Platelet status in cancer cachexia progression in ApcMin/+ mice.

Cachexia, a complex wasting syndrome, significantly affects the quality of life and treatment options for cancer patients. Studies have reported a strong correlation between high platelet count and decreased survival in cachectic individuals. Therefore, this study aimed to investigate the immunopathogenesis of cancer cachexia using the ApcMin/+ mouse model of spontaneous colorectal cancer. The research focused on identifying cellular elements in the blood at different stages of cancer cachexia, assessing inflammatory markers and fibrogenic factors in the skeletal muscle, and studying the behavioral and metabolic phenotype of ApcMin/+ mice at the pre-cachectic and severely cachectic stages. Platelet measurements were also obtained from other animal models of cancer cachexia - Lewis Lung Carcinoma and Colon 26 adenocarcinoma. Our study revealed that platelet number is elevated prior to cachexia development in ApcMin/+ mice and can become activated during its progression. We also observed increased expression of TGFß2, TGFß3, and SMAD3 in the skeletal muscle of pre-cachectic ApcMin/+ mice. In severely cachectic mice, we observed an increase in Ly6g, CD206, and IL-10 mRNA. Meanwhile, IL-1ß gene expression was elevated in the pre-cachectic stage. Our behavioral and metabolic phenotyping results indicate that pre-cachectic ApcMin/+ mice exhibit decreased physical activity. Additionally, we found an increase in anemia at pre-cachectic and severely cachectic stages. These findings highlight the altered platelet status during early and late stages of cachexia and provide a basis for further investigation of platelets in the field of cancer cachexia.

Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases.

(1) Background: Gastrointestinal pain and fatigue are the most reported concerns of patients with inflammatory bowel disease (IBD). Commonly prescribed drugs focus on decreasing excessive inflammation. However, up to 20% of IBD patients in an "inactive" state experience abdominal pain. The medicinal herb Ojeok-san (OJS) has shown promise in the amelioration of visceral pain. However, no research on OJS has been conducted in preclinical models of IBD. The mechanism by which OJS promotes analgesia is still elusive, and it is unclear if OJS possesses addictive properties. (2) Aims: In this study, we examined the potential of OJS to promote analgesic effects and rewarding behavior. Additionally, we investigated if tumor necrosis factor alpha (TNFα) from macrophages is a primary culprit of IBD-induced nociception. (3) Methods: Multiple animal models of IBD were used to determine if OJS can reduce visceral nociception. TNFα-macrophage deficient mice were used to investigate the mechanism of action by which OJS reduces nociceptive behavior. Mechanical sensitivity and operant conditioning tests were used to determine the analgesic and rewarding effects of OJS. Body weight, colon length/weight, blood in stool, colonic inflammation, and complete blood count were assessed to determine disease progression. (4) Results: OJS reduced the evoked mechanical nociception in the dextran sulphate sodium model of colitis and IL-10 knockout (KO) mice and delayed aversion to colorectal distension in C57BL/6 mice. No rewarding behavior was observed in OJS-treated IL-10 KO and mdr1a KO mice. The analgesic effects of OJS are independent of macrophage TNFα levels and IBD progression. (5) Conclusions: OJS ameliorated elicited mechanical and visceral nociception without producing rewarding effects. The analgesic effects of OJS are not mediated by macrophage TNFα.