RESUMEN
Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients' quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.
Asunto(s)
Dolor Crónico , Bulbo Olfatorio , Humanos , Dolor Crónico/terapia , Animales , Bulbo Olfatorio/citología , Neuroglía , Trasplante de Células/métodosRESUMEN
Neuropathic pain is a common symptom experienced by most clinical diseases at different levels, and its treatment has always been a clinical difficulty. Therefore, it is particularly important to explore new and effective treatment methods. The role of olfactory ensheathing cells (OECs) in nerve injury and pain is recognized by different studies. Our previous study found that transplantation of OECs alleviated hyperalgesia in rats. However, single-cell transplantation lacks medium adhesion and support, and exerts limited analgesic effect. Therefore, on the basis of the previous study, this study investigated the effect of pain relief by co-transplanting OECs with chitosan (CS) (a biological tissue engineering material, as OECs were transplanted into the host medium) to the injured sciatic nerve. The results showed that the pain threshold of sciatic nerve injury of rats was significantly reduced, and the expression level of P2×4 receptor in the spinal cord was significantly increased. While olfactory ensheathing cells combined with chitosan (OECs+CS) transplantation could significantly relieve pain, and the analgesic effect was stronger than that of OECs transplantation alone. OECs+CS transplantation promoted the formation of sciatic nerve remyelination, improved the changes of demyelination, and promoted the repair of sciatic nerve injury more significantly. In addition, the effect of OECs+CS to down-regulate the expression of P2×4 receptor was significantly stronger than that of OECs transplantation, and exerted a better analgesic effect. These data reveal that OECs+CS have a better analgesic effect in relieving neuropathic pain induced by sciatic nerve injury, and provide a new therapeutic strategy for pain treatment.
Asunto(s)
Quitosano , Neuralgia , Neuropatía Ciática , Traumatismos de la Médula Espinal , Ratas , Animales , Materiales Biocompatibles/metabolismo , Ratas Sprague-Dawley , Quitosano/farmacología , Quitosano/uso terapéutico , Quitosano/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Neuropatía Ciática/metabolismo , Nervio Ciático/fisiología , Neuralgia/terapia , Neuralgia/metabolismo , Analgésicos/farmacología , Analgésicos/uso terapéutico , Analgésicos/metabolismo , Bulbo Olfatorio/metabolismo , Regeneración Nerviosa/fisiologíaRESUMEN
Neuropathic pain (NPP) is a common syndrome associated with most forms of disease, which poses a serious threat to human health. NPP may persist even after the nociceptive stimulation is eliminated, and treatment is extremely challenging in such cases. Schwann cells (SCs) form the myelin sheaths around neuronal axons and play a crucial role in neural information transmission. SCs can secrete trophic factors to nourish and protect axons, and can further secrete pain-related factors to induce pain. SCs may be activated by peripheral nerve injury, triggering the transformation of myelinated and non-myelinated SCs into cell phenotypes that specifically promote repair. These differentiated SCs provide necessary signals and spatial clues for survival, axonal regeneration, and nerve regeneration of damaged neurons. They can further change the microenvironment around the regions of nerve injury, and relieve the pain by repairing the injured nerve. Herein, we provide a comprehensive overview of the biological characteristics of SCs, discuss the relationship between SCs and nerve injury, and explore the potential mechanism of SCs and the occurrence of NPP. Moreover, we summarize the feasible strategies of SCs in the treatment of NPP, and attempt to elucidate the deficiencies and defects of SCs in the treatment of NPP.
Asunto(s)
Neuralgia , Traumatismos de los Nervios Periféricos , Humanos , Células de Schwann , Vaina de Mielina , Axones , Regeneración NerviosaRESUMEN
Visceral pain (VP) is caused by internal organ disease. VP is involved in nerve conduction and related signaling molecules, but its specific pathogenesis has not yet been fully elucidated. Currently, there are no effective methods for treating VP. The role of P2X2/3 in VP has progressed. After visceral organs are subjected to noxious stimulation, cells release ATP, activate P2X2/3, enhance the sensitivity of peripheral receptors and the plasticity of neurons, enhance sensory information transmission, sensitize the central nervous system, and play an important role in the development of VP. However, antagonists possess the pharmacological effect of relieving pain. Therefore, in this review, we summarize the biological functions of P2X2/3 and discuss the intrinsic link between P2X2/3 and VP. Moreover, we focus on the pharmacological effects of P2X2/3 antagonists on VP therapy and provide a theoretical basis for its targeted therapy.
Asunto(s)
Dolor Visceral , Humanos , Neuronas , Sistema Nervioso Central , Transducción de Señal , Adenosina TrifosfatoRESUMEN
Studies have revealed the contribution of ATP-G-protein-coupled P2Y2 receptor (P2RY2) in tumor progression, but the role of P2RY2 in regulating the progression of gastric cancer (GC) and related molecular mechanisms are relatively lacking. Therefore, this study investigates the effects of P2RY2 on the proliferation and migration of GC through in vivo and in vitro experiments. The results showed that P2RY2 was expressed in GC tissues and GC cell lines. Adenosine triphosphate (ATP) increased the calcium influx in AGS and HGC-27 cells, and was dose-dependent with ATP concentration. ATP and UTP increased the intracellular glycogen content, enhanced the actin fiber stress response, and promoted the proliferation and migration of GC cells, while P2RY2 competitive antagonist AR-C118925XX reversed the changes induced by ATP. Knockdown of P2RY2 expression by shRNA inhibited the proliferation of GC cells. Activation of P2RY2 increased the expression of Snail, Vimentin, and ß-catenin in GC cells, and down-regulated the expression of E-cadherin, while AR-C118925XX decreased the expression of these genes induced by ATP. Activation of P2RY2 activated AKT/GSK-3beta/VEGF signal to promote the proliferation of GC cells, and the P13/AKT signaling pathway LY294002 reversed the corresponding phenomenon, but no synergistic pharmacological properties of AR-C118925XX and LY294002 have been found. In vivo experiments showed that ATP-induced tumor growth, while AR-C118925XX inhibited ATP-induced tumor growth. Our conclusion is that P2RY2 activated the AKT/GSK-3beta/VEGF signal to promote the proliferation and migration of GC, suggesting that P2RY2 may be a new potential target for the treatment of GC.
Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Neoplasias Gástricas , Humanos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Factor A de Crecimiento Endotelial Vascular , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Transducción de Señal , Proliferación Celular , Adenosina Trifosfato/farmacología , Movimiento Celular , Receptores Purinérgicos P2Y2/genéticaRESUMEN
Since the outbreak of SARS-CoV-2/COVID-19 in Wuhan, China in 2019, it has rapidly spread to the world, and the number of infections has gradually increased. The hospitalization rate of patients has also gradually increased, which poses a huge challenge to hospitals and medical staff for patients with SARS-CoV-2 requiring surgical treatment. Therefore, avoiding cross-infection in the operating room is an important protective work. The operating room is an important department of the hospital, scientific and reasonable management is particularly important. Therefore, we have put forward corresponding suggestions and strategies for preoperative preparation and evaluation of patients, intraoperative management, postoperative terminal management, and protection of medical staff, and hope that these measures can better prevent and control the infection of SARS-CoV-2 in the operating room.
RESUMEN
Different studies have confirmed P2X7 receptor-mediated inflammatory mediators play a key role in the development of pain. P2X7 receptor activation can induce the development of pain by mediating the release of inflammatory mediators. In view of the fact that P2X7 receptor is expressed in the nervous system and immune system, it is closely related to the stability and maintenance of the nervous system function. ATP activates P2X7 receptor, opens non-selective cation channels, activates multiple intracellular signaling, releases multiple inflammatory cytokines, and induces pain. At present, the role of P2X7 receptor in inflammatory response and pain has been widely recognized and affirmed. Therefore, in this paper, we discussed the pathological mechanism of P2X7 receptor-mediated inflammation and pain, focused on the internal relationship between P2X7 receptor and pain. Moreover, we also described the effects of some antagonists on pain relief by inhibiting the activities of P2X7 receptor. Thus, targeting to inhibit activation of P2X7 receptor is expected to become another potential target for the relief of pain.
Asunto(s)
Inflamación , Receptores Purinérgicos P2X7 , Adenosina Trifosfato , Citocinas/metabolismo , Humanos , Mediadores de Inflamación , Dolor , Antagonistas del Receptor Purinérgico P2X/farmacologíaRESUMEN
Neuropathic pain is a common clinical symptom of various diseases, and it seriously affects the physical and mental health of patients. Owing to the complex pathological mechanism of neuropathic pain, clinical treatment of pain is challenging. Therefore, there is growing interest among researchers to explore potential therapeutic strategies for neuropathic pain. A large number of studies have shown that development of neuropathic pain is related to nerve conduction and related signaling molecules. P2X3 receptors (P2X3R) are ATP-dependent ion channels that participate in the transmission of neural information and related signaling pathways, sensitize the central nervous system, and play a key role in the development of neuropathic pain. In this paper, we summarized the structure and biological characteristics of the P2X3R gene and discussed the role of P2X3R in the nervous system. Moreover, we outlined the related pathological mechanisms of pain and described the relationship between P2X3R and chronic pain to provide valuable information for development of novel treatment strategies for pain.
Asunto(s)
Ganglios Espinales , Neuralgia , Animales , Ganglios Espinales/patología , Humanos , Hiperalgesia/tratamiento farmacológico , Neuralgia/patología , Ratas , Ratas Sprague-Dawley , Receptores Purinérgicos P2X3/metabolismoRESUMEN
Objectives: The purpose of this study is to investigate the effects of transplantation of microencapsulated neural stem cells (MC-NSCs), which downregulate the P2 × 4 receptor (P2 × 4R) overexpression and relieve neuropathic pain (NPP). Methods: Neural stem cells (NSCs) and MC-NSCs were transplanted to the injured sciatic nerve. Transmission electron microscope and immunofluorescence were used to observe the changes of injured sciatic nerve. Behavioral methods were used to detect mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats. Expression levels of P2 × 4Rs and p-p65 in the spinal cord segment of rats were measured by using molecular biology methods. The concentrations of IL-1ß and TNF-α were detected in serum of rats by ELISA. Results: After sciatic nerve injury, the sciatic nerve fibers had the myelinated lamina separated, and disintegrated fragments could be seen. The fluorescence intensity of myelin MBP was weakened. The MWT and TWL were significantly decreased, the expression of P2 × 4Rs and p-p65 were significantly increased, and the concentrations of IL-1ß and TNF-α were increased. After NSC and MC-NSC transplantation, the myelin sheath of the sciatic nerve was relatively intact, some demyelination changes could be seen, and the injured sciatic nerve has been improved. The fluorescence intensity of myelin MBP was increased. The MWT and TWL were increased, expression levels of P2 × 4Rs and p-p65 were decreased, and the concentrations of IL-1ß and TNF-α were significantly decreased. Compared with NSC transplantation, transplantation of MC-NSCs could better repair the damaged sciatic nerve, decrease the expression of P2 × 4Rs and p-p65, decrease the level of IL-1ß and TNF-α, and relieve pain (all p-values < 0.05). Conclusion: NSCs and MC-NSCs transplantation may alleviate pain by reducing the expression of P2 × 4Rs and inhibiting the activation of NF-KB signaling, while MC-NSCs transplantation has a better effect of suppressing pain. Our experimental results provide new data support for the treatment of NPP.
RESUMEN
The pathological mechanism of colon cancer is very complicated. Therefore, exploring the molecular basis of the pathogenesis of colon cancer and finding a new therapeutic target has become an urgent problem to be solved in the treatment of colon cancer. ATP plays an important role in regulating the progression of tumor cells. P2 × 7 belongs to ATP ion channel receptor, which is involved in the progression of tumors. In this study, we explored the effect and molecular mechanism of ATP-mediated P2 × 7 receptor on the migration and metastasis of colon cancer cells. The results showed that ATP and BzATP significantly increased the inward current and intracellular calcium concentration of LOVO and SW480 cells, while the use of antagonists (A438079 and AZD9056) could reverse the above phenomenon. We found that ATP promoted the migration and invasion of LOVO and SW480 cells and is dose-dependent on ATP concentration (100-300 µM). Similarly, BzATP (10, 50, and 100 µM) also significantly promoted the migration and invasion of colon cancer cells in a concentration-dependent manner. While P2 × 7 receptor antagonists [A438079 (10 µM), AZD9056 (10 µM)] or P2 × 7 siRNA could significantly inhibit ATP-induced colon cancer cell migration and invasion. Moreover, in vivo experiments showed that ATP-induced activation of P2 × 7 receptor promoted the growth of tumors. Furthermore, P2 × 7 receptor activation down-regulated E-cadherin protein expression and up-regulated MMP-2 mRNA and concentration levels. Knocking down the expression of P2 × 7 receptor could significantly inhibit the increase in the expression of N-cadherin, Vimentin, Zeb1, and Snail induced by ATP. In addition, ATP time-dependently induced the activation of STAT3 via the P2 × 7 receptor, and the STAT3 pathway was required for the ATP-mediated invasion and migration. Our conclusion is that ATP-induced P2 × 7 receptor activation promotes the migration and invasion of colon cancer cells, possibly via the activation of STAT3 pathway. Therefore, the P2 × 7 receptor may be a potential target for the treatment of colon cancer.
RESUMEN
Chronic pain is a common symptom of most clinical diseases, which seriously affects the psychosomatic health of patients and brings some pain to patients. Due to its pathological mechanism is very complicated and the treatment of chronic pain has always been a difficult problem in clinical. Normally, drugs are usually used to relieve pain, but the analgesic effect is not good, especially for cancer pain patients, the analgesic effect is poor. Therefore, exploring the pathogenesis and treatment of chronic pain has aroused the interest of many researchers. A large number of studies have shown that the role of ATP and P2X4 receptor (P2X4R) play an important role in the pathogenesis of chronic pain. P2X4R is dependent on ATP ligand-gated ion channel receptor, which can be activated by ATP and plays an important role in the information transmission of nerve system and the formation of pain. Therefore, in this paper, we comprehensively described the structure and biological functions of P2X4R, and outlined behavioral evaluation methods of chronic pain models. Moreover, we also explored the inherent relationship between P2X4R and chronic pain, and described the therapeutic effect of P2X4R antagonist on chronic pain, and provided some valuable help for the treatment of chronic pain.
Asunto(s)
Analgésicos/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Antagonistas del Receptor Purinérgico P2X/uso terapéutico , Receptores Purinérgicos P2X4/metabolismo , Adenosina Trifosfato/metabolismo , Regulación Alostérica/efectos de los fármacos , Analgésicos/química , Animales , Sitios de Unión , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Dolor Crónico/metabolismo , Humanos , Microglía/efectos de los fármacos , Microglía/metabolismo , Estructura Molecular , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Antagonistas del Receptor Purinérgico P2X/química , Transducción de SeñalRESUMEN
BACKGROUND: Neuropathic pain (NPP) is the common symptom of most clinical diseases, and its treatment has always been a difficult problem at present. Therefore, the purpose of this study is to explore a new method for the treatment of NPP by transplanting olfactory ensheathing cells combined with chitosan (OECs-CS). METHODS: Animal model of chronic compression sciatic nerve injury (CCI) was made, olfactory ensheathing cells (OECs) were cultured, chitosan (CS) biomaterials were prepared, and biocompatibility of OECs and CS were detected by MTT method, OECs and OECs-CS were transplanted into the site of the injured sciatic nerve respectively, behavioral method was used to measured the mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats. On days 7 and 14 after surgery, the expression level of P2X7 receptor (P2X7R) in the L4-5 spinal cord was measured by using in situ hybridization, western-blotting and qRT-PCR. To explore the therapeutic effect of OECs-CS transplantation on pain suppression. RESULTS: After chronic compression sciatic nerve injury, the MWT and TWL of rats were significantly reduced, and the expression levels of P2X7R protein and mRNA in the L4-5 spinal cord was significantly increased. After the transplantation of OECs and OECs-CS, the expression levels of P2X7R was significantly reduced, and the MWT and TWL of rats were significantly increased. Importantly, compared with the transplantation of OECs, OECs-CS transplantation could better reduce the expression levels of P2X7R, and relieve hyperalgesia in rats. Moreover, compared with the CCI + OECs-CS group on days 7 after surgery, the expression levels of P2X7R in the CCI + OECs-CS group was reduced on days 14 after surgery, and the pain in rats was relieved. CONCLUSION: OECs and OECs-CS transplantation can inhibit P2X7R overexpression mediated NPP, while OECs-CS transplantation has better therapeutic effect than OECs transplantation alone. Our results provide a novel method and theoretical basis for the treatment of NPP.
