RESUMEN
Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver. As the global obesity rate rises, non-alcoholic fatty liver disease (NAFLD) has emerged as the most rapidly increasing cause of HCC. Consequently, the regulation of lipid metabolism has become a crucial target for the prevention and treatment of HCC. Liquidambaric acid (LDA), a pentacyclic triterpenoid compound derived from various plants, exhibits diverse biological activities. We found that LDA could inhibit HCC cell proliferation by arresting cell cycle and prompting apoptosis. Additionally, LDA can augment the therapeutic efficacy of Regorafenib in HCC in vitro and vivo. Our study utilized transcriptome analysis, luciferase reporter assays, and co-immunocoprecipitation experiments to elucidate the anti-HCC mechanism of LDA. We discovered that LDA disrupts the formation of the PPARα-RXRα heterodimer, leading to the down-regulation of the ACSL4 gene and subsequently impacting the fatty acid metabolism of HCC cells, ultimately inhibiting HCC proliferation. Our research contributes to the identification of novel therapeutic agents and targets for the treatment of HCC.
Asunto(s)
Carcinoma Hepatocelular , Proliferación Celular , Coenzima A Ligasas , Regulación hacia Abajo , Ácidos Grasos , Neoplasias Hepáticas , PPAR alfa , Receptor alfa X Retinoide , PPAR alfa/metabolismo , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Receptor alfa X Retinoide/metabolismo , Receptor alfa X Retinoide/genética , Animales , Ácidos Grasos/metabolismo , Coenzima A Ligasas/metabolismo , Coenzima A Ligasas/genética , Células Hep G2 , Ratones Desnudos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ratones , Compuestos de Fenilurea/farmacología , Masculino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Endogámicos BALB C , Metabolismo de los Lípidos/efectos de los fármacos , PiridinasRESUMEN
Background: We conducted a prospective study of surgical inpatients at a teaching hospital to assess the incidence and potential risk factors for major complications of caudal anesthesia in anorectal surgery. Methods: A total of 973 patients undergoing anorectal surgery under caudal block were included in this prospective, observer-blinded trial after providing consent. Demographic information, detailed perioperative information, anesthesia-related complications and postoperative follow-up information were recorded. Meanwhile, the incidence and risk factors for major caudal anesthesia-related complications were analyzed. Results: A total of 973 patients underwent caudal block. The effective rate was 95.38 % (928 cases). However, there were still 38 (3.91 %) cases with insufficient block and 7 (0.72 %) cases with no block. The major anesthesia-related complications were local anesthetic systemic toxicity (9, 0.92 %), cauda equine syndrome (1, 0.10 %), transient neurological symptoms (3, 0.31 %) and localized pain at the caudal insertion site (30, 3.08 %). The identified risk factor for local anesthetic systemic toxicity was multiple attempts locating the caudal space (OR = 5.30; 1.21-23.29). The identified risk factor for localized pain at the caudal insertion site was multiple attempts locating the caudal space (OR = 10.57; 4.89-22.86). Conclusion: The main complications of caudal block in adult patients are transient neurological symptoms, cauda equine syndrome, serious local anesthetic systemic toxicity and localized pain at the caudal insertion site. Overall, the incidence of complications is low and symptoms are mild. Caudal block is still a safe and reliable method for anesthesia in adult anorectal surgery.
RESUMEN
Objective: To evaluate the safety and efficacy of the thoracolumbar interfascial block (TLIPB) in percutaneous kyphoplasty (PKP), and to confirm that the TLIPB further minimizes perioperative pain and residual back pain on the basis of local anesthesia. Method: From April 2021 to May 2022, 60 patients with osteoporotic vertebral compression fractures were included in this prospective randomized controlled trial. Patients were randomly assigned to a local anesthesia group (A group) or a TLIPB on the basis of local anesthesia group (A + TLIPB group) before PKP. Pain level (visual analog scale, VAS), amount of analgesic rescue drugs (parecoxib), operative time, mean arterial pressure, heart rate, and complications were assessed and compared between the two groups. Results: Compared with the A group, VAS scores were lower in the A + TLIPB group, respectively, when the trocar punctured the vertebral body (7.4 ± 0.7 vs. 4.5 ± 0.9; P < 0.01), during balloon dilatation (6.6 ± 0.9 vs. 4.6 ± 0.9; P < 0.01), during bone cement injection (6.3 ± 0.6 vs. 4.3 ± 0.8; P < 0.01), 1â h after surgery (3.5 ± 0.7 vs. 2.9 ± 0.7; P < 0.01), and 24â h after surgery (2.5 ± 0.8 vs. 1.9 ± 0.4; P < 0.01). Residual back pain (VAS: 1.9 ± 0.9 vs. 0.9 ± 0.8; P < 0.01) and the incidence of rescue analgesic use (P = 0.02) in the A + TLIPB group were lower compared with the A group. Compared with the A group, mean arterial pressure and heart rate were lower in the A + TLIPB group when the trocar punctured the vertebral body, and with balloon dilatation and bone cement injection; however, there were no statistical differences between the groups 1 and 24â h after surgery. The incidences of bone cement leakage, constipation, and nausea were similar between the two groups. No patient developed infection, neurological injuries, constipation in either group. Conclusion: The addition of the TLIPB to local anesthesia can further minimize perioperative pain and residual back pain, and reduce perioperative rescue analgesic use. When added to local anesthesia, the TLIPB is an effective and safe anesthetic method for PKP. Clinical trial registration: This study has been registered in the Clinical Trial registration: ChiCTR-2100044236.
RESUMEN
Midazolam is a sedative used by patients with mechanical ventilation. However, the potential clinical value is not fully explored. In this report, we made use of a neuroblastoma-spinal cord hybrid motor neuron-like cell line NSC34, and elucidated the potential role of Midazolam on these cells under the insult of oxidative stress. We found the protective effect of Midazolam on motor neurons against cytotoxicity induced by the combination of oligomycin A and rotenone (O/R) or phenylarsine oxide. The characteristics of apoptosis, such as the ratio of TUNEL+ cells or the expression level of cleaved Caspase-3, was decreased by 22 or 45% in the presence of Midazolam. Furthermore, this effect was correlated with the JNK-ERK signaling pathway. Either phosphorylation of ERK or JNK was positively or negatively modulated with the treatment of Midazolam in NSC34 cells attacked by reactive oxygen species. Meanwhile, inhibition or activation of the JNK-ERK pathway regulated the protective effect of Midazolam on NSC34 cells with oxidative stress insult. Collectively, this study elucidated a previously unidentified clinical effect of Midazolam, and put forward the great promise that Midazolam may be considered as a potential candidate to the treatment of motor neuron disease.
Asunto(s)
Muerte Celular/efectos de los fármacos , Muerte Celular/genética , Hipnóticos y Sedantes/farmacología , Sistema de Señalización de MAP Quinasas/fisiología , Midazolam/farmacología , Neuronas Motoras/patología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Línea Celular , Humanos , Hipnóticos y Sedantes/uso terapéutico , Midazolam/uso terapéutico , Enfermedad de la Neurona Motora/tratamiento farmacológicoRESUMEN
OBJECTIVE: To explore the effects of manganese poisoning on the proliferation of neural stem cells (NSCs) in mice's hippocampus. METHODS: The mice (weight 8 approximately 10 g) were divided into control group(CG) low-dose group(LDG) middle-dose group(MDG) and high-dose group(HDG)by intraperitoneal injection of 0, 5, 20, 50 mg x kg(-1) x d(-1) of manganese chloride dissolved in physiological saline. The ability of learning and memory was detected by Morris Water Maze, and the proliferation of NSCs in subgranular zone (SGZ) in these mice's hippocampus was also detected by immunohistochemistry. RESULTS: 1) Compared with the CG, the ability of learning and memory in all manganism group decreased significantly (P < 0.01) and this phenomenon in HDG was most notable (P < 0.01). Meanwhile, the ability of memory was negatively correlated with the dose of manganese chloride (r(s) = -0.598, P < 0.01), but the difference of swimming speed in every group was of no statistic significance. (2) The numbers of NSCs in proliferation period in SGZ of all manganism groups was much lower than that of CG (P < 0.01) negatively correlated with the dose of manganese chloride (r(s) = -0.666, P < 0.01). (3) The reduction of NSCs had a positive correlation to the depression of learning and memory (r(s) = 0.734, P < 0.01). CONCLUSIONS: Manganismus can affect the ability of learning and memory, which is probably caused by the inhalation of manganese on NSCs in hippocampus.