement: A Systematic Review.

BACKGROUND: Various stimulation methods, including electrical, ultrasound, mechanical, and biological interventions, are explored, each leveraging intricate cellular and molecular dynamics to expedite healing. The advent of stromal vascular fraction (SVF) marks a significant stride, offering multifarious benefits in bone healing, from enhanced bone formation to optimal vascular integration, drawing a harmonious balance between innate mechanisms and scientific advancements. METHODS: This systematic review was conducted focusing on literature from 2016 to 2023 and encompassing various bone healing stimulation mechanisms like SVF, electrical, ultrasound, and mechanical stimulation. The extracted data underwent meticulous synthesis and analysis, emphasizing comparative evaluations of mechanisms, applications, and outcomes of each intervention. RESULTS: The reviewed studies reveal the potential of SVF in bone fracture healing, with its regenerative and anti-inflammatory effects. The purification of SVF is crucial for safe therapeutic use. Characterization involves flow cytometry and microscopy. Studies show SVF's efficacy in bone regeneration, versatility in various contexts, and potential for clinical use. SVF appears superior to electrical, ultrasound, and mechanical stimulation, with low complications. CONCLUSIONS: This review compares bone healing methods, including SVF. It provides valuable insights into SVF's potential for bone regeneration. However, due to limited human studies and potential bias, cautious interpretation is necessary. Further research is essential to validate these findings and determine the optimal SVF applications in bone healing.

Analyzing the Clinical Potential of Stromal Vascular Fraction: A Comprehensive Literature Review.

Background: Regenerative medicine is evolving with discoveries like the stromal vascular fraction (SVF), a diverse cell group from adipose tissue with therapeutic promise. Originating from fat cell metabolism studies in the 1960s, SVF's versatility was recognized after demonstrating multipotency. Comprising of cells like pericytes, smooth muscle cells, and, notably, adipose-derived stem cells (ADSCs), SVF offers tissue regeneration and repair through the differentiation and secretion of growth factors. Its therapeutic efficacy is due to these cells' synergistic action, prompting extensive research. Methods: This review analyzed the relevant literature on SVF, covering its composition, action mechanisms, clinical applications, and future directions. An extensive literature search from January 2018 to June 2023 was conducted across databases like PubMed, Embase, etc., using specific keywords. Results: The systematic literature search yielded a total of 473 articles. Sixteen articles met the inclusion criteria and were included in the review. This rigorous methodology provides a framework for a thorough and systematic analysis of the existing literature on SVF, offering robust insights into the potential of this important cell population in regenerative medicine. Conclusions: Our review reveals the potential of SVF, a heterogeneous cell mixture, as a powerful tool in regenerative medicine. SVF has demonstrated therapeutic efficacy and safety across disciplines, improving pain, tissue regeneration, graft survival, and wound healing while exhibiting immunomodulatory and anti-inflammatory properties.

Stromal Vascular Fraction Therapy for Knee Osteoarthritis: A Systematic Review.

Background and Objectives: Knee osteoarthritis (OA) is a widespread joint disease, set to increase due to aging and rising obesity. Beyond cartilage degeneration, OA involves the entire joint, including the synovial fluid, bones, and surrounding muscles. Existing treatments, such as NSAIDs and corticosteroid injections, mainly alleviate symptoms but can have complications. Joint replacement surgeries are definitive but carry surgical risks and are not suitable for all. Stromal vascular fraction (SVF) therapy is a regenerative approach using cells from a patient's adipose tissue. SVF addresses as degenerative and inflammatory aspects, with potential for cartilage formation and tissue regeneration. Unlike traditional treatments, SVF may reverse OA changes. Being autologous, it reduces immunogenic risks. Materials and Methods: A systematic search was undertaken across PubMed, Medline, and Scopus for relevant studies published from 2017 to 2023. Keywords included "SVF", "Knee Osteoarthritis", and "Regenerative Medicine". Results: This systematic search yielded a total of 172 articles. After the removal of duplicates and an initial title and abstract screening, 94 full-text articles were assessed for eligibility. Of these, 22 studies met the inclusion criteria and were subsequently included in this review. Conclusions: This review of SVF therapy for knee OA suggests its potential therapeutic benefits. Most studies confirmed its safety and efficacy, and showed improved clinical outcomes and minimal adverse events. However, differences in study designs and sizes require a careful interpretation of the results. While evidence supports SVF's positive effects, understanding methodological limitations is key. Incorporating SVF is promising, but the approach should prioritize patient safety and rigorous research.

The Role of Oxidative Stress in the Induction and Development of Psoriasis.

Psoriasis cannot be completely cured and is often difficult to diagnose, which is why the search for new effective therapies and diagnostics is a highly relevant area of research. To identify new therapeutic compounds, the first step is to study the role of various factors underlying the development of psoriasis. One such factor is oxidative stress. In this review, we will consider the role of oxidative stress at different stages of psoriasis development, as well as biomarkers of oxidative stress that can potentially be used in the diagnosis of psoriasis and antioxidants, which are likely to be applied in the treatment of this disease.

Diagnostics of atherosclerosis: Overview of the existing methods.

Atherosclerosis was and remains an extremely common and serious health problem. Since the elderly are most at risk of cardiovascular risk, and the average life expectancy is increasing, the spread of atherosclerosis and its consequences increases as well. One of the features of atherosclerosis is its asymptomaticity. This factor makes it difficult to make a timely diagnosis. This entails the lack of timely treatment and even prevention. To date, in the arsenal of physicians, there is only a limited set of methods to suspect and fully diagnose atherosclerosis. In this review, we have tried to briefly describe the most common and effective methods for diagnosing atherosclerosis.

Hypotheses on Atherogenesis Triggering: Does the Infectious Nature of Atherosclerosis Development Have a Substruction?

Since the end of the 20th century, it has been clear that atherosclerosis is an inflammatory disease. However, the main triggering mechanism of the inflammatory process in the vascular walls is still unclear. To date, many different hypotheses have been put forward to explain the causes of atherogenesis, and all of them are supported by strong evidence. Among the main causes of atherosclerosis, which underlies these hypotheses, the following can be mentioned: lipoprotein modification, oxidative transformation, shear stress, endothelial dysfunction, free radicals' action, homocysteinemia, diabetes mellitus, and decreased nitric oxide level. One of the latest hypotheses concerns the infectious nature of atherogenesis. The currently available data indicate that pathogen-associated molecular patterns from bacteria or viruses may be an etiological factor in atherosclerosis. This paper is devoted to the analysis of existing hypotheses for atherogenesis triggering, and special attention is paid to the contribution of bacterial and viral infections to the pathogenesis of atherosclerosis and cardiovascular disease.

HDL-Based Therapy: Vascular Protection at All Stages.

It is known that lipid metabolism disorders are involved in a wide range of pathologies. These pathologies include cardiovascular, metabolic, neurodegenerative diseases, and even cancer. All these diseases lead to serious health consequences, which makes it impossible to ignore them. Unfortunately, these diseases most often have a complex pathogenesis, which makes it difficult to study them and, in particular, diagnose and treat them. HDL is an important part of lipid metabolism, performing many functions under normal conditions. One of such functions is the maintaining of the reverse cholesterol transport. These functions are also implicated in pathology development. Thus, HDL contributes to vascular protection, which has been demonstrated in various conditions: Alzheimer's disease, atherosclerosis, etc. Many studies have shown that serum levels of HDL cholesterol correlate negatively with CV risk. With these data, HDL-C is a promising therapeutic target. In this manuscript, we reviewed HDL-based therapeutic strategies that are currently being used or may be developed soon.

Proprotein Convertase Subtilisin/Kexin 9 as a Modifier of Lipid Metabolism in Atherosclerosis.

Despite being the most common treatment strategy in the management of atherosclerosis and subsequent cardiovascular disease, classical statin therapy has certain disadvantages, including numerous side effects. In addition, a regimen with daily administration of the drug is hard to comply with. Thus, there is a need for modern and more efficient therapeutic strategies in CVD treatment. There is extensive evidence indicating that PCSK9 promotes atherogenesis through a variety of mechanisms. Thus, new treatment methods can be developed that prevent or alleviate atherosclerotic cardiovascular disease by targeting PCSK9. Comprehensive understanding of its atherogenic properties is a necessary precondition for the establishment of new therapeutic strategies. In this review, we will summarize the available data on the role of PCSK9 in the development and progression of atherosclerosis. In the last section, we will consider existing PCSK9 inhibitors.

