Beneficial effects of buspirone in endothelin-1 induced stroke cachexia in rats.

Stroke cachexia is associated with prolonged inflammation, muscle loss, poor prognosis, and early death of stroke patients. No particular treatment is available to cure the symptoms or disease. The present study aimed to evaluate the effect of a 5-HT1a agonist, buspirone on stroke cachexia. Wistar rats were injected with endothelin-1 to the bregma region of the brain to induce ischemic stroke followed by induction of cachexia after 4 days. Treatment with buspirone (3 mg/kg p.o) was given for 4 weeks after confirmation of cachexia in animals. Disease control animals exhibited decrease in wire hanging time and increase in foot fault numbers compared to normal animals. Disease control animals also showed weight loss, decrease in food intake, increased serum glucose and lipid profile along with high serum levels of inflammatory cytokines-TNF-α, IL-6 and decrease in weight of skeletal muscle and adipose tissues. Treatment with buspirone improves behavioural parameters along with increases food intake and body weight, decreased inflammatory cytokines IL-6 and TNF-α and serum glucose levels with increase in lipid profile. Buspirone also increased the weight of adipose tissue and maintain the skeletal muscle architecture and function as depicted in histopathological studies. Our study suggests that buspirone produces beneficial role in stroke cachexia by increasing body weight, food intake and adipose tissue depots by activating on 5-HT receptors. Buspirone decreases inflammatory markers in stroke cachexia although mechanism behind it was not fully understood. Buspirone decreases circulating blood glucose by stimulating glucose uptake in skeletal muscle via 5-HT receptors and maintained lipid profile. Buspirone was found to be effective in ameliorating cachectic conditions in stroke.

Role of NIMA-related kinase 2 in lung cancer: Mechanisms and therapeutic prospects.

The second most common cancer in both males and females is lung cancer. Chemotherapeutic resistance is the main problem associated with the treatment of lung cancer. Radiation therapy and surgery also produce recurrence in lung cancer patients; this shows the need to develop novel agents acting on new targets. A never in mitosis (NIMA)-related kinase 2 (NEK2) is a serine/threonine kinase associated with the family of NIMA-related kinase (NEK). NEK2 plays an important role in the regulating mitotic processes, such as centrosome duplication and separation, kinetochore attachment, spindle assembly checkpoint, and microtubule stabilization. Several in vitro, in vivo, and clinical studies have confirmed the overexpression of NEK2 in various types of cancers including lung cancer. Overexpression of NEK2 in non-small cell lung cancer (NSCLC) cells increased cell proliferation and chromosomal instability. The overexpression of NEK2 results in the activation of its downstream proteins such as ß-catenin, MAD2, Hec1, rootletin, C-Nap1, CDC20, Cep68, and Sgo1. Activation of the Akt, ß-catenin, and Wnt pathways could promote growth and metastasis of lung cancer cells. Such confirmation suggests that NEK2 is a novel target for treating many cancers including lung cancer. The current review provides an idea about functions and regulation of NEK2 and emphasizes about the role of NEK2 in lung cancer by discussing in vitro, in vivo, and clinical studies pertaining to the same.

Decompressive craniectomy for elevated intracranial pressure and its effect on the cumulative ischemic burden and therapeutic intensity levels after severe traumatic brain injury.

BACKGROUND: Increased intracranial pressure (ICP) can cause brain ischemia and compromised brain oxygen (PbtO2 < or = 20 mm Hg) after severe traumatic brain injury (TBI). OBJECTIVE: We examined whether decompressive craniectomy (DC) to treat elevated ICP reduces the cumulative ischemic burden (CIB) of the brain and therapeutic intensity level (TIL). METHODS: Ten severe TBI patients (mean age, 31.4 +/- 14.2 years) who had continuous PbtO2 monitoring before and after delayed DC were retrospectively identified. Patients were managed according to the guidelines for the management of severe TBI. The CIB was measured as the total time spent between a PbtO2 of 15 to 20, 10 to 15, and 0 to 10 mm Hg. The TIL was calculated every 12 hours. Mixed-effects models were used to estimate changes associated with DC. RESULTS: DC was performed on average 2.8 days after admission. DC was found to immediately reduce ICP (mean [SEM] decrease was 7.86 mm Hg [2.4 mm Hg]; P = .005). TIL, which was positively correlated with ICP (r = 0.46, P < or = .001), was reduced within 12 hours after surgery and continued to improve within the postsurgical monitoring period (P