Adipose-derived stem cells (AT-MSCs) exhibit great potential for application in stem cell therapy, primarily due to their unique pro-regenerative capabilities, which include supporting skin regeneration. AT-MSCs secrete a variety of biomolecules with immunomodulatory, re-epithelializing, antifibrotic, antiapoptotic, proangiogenic, and neurotrophic activity as well as the ability to promote proliferation and migration of skin cells. Recently, therapy using AT-MSC secretome alone has garnered increasing attention due to its potentially safer and more effective application ability than the use of whole AT-MSCs. This review provides a comprehensive summary of the current state of knowledge regarding the potential use of AT-MSC secretome as a promising cell-free therapeutic strategy for wound healing, alopecia, skin rejuvenation, and skin inflammatory diseases. We critically analyze and discuss findings from in vitro, in vivo, and clinical studies. Moreover, we briefly discuss possible approaches to enhance the secretion of AT-MSC biomolecules, such as AT-MSC preconditioning with low-frequency electromagnetic fields and hypoxia. In conclusion, the evidence presented in this review paper underscores that the AT-MSC secretome alone can be a highly effective approach as a stem cell-free therapy for skin repair, with significant translational potential.

Endoplasmic reticulum stress, oxidative stress, and mitochondrial dysfunction are interconnected processes involved in the pathogenesis of diabetes mellitus (DM). In the present study, we demonstrate a distinct unfolded protein response (UPR) signaling pathways in two mammalian models of DM: β-TC-6 cell line and streptozotocin-induced type 1 diabetes model in rats. However, a feature common to both systems was the upregulation of the GRP78 protein. Moreover, in vivo studies showed the disruption of the antioxidant system and an escalation of mitophagy against the background of a depletion of the level of ATP in pancreatic cells. In conclusion, we suggest that glucotoxic conditions induced GRP78 upregulation, and next cause depletion of the antioxidant pool and disruption of the functioning of antioxidant defense enzymes and in consequence promote mitophagy in pancreatic cells. Therefore, GRP78 may be considered as a potential therapeutic factor in patients with diabetes.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with an etiology that remains incompletely understood. Its development is influenced by both environmental and molecular factors, with growing attention to epigenetic mechanisms. Among these, PIWI-interacting RNAs (PIRs) have emerged as molecules of interest. PIRs are small, single-stranded noncoding RNAs, and play a crucial role in maintaining genome stability in germline cells; however, they were also found in somatic cells. Purpose: The aim of this study was to identify PIRs whose expression may be associated with the severity of RA. Patients and Methods: A total of 57 individuals were enrolled in the study, including 37 patients with RA and 20 healthy controls (HCs). Quantitative real-time polymerase chain reaction (qPCR) and digital polymerase chain reaction (dPCR) were used to evaluate the plasma concentrations and peripheral blood mononuclear cells (PBMCs) expression levels of selected PIRs. Results: In PBMCs, PIR27124 showed elevated expression in RA compared to HCs (p=0.04). Additionally, both PIR27731 and PIR35982 showed increased expression in rheumatoid factor (RF)-negative RA patients relative to RF-positive patients (p-values 0.045 for both). In plasma, PIR35982 showed a decreased concentration in RA compared to HCs (p=0.001). Furthermore, both qPCR and dPCR confirmed that RF-negative RA patients had decreased plasma levels of PIR35982 compared to HCs (p=0.01 and p=0.02, respectively). Conclusion: PIR35982 can be considered a potential molecular marker associated with RA and may be useful for identifying RF-negative patients. Moreover, dPCR represents a promising tool for the discovery and evaluation of novel biomarkers, such as PIRs.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by inflammation of the synovial tissue, leading to joint destruction, pain, stiffness, and progressive impairment of motor functions. Despite significant advances in diagnosis and treatment, RA remains a major clinical and social challenge, negatively impacting patients’ quality of life. The aim of this study was to assess the relationship between the expression of selected microRNAs (miRNAs) and the activity of the disease. A total of 46 RA patients and 20 healthy controls (HCs) were enrolled in the study. A quantitative real-time polymerase chain reaction was used to evaluate the expression of miRNAs in whole blood. MiRNA-186 exhibited decreased concentrations in RA patients compared to HCs (p = 0.03). Patients with an active form of the disease (DAS28 > 3.2) exhibited lower expression of miRNA-186 than HCs (p = 0.04). Additionally, ACPA-negative patients also demonstrated reduced miRNA-186 expression compared to controls. AUC analysis confirmed that the combination of miRNA-186, the erythrocyte sedimentation rate (ESR), and Visual Analog Scale—Patient Global Assessment (VAS PGA) may be effective in identifying RA exacerbation. The combination of classical laboratory markers, clinical data, and molecular markers enhances the ability to assess RA exacerbation. MiRNA-186 may be considered a potential marker of disease activity in RA.

Introduction: Rheumatoid arthritis (RA) is a chronic, multifactorial autoimmune disease characterized by symmetrical polyarthritis, joint pain, and swelling, which can lead to disability and premature death. Increasing attention has focused on epigenetic mechanisms, including non-coding RNAs in circular and linear forms, in RA pathogenesis. Purpose: This study aimed to identify novel supportive RNA-based biomarkers associated with RA disease activity. Patients and methods: The discovery cohort included 18 RA patients and 10 healthy controls (HCs). Peripheral blood mononuclear cells were analyzed using targeted RNA sequencing, encompassing both linear (LINOUT) and circular (CIRC) RNA forms, to assess differences between RA patients and HCs, as well as between high (HDA; DAS28 > 5.1; n = 10) and low disease activity/remission (LDA/REM; DAS28 ≤ 3.2; n = 8) disease activity groups. The results were validated in cohort of 45 patients with RA, divided into a high disease activity group (HDA; DAS28 > 5.1; n = 22) and a non-high disease activity group (non-HDA; DAS28 ≤ 5.1; n = 23) along with 24 control subjects, using quantitative PCR (qPCR). Results: LMTK2 LINOUT expression correlated negatively with disease activity ( r s = -0.30) and distinguished RF-negative patients (n = 17) from HCs (p = 0.027). Expression was significantly lower in the high activity group (n = 22) versus the non-high activity group (n = 23; p = 0.022). Post-hoc ANOVA showed significant differences among HDA, non-HDA, and HCs (p = 0.001), with reduced expression in HDA versus non-HDA (p = 0.038) and increased expression in non-HDA versus controls (p = 0.001). EML6 LINOUT expression exhibited activity-dependent changes (p = 0.034) and positively correlated with disease activity ( r s = 0.303). Integration with erythrocyte sedimentation rate (ESR) improved discriminative performance. Combining LMTK2 LINOUT + EML6 LINOUT + ESR yielded the highest accuracy (AUC = 0.923). Conclusion: LMTK2 and EML6 show disease activity-dependent expression in RA and provide complementary information to conventional inflammatory parameters such as ESR. Their integration may improve diagnostic performance, highlighting their potential as novel supportive molecular biomarkers in RA.