The Role of Pericytes in Regulation of Innate and Adaptive Immunity.

Pericytes are perivascular multipotent cells wrapping microvascular capillaries, where they support vasculature functioning, participate in tissue regeneration, and regulate blood flow. However, recent evidence suggests that in addition to traditionally credited structural function, pericytes also manifest immune properties. In this review, we summarise recent data regarding pericytes' response to different pro-inflammatory stimuli and their involvement in innate immune responses through expression of pattern-recognition receptors. Moreover, pericytes express various adhesion molecules, thus regulating trafficking of immune cells across vessel walls. Additionally, the role of pericytes in modulation of adaptive immunity is discussed. Finally, recent reports have suggested that the interaction with cancer cells evokes immunosuppression function in pericytes, thus facilitating immune evasion and facilitating cancer proliferation and metastasis. However, such complex and multi-faceted cross-talks of pericytes with immune cells also suggest a number of potential pericyte-based therapeutic methods and techniques for cancer immunotherapy and treatment of autoimmune and auto-inflammatory disorders.

Emerging role of pericytes in therapy of cardiovascular diseases.

Pericytes are mural vascular cells covering microvascular capillaries, where they contribute to the formation, maturation, maintenance, stabilisation and remodelling of vasculature. They actively interact and communicate with other cells to maintain the capillary structural integrity, vascular permeability and blood flow. Pericytes are crucial participants in the physiological and pathological processes of cardiovascular disease. In this review, we summarise recent data regarding pericyte metabolism, trans-differentiation, angiogenesis and immunomodulation in connection with different cardiovascular pathologies. Further, we discuss an application of pericytes as a new cell therapy approach to treat coronary artery disease, congenital heart disease, atherosclerotic plaques calcification and calcific valvular heart disease in different in vivo animal models and in vitro studies. Also, we discuss different methods and pharmacological therapies for CVDs treatment with pericyte-mediated effects. Finally, we present a comprehensive overview of the role of pericytes in CVDs and as a pharmacological target for different novel drugs and techniques and highlight the potential application of pericytes to treat CVDs.

Differences in Synovial Cytokine Profile Associated with Long-Term Clinical Outcomes in Patients with Knee Osteoarthritis Undergoing Corrective Osteotomy with Platelet-Rich Plasma or Stromal Vascular Fraction Post-Treatments.

Functional outcomes and synovial fluid (SF) cytokine concentrations in response to platelet-rich plasma (PRP) or stromal vascular fraction (SVF) post-treatments following open wedge high tibial osteotomy (HTO) in 20 patients with knee osteoarthritis (OA) were examined. Six weeks after surgery, the knees of 10 patients were injected with autologous PRP (PRP subgroup), while another 10 patients were injected with autologous SVF (SVF subgroup) and monitored for 1.5 years. Pain assessment (VAS score) and functional activity (KOOS, KSS, Outerbridge, and Koshino scores) were applied. PRP subgroup performed better compared with the SVF subgroup according to KOOS, KSS, and VAS scores, while the SVF subgroup demonstrated better results according to Outerbridge and Koshino testing and produced more pronounced cartilage regeneration in the medial condyle and slowed down cartilage destruction in its lateral counterpart. SF was collected before and one week after PRP or SVF injections and tested for concentrations of 41 cytokines (Multiplex Assay). In the PRP subgroup, a significant decrease in IL-6 and CXCL10 synovial concentrations was accompanied by an increase in IL-15, sCD40L, and PDGF-AB/BB amounts. The SVF subgroup demonstrated a significant decrease in synovial TNFα, FLT-3L, MIP-1ß, RANTES, and VEGF concentrations while SF concentrations of MCP-1 and FGF2 increased. Both post-treatments have a potential for increased tissue regeneration, presumably due to the downregulation of inflammation and augmentation of synovial growth factor concentrations.

Molecular Mechanisms Underlying Pathological and Therapeutic Roles of Pericytes in Atherosclerosis.

Pericytes are multipotent mesenchymal stromal cells playing an active role in angiogenesis, vessel stabilisation, maturation, remodelling, blood flow regulation and are able to trans-differentiate into other cells of the mesenchymal lineage. In this review, we summarised recent data demonstrating that pericytes play a key role in the pathogenesis and development of atherosclerosis (AS). Pericytes are involved in lipid accumulation, inflammation, growth, and vascularization of the atherosclerotic plaque. Decreased pericyte coverage, endothelial and pericyte dysfunction is associated with intraplaque angiogenesis and haemorrhage, calcification and cholesterol clefts deposition. At the same time, pericytes can be used as a novel therapeutic target to promote vessel maturity and stability, thus reducing plaque vulnerability. Finally, we discuss recent studies exploring effective AS treatments with pericyte-mediated anti-atherosclerotic, anti-inflammatory and anti-apoptotic effects.

Superconducting Instabilities in Strongly Correlated Infinite-Layer Nickelates.

The discovery of superconductivity in infinite-layer nickelates has added a new family of materials to the fascinating growing class of unconventional superconductors. By incorporating the strongly correlated multiorbital nature of the low-energy electronic degrees of freedom, we compute the leading superconducting instability from magnetic fluctuations relevant for infinite-layer nickelates. Specifically, by properly including the doping dependence of the Ni d_{x^{2}-y^{2}} and d_{z^{2}} orbitals as well as the self-doping band, we uncover a transition from d-wave pairing symmetry to nodal s_{±} superconductivity, driven by strong fluctuations in the d_{z^{2}}-dominated orbital states. We discuss the properties of the resulting superconducting condensates in light of recent tunneling and penetration depth experiments probing the detailed superconducting gap structure of these materials.

Signatures of collective modes in fifth harmonic generation of BCS superconductor.

Recent advances in the field of THz spectroscopy allow for controlled experiments to measure signatures of collective excitations in the conventional s-wave superconductor in the fifth harmonic generation current (FHG). Here, we analyze this process theoretically within the Anderson pseudospin formalism and use a periodic multicycle pulse setup, where the driving electromagnetic field points in the direction of a lattice vector. We investigate the interplay of the Higgs mode contribution to the fifth harmonic generation current and compare it to other contributing mechanisms, such as charge density fluctuations (CDF). Similar to the third harmonic generating current we show that the signal in the FHG is also dominated by the CDF. Most importantly, we predict a double peak signature in the frequency dependence of the intensity amplitude of the FHG current with one peak located at Ω = Δ0 (4Ω = 4Δ0) and another one at Ω = Δ0/2 (4Ω = 2Δ0). The resonant enhancement in the latter case is indicative of the higher order coupling to the Higgs mode or CDF, while the former is reminiscent of the THG describing the coupling of CDF and the Higgs mode with 2 single photons.

Different levels of EGF, VEGF, IL-6, MCP-1, MCP-3, IP-10, Eotaxin and MIP-1α in the adipose-derived stem cell secretome in androgenetic alopecia.

Hair folliculogenesis and hair growth mediated by the secretory properties of white adipocytes may pave the way for the adipose-derived (AD) regenerative therapy for androgenetic alopecia (AGA). Quantitative and qualitative secretome profiling of AD stem cells (ADSCs) from different zones of hair growth in patients with AGA were analysed. 1-mm punch samples of adipose tissue associated with hair follicles, of three scalp areas (balding, non-balding and transition zones) and one periumbilical sample, were used for ADCS isolation. The ADCS secretome was analysed in conditioned media using a 41plex assay. Among the thirty-five signalling proteins analysed, the levels of VEGF, EGF, IL-6, Eotaxin, MCP-3, IFNγ-inducible protein-10 and MIP-1α were higher in the balding zone compared with the non-balding and periumbilical zones. In contrast, MCP-1 was the lowest in the balding zone in comparison with the other zones. The observed differences in the secretome suggest crosstalk between angiogenic and inflammatory processes underlying AGA aetiology and may prove relevant in both the diagnosis of AGA and the application of ADSC secretome for AGA treatment.

