Interleukin (IL)-6 family cytokines act through a receptor complex with gp130 subunits. IL-6 is a pleiotropic cytokine that regulates inflammation and liver regeneration. Mitochondria are the first to respond to stress and adapt their dynamics in conditions of damage. In this regard, the study aimed to investigate the role of the IL-6 cytokine family (sIL-6Ra, gp130/sIL-6Rb, and IL-11) in the regulation of mitochondrial dynamics in the liver in obese patients and to assess the contribution of these cytokines to the pathogenesis of type 2 diabetes mellitus (T2DM). We studied 134 obese patients with and without T2DM and 41 healthy donors. We found that increasing the concentration of sIL-6Ra and gp130/sIL-6Rb protected against carbohydrate disorders in obese patients and prevented non-alcoholic fatty liver disease (NAFLD) progression in obese patients. An increase in plasma IL-6 levels is associated with decreased, mitochondrial transcription factor A (TFAM) protein production in liver biopsies in obese patients with and without T2DM. Replication, transcription, and division processes in liver biopsy were reduced in patients with T2DM. Inflammatory processes stimulate liver cell apoptosis in obese patients with T2DM. The increase in IL-11 levels is associated with decreased pro-apoptotic Bcl-2-associated X protein (BAX) protein production in obese patients with and without T2DM.

Chronic inflammation may not begin with local tissue disorders, such as hypoxia, but with the accumulation of critically activated macrophages in one site. The purpose of this review is to analyze the data reported in the scientific literature on the features of the functions of macrophages and their contributions to the development of pathology in various tissues during aseptic inflammation in obese subjects. In individuals with obesity, increased migration of monocytes from the peripheral blood to various tissues, the proliferation of resident macrophages and a change in the balance between alternatively activated anti-inflammatory macrophages (M2) and pro-inflammatory classically activated macrophages (M1) towards the latter have been observed. The primary cause of some metabolic pathologies has been precisely identified as the recruitment of macrophages with an altered phenotype, which is probably typical for many other pathologies. Recent studies have identified phenotypes, such as metabolically activated M (MMe), oxidized (Mox), hemoglobin-related macrophages (Mhem and MHb), M4 and neuroimmunological macrophages (NAM, SAM), which directly and indirectly affect energy metabolism. The high heterogeneity of macrophages in tissues contributes to the involvement of these cells in the development of a wide range of immune responses, including pathological ones. The replenishment of tissue-specific macrophages occurs at the expense of infiltrating monocyte-derived macrophages (MoMFs) in the pathological process. The origin of MoMFs from a general precursor retains their common regulatory mechanisms and similar sensitivity to regulatory stimuli. This makes it possible to find universal approaches to the effect on these cells and, as a consequence, universal approaches for the treatment of various pathological conditions.

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New TiNb-based alloys, such as Ti–6Al–7Nb, are currently being studied around the world as an alternative to other Ti alloys, e.g., instead of Ti–6Al–4V. We conducted a pilot study where thin (approximately 1.2 micron) CaP coatings containing low doses of Zn2+ (0.4–0.8 wt.%) were prepared by the radio frequency magnetron sputtering (RFMS) of Zn-hydroxyapatite (HA) target on Ti–6Al–4V and Ti–6Al–7Nb substrates and investigated their physicochemical properties, in vitro solubility, cytotoxicity, and antibacterial and osteogenic activities. The thickness of the obtained coatings was approximately 1.2–1.3 microns. Zn substitution did not result in roughness or structural or surface changes in the amorphous CaP coatings. The distributions of Ca, P, and Zn were homogeneous across the film thickness as shown by the EDX mapping of these elements. Zn doping of CaP coatings on both types of Ti-based alloys statistically influenced the results of the scratch-test. However, obtained values are satisfactory to use Zn-CaP coatings on biomedical implants. Increased Zn2+ release vs. tapered output of Ca and phosphate ions occurred during 5 weeks of an in vitro immersion test in 0.9% NaCl solution. Ti–6Al–7Nb alloy, unlike Ti–6Al–4V, promoted more linear biodegradation of CaP coatings in vitro. As a result, CaP-based surfaces on Ti–6Al–7Nb, compared with on Ti–6Al–4V alloy, augmented the total areas of Alizarin red staining in a 21-day culture of human adipose-derived mesenchymal stem cells in a statistically significant manner. Moreover, Zn–CaP coatings statistically reduced leukemic Jurkat T cell survival within 48 h of in vitro culture. Along with the higher solubility of the Zn–CaP surface, a greater reduction (4- to 5.5-fold) in Staphylococcus aureus growth was observed in vitro when 7-day extracts of the coatings were added into the microbial culture. Hence, Zn–CaP-coated Ti–6Al–7Nb alloy with controllable biodegradation as prepared by RFMS is a prospective material suitable for bone applications in cases where there is a risk of bacterial contamination with severe consequences, for example, in leukemic patients. Further research is needed to closely investigate the mechanical features and pathways of their solubility and antimicrobial, antitumor, and osteogenic activities.

Calcium phosphate (CaP) materials do not always induce ectopic vascularization and bone formation; the reasons remain unclear, and there are active discussions of potential roles for post-implantation hematoma, circulating immune and stem cells, and pericytes, but studies on adipose-derived stem cells (AMSCs) in this context are lacking. The rough (average surface roughness Ra = 2–5 µm) scaffold-like CaP coating deposited on pure titanium plates by the microarc oxidation method was used to investigate its subcutaneous vascularization in CBA/CaLac mice and in vitro effect on cellular and molecular crosstalk between human blood mononuclear cells (hBMNCs) and AMSCs (hAMSCs). Postoperative hematoma development on the CaP surface lasting 1–3 weeks may play a key role in the microvessel elongation and invasion into the CaP relief at the end of the 3rd week of injury and BMNC migration required for enhanced wound healing in mice. Satisfactory osteogenic and chondrogenic differentiation but poor adipogenic differentiation of hAMSCs on the rough CaP surface were detected in vitro by differential cell staining. The fractions of CD73+ (62%), CD90+ (0.24%), and CD105+ (0.41%) BMNCs may be a source of autologous circulating stem/progenitor cells for the subcutis reparation, but allogenic hBMNC participation is mainly related to the effects of CD4+ T cells co-stimulated with CaP coating on the in vitro recruitment of hAMSCs, their secretion of angiogenic and osteomodulatory molecules, and the increase in osteogenic features within the period of in vivo vascularization. Cellular and molecular crosstalk between BMNCs and AMSCs is a model of effective subcutis repair. Rough CaP surface enhanced angio- and osteogenic signaling between cells. We believe that preconditioning and/or co-transplantation of hAMSCs with hBMNCs may broaden their potential in applications related to post-implantation tissue repair and bone bioengineering caused by microarc CaP coating.