Asunto(s)
Trasplante de Células/métodos , Quitosano/uso terapéutico , Regulación hacia Abajo/efectos de los fármacos , Neuralgia/tratamiento farmacológico , Receptores Purinérgicos P2X7/metabolismo , Médula Espinal/efectos de los fármacos , Animales , Quitosano/farmacología , Femenino , Masculino , Neuralgia/genética , Neuralgia/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Purinérgicos P2X7/genética , Médula Espinal/metabolismoRESUMEN
Emphysematous cystitis (EC) is a rare bladder infection characterized by the presence of gas in the wall or cavity of the bladder. Most patients with EC will present with the typical symptoms of cystitis (e.g. frequent micturition, urgent micturition and dysuria), but other signs include distension and pain in the lower abdomen, drum sounds on percussion and a large amount of gas in the bladder. There can also be other complications such as sepsis. However, it is usually characterized by the typical symptoms of infection combined with pneumatinuria, the passage of gas mixed with urine. The early stage of EC is mostly limited to the submucosa and the symptoms of infection can be mild. Some patients may have no obvious clinical symptoms. If the infection becomes severe, it may result in difficulty urinating and kidney dysfunction. Therefore, timely treatment of these rare bladder infections is essential. This current case report describes an 80-year-old female patient with severe EC complicated by significant bilateral ureteral dilatation, bilateral renal cortical atrophy and sepsis. The patient was successfully treated with antibiotics and surgery. This report provides clinical data, test results and treatment experience that might be useful for clinicians that are involved in the treatment of EC.
Asunto(s)
Cistitis , Enfisema , Sepsis , Anciano de 80 o más Años , Atrofia , Cistitis/complicaciones , Cistitis/diagnóstico por imagen , Enfisema/complicaciones , Enfisema/diagnóstico por imagen , Femenino , Humanos , Sepsis/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
The occurrence and development of tumors is a multi-factor, multi-step, multi-gene pathological process, and its treatment has been the most difficult problem in the field of medicine today. Therefore, exploring the relevant factors involved in the pathogenesis of tumors, improving the diagnostic rate, treatment rate, and prognosis survival rate of tumors have become an urgent problem to be solved. A large number of studies have shown that the P2X7 receptor (P2X7R) and the tumor microenvironment play an important role in regulating the growth, apoptosis, migration and invasion of tumor cells. P2X7R is an ATP ligand-gated cationic channel receptor, which exists in most tissues of the human body. The main function of P2X7R is to regulate the relevant cells (such as macrophages, lymphocytes, and glial cells) to release damaging factors and induce apoptosis and cell death. In recent years, with continuous research and exploration of P2X7R, it has been found that P2X7R exists on the surface of most tumor cells and plays an important role in tumor pathogenesis. The activation of the P2X7R can open the ion channels on the tumor cell membrane (sodium ion, calcium ion influx and potassium ion outflow), trigger rearrangement of the cytoskeleton and changes in membrane fluidity, allow small molecule substances to enter the cell, activate enzymes and kinases in related signaling pathways in cells (such as PKA, PKC, ERK1/2, AKT, and JNK), thereby affecting the development of tumor cells, and can also indirectly affect the growth, apoptosis and migration of tumor cells through tumor microenvironment. At present, P2X7R has been widely recognized for its important role in tumorigenesis and development. In this paper, we give a comprehensive description of the structure and function of the P2X7R gene. We also clarified the concept of tumor microenvironment and its effect on tumors, discussed the relevant pathological mechanisms in the development of tumors, and revealed the intrinsic relationship between P2X7R and tumors. We explored the pharmacological properties of P2X7R antagonists or inhibitors in reducing its expression as targeted therapy for tumors.
Asunto(s)
Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Susceptibilidad a Enfermedades , Neoplasias/etiología , Neoplasias/metabolismo , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Adenosina Trifosfato , Animales , Biomarcadores , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunomodulación , Activación del Canal Iónico , Ligandos , Neoplasias/patología , Neoplasias/terapia , Unión Proteica , Antagonistas del Receptor Purinérgico P2X/química , Antagonistas del Receptor Purinérgico P2X/farmacología , Receptores Purinérgicos P2X7/química , Transducción de Señal , Relación Estructura-Actividad , Microambiente Tumoral/genéticaRESUMEN
INTRODUCTION: Small intestinal telangiectasia is a clinically rare disease, which is mainly characterized by gastrointestinal bleeding. There is a lack of specific and effective diagnostic methods in clinical practice due to its unknown etiology and difficult localization, it is often difficult to find the location of the lesion even through observation, touch, endoscope or intestinal incision. CASE PRESENTATION: A 39-year-old female patient, who had black stool twice without obvious inducement 3 days ago, and came to our hospital for treatment and was hospitalized with gastrointestinal bleeding. the main manifestation of this patient was repeated black stool, sometimes dark red. Initially, we considered other diseases of the digestive tract (gastric ulcers, duodenal ulcers and intestinal tumors). However, no abnormalities were found by CT, gastroscopy and enteroscopy. Later, we considered that there was a greater possibility of intestinal vascular disease, and then blood clots was found in the upper and middle segment of the jejunum through capsule endoscopy, but no bleeding site was found. Therefore, we decided to open the abdomen for further intraoperative enteroscopy exploration, finally found the bleeding point, and then stopped the bleeding by suture. Later, through further follow-up, no rebleeding was found in the patient. CONCLUSION: Jejunal telangiectasia with bleeding is a very rare intestinal vascular disease, which is difficult to identify and diagnose clinically. Therefore, the possibility of this disease should be considered in patients with negative results through some examinations such as gastroscopy, enteroscopy, gastrointestinal barium meal radiography, etc. In order to treat in time and prevent bleeding.
RESUMEN
The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans, while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters. In this study, we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences. The severe controlled cortical impact model was produced by an electronic controlled cortical impact device, while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube. Body temperature and mortality were recorded, and neurological deficits were assessed with the modified neurological severity score. Brain edema and blood-brain barrier damage were evaluated by assessing brain water content and Evans blue extravasation. In addition, a cytokine array kit was used to detect inflammatory cytokines. Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining. Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations. More severe motor dysfunction was observed in the severe controlled cortical impact model, while more severe cognitive dysfunction was observed in the severe free weight drop model. Brain edema, inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group. The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage, with higher mortality and lower repeatability compared with the severe controlled cortical impact group. Severe brainstem damage was not found in the severe controlled cortical impact model. These results indicate that the severe controlled cortical impact model is relatively more stable, more reproducible, and shows obvious cerebral pathological changes at an earlier stage. Therefore, the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury, while the severe free weight drop model may be more apt for studies on diffuse axonal injury. All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University, China (approval No. IRB2012-028-02) in February 2012.
RESUMEN
BACKGROUND: As the first-line regimens for the treatment of advanced gastric cancer, both docetaxel, cisplatin, and 5-fluorouracil (DCF) and epirubicin, cisplatin, and 5-fluorouracil (ECF) regimens are commonly used in clinical practice, but there is still controversy about which is better. AIM: To compare the efficacy and safety of DCF and ECF regimens by conducting this meta-analysis. METHODS: Computer searches in PubMed, EMBASE, Ovid MEDLINE, Science Direct, Web of Science, The Cochrane Library and Scopus were performed to find the clinical studies of all comparisons between DCF and ECF regimens. We used progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse effects (AEs) as endpoints for analysis. RESULTS: Our meta-analysis included seven qualified studies involving a total of 598 patients. The pooled hazard ratios between the DCF and ECF groups were comparable in PFS (95%CI: 0.58-1.46, P = 0.73), OS (95%CI: 0.65-1.10, P = 0.21), and total AEs (95%CI: 0.93-1.29, P = 0.30). The DCF group was significantly better than the ECF group in terms of ORR (95%CI: 1.13-1.75, P = 0.002) and DCR (95%CI: 1.03-1.41, P = 0.02). However, the incidence rate of grade 3-4 AEs was also greater in the DCF group than in the ECF group (95%CI: 1.16-1.88, P = 0.002), especially for neutropenia and febrile neutropenia. CONCLUSION: With better ORR and DCR values, the DCF regimen seems to be more suitable for advanced gastric cancer than the ECF regimen. However, the higher rate of AEs in the DCF group still needs to be noticed.
RESUMEN
Colon cancer remains one of the most common digestive system malignancies in the World. This study investigated the possible interaction between RAD51 and minichromosome maintenance proteins (MCMs) in HCT116 cells, which can serve as a model system for forming colon cancer foci. The interaction between RAD51 and MCMs was detected by mass spectrometry. Silenced MCM vectors were transfected into HTC116 cells. The expressions of RAD51 and MCMs were detected using Western blotting. Foci forming and chromatin fraction of RAD51 in HCT116 cells were also analyzed. The results showed that RAD51 directly interacted with MCM2, MCM3, MCM5, and MCM6 in colon cancer HTC116 cells. Suppression of MCM2 or MCM6 by shRNA decreased the chromatin localization of RAD51 in HTC116 cells. Moreover, silenced MCM2 or MCM6 decreased the foci forming of RAD51 in HTC116 cells. Our study suggests that the interaction between MCMs and RAD51 is essential for the chromatin localization and foci forming of RAD51 in HCT116 cell DNA damage recovery, and it may be a theoretical basis for analysis of RAD51 in tumor samples of colon cancer patients.
Asunto(s)
Neoplasias del Colon/metabolismo , Proteínas de Mantenimiento de Minicromosoma/metabolismo , Recombinasa Rad51/metabolismo , Células Cultivadas , Neoplasias del Colon/química , Células HCT116 , Células HEK293 , Humanos , Espectrometría de Masas , Proteínas de Mantenimiento de Minicromosoma/análisis , Proteínas de Mantenimiento de Minicromosoma/antagonistas & inhibidores , ARN Interferente Pequeño/farmacología , Recombinasa Rad51/análisis , Recombinasa Rad51/antagonistas & inhibidoresRESUMEN
PURPOSE: To explore the association between HOTAIR rs4759314 and cancer risk. METHODS: A comprehensive online search was conducted using PubMed, EMBASE, and CNKI databases to identify relevant studies. The case-control studies related to HOTAIR rs4759314 polymorphism and cancer risk were selected according to the inclusion and exclusion criteria. The retrieval time was until November 2015. After extracting the basic data information and performing an evaluation of the quality of the literature, the meta-analysis was performed using STATA 12.0 software, by calculating the odds ratio (OD) and 95% confidence interval (95% CI), and further subgroup analysis, literature publication bias testing, and sensitivity analysis. RESULTS: The studies included a total of 5025 patients with cancer and 5657 controls. The results found no significant association between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population (G vs A, OR=1.06, 95% CI :0.87-1.30 ; GG/GA vs AA, OR=1.07, 95% CI: 0.87-1.32; GG vs GA/AA, OR=0.75, 95% CI:0.39-1.43; GA vs AA, OR=1.08, 95% CI: 0.88-1.33; GG vs AA, OR=0.76, 95% CI:0.39-1.45) (all p<0.05). However, A allelic gene was associated with lower risk of gastric cancer, while G allelic gene may act as a genetic susceptibility factor for gastric cancer in Chinese population. CONCLUSION: No significant association was noted between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético/genética , ARN Largo no Codificante/genética , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Humanos , Factores de RiesgoRESUMEN
BACKGROUND: Numerous studies have shown that the expression of UCA1 was aberrantly upregulated in various cancer types. High expression of UCA1 was reported to be associated with unfavorable prognosis in cancer patients. RESULTS: A total of 1240 patients from 15 articles were included. The results indicated that a significantly shorter OS was observed in patients with high expression level of UCA1 (HR = 1.71, 95% CI: 1.43-1.99), in the subgroup analysis, the association was also observed in patients with cancers of digestive system (HR = 2.12, 95% CI: 1.59-2.66). Statistical significance was also observed in subgroup meta-analysis stratified by the cancer type, cut-off value, analysis type and sample size. Furthermore, poorer DFS was observed in patients with high expression level of UCA1 (HR = 2.54; 95% CI: 1.09-4.00). Additionally, the pooled odds ratios (ORs) showed that increased UCA1 was also related to positive lymph node metastasis (OR = 2.98, 95% CI: 2.06-4.30), distant metastasis (OR = 3.14, 95% CI: 1.77-5.58) and poor clinical stage (OR = 2.76, 95% CI: 2.08-3.68). MATERIALS AND METHODS: A comprehensive retrieval was conducted in multiple databases, including PubMed, Embase, Web of Science and CNKI. We collected relevant articles to explore the association between the expression levels of UCA1 and prognosis. CONCLUSIONS: High expression level of UCA1 was associated with poor clinical outcome. UCA1 could serve as a novel biomarker for prognosis and might be a potential predictive factor for clinicopathological characteristics in various cancers. Further studies should be performed to verify the clinical utility of UCA1 in human solid tumors.