Peripheral arterial disease (PAD), leading to intermittent claudication, critical ischemia with rest pain, and/or tissue damage, is a public health issue associated with significant morbidity and mortality. Little is known about the link between PAD, cognitive function, and whether exercise might reduce cognitive dysfunction in PAD patients, as previously observed concerning both quality of life and prognosis. This review highlights the fact that patients suffering from PAD often demonstrate cognitive dysfunction characterized by reduced performance in nonverbal reasoning, reduced verbal fluency, and decreased information processing speed and a greater risk for progression toward dementia. Further, the data presented support that physical exercise, likely through myokine secretion and microglial anti-inflammatory phenotype enhancement, might participate in the cognition protection in common clinical settings.

Megakaryocytes (MKs) are specialized hematopoietic cells long recognized for their ability to produce platelets. Increasing evidence now highlights MKs as multifunctional immune effectors that bridge hematopoiesis with host immunity. In the bone marrow (BM), MKs arise through thrombopoietin (TPO)-mediated differentiation of hematopoietic stem cells (HSCs) and show substantial heterogeneity, with discrete subsets specialized for platelet production (thrombopoiesis), HSC niche maintenance, or immune modulation. Outside the BM, MKs in the lungs and spleen perform tissue-specific immune functions, including pathogen recognition, phagocytosis, antigen presentation, and secretion of cytokines. During bacterial infections and sepsis, infectious or inflammatory cues reprogram MKs to amplify immune signaling and host responses, but can also drive coagulopathy and contribute to organ failure. Collectively, these findings redefine MKs as dynamic immunomodulatory cells positioned at the interface of thrombopoiesis and innate and adaptive immunity. In this review, we synthesize emerging literature on MK biogenesis, functional diversity, and immune modulation, with a special focus on their roles in bacterial infections and sepsis.