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1.
Nutr Hosp ; 41(3): 602-611, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38726634

ABSTRACT

Introduction: Introduction: the prognostic nutritional index (PNI) and platelet-lymphocyte ratio (PLR) have been found to correlate with outcomes following radical gastrectomy for gastric cancer (GC). Objectives: to construct a nomogram combining PNI and PLR for individually forecasting the risk of postoperative pulmonary infection (POI) following D2 radical gastrectomy for GC. Methods: retrospectively, clinical data was gathered from 404 patients treated with D2 radical gastrectomy for GC. The study used multivariate logistic regression analysis to screen independent risk factors for POI after surgery. Subsequently, a nomogram was developed based on the above factors to forecast the POI probability accurately. Results: the multivariate logistic regression analysis identified age, PNI, PLR, CA199 level, ASA score, and ICU treatment as independent risk variables for POI following D2 radical gastrectomy (p < 0.001 or 0.05). The nomogram's area under the receiver operating characteristic curve (AUC) for predicting the risk of POI was 0.736 (95 % confidence interval (CI) = 0.678-0.794). The nomogram was internally validated using the bootstrap approach, involving repeated sampling 1000 times. The result yielded a concordance index (c-index) of 0.707 (95 % CI = 0.705-0.709). The calibration curves demonstrated an excellent concordance between the predicted values of the nomogram and the observed values. The nomogram's clinical value was shown to be high using decision analysis curves. Conclusions: a nomogram combining PNI and PLR is a dependable tool for forecasting the probability of POI following D2 radical gastrectomy for GC.


Introducción: Introducción: se ha observado que el índice nutricional pronóstico (INP) y el cociente plaquetas/linfocitos (PLR) se correlacionan con los resultados tras la gastrectomía radical por cáncer gástrico (CG). Objetivos: diseñar un nomograma que combine el INP y la RPL para predecir individualmente el riesgo de infección pulmonar postoperatoria (POI) tras una gastrectomía radical D2 por CG. Métodos: de forma retrospectiva, se recopilaron datos clínicos de 404 pacientes tratados con gastrectomía radical D2 por CG. El estudio utilizó un análisis de regresión logística multivariante para detectar factores de riesgo independientes de IOP tras la cirugía. Posteriormente, se desarrolló un nomograma basado en los factores mencionados para pronosticar con precisión la probabilidad de POI. Resultados: el análisis de regresión logística multivariante identificó la edad, el INP, el PLR, el nivel de CA199, la puntuación ASA y el tratamiento en la UCI como variables de riesgo independientes para el POI tras la gastrectomía radical D2 (p < 0,001 o 0,05). El área bajo la curva ROC (característica operativa del receptor) AUC del nomograma para predecir el riesgo de POI fue de 0,736 (intervalo de confianza [IC] del 95 % = 0,678-0,794). El nomograma se validó internamente mediante el método bootstrap, que consiste en repetir el muestreo 1000 veces. El resultado fue un índice de concordancia (índice c) de 0,707 (IC del 95 % = 0,705-0,709). Las curvas de calibración demostraron una excelente concordancia entre los valores predichos del nomograma y los valores observados. El valor clínico del nomograma se demostró elevado mediante curvas de análisis de decisión. Conclusiones: un nomograma que combina INP y PLR es una herramienta fiable para predecir la probabilidad de POI tras gastrectomía radical D2 por CG.


Subject(s)
Gastrectomy , Nomograms , Nutrition Assessment , Postoperative Complications , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Gastrectomy/adverse effects , Male , Female , Middle Aged , Retrospective Studies , Postoperative Complications/etiology , Postoperative Complications/blood , Postoperative Complications/epidemiology , Postoperative Complications/diagnosis , Prognosis , Aged , Platelet Count , Lymphocyte Count , Blood Platelets , Lymphocytes , Adult , Risk Factors
2.
J Agric Food Chem ; 72(9): 4538-4551, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38377566

ABSTRACT

Phenolic acids are important natural bioactive compounds with varied physiological functions. They are extensively used in food, pharmaceutical, cosmetic, and other chemical industries and have attractive market prospects. Compared to plant extraction and chemical synthesis, microbial fermentation for phenolic acid production from renewable carbon sources has significant advantages. This review focuses on the structural information, physiological functions, current applications, and biosynthesis pathways of phenolic acids, especially advances in the development of metabolically engineered microbes for the production of phenolic acids. This review provides useful insights concerning phenolic acid production through metabolic engineering of microbial cell factories.


Subject(s)
Hydroxybenzoates , Metabolic Engineering , Hydroxybenzoates/metabolism , Biosynthetic Pathways , Food
3.
Cell Biochem Biophys ; 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38133792

ABSTRACT

The mammalian central nervous system consists of a large number of cells, which contain not only different types of neurons, but also a large number of glial cells, such as astrocytes, oligodendrocytes, and microglia. These cells are capable of performing highly refined electrophysiological activities and providing the brain with functions such as nutritional support, information transmission and pathogen defense. The diversity of cell types and individual differences between cells have brought inspiration to the study of the mechanism of central nervous system diseases. In order to explore the role of different cells, a new technology, single-cell sequencing technology has emerged to perform specific analysis of high-throughput cell populations, and has been continuously developed. Single-cell sequencing technology can accurately analyze single-cell expression in mixed-cell populations and collect cells from different spatial locations, time stages and types. By using single-cell sequencing technology to compare gene expression profiles of normal and diseased cells, it is possible to discover cell subsets associated with specific diseases and their associated genes. Therefore, scientists can understand the development process, related functions and disease state of the nervous system from an unprecedented depth. In conclusion, single-cell sequencing technology provides a powerful technology for the discovery of novel therapeutic targets for central nervous system diseases.

4.
Neuropharmacology ; 240: 109728, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37742716

ABSTRACT

Post-traumatic stress disorder (PTSD) is a complex mental disorder, closely associated with stress and traumatic events. Salidroside (Sal) has been reported to possess neuroprotective effects. However, the behavioral effects and mechanisms of Sal on PTSD remain unknown. In this study, we utilized a rat model of PTSD induced by single prolonged stress (SPS) and administered Sal intraperitoneally (25, 50, 75 mg/kg/d) for 14 days. We then examined the behavioral effects and underlying mechanisms of Sal on SPS-induced PTSD rats. Our findings demonstrated that Sal alleviated anxiety-like behavior and spatial learning and memory impairment in SPS-induced PTSD rats. Furthermore, Sal treatment preserved the histomorphology of the hippocampal region. It was observed that Sal protected against hippocampal neuronal apoptosis in PTSD rats by reducing the number of TUNEL-positive cells and modulating apoptosis-related proteins (Bcl-2 and Bax). Additionally, Sal inhibited the activation of the NF-κB/iNOS/COX-2 signaling pathway in the hippocampus of PTSD rats, thereby suppressing the release of inflammatory factors (TNF-α and IL-1ß) and the activation of microglia. Notably, Sal increased the expression of synapse-associated proteins PSD95 and Synapsin I in the hippocampus, while also enhancing dendritic density in the region. In conclusion, our results demonstrated that Sal could attenuate SPS-induced PTSD-like behaviors by inhibiting hippocampal neuronal apoptosis, enhancing hippocampal synaptic plasticity, and reducing neuroinflammatory responses. These findings may provide a foundation for the potential clinical application of Sal in the treatment of PTSD.


Subject(s)
Stress Disorders, Post-Traumatic , Humans , Rats , Animals , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/metabolism , Glucosides/pharmacology , Glucosides/therapeutic use , Phenols/pharmacology , Phenols/therapeutic use , Hippocampus/metabolism , Disease Models, Animal
5.
Phytomedicine ; 120: 155032, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37611463

ABSTRACT

BACKGROUND: In recent years, Salvia miltiorrhiza and its active substances have remarkably progressed in treating central neurological disorders. Tanshinone IIA (TSA) is an active ingredient derived from the rhizome of Salvia miltiorrhiza that has been found to alleