Search Results (57)

Background/Objectives: A significantly higher fracture risk characterizes Type 2 diabetes mellitus (T2DM) patients when compared to the non-diabetic population, even though their average bone mineral density (BMD) tends to be normal or high. This elevated risk is primarily driven by defective bone quality. The trabecular bone score (TBS) and radiofrequency echographic multispectrometry (REMS) have recently been proposed to improve the assessment of bone quality in T2DM individuals. This study aimed to evaluate whether TBS and REMS can improve the identification of osteoporosis and fracture risk in these patients. Methods: BMD was measured in 223 consecutive T2DM patients (126 women and 97 man) and 102 controls. BMD values for the lumbar spine (LS), femoral neck (FN), and total hip (TH) were obtained via both dual-energy X-ray absorptiometry (DXA) and radiofrequency echographic multi-spectrometry (REMS). In all patients, TBS and Fragility Score (FS) by REMS were measured and prior major osteoporotic fractures (MOF) were assessed. Results: All BMD T-scores measured by REMS were significantly lower than those obtained by DXA at both lumbar and femoral sites. T2DM patients with previous MOF exhibited lower T-scores for both BMD-LS and BMD-TH, as assessed by DXA and REMS, compared with patients without fractures. However, these differences reached statistical significance for BMD-TH with both techniques and for BMD-LS with REMS, but not for BMD-LS with DXA. Moreover, patients with a history of MOF had significantly lower TBS values (p < 0.05) and significantly higher FS values at both lumbar (p < 0.05) and femoral (p < 0.01) sites compared with those without fractures. Conclusions: The results of this study suggest that the parameters obtained using REMS technology (BMD and FS) may be valuable tools for improving the diagnosis of osteoporosis and assessing fracture risk in patients with T2DM. Full article

Diabetes mellitus (DM) and osteoporosis are among the most common non-communicable diseases worldwide. Beyond their considerable socio-economic burden, both conditions significantly impair quality of life and reduce life expectancy, representing major causes of disability. DM-induced osteoporosis has recently emerged as a notable and frequent complication. Patients with type 2 DM have a twofold increased risk of fragility fractures, while those with longstanding type 1 DM exhibit a fivefold higher risk of hip, vertebral, and non-vertebral fractures. Bone mineral density (BMD) assessed by Dual Energy X-ray Absorptiometry (DXA) often fails to predict fracture risk in this population, as bone mass tends to be normal, slightly reduced, or even elevated. However, DXA-derived indices can offer additional clinical value. The Trabecular Bone Score (TBS), which reflects bone microarchitecture, is frequently reduced in patients with DM and is associated with increased fracture risk, particularly in postmenopausal women. TBS is also linked to glycemic control and microvascular complications and can improve with bone-active medications, thus aiding follow-up assessments. Another useful DXA-based tool is the Bone Strain Index (BSI), which evaluates load resistance and has been shown to be degraded in diabetic patients, offering further predictive value for fractures. Additionally, Hip Structural Analysis (HSA) provides information on the mechanical integrity of the proximal femur, which may be compromised in DM. Based on the available evidence, this review aims to highlight the clinical utility of DXA-derived tools in DM-induced osteoporosis, emphasizing their ability to provide quantitative and qualitative information on bone health and to predict the risk of fragility fractures. Full article

Type 2 diabetes mellitus (T2DM) is known to increase the risk of fragility fractures; however, the underlying mechanism is still elusive. Reduced miR-155 and elevated RHOA are known to drive bone resorption, but their role in T2DM remains unclear. This study investigates bone remodeling imbalances in T2DM through miR-155 and RHOA expression profiling. Three-month-old female Wistar rats were fed a high-calorie diet for 3 weeks, followed by intraperitoneal injections of two lower doses of streptozotocin at weekly intervals to induce T2DM. Bone analysis from diabetic rats tested using qRT-PCR showed significantly reduced miR-155 levels and elevated RHOA. Histological analysis showed a 12.65% increase in Tb.Sp, 10.07% decrease in Tb.Th, and significant increase (p < 0.05) in apoptotic osteocytes. The bone turnover marker CTx-1 level was increased by 20.84%, and RANKL levels were significantly increased in T2DM. IL-1β and TNF-α were increased in T2DM. Bone resorption is more likely to occur in T2DM as both IL-1β and TNF-α work synergistically to promote osteoclastogenesis. MiR-155 could be an important modulator of bone remodeling in T2DM and a potential therapeutic target for diabetic osteopathy. Full article

Background: Tuberculosis (TB) and diabetes mellitus (DM) comorbidity (TB-DM) presents a significant global health challenge, with diabetes increasing susceptibility to TB, worsening clinical outcomes, and impairing immune responses. Among these dysfunctions, macrophages—the primary immune cells responsible for pathogen recognition, phagocytosis, and bacterial clearance—exhibit profound alterations in TB-DM. However, the complex interplay between metabolic dysregulation, immune impairment, and macrophage dysfunction remains poorly defined. Objective: This scoping review systematically maps the literature on macrophage dysfunction in TB-DM, identifying key immunological impairments affecting phagocytosis, cytokine production, antigen presentation, macrophage polarisation, reactive oxygen species (ROS) and nitric oxide (NO) regulation, and chronic inflammation. Methods: A systematic search was conducted in PubMed, Web of Science, and Embase, covering studies from 2014 to 2024. Inclusion criteria focused on human studies investigating macrophage-specific mechanisms in TB-DM. Data extraction and synthesis were performed using Covidence, with findings grouped into key immunological themes. Results: A total of 44 studies were included, revealing significant impairments in macrophage function in TB-DM. Findings indicate reduced NO production, variable ROS dysregulation, altered M1/M2 polarisation, defective antigen presentation, and chronic inflammation. Elevated IL-10 and VEGF were associated with immune suppression and granuloma destabilisation, while eicosanoids (PGE2, LXA4) contributed to sustained inflammation. Conclusions: Macrophage dysfunction emerges as a central driver of immune failure in TB-DM, creating a self-perpetuating cycle of inflammation, immune exhaustion, and bacterial persistence. Understanding these mechanisms is essential for developing biomarker-driven diagnostics, host-directed therapies, targeted immunomodulation, and improving TB outcomes in diabetic populations. Future research should explore macrophage-targeted interventions to enhance immune function and mitigate TB-DM burden. Full article

Diabetes mellitus (DM) and tuberculosis (TB) are two global health challenges that significantly impact population health, with DM increasing susceptibility to TB infections. However, early risk prediction methods for DM patients complicated with TB (DM–TB) are lacking. This study mined transcriptome data of DM–TB patients from the GEO database (GSE181143 and GSE114192) and used differential analysis, weighted gene co-expression network analysis (WGCNA), intersecting immune databases, combined with ten machine learning algorithms, to identify immune biomarkers associated with DM–TB. An early alert model for DM–TB was constructed based on the identified core differentially expressed genes (DEGs) and validated through a prospective cohort study and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) for gene expression levels. Furthermore, we performed a detailed immune status analysis of DM–TB patients using the CIBERSORT algorithm. We identified 1090 DEGs associated with DM–TB and further pinpointed CETP (cholesteryl ester transfer protein) (AUC = 0.804, CI: 0.744–0.864), TYROBP (TYRO protein tyrosine kinase binding protein) (AUC = 0.810, CI: 0.752–0.867), and SECTM1 (secreted and transmembrane protein 1) (AUC = 0.811, CI: 0.757–0.864) as immune-related biomarkers for DM–TB patients. An early alert model was developed based on these three genes (AUC = 0.86, CI: 0.813–0.907), with a sensitivity of 0.80829 and a specificity of 0.75758 at a Youden index of 0.56587. External validation using the GSE114192 dataset showed an AUC of 0.901 (CI: 0.847–0.955). Population cohort research and RT-qPCR verified the expression levels of these three genes, demonstrating consistency with trends seen in the training set. KEGG enrichment analysis revealed that NF-κB and MAPK signaling pathways play crucial roles in the DM–TB pathogenic mechanism, and immune infiltration analysis showed significant suppression of certain adaptive immune cells and activation of inflammatory cells in DM–TB patients. This study identified three potential immune-related biomarkers for DM–TB, and the constructed risk assessment model demonstrated significant predictive efficiency, providing an early screening strategy for DM–TB. Full article

Extrapulmonary tuberculosis (EPTB) accounts for approximately 17% of all Mycobacterium tuberculosis (M.tb) infections globally. Immunocompromised individuals, such as those with HIV infection or type 2 diabetes mellitus (T2DM), are at an increased risk for EPTB. Previous studies have demonstrated that patients with HIV and T2DM exhibit diminished synthesis of glutathione (GSH) synthesizing enzymes. In a murine model, we showed that the diethyl maleate (DEM)-induced depletion of GSH in the lungs led to increased M.tb burden and an impaired pulmonary granulomatous response to M.tb infection. However, the effects of GSH depletion during active EPTB in the liver and spleen have yet to be elucidated. In this study, we evaluated hepatic GSH and malondialdehyde (MDA) levels, as well as cytokine profiles, in untreated and DEM-treated M.tb-infected wild-type (WT) C57BL/6 mice. Additionally, we assessed hepatic and splenic M.tb burdens and tissue pathologies. DEM treatment resulted in a significant decrease in the levels of the reduced form of GSH and an increase in MDA, oxidized GSH, and interleukin (IL)-6 levels. Furthermore, DEM-induced GSH decrease was associated with decreased production of IL-12 and IL-17 and elevated production of interferon-gamma (IFN-γ), tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β. A significant increase in M.tb growth was detected in the liver and spleen in DEM-treated M.tb-infected mice. Large, disorganized lymphocyte infiltrates were detected in the hepatic tissues of DEM-treated mice. Overall, GSH diminishment impaired the granulomatous response to M.tb in the liver and exacerbated M.tb growth in both the liver and spleen. These findings provide critical insights into the immunomodulatory role of GSH in TB pathogenesis and suggest potential therapeutic avenues for the treatment of extrapulmonary M.tb infections. Full article

The aim of this study was to investigate the combination effects of α-glycerol monolaurate (GML) and glyceryl tributyrate (TB) on growth performance, nutrient digestibility, gut microbiota, and immune function in weaned piglets. A total of 120 weaned piglets with an average body weight (BW) of 6.88 kg were randomly allocated to one of the three dietary treatments: (1) CON: a basal diet; (2) 0.1%: a basal diet with 0.1% MSCFA (GML/TB = 1:1); (3) 0.2%: a basal diet with 0.2% MSCFA (GML/TB = 1:1). The experiment lasted 28 days. There were no differences on average daily growth (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR). Supplementation with 0.1% MSCFA increased apparent total tract digestibility (ATTD) of crude protein (CP) and gross energy (GE, p < 0.05) on d 14 and increased GE (p < 0.05) on d 28 compared with the CON group. The ATTD of dry matter (DM), organic matter (OM) and crude protein (CP) of piglets supplemented with 0.1% MSCFA was higher (p < 0.05). Compared with the CON group, supplementation with 0.1% MSCFA increased immunoglobulin M (IgM) concentration, decreased interleukin-6 (IL-6) content (p < 0.05) on d 14 and decreased malonaldehyde (MDA), interleukin-1beta (IL-1β), IL-6 concentrations (p < 0.05) on d 28. Supplementation with 0.1% MSCFA increased total antioxidant capacity (T-AOC) concentration (p < 0.05), decreased GSH-Px, MDA content (p < 0.05) in jejunum compared with the CON group. Moreover, supplementation with MSCFA increased the activity of duodenal lipase (p < 0.05) and the abundance of firmicutes and decreased the abundance of proteobacteria compared with the CON group. Overall, supplementation with MSCFA can improve nutrient digestibility, enhance immunity and antioxidant capacity, and improve the intestinal health of piglets. The combined use of MSCFA is a nutrition regulation strategy worthy of further exploration in modern animal husbandry. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the leading infectious causes of death globally, with drug resistance presenting a significant challenge to control efforts. The interplay between type 2 diabetes mellitus (T2DM) and TB introduces additional complexity, as T2DM triples the risk of active TB and exacerbates drug resistance development. This review explores how T2DM-induced metabolic and immune dysregulation fosters the survival of Mtb, promoting persistence and the emergence of multidrug-resistant strains. Mechanisms such as efflux pump activation and the subtherapeutic levels of isoniazid and rifampicin in T2DM patients are highlighted as key contributors to resistance. We discuss the dual syndemics of T2DM–TB, emphasizing the role of glycemic control and innovative therapeutic strategies, including efflux pump inhibitors and host-directed therapies like metformin. This review underscores the need for integrated diagnostic, treatment, and management approaches to address the global impact of T2DM–TB comorbidity and drug resistance. Full article