Direct visualization of a static incommensurate antiferromagnetic order in Fe-doped Bi2Sr2CaCu2O8+δ.

In cuprate superconductors, due to strong electronic correlations, there are multiple intertwined orders which either coexist or compete with superconductivity. Among them, the antiferromagnetic (AF) order is the most prominent one. In the region where superconductivity sets in, the long-range AF order is destroyed. Yet the residual short-range AF spin fluctuations are present up to a much higher doping, and their role in the emergence of the superconducting phase is still highly debated. Here, by using a spin-polarized scanning tunneling microscope, we directly visualize an emergent incommensurate AF order in the nearby region of Fe impurities embedded in the optimally doped Bi2Sr2CaCu2O8+δ (Bi2212). Remarkably, the Fe impurities suppress the superconducting coherence peaks with the gapped feature intact, but pin down the ubiquitous short-range incommensurate AF order. Our work shows an intimate relation between antiferromagnetism and superconductivity.

Dictionary learning in Fourier-transform scanning tunneling spectroscopy.

Modern high-resolution microscopes are commonly used to study specimens that have dense and aperiodic spatial structure. Extracting meaningful information from images obtained from such microscopes remains a formidable challenge. Fourier analysis is commonly used to analyze the structure of such images. However, the Fourier transform fundamentally suffers from severe phase noise when applied to aperiodic images. Here, we report the development of an algorithm based on nonconvex optimization that directly uncovers the fundamental motifs present in a real-space image. Apart from being quantitatively superior to traditional Fourier analysis, we show that this algorithm also uncovers phase sensitive information about the underlying motif structure. We demonstrate its usefulness by studying scanning tunneling microscopy images of a Co-doped iron arsenide superconductor and prove that the application of the algorithm allows for the complete recovery of quasiparticle interference in this material.

Interaction of Skyrmions and Pearl Vortices in Superconductor-Chiral Ferromagnet Heterostructures.

We investigate a hybrid heterostructure with magnetic skyrmions (Sk) inside a chiral ferromagnet interfaced by a thin superconducting film via an insulating barrier. The barrier prevents electronic transport between the superconductor and the chiral magnet, such that the coupling can occur only through the magnetic fields generated by these materials. We find that Pearl vortices (PV) are generated spontaneously in the superconductor within the skyrmion radius, while anti-Pearl vortices (PV[over ¯]) compensating the magnetic moment of the Pearl vortices are generated outside of the Sk radius, forming an energetically stable topological hybrid structure. Finally, we analyze the interplay of skyrmion and vortex lattices and their mutual feedback on each other. In particular, we argue that the size of the skyrmions will be greatly affected by the presence of the vortices, offering another prospect of manipulating the skyrmionic size by the proximity to a superconductor.

Shambhala: a platform-agnostic data harmonizer for gene expression data.

BACKGROUND: Harmonization techniques make different gene expression profiles and their sets compatible and ready for comparisons. Here we present a new bioinformatic tool termed Shambhala for harmonization of multiple human gene expression datasets obtained using different experimental methods and platforms of microarray hybridization and RNA sequencing. RESULTS: Unlike previously published methods enabling good quality data harmonization for only two datasets, Shambhala allows conversion of multiple datasets into the universal form suitable for further comparisons. Shambhala harmonization is based on the calibration of gene expression profiles using the auxiliary standardization dataset. Each profile is transformed to make it similar to the output of microarray hybridization platform Affymetrix Human Gene. This platform was chosen because it has the biggest number of human gene expression profiles deposited in public databases. We evaluated Shambhala ability to retain biologically important features after harmonization. The same four biological samples taken in multiple replicates were profiled independently using three and four different experimental platforms, respectively, then Shambhala-harmonized and investigated by hierarchical clustering. CONCLUSION: Our results showed that unlike other frequently used methods: quantile normalization and DESeq/DESeq2 normalization, Shambhala harmonization was the only method supporting sample-specific and platform-independent biologically meaningful clustering for the data obtained from multiple experimental platforms.