Mpox virus (MPXV), a member of the Orthopoxvirus genus in the Poxviridae family, has long been endemic in Africa. The interaction between MPXV infection and peripheral immune responses is of great significance. However, the activation of signaling pathways and molecular changes in peripheral blood mononuclear cells (PBMCs) following MPXV infection remain poorly understood. This study evaluated the transcriptomic profiles of rabbit PBMCs during the mpox acute and recovery phases. The results showed that MPXV infection significantly altered the transcriptomic profiles of PBMCs. At 6 days post-infection, pathways related to pathogenic infection and IL-1 response were enriched, while at 14 days post-infection, the T cell receptor signaling pathway was enriched. During the mpox acute phase, inflammatory cytokines in serum such as IL-1α, IL-1β, IL-8, and IL-21 were upregulated, while MMP-9 and NCAM-1 were downregulated. In rabbits and rhesus monkeys, key genes upregulated in common during the mpox acute period were associated with the interferon pathway (e.g., the ISG15, OAS, and IFIT families), while downregulated genes were related to B-cell activation and differentiation (e.g., the MS4A1 and FCRL families). Additionally, rabbits developed protective immunity against reinfection, with neutralizing antibodies effectively activated. These findings provide insights into the molecular characteristics of PBMCs changes in in vivo models of MPXV infection, and offer references for the diagnosis, vaccine development, and therapeutic research of mpox.

Background/Objectives: Cancer cachexia (CC) is a metabolic syndrome characterized by the progressive loss of skeletal muscle and adipose tissue during tumor progression. Despite its clinical prevalence, effective therapeutic options are currently lacking. Phloretin, a natural flavonoid with potent anti-inflammatory and antioxidant properties, has unclear efficacy against CC. This study investigates the therapeutic potential of phloretin in ameliorating cancer cachexia. Methods: Mouse models of CC were established using BALB/c mice implanted with C26 colon carcinoma cells and C57BL/6 mice implanted with Lewis lung carcinoma (LLC) cells. Upon the detection of palpable tumors, phloretin (10 mg/kg) was administered daily via intraperitoneal injection. At the endpoint, hind limb skeletal muscle, inguinal white adipose tissue (iWAT), and hearts were harvested and weighed. Lean body mass was assessed by analyzing the weight of the carcass following the excision of skin, subcutaneous fat, and visceral organs. Gene expression and protein levels in muscle tissues were subsequently quantified. Results: Phloretin administration significantly alleviated tumor-induced loss of tumor-free body weight. It effectively preserved skeletal muscle mass in both C26 and LLC cachexia models, while significantly attenuating adipose tissue depletion in the C26 model. In vitro, phloretin treatment mitigated myotube atrophy induced by C26 conditioned medium. Mechanistically, phloretin inhibited STAT3 activation in skeletal muscle. This inhibition suppressed the expression of the E3 ubiquitin ligases MuRF-1 and Atrogin-1. Furthermore, phloretin concurrently modulated the autophagy pathway. Conclusions: Phloretin effectively ameliorates cancer cachexia-induced muscle wasting by targeting STAT3-mediated protein degradation and autophagy pathways. These findings suggest that phloretin represents a promising therapeutic agent for the clinical management of cancer-associated cachexia.