Achillea cucullata is a perennial herbaceous plant that has a long history of medical use in many cultures. The present research focuses on the biological activity and therapeutic potential of A. cucullata, namely its antibacterial and anticancer properties. While previous studies have shed light on the cytotoxic and antibacterial capabilities of Achillea cucullata aerial parts, there is still a considerable gap in knowledge concerning the anticancer potential of leaf and flower extracts. A. cucullata’s leaves and flowers were extracted using methanol. The total phenolic and flavonoid contents were evaluated. The antioxidant, cytotoxic, and antibacterial properties were evaluated against both Gram-positive and Gram-negative bacteria. The Gas Chromatography–Mass Spectrometry (GC–MS) analysis of A. cucullata leaf and flower extracts showed numerous amounts of bioactive components, including carvacrol, a TBDMS derivative; 2-Myristynoyl-glycinamide, acetylaminobenzothiazol-2-yl)-2-(adamantan-1-yl); Isolongifolol; (3E,10Z)-Oxacyclotrideca-3,10-diene-2,7-dione; and 3-Heptanone, 5-hydroxy-1,7-diphenyl. The extract has a high level of phenols and flavonoids. Cytotoxicity studies found that A. cucullata leaves and flowers had dose-dependent toxicity against MCF-7 and HepG2 cancer cell lines, with flowers being more effective. Apoptotic genes (caspase-3, 8, 9, and Bax) were upregulated in treated MCF-7 and HepG2 cells, whereas anti-apoptotic genes (Bcl-xL and Bcl-2) were reduced. Antibacterial screening revealed significant activity against both Gram-positive and Gram-negative pathogens. Overall, the research highlights the varied therapeutic potentials of A. cucullata, adding to the knowledge of plant-derived extracts in lowering disease risks. Future research should concentrate on in vivo studies to assess the effectiveness and safety of these substances. Full article

An insect neuroactive helix ring peptide called U₁₁-MYRTX-Tb1a (abbreviated as U₁₁) from the venom of the ant, Tetramorium bicarinatum. U₁₁ is a 34-amino-acid peptide that is claimed to be one of the most paralytic peptides ever reported from ant venoms acting against blowflies and honeybees. The peptide features a compact triangular ring helix structure stabilized by a single disulfide bond, which is a unique three-dimensional scaffold among animal venoms. Pharmacological assays using Drosophila S2 cells have demonstrated that U₁₁ is not cytotoxic but instead suggest that it may modulate potassium channels via the presence of a functional dyad. In our work described here, we have tested this hypothesis by investigating the action of synthetically made U₁₁ on a wide array of voltage-gated K and Na channels since it is well known that these channels play a crucial role in the phenomenon of paralysis. Using the Xenopus laevis oocyte heterologous expression system and voltage clamp, our results have not shown any modulatory effect of 1 μM U₁₁ on the activity of Kv1.1, Kv1.3, Kv1.4, Kv1.5, Shaker IR, Kv4.2, Kv7.1, Kv10.1, Kv11.1 and KQT1, nor on DmNav and BgNav. Instead, 10 μM U₁₁ caused a quick and irreversible cytolytic effect, identical to the cytotoxic effect caused by Apis mellifera venom, which indicates that U₁₁ can act as a pore-forming peptide. Interestingly, the paralytic dose (PD₅₀) on blowflies and honeybees corresponds with the concentration at which U₁₁ displays clear pore-forming activity. In conclusion, our results indicate that the insecticidal and paralytic effects caused by U₁₁ may be explained by the putative pore formation of the peptide. Full article

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic diseases in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search for differences in clinical characteristics. Methods: This is a single-center retrospective, case–controlled study. A total of 589 patients attending CTO Bone Unit between 2 January 2010 and 31 May 2023, due to osteoporosis and fragility fractures, were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 12.7%. Compared to patients without DM, the median age at the time of first fracture was similar: 72 years ± 13.5 interquartile range (IQR) vs. 71 years ± 12 IQR; prevalence of combination of vertebral and hip fractures was higher (p = 0.008), as well as prevalence of males (p = 0.016). Bone mineral density (BMD) at all sites was higher in DM group; trabecular bone score (TBS), instead, was significantly lower (p < 0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and, therefore, might be used as a diagnostic tool in clinical practice. Full article

Tuberculosis (TB) is a disease caused by the bacillus Mycobacterium tuberculosis (MTB). Human immunodeficiency virus (HIV) infection and type 2 diabetes mellitus (T2DM) are among the main risk factors for the development of TB and increase the risk of drug-resistant TB developing (DR-TB). The aim of this study was to estimate the prevalence of DR-TB in patients with HIV or T2DM in Sinaloa, Mexico. This was an observational and cross-sectional study. The analysis was conducted using the clinical data of patients registered on the National Epidemiological Surveillance System for TB (SINAVE/PUI-TB) platform with a presumed diagnosis of TB during 2019 to 2021 in Sinaloa, Mexico. The prevalence of DR-TB was estimated in HIV and T2DM patients, as well as the odds ratios for their sociodemographic variables, using the Chi-square test. There were 2, 4, and 4 TB-HIV cases and 2, 6, and 9 TB-T2DM cases during 2019, 2020, and 2021, respectively, whereas there were 2 and 1 DRTB-HIV and DRTB-T2DM cases, respectively. The results indicated that the WHO guidelines for DR-TB were not properly applied to this high-risk population. Hence, the appropriate application of guidelines for TB and DR-TB detection in these patients needs to be immediately implemented by the State health system. Full article

Genetic variation in tuberculosis is influenced by the host environment, patients with comorbidity, and tuberculosis–type 2 diabetes mellitus (TB-T2DM) and implies a higher risk of treatment failure and development of drug resistance. Considering the above, this study aimed to evaluate the influence of T2DM on the dynamic of polymorphisms related to antibiotic resistance in TB. Fifty individuals with TB-T2DM and TB were initially characterized, and serial isolates of 29 of these individuals were recovered on day 0 (diagnosis), 30, and 60. Genomes were sequenced, variants related to phylogeny and drug resistance analyzed, and mutation rates calculated and compared between groups. Lineage X was predominant. At day 0 (collection), almost all isolates from the TB group were sensitive, apart from four isolates from the TB-T2DM group showing the mutation katG S315T, from which one isolate had the mutations rpoB S450L, gyrA A90G, and gyrA D94G. This pattern was observed in a second isolate at day 30. The results provide a first overview of the dynamics of mutations in resistance genes from individuals with TB-T2DM, describing an early development of resistance to isoniazid and a rapid evolution of resistance to other drugs. Although preliminary, these results help to explain the increased risk of drug resistance in individuals with TB and T2DM. Full article

Two isostructural lanthanide complexes were synthesized by solvent evaporation with 3-dimethylaminobenzoic acid and 5,5′-dimethyl-2,2′-bipyridine as ligands. The general formula of the structure is a [Ln(3-N,N-DMBA)₃(5,5′-DM-2,2′-bipy)]₂·2(3-N,N-DMHBA), Ln = (Gd(1), Tb(2)), 3-N,N-DMBA = 3-Dimethylamino benzoate, 5,5′-DM-2,2′-bipy = 5,5′-dimethyl-2,2′ bipyridine. Both complexes exhibited dimeric structures based on X-ray diffraction analysis. At the same time, infrared spectroscopy and Raman spectroscopy were used to measure the spectra of the complex. A thermogravimetric infrared spectroscopy experiment was performed to investigate the thermal stability and decomposition mechanism of the complexes. Measurements of the low-temperature heat capacity of the complexes were obtained within the temperature range of 1.9 to 300 K. The thermodynamic function was calculated by heat capacity fitting. In addition, the fluorescence spectra of complex 2 were studied and the fluorescence lifetime values were determined, and the energy transfer mechanism of complex 2 was elucidated. Full article

This article describes the synthesis of fullerenol—${\mathrm{C}}_{60}(\mathrm{O}{\mathrm{H})}_{24}$ adducts with some heavy metals—${\mathrm{C}}_{60}\left({\mathrm{O}\mathrm{N}\mathrm{a})}_{\mathrm{x}}\right({\mathrm{O}}_2\mathrm{M}\mathrm{e}{)}_{(24-\mathrm{x})/2};{\mathrm{C}}_{60}\left({\mathrm{O}\mathrm{N}\mathrm{a})}_{\mathrm{x}}\right({\mathrm{O}}_3\mathrm{M}\mathrm{e}{)}_{(24-\mathrm{x})/3}$; Me=Co; Cu; Mn; Zn; Gd; Tb. The identification of adducts was carried out by the methods of: elemental analysis, infrared and electronic spectroscopy, complex thermal analysis, high-performance liquid chromatography and dynamic light scattering. The solubility of adducts in aqueous solutions in the ambient temperature range has been studied. The solubility was significant and ranged from a few tenths to 1 g/dm³. The use of these adducts as micronutrients for spring barley crops in the Republic of Kazakhstan is considered. When using these nanopreparations, a general increase in yield (tens, up to 80 rel.%), nutrient content and moisture content of seeds (4–5 rel. mass %), as well as the resistance of the latter to the effects of pathogenic microorganisms (percentage of healthy seeds growth up to 10 rel.%), was noted. Full article