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1.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 225-232, 2024 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-38716593

RESUMO

Objective: To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) . Methods: Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified. Results: ① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123(+) tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group (P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10(5)/ml to 3.2×10(6)/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8(+) PD-1(+) LAG-3(+) T cells was 10.90%, and the proportion of propidium iodide (PI) (-) Annexin Ⅴ(+) T cells and PI(+) Annexin Ⅴ(+) T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group (P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group (P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group (P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123(+) tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123(+) MV4-11 cells, CD123(+) Molm13 cells, and CD123(+) THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group (P<0.05) . Conclusion: In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123(+) tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.


Assuntos
Anticorpos Biespecíficos , Subunidade alfa de Receptor de Interleucina-3 , Leucemia Mieloide Aguda , Humanos , Subunidade alfa de Receptor de Interleucina-3/imunologia , Leucemia Mieloide Aguda/imunologia , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/imunologia , Linfócitos T/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia
2.
Zhonghua Yi Xue Za Zhi ; 104(13): 1028-1035, 2024 Apr 02.
Artigo em Chinês | MEDLINE | ID: mdl-38561297

RESUMO

Objective: To investigate the impact of lumbar paraspinal muscle degeneration and postoperative failure to restore ideal Roussouly classification on the occurrence of mechanical complications (MC) following long-segment spinal correction surgery in female patients with degenerative scoliosis (DS). Methods: The clinical data of 72 female DS patients who underwent long-segment spinal correction surgery in Gulou Hospital from June 2017 to November 2021 were retrospectively analyzed. According to whether restoring the ideal Roussouly classification after surgery, the patients were divided into R group(recovery group) (n=51) and N group(non-recovery group) (n=21). According to whether mechanical complications occurred after operation within two years, the patients were divided into MC (mechanical complications)group (n=24) and NMC(non-mechanical complications) group (n=48). The RM group (n=14) experienced mechanical complications in the R group, while the RN group (n=37) did not. The NM group (n=10) experienced mechanical complications in the N group, while the NN group (n=11) did not.Radiographic assessment included Sagittal parameters of spine and pelvis, standardized cross-sectional area (SCSA) and fat infiltration rate (FI%) of paraspinal muscle at each lumbar disc level. Results: The age of DS patients in this study was (61.4±6.2) years.The incidence of MC was 33.33%(n=24)in all patients. The incidence of MC was 27.45%(n=14)in group R and 47.62%(n=10) in group N. The correction amount of pelvic tilt angle (PT) (-11.62°±10.06° vs -7.04°±8.45°, P=0.046) and T1 pelvic angle(TPA)(-12.88°±11.23° vs -7.31°±9.55°, P=0.031)during surgery were significantly higher in MC group compared to the NMC group. In group R, the FI% of paraspinal muscles in each lumbar segment of patients with postoperative MC was higher than that in patients without MC (P<0.05). In the R and N groups, there was no significant difference inthe SCSA of the lumbar paravertebral muscles between patients with postoperative MC and those without MC at each level (all P>0.05). Multivariate logistic regression analysis showed that the average FI% of lumbar PSM was correlated with the occurrence of MC after spinal fusion in DS patients.The average FI% of lumbar PSM≥22.63% was a risk factors for MC after spinal fusion (P=0.010,OR=1.088, 95%CI:1.020-1.160). Conclusions: Female DS patients with higher degree of preoperative paraspinal muscle degeneration have a higher incidence of postoperative mechanical complications. For these patients,.there is still a higher risk of mechanical complications after surgery even if the ideal Roussouly classification is restored after surgery.


Assuntos
Escoliose , Fusão Vertebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Escoliose/cirurgia , Músculos Paraespinais , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fatores de Risco , Atrofia Muscular , Complicações Pós-Operatórias , Fusão Vertebral/efeitos adversos
4.
Zhonghua Xin Xue Guan Bing Za Zhi ; 52(4): 384-390, 2024 Apr 24.
Artigo em Chinês | MEDLINE | ID: mdl-38644253

RESUMO

Objective: To investigate the risk factors and long-term prognosis of major adverse cardiovascular events(MACEs) in patients with dilated cardiomyopathy (DCM). Methods: This study was a single-center retrospective cohort study. Clinical information from 300 patients with DCM hospitalized in Peking Union Medical College Hospital from April 2013 to April 2023 was collected. Based on echocardiography results, the patients were divided into two groups: isolated DCM and DCM with left ventricular non-compaction cardiomyopathy (LVNC). The MACEs, including major heart failure events, severe ventricular arrhythmias, and cardiovascular death, were recorded by outpatient or telephone follow-up. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the prognosis of patients with DCM. Kaplan-Meier curve and log-rank were used for survival analysis to compare the difference in the incidence of cardiovascular events between the two groups. Results: The included 300 DCM patients were (47.8±16.8) years old, with 197 males (65.7%), of which 237 (79.0%) were isolated DCM and 63 (21.0%) were DCM with LVNC. The follow-up time was 4.0 (1.9, 6.2) years. A total of 142 (47.3%) MACEs occurred, including 117 (39.0%) major heart failure events, 20 (6.7%) severe ventricular arrhythmia events, and 53 (17.7%) cardiovascular death events. Multivariate Cox proportional hazard regression analysis showed that increased left ventricular end-diastolic diameter (HR=1.21, 95%CI: 1.01-1.44, P=0.042), moderate or severe mitral regurgitation (HR=1.71, 95%CI: 1.19-2.47, P=0.004), increased ln (N-terminal pro-B-type natriuretic peptide) (HR=1.30, 95%CI: 1.10-1.54, P=0.002) were independent risk factors for dverse cardiovascular events in DCM patients, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI) treatment (HR=0.45, 95%CI: 0.26-0.78, P=0.004) was independent protective factor. Kaplan-Meier survival analysis found no significant difference in the risk of MACEs between isolated DCM and DCM with LVNC (P=0.22). Similarly, there were no significant differences in the incidence of major heart failure, severe ventricular arrhythmia, and cardiovascular death between the two groups (all P>0.05). Conclusion: An increase in left ventricular end-diastolic diameter, moderate or severe mitral regurgitation, elevated N-terminal pro-B-type natriuretic peptide, and non use of ACEI/ARB/ARNI are independent predictors of cardiovascular events in DCM patients. There was no significant risk of MACEs in patients with isolated DCM and DCM with LVNC, and suggested that LVNC may be a unique phenotype and should be accurately managed in combination with genetic background.


Assuntos
Cardiomiopatia Dilatada , Humanos , Cardiomiopatia Dilatada/complicações , Estudos Retrospectivos , Masculino , Fatores de Risco , Pessoa de Meia-Idade , Prognóstico , Feminino , Insuficiência Cardíaca/epidemiologia , Modelos de Riscos Proporcionais , Adulto
6.
Artigo em Inglês | MEDLINE | ID: mdl-38395686

RESUMO

Congenital infiltrating lipomatosis of the face (CILF) is a rare congenital disease of the head and neck region. In this study, the cases of 20 patients diagnosed with CILF were reviewed retrospectively to analyse the characteristics of the disease. The symptoms, signs, and clinical progression were investigated. Radiological changes were analysed according to the distribution of the trigeminal nerve. The pathological features of the fatty facial lesions, jaw hyperplasia, and lingual lesions were further identified. All 20 patients demonstrated hemifacial hypertrophy at birth. None had a family history of the disease. Significant radiological features of CILF (prevalence ≥90%) included thickened buccal subcutaneous fat, palatal submucosal fat, and temporal subcutaneous fat, maxillary tuberosity heteroplasia, and fatty infiltration of the masseteric intermuscular space. With regard to the trigeminal nerve, the frontal branch region (CNV1) was rarely affected, while the maxillary (CNV2) and mandibular (CNV3) branch regions showed considerable changes. Pathologically, CILF was observed to be characterized by the infiltration of mature adipose tissue into the adjacent buccal soft tissue, osteal remodelling surrounded by sheets of mature lipocytes and supporting fibrovascular stroma, and lingual hamartoma. In summary, CILF exhibits distinct characteristics that are related to the regions controlled by the maxillary and mandibular branches of the trigeminal nerve, suggesting that CILF may be associated with early neural development.

9.
Zhonghua Wai Ke Za Zhi ; 61(12): 1130-1134, 2023 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-37932151

RESUMO

The limited coverage of soft tissue and complex biomechanical factors make resection and reconstruction of distal tibial tumors extremely challenging. Megaprosthesis can provide good mechanical strength for tumor en bloc resection, but there are many postoperative complications, and the problems of insufficient soft tissue coverage and postoperative ankle instability must be solved. The development of three-dimensional digital technology may provide a new treatment strategy for distal tibial reconstruction. Compared to ankle joint preservation endoprostheses, the rapid osseointegration effect of three dimensional-printed megaprosthesis with ankle arthrodesis provides better ankle joint stability and postoperative function. In addition, the three dimensional-printed megaprosthesis may improve complications such as insufficient soft tissue coverage and talus collapse by reducing the circumference of the prosthesis and matching it with the talus through personalized design. Of course, there are few research reports on distal tibial prostheses, and the safety of three dimensional-printed megaprosthesis with ankle arthrodesis needs to be confirmed through extensive long-term follow-up studies. The selection of proximal and distal fixation methods for prostheses needs to be explored in future research.


Assuntos
Neoplasias Ósseas , Tíbia , Humanos , Tíbia/cirurgia , Resultado do Tratamento , Neoplasias Ósseas/cirurgia , Articulação do Tornozelo/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos
11.
Eur Rev Med Pharmacol Sci ; 27(18): 8812-8828, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37782191

RESUMO

OBJECTIVE: The purpose of this study is to use bibliometrics to explore the research overview and research hotspots. MATERIALS AND METHODS: The relevant literature on intestinal flora and diabetic nephropathy in the Web of Science Core Collection was sorted out, and VOSviewer, CiteSpace, Scimago Graphica and other software were used to conduct data visualization analysis on the number of publications, countries, institutions, journals, authors, keywords and citations. RESULTS: A total of 124 relevant literatures were included. From 2015 to 2022, the number of published papers increased every year. The countries, institutions and journals that published the most articles in this field are China, Isfahan University Medical Science and Frontiers in Pharmacology. Liu Bicheng and Mirlohi Maryam are the authors with the most published articles in this field. The main keywords of research in this field are obesity, inflammation, oxidative stress, indoxyl sulfate, short-chain fatty acids (SCFAs) and Chinese herbal medicine. CONCLUSIONS: This is the first bibliometric analysis of diabetic nephropathy and gut microbiota, reporting hot spots and emerging trends. Obesity, inflammation, oxidative stress, indoxyl sulfate, SCFAs and Chinese herbal medicine are the main keywords of current research, and SCFAs and Chinese herbal medicine may be the hotspots of future research.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Humanos , Indicã , Bibliometria , Inflamação , Obesidade
12.
Int Rev Neurobiol ; 171: 125-162, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37783554

RESUMO

Sleep deprivation is quite frequent in military during combat, intelligence gathering or peacekeeping operations. Even one night of sleep deprivation leads to accumulation of amyloid beta peptide burden that would lead to precipitation of Alzheimer's disease over the years. Thus, efforts are needed to slow down or neutralize accumulation of amyloid beta peptide (AßP) and associated Alzheimer's disease brain pathology including phosphorylated tau (p-tau) within the brain fluid environment. Sleep deprivation also alters serotonin (5-hydroxytryptamine) metabolism in the brain microenvironment and impair upregulation of several neurotrophic factors. Thus, blockade or neutralization of AßP, p-tau and serotonin in sleep deprivation may attenuate brain pathology. In this investigation this hypothesis is examined using nanodelivery of cerebrolysin- a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies against AßP, p-tau and serotonin (5-hydroxytryptamine, 5-HT). Our observations suggest that sleep deprivation induced pathophysiology is significantly reduced following nanodelivery of cerebrolysin together with monoclonal antibodies to AßP, p-tau and 5-HT, not reported earlier.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Humanos , Peptídeos beta-Amiloides , Doença de Alzheimer/metabolismo , Serotonina/metabolismo , Privação do Sono/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Encéfalo/metabolismo , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/farmacologia , Fatores de Crescimento Neural/uso terapêutico
13.
Int Rev Neurobiol ; 171: 3-46, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37783559

RESUMO

Alzheimer's disease is one of the devastating neurodegenerative diseases affecting mankind worldwide with advancing age mainly above 65 years and above causing great misery of life. About more than 7 millions are affected with Alzheimer's disease in America in 2023 resulting in huge burden on health care system and care givers and support for the family. However, no suitable therapeutic measures are available at the moment to enhance quality of life to these patients. Development of Alzheimer's disease may reflect the stress burden of whole life inculcating the disease processes of these neurodegenerative disorders of the central nervous system. Thus, new strategies using nanodelivery of suitable drug therapy including antibodies are needed in exploring neuroprotection in Alzheimer's disease brain pathology. In this chapter role of stress in exacerbating Alzheimer's disease brain pathology is explored and treatment strategies are examined using nanotechnology based on our own investigation. Our observations clearly show that restraint stress significantly exacerbate Alzheimer's disease brain pathology and nanodelivery of a multimodal drug cerebrolysin together with monoclonal antibodies (mAb) to amyloid beta peptide (AßP) together with a serotonin 5-HT6 receptor antagonist SB399885 significantly thwarted Alzheimer's disease brain pathology exacerbated by restraint stress, not reported earlier. The possible mechanisms and future clinical significance is discussed.


Assuntos
Doença de Alzheimer , Humanos , Idoso , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Serotonina , Qualidade de Vida , Encéfalo/patologia
14.
Int Rev Neurobiol ; 171: 47-82, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37783563

RESUMO

Stress is one of the most serious consequences of life leading to several chronic diseases and neurodegeneration. Recent studies show that emotional stress and other kinds of anxiety and depression adversely affects Parkinson's disease symptoms. However, the details of how stress affects Parkinson's disease is still not well known. Traumatic brain injury, stroke, diabetes, post-traumatic stress disorders are well known to modify the disease precipitation, progression and persistence. However, show stress could influence Parkinson's disease is still not well known. The present investigation we examine the role of immobilization stress influencing Parkinson's disease brain pathology in model experiments. In ore previous report we found that mild traumatic brain injury exacerbate Parkinson's disease brain pathology and nanodelivery of dl-3-n-butylphthalide either alone or together with mesenchymal stem cells significantly attenuated Parkinson's disease brain pathology. In this chapter we discuss the role of stress in exacerbating Parkinson's disease pathology and nanowired delivery of dl-3-n-butylphthalide together with monoclonal antibodies to alpha synuclein (ASNC) is able to induce significant neuroprotection. The possible mechanisms of dl-3-n-butylphthalide and ASNC induced neuroprotection and suitable clinical therapeutic strategy is discussed.


Assuntos
Doença de Parkinson , Angústia Psicológica , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , alfa-Sinucleína , Neuroproteção , Anticorpos , Encéfalo/metabolismo
15.
Int Rev Neurobiol ; 171: 83-121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37783564

RESUMO

Concussive head injury (CHI) is one of the major risk factors for developing Parkinson's disease in later life of military personnel affecting lifetime functional and cognitive disturbances. Till date no suitable therapies are available to attenuate CHI or PD induced brain pathology. Thus, further exploration of novel therapeutic agents are highly warranted using nanomedicine in enhancing the quality of life of veterans or service members of US military. Since PD or CHI induces oxidative stress and perturbs neurotrophic factors regulation associated with phosphorylated tau (p-tau) deposition, a possibility exists that nanodelivery of agents that could enhance neurotrophic factors balance and attenuate oxidative stress could be neuroprotective in nature. In this review, nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies to neuronal nitric oxide synthase (nNOS) with p-tau antibodies was examined in PD following CHI in model experiments. Our results suggest that combined administration of nanowired antibodies to nNOS and p-tau together with cerebrolysin significantly attenuated CHI induced exacerbation of PD brain pathology. This combined treatment also has beneficial effects in CHI or PD alone, not reported earlier.


Assuntos
Lesões Encefálicas Traumáticas , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Óxido Nítrico Sintase Tipo I , Qualidade de Vida , Lesões Encefálicas Traumáticas/tratamento farmacológico , Encéfalo/patologia , Fatores de Crescimento Neural , Fármacos Neuroprotetores/uso terapêutico
16.
Int Rev Neurobiol ; 172: 145-185, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37833011

RESUMO

dl-3-n-Butylphthalide is a potent synthetic Chinese celery extract that is highly efficient in inducing neuroprotection in concussive head injury (CHI), Parkinson's disease, Alzheimer's disease, stroke as well as depression, dementia, anxiety and other neurological diseases. Thus, there are reasons to believe that dl-3-n-butylphthalide could effectively prevent Alzheimer's disease brain pathology. Military personnel during combat operation or veterans are often the victims of brain injury that is a major risk factor for developing Alzheimer's disease in their later lives. In our laboratory we have shown that CHI exacerbates Alzheimer's disease brain pathology and reduces the amyloid beta peptide (AßP) inactivating enzyme neprilysin. We have used TiO2 nanowired-dl-3-n-butylphthalide in attenuating Parkinson's disease brain pathology exacerbated by CHI. Nanodelivery of dl-3-n-butylphthalide appears to be more potent as compared to the conventional delivery of the compound. Thus, it would be interesting to examine the effects of nanowired dl-3-n-butylphthalide together with nanowired delivery of neprilysin in Alzheimer's disease model on brain pathology. In this investigation we found that nanowired delivery of dl-3-n-butylphthalide together with nanowired neprilysin significantly attenuated brain pathology in Alzheimer's disease model with CHI, not reported earlier. The possible mechanism and clinical significance is discussed based on the current literature.


Assuntos
Doença de Alzheimer , Concussão Encefálica , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Doença de Alzheimer/tratamento farmacológico , Concussão Encefálica/complicações , Concussão Encefálica/patologia , Peptídeos beta-Amiloides , Neprilisina/uso terapêutico , Neuroproteção , Doença de Parkinson/complicações , Fármacos Neuroprotetores/uso terapêutico
17.
Int Rev Neurobiol ; 172: 189-233, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37833012

RESUMO

Nicotine abuse is frequent worldwide leading to about 8 millions people die every year due to tobacco related diseases. Military personnel often use nicotine smoking that is about 12.8% higher than civilian populations. Nicotine smoking triggers oxidative stress and are linked to several neurodegenerative diseases such as Alzheimer's disease. Nicotine neurotoxicity induces significant depression and oxidative stress in the brain leading to neurovascular damages and brain pathology. Thus, details of nicotine neurotoxicity and factors influencing them require additional investigations. In this review, effects of engineered nanoparticles from metals Ag and Cu (50-60 nm) on nicotine neurotoxicity are discussed with regard to nicotine smoking. Military personnel often work in the environment where chances of nanoparticles exposure are quite common. In our earlier studies, we have shown that nanoparticles alone induces breakdown of the blood-brain barrier (BBB) and exacerbates brain pathology in animal models. In present investigation, nicotine exposure in with Ag or Cu nanoparticles intoxicated group exacerbated BBB breakdown, induce oxidative stress and aggravate brain pathology. Treatment with nanowired H-290/51 a potent chain-breaking antioxidant together with nanowired ondansetron, a potent 5-HT3 receptor antagonist significantly reduced oxidative stress, BBB breakdown and brain pathology in nicotine exposure associated with Ag or Cu nanoparticles intoxication. The functional significance of this findings and possible mechanisms of nicotine neurotoxicity are discussed based on current literature.


Assuntos
Edema Encefálico , Nanopartículas , Fármacos Neuroprotetores , Animais , Humanos , Ondansetron/farmacologia , Antioxidantes/farmacologia , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia , Nicotina/farmacologia , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Encéfalo
18.
Int Rev Neurobiol ; 172: 3-35, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37833015

RESUMO

Hallmark of Alzheimer's disease include amyloid beta peptide and phosphorylated tau deposition in brain that could be aggravated following traumatic of concussive head injury. However, amyloid beta peptide or p-tau in spinal cord following injury is not well known. In this investigation we measured amyloid beta peptide and p-tau together with tumor necrosis factor-alpha (TNF-α) in spinal cord and brain following 48 h after spinal cord injury in relation to the blood-spinal cord and blood-brain barrier, edema formation, blood flow changes and cell injury in perifocal regions of the spinal cord and brain areas. A focal spinal cord injury was inflicted over the right dorsal horn of the T10-11 segment (4 mm long and 2 mm deep) and amyloid beta peptide and p-tau was measured in perifocal rostral (T9) and caudal (T12) spinal cord segments as well as in the brain areas. Our observations showed a significant increase in amyloid beta peptide in the T9 and T12 segments as well as in remote areas of brain and spinal cord after 24 and 48 h injury. This is associated with breakdown of the blood-spinal cord (BSCB) and brain barriers (BBB), edema formation, reduction in blood flow and cell injury. After 48 h of spinal cord injury elevation of amyloid beta peptide, phosphorylated tau (p-tau) and tumor necrosis factor-alpha (TNF-α) was seen in T9 and T12 segments of spinal cord in cerebral cortex, hippocampus and brain stem regions associated with microglial activation as seen by upregulation of Iba1 and CD86. Repeated nanowired delivery of cerebrolysin topically over the traumatized segment repeatedly together with monoclonal antibodies (mAb) to amyloid beta peptide (AßP), p-tau and TNF-α significantly attenuated amyloid beta peptide, p-tau deposition and reduces Iba1, CD68 and TNF-α levels in the brain and spinal cord along with blockade of BBB and BSCB, reduction in blood flow, edema formation and cell injury. These observations are the first to show that spinal cord injury induces Alzheimer's disease like symptoms in the CNS, not reported earlier.


Assuntos
Doença de Alzheimer , Traumatismos da Medula Espinal , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Anticorpos Monoclonais , Edema , Medula Espinal/irrigação sanguínea , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Fator de Necrose Tumoral alfa , Animais , Ratos , Nanofios/uso terapêutico
19.
Int Rev Neurobiol ; 172: 37-77, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37833018

RESUMO

Military personnel are often victims of spinal cord injury resulting in lifetime disability and decrease in quality of life. However, no suitable therapeutic measures are still available to restore functional disability or arresting the pathophysiological progression of disease in victims for leading a better quality of life. Thus, further research in spinal cord injury using novel strategies or combination of available neuroprotective drugs is urgently needed for superior neuroprotection. In this regard, our laboratory is engaged in developing TiO2 nanowired delivery of drugs, antibodies and enzymes in combination to attenuate spinal cord injury induced pathophysiology and functional disability in experimental rodent model. Previous observations show that histamine antagonists or antioxidant compounds when given alone in spinal cord injury are able to induce neuroprotection for short periods after trauma. In this investigation we used a combination of histaminergic drugs with antioxidant compound H-290/51 using their nanowired delivery for neuroprotection in spinal cord injury of longer duration. Our observations show that a combination of H3 receptor inverse agonist BF-2549 with H3 receptor antagonist and H4 receptor agonist clobenpropit induced neuroprotection is potentiated by antioxidant compound H-290/51 in spinal cord injury. These observations suggests that histamine receptors are involved in the pathophysiology of spinal cord injury and induce superior neuroprotection in combination with an inhibitor of lipid peroxidation H-290/51, not reported earlier. The possible mechanisms and significance of our findings in relation to future clinical approaches in spinal cord injury is discussed.


Assuntos
Nanofios , Receptores Histamínicos H3 , Traumatismos da Medula Espinal , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Agonismo Inverso de Drogas , Agonistas dos Receptores Histamínicos/farmacologia , Agonistas dos Receptores Histamínicos/uso terapêutico , Neuroproteção , Qualidade de Vida , Receptores Histamínicos H3/uso terapêutico , Receptores Histamínicos H4
20.
Zhonghua Gan Zang Bing Za Zhi ; 31(9): 961-968, 2023 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-37872092

RESUMO

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.


Assuntos
Encefalopatia Hepática , Humanos , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/epidemiologia , Encefalopatia Hepática/etiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Psicometria/métodos
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