Pharmacological Research - Reports最新文献

Spinal cord injury (SCI) is a cause of long-term disability, and one of the main problems is sensorimotor response impairment. Thus, become important treatments that reduce the progressive secondary damage that causes the loss of spared neurons. Due to the oxidative stress and inflammation interaction after damage, we tested if diacerein, a classic pharmacologic anti-inflammatory, could reduce the cell damage in the long term and recover sensorimotor responses after SCI in rats. Clip-compression SCI model in female Wistar rats caused severe locomotory loss performance showed through assessment by the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and induced thermal hyperalgesia observed by Plantar Test Apparatus. When diacerein was administered twice a day for thirty-five days, the data presented a significant recovery of locomotion and an attenuation of thermal hyperalgesia. The increased adrenal glands’ weight and reduced soleus muscle mass were attenuated by diacerein. The immunoblotting showed that diacerein prevented progressive damage at the site of injury demonstrated by the recovery of nuclear factor erythroid-2 related factor 2 (Nrf2) levels, reduction of protein nitration by 3-nitrotyrosine (3-NT) expression and inflammation decreased showed by a less expression in glial fibrillary acidic protein (GFAP) immune content induced by injury. Therefore, the present data suggest that blockage of secondary damage by diacerein can inhibit the oxidative/inflammatory process by increasing Nrf2 and improving sensorimotor recovery in rats.

Lesions induced by the obligate intracellular bacterium Lawsonia intracellularis, the etiological agent of porcine proliferative enteropathy, are characterized by crypt hyperplasia in the intestinal epithelium with minimal inflammatory infiltration. An increased population of immature enterocytes at the expense of reduced goblet cells suggests that dysregulated apoptosis may be crucial in the pathogenesis of L. intracellularis.

Fosfomycin, a widely employed antibiotic in swine production, has also exhibited non-microbicidal effects, encompassing immunomodulation, augmentation of phagocytosis, and the promotion of cell survival. In this study, we assessed the immunomodulatory impact of fosfomycin on intestinal epithelial homeostasis using porcine intestinal explants challenged with L. intracellularis.

Our findings reveal that L. intracellularis elicited significant nuclear alterations, increased apoptotic indices, and prompted extensive mucin secretion in the intestinal explants. When fosfomycin was added to L. intracellularis-challenged intestinal explants, it mitigated the degree of apoptosis but also induced an inflammatory response. Consequently, treatment with fosfomycin in the context of L. intracellularis challenge appears to initiate an early mucosal response, maintaining cell viability, preserving the mucin barrier, and fostering inflammatory recruitment.

Pancreatic cancer is a highly lethal cancer with limited treatment options. The number of pancreatic cancer patients is increasing rapidly worldwide. Many natural products have been shown to have anticancer activity in a range of studies. Sotetsuflavone is derived from Cycas revoluta Thunb. and exhibits anticancer activity. The present study incorporates network pharmacology, single gene survival analysis, gene expression analysis and molecular docking to reveal the mechanism of Sotetsuflavone in the treatment of pancreatic cancer. We have acquired 31 hub targets for the treatment of pancreatic cancer by Sotetsuflavone, namely ABCB1, AURKA, CDK1, and so on. Kaplan-Meier survival analyses demonstrated that ABCB1, AURKA, CDK1, HDAC6, MET, and MMP3 are promising hub targets that can be used as biomarkers for pancreatic cancer diagnosis and prognosis. These hub targets are highly expressed in pancreatic cancer tissues compared to normal tissues. The molecular docking results showed a strong binding capacity of Sotetsuflavone to these hub targets. In summary, it is proposed that Sotetsuflavone is a new anticancer drug, which can regulate pancreatic cancer-related signalling pathways by inhibiting the activities of ABCB1, AURKA, CDK1, HDAC6, MET, and MMP3, which are hub targets with up-regulated expression in pancreatic cancer tissues, in order to treat pancreatic cancer. However, it also requires a series of in vivo and in vitro studies to ensure its safety and efficacy.

Diabetes mellitus is often associated with metabolic disorders like hyperglycemia, hyperlipidemia, oxidative stress and obesity. Health problems related to these disorders are on a rise globally. Although nanotechnology based approaches have been explored for diabetes treatment, specific information on alleviation of the associated health problem is scanty. Here we report the beneficial effects of copper oxide nanoparticles (CuOnpls) for the control of hyperlipidemia and oxidative stress caused due to diabetes. Wistar rats were fasted overnight and type 2 diabetes was induced by intraperitoneal (i.p.) injection of freshly prepared nicotinamide followed by streptozotocin. Induction of diabetes was confirmed by estimation of blood glucose levels of the animals. Estimation of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein-cholesterol (HDL-c) from the serum was carried out for ascertaining hyperlipidemia. Biogenic CuOnpls (spherical, 88.25 nm diameter) capped with bud extract of Syzygium aromaticum and α-tocopherol were administered in the animals per-oral route. Superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels were determined to evaluate antioxidant activity of CuOnpls. The nanoparticles were characterized for surface chemical groups by FTIR and HRLC-MS. The nanoparticles revealed novel surface groups responsible for site-specific delivery and beneficial effects. Diabetic rats showed enhanced serum BG, TC, TG and LDL levels and reduction in levels of HDL-c, SOD, CAT and GSH. Administration of CuOnpls caused significant reversal of the effects of diabetes on lipid profile and oxidative stress enzymes. The results pointed to the beneficial effects of CuOnpls for management of post-diabetes complications.

Hepatic liver diseases are among the most common chronic diseases worldwide, with few available treatments. Bone diseases, such as osteoporosis, are associated with liver disease and other conditions and represent another challenge to treatment. The present study investigated effects of the antidiabetic glucagon-like peptide 1 (GLP-1) analogs semaglutide and dulaglutide on hepatic and osteogenic parameters in an acute CCl₄-induced hepatotoxicity model. Two protocols were used in male Swiss mice: treatment and pretreatment with one or two administrations of semaglutide (0.021 mg/kg, i.p.), dulaglutide (0.014 mg/kg, i.p.), silymarin (100 mg/kg, p.o., positive control), or vehicle (10 ml/kg, i.p.). The mice were euthanized 48 h after the challenge with 1.5 % CCl₄ (0.25 ml, i.p.). The results indicated that dulaglutide exerted greater hepatoprotective effects than semaglutide, reducing liver necrosis, hepatic glutathione-S-transferase activity, and plasma alanine aminotransferase levels. Semaglutide improved the biliary excretion of cholesterol, benefiting more the biliary system than the hepatic parenchyma. Both drugs induced the gene expression of Cyclin D1, improving the proliferative phase of liver regeneration. With regard to bone remodeling, semaglutide increased the osteoblast surface (O.b/S) and its function by increasing the osteoid surface (OS/BS), suggesting an increase in bone formation. These data indicate that dulaglutide has potential as an alternative treatment for hepatotoxicity that is mainly induced by drugs, and semaglutide can improve bone development, demonstrating the potential of this GLP-1 analog for the prevention of bone fragility that is related to liver diseases.