Bacterial infections and antimicrobial resistance are posing substantial difficulties to the worldwide healthcare system. The constraints of conventional diagnostic and therapeutic approaches in dealing with continuously changing infections highlight the necessity for innovative solutions. Aptamers, which are synthetic oligonucleotide ligands with a high degree of specificity and affinity, have demonstrated significant promise in the field of bacterial infection management. This review examines the use of aptamers in the diagnosis and therapy of bacterial infections. The scope of this study includes the utilization of aptasensors and imaging technologies, with a particular focus on their ability to detect conditions at an early stage. Aptamers have shown exceptional effectiveness in suppressing bacterial proliferation and halting the development of biofilms in therapeutic settings. In addition, they possess the capacity to regulate immune responses and serve as carriers in nanomaterial-based techniques, including radiation and photodynamic therapy. We also explore potential solutions to the challenges faced by aptamers, such as nuclease degradation and in vivo instability, to broaden the range of applications for aptamers to combat bacterial infections.

Background: Mesenchymal stromal/stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) hold promise as a disease modifying treatment in osteoarthritis (OA). Obesity, and its associated inflammation, contribute to OA development and metabolic OA represents a specific and significant group of the OA patient population. Given their immunomodulatory properties, MSC and MSC-EVs are especially interesting for this group of patients as a therapeutic option. Here, we were the first to compare the therapeutic efficacy of MSCs and MSC-EVs in a mild OA model taking these metabolic aspects into consideration. Methods: Male Wistar-Han rats (Crl:WI(Han) (n = 36) were fed a high fat diet for 24 weeks, with unilateral induction of OA by groove surgery after 12 weeks. Eight days after surgery rats were randomized in three treatment groups receiving MSCs, MSC-EVs or vehicle injection. Pain-associated behavior, joint degeneration, and local and systemic inflammation were measured. Results: We demonstrated that despite not having a significant therapeutic effect, MSC-EV treatment results in lower cartilage degeneration, less pain behaviour, osteophytosis and joint inflammation, than MSC treatment. Suggesting that MSC-EVs could be a more promising therapeutic strategy than MSCs in this mild metabolic OA model. Conclusion: In summary, we find that MSC treatment has negative effects on the joint in metabolic mild OA. This is an essential finding for the significant group of patients with metabolic OA phenotype, and might help to understand why clinical translation of MSC treatment shows varying therapeutic efficacy thus far. Our results also suggest that MSC-EV-based treatment might be a promising option for these patients, however MSC-EV therapeutic efficacy will need improvement.

Introduction: Obesogenic diets aggravate osteoarthritis (OA) by inducing low-grade systemic inflammation, and diet composition may affect OA severity. Here, we investigated the effect of diet on joint damage and inflammation in an OA rat model. Methods: Wistar-Han rats (n = 24) were fed a chow, a high-fat (HF) diet, or a high-fat/high-sucrose (HFS) for 24 weeks. OA was induced unilaterally 12 weeks after the diet onset by groove surgery, and compared to sham surgery or no surgical intervention (contralateral limb). Knee OA severity was determined by OARSI histopathology scoring system. At several timepoints monocyte populations were measured using flow cytometry, and joint macrophage response was determined via CD68 immunohistochemistry staining. Results: Groove surgery combined with HF or HFS diet resulted in higher OARSI scores, and both HF and HFS diet showed increased circulating intermediate monocytes compared to chow fed rats. Additionally, in the HFS group, minimal damage by sham surgery resulted in an increased OARSI score. HFS diet resulted in the largest metabolic dysregulation, synovial inflammation and increased CD68 staining in tibia epiphysis bone marrow. Conclusion: Obesogenic diets resulted in aggravated OA development, even with very minimal joint damage when combined with the sucrose/fat-rich diet. We hypothesize that diet-induced low-grade inflammation primes monocytes and macrophages in the blood, bone marrow, and synovium, resulting in joint damage when triggered by groove OA inducing surgery. When the metabolic dysregulation is larger, as observed here for the HFS diet, the surgical trigger required to induce joint damage may be smaller, or even redundant.

Osteoarthritis (OA) is a common and debilitating joint disorder that leads to progressive joint breakdown and loss of articular cartilage. Accompanied by a state of low-grade inflammation, its etiology extends beyond that of a wear-and-tear disease, and the immune system might have a role in its initiation and progression. Obesity, which is directly associated with an increased incidence of OA, alters adipokine release, increases pro-inflammatory macrophage activity, and affects joint immune regulation. Studying inflammatory macrophage expression and strategies to inhibit inflammatory macrophage phenotype polarization might provide insights into disease pathogenesis and therapeutic applications. In pre-clinical studies, the detection of OA in its initial stages was shown to be possible using imaging techniques such as SPECT-CT, and advances are made to detect OA through blood-based biomarker analysis. In this review, obesity-induced osteoarthritis and its mechanisms in inducing joint degeneration are summarized, along with an analysis of the current developments in patient imaging and biomarker use for diagnostic and therapeutic strategies.