Background/Objectives: Prediabetes (PreDM) is a heterogeneous condition, impacting hundreds of millions worldwide, associated with a substantially high risk of Type 2 Diabetes Mellitus (T2DM) and cardiovascular complications. Early identification of subgroups within the PreDM population may support tailored prevention strategies. Methods: We conducted a cross-sectional study using data from annual health check-ups of 419 university staff (aged 27–69) in Kazakhstan. Latent Class Analysis (LCA) was applied to identify subgroups of individuals with PreDM based on cardiovascular risk factors. Differences in glucose metabolism markers (fasting glucose, OGTT, HOMA-IR, HOMA-β) were compared across identified classes. Results: PreDM prevalence was 43.4%. LCA revealed four distinct classes: Class 1: healthy, low-risk individuals; Class 2: overweight with moderate metabolic risk; Class 3: older, overweight individuals with high cardio-metabolic risk; and Class 4: obese, middle-aged to older individuals with very high cardio-metabolic risk. Significant differences were found in glucose metabolism profiles across the classes. IFG predominated in Class 1 (95%), while Classes 3 and 4 had higher rates of β-cell dysfunction and combined IFG/IGT patterns. HOMA-β differed significantly between classes (p < 0.001), while HOMA-IR did not. Conclusions: PreDM is highly prevalent in this working-age Kazakh population and demonstrates marked heterogeneity. Based on easily obtainable cardiovascular risk factors, we have identified four subgroups with distinct glucose profiles that may inform personalized interventions. These distinct subgroups may require differentiated prevention strategies, moving beyond a one-size-fits-all approach.

Background/Objectives: Acute pneumonia remains one of the leading causes of mortality worldwide. The pathogenesis of the disease is determined by the nature of the host immune response. The balance between effector and regulatory T cells (Treg) is critical, as it determines the severity of inflammation and the regenerative capacity of lung tissue. The development of new approaches to modulate the immune response using promising synthetic compounds opens up the possibility of targeted cytokine balance restoration of cytokine balance and Tregs functions This study investigated the effects of the newly synthesized complex of 1-(2-Ethoxypropyl)-4-(pent-1-yn-1-yl)piperidin-4-yl Propionate with β-Cyclodextrin (MXF-22), on the populations of CD4⁺, CD4⁺CD25⁺ and CD4⁺FoxP3⁺ T cells in an oleic acid-induced acute lung injury rat model. Methods: Quantitative analysis of CD4⁺, CD4⁺CD25⁺, and CD4⁺FoxP3⁺ T cell subsets and serum IL-4 and TGF-β levels were determined by flow cytometry and ELISA assays, respectively. Results: The study revealed a significant decrease in the number of CD4⁺ T cells and their regulatory subsets (CD4⁺CD25⁺, CD4⁺FoxP3⁺) during acute pneumonia. Oral administration of MXF-22 contributed to a pronounced recovery of these parameters, accompanied by increased levels of IL-4 and TGF-β, which indicated the activation of anti-inflammatory and reparative processes. Conclusions: MXF-22 showed a pronounced immunomodulatory effect contributing to the restoration of the function of CD4⁺ FoxP3⁺ T regs in acute pneumonia rat model.

Psoriasis is a chronic immune-mediated inflammatory disease associated with dysregulation of T-cell responses and cytokine signaling. The aim of this study was to synthesize and structurally characterize a piperidine α-hydroxyphosphonate (OPP) and to comparatively evaluate the effects of OPP and the vivo-phosphorodiamidate morpholino oligomer (vPMO) in a preclinical model of imiquimod-induced psoriasis. OPP was synthesized by hydrophosphorylation of 1-(3-isopropoxypropyl)piperidin-4-one with dimethyl phosphite; its structure was confirmed by IR, NMR spectroscopy, and elemental analysis. Psoriasis was induced in rats by topical application of imiquimod (IMQ). The animals were randomly allocated into six groups: control (C), experimental psoriasis (Ps), vehicle-treated (Ps/V), glucocorticosteroid-treated (Ps/GCS), piperidine α-hydroxyphosphonate-treated (Ps/OPP), and vivo-phosphorodiamidate morpholino oligomer-treated (Ps/vPMO) groups. Clinical manifestations were assessed on Days 3, 5, and 7 using a modified Psoriasis Area and Severity Index (PASI). During the 7-day observation period, body weight and the modified Psoriasis Area and Severity Index (PASI) score were assessed on Days 3, 5, and 7. Histopathological changes were evaluated using hematoxylin and eosin (H&E) staining. On day 7, CD3⁺CD45R⁻, CD4⁺CD8⁻, and CD4⁺CD25⁺ T-cell subpopulations were determined by flow cytometry, while serum concentrations of IL-6, TNF-α, IL-10, TGF-β1, IL-17A, and IL-22 were measured using an enzyme-linked immunosorbent assay (ELISA). IMQ administration resulted in the progressive development of psoriasiform skin lesions characterized by hyperkeratosis, acanthosis, inflammatory infiltration of the dermis, body weight loss, decreased numbers of CD3⁺CD45R⁻ and CD4⁺CD8⁻ cells, increased levels of IL-6, IL-17A, and IL-22, and reduced IL-10 levels. OPP treatment was associated with a reduction in the total PASI score and the severity of scaling, as well as decreased serum concentrations of IL-6, IL-17A, and IL-22 and an increased IL-10 concentration. In addition, OPP increased the number of CD4⁺CD8⁻ cells compared with the psoriasis group, whereas the number of CD4⁺CD25⁺ cells remained below the control level. In contrast, vPMO treatment exhibited a distinct response profile characterized by increased numbers of CD3⁺CD45R⁻ and CD4⁺CD8⁻ cells, decreased IL-17A and IL-22 levels, increased IL-10 levels, and a particularly pronounced increase in TGF-β1 while producing less pronounced changes in certain cutaneous manifestations. Overall, OPP was characterized by a more consistent pattern of clinical, histopathological, and immunological changes, whereas vPMO treatment predominantly resulted in more pronounced alterations in systemic immunological parameters. These findings indicate distinct patterns of biological effects of OPP and vPMO in the IMQ-induced psoriasiform skin lesion model and support further preclinical investigation of these compounds. However, the observed changes do not allow definitive conclusions to be drawn regarding the underlying molecular mechanisms or the involvement of specific cellular pathways and should be interpreted in light of the limited observation period, the restricted panel of cellular markers examined, the absence of certain experimental controls, and the lack of pharmacokinetic data.