Tuberculosis (TB) is a highly infectious bacterial disease that primarily attacks the lungs. TB is manifested either as latent TB infection (LTBI) or active TB disease, the latter posing a greater threat to life. The risk of developing active TB disease from LTBI is three times higher in individuals with type 2 diabetes mellitus (T2DM). The association between TB and T2DM is becoming more prominent as T2DM is rapidly increasing in settings where TB is endemic. T2DM is a chronic metabolic disorder characterized by elevated blood glucose, insulin resistance, and relative insulin deficiency. Insulin resistance and stress-induced hyperglycemia have been shown to be increased by TB and to return to normal upon treatment. Previously, we demonstrated that adipocytes (or fat tissue) regulate pulmonary pathology, inflammation, and Mycobacterium tuberculosis (Mtb) load in a murine model of TB. Metabolic disturbances of adipose tissue and/or adipocyte dysfunction contribute to the pathogenesis of T2DM. Thus, pathological adipocytes not only regulate pulmonary pathology, but also increase the risk for T2DM during TB infection. However, the cellular and molecular mechanisms driving the interaction between hyperglycemia, T2DM and TB remain poorly understood. Here, we report the impact of Mtb infection on the development of insulin resistance in mice fed on a regular diet (RD) versus high-fat diet (HFD) and, conversely, the effect of hyperglycemia on pulmonary pathogenesis in juvenile and adult mouse models. Overall, our study demonstrated that Mtb persists in adipose tissue and that Mtb infection induces irregular adipocyte lipolysis and loss of fat cells via different pathways in RD- and HFD-fed mice. In RD-fed mice, the levels of TNFα and HSL (hormone sensitive lipase) play an important role whereas in HFD-fed mice, ATGL (adipose triglyceride lipase) plays a major role in regulating adipocyte lipolysis and apoptosis during Mtb infection in adult mice. We also showed that Mtb infected adult mice that were fed an RD developed insulin resistance similar to infected adult mice that were overweight due to a HFD diet. Importantly, we found that a consequence of Mtb infection was increased lipid accumulation in the lungs, which altered cellular energy metabolism by inhibiting major energy signaling pathways such as insulin, AMPK and mToR. Thus, an altered balance between lipid metabolism and glucose metabolism in adipose tissue and other organs including the lungs may be an important component of the link between Mtb infection and subsequent metabolic syndrome.

Atherosclerosis is the principal cause of vascular diseases and one of the leading causes of worldwide death. Even though several insights into its natural course, risk factors and interventions have been identified, it is still an ongoing global pandemic. Since the structure and biochemical composition of the plaques show high heterogeneity, a comprehensive understanding of the intraplaque composition, its microenvironment, and the mechanisms of the progression and instability across different vascular beds at their progression stages is crucial for better risk stratification and treatment modalities. Even though several cell-based studies, animal studies, and extensive multicentric population studies have been conducted concerning cardiovascular diseases for assessing the risk factors and plaque biology, the studies on human clinical samples are very limited. New novel approaches utilize samples from percutaneous coronary interventions, which could possibly gain more access to clinical samples at different stages of the diseases without complex invasive resections. As an emerging technological platform in disease discovery research, mass spectrometry-based omics technologies offer capabilities for a comprehensive understanding of the mechanisms linked to several vascular diseases. Here, we discuss the cellular and molecular processes of atherosclerosis, different mass spectrometry-based omics approaches, and the studies mostly done on clinical samples of atheroma plaque using mass spectrometry-based proteomics, metabolomics and lipidomics approaches.

Background: Myocardial infarction (MI) continues to pose a significant global healthcare burden despite advances in treatment options and their effectiveness. The incidence, prevalence, and mortality rates associated with MI are rising, emphasizing the need for improved therapeutic strategies. Traditional invasive surgical methods, aimed at recanalizing blood flow to the coronary arteries, have proven insufficient in fully addressing the complexities of MI. This ongoing challenge necessitates the exploration of novel approaches to enhance treatment efficacy and outcomes for MI patients. Main text: One promising approach is the use of nanoparticle delivery systems for targeted therapy to the infarct site. When conventional methods fail to achieve adequate permeability and retention, nanoparticle strategies offer a potential solution. Functionalizing nanoparticles is a particularly effective technique, allowing these particles to conjugate with specific ligands. These ligands possess the intrinsic ability to selectively bind to receptors that are overexpressed or uniquely present at the infarct site, thereby conferring “smartness” to the nanoparticle constructs. This review delves into the various strategies employed in nanoparticle-ligand functionalization, highlighting the versatility and potential of these approaches. It provides a detailed cross section of several ligand classes, each with unique properties and binding affinities that make them suitable for targeted delivery in the context of MI. The focus is on identifying ligands that are either unique to the infarcted myocardium or significantly upregulated during MI, ensuring precise and efficient targeting of therapeutic agents. Conclusion: In summary, while traditional surgical methods for restoring blood flow in MI patients remain important, they are not sufficient on their own. By leveraging the specificity of these ligands, nanoparticles can be directed precisely to the infarct site, enhancing the delivery and efficacy of therapeutic agents. This review underscores the need for continued research into nanoparticle-ligand functionalization strategies, aiming to improve outcomes for MI patients and reduce the global burden of this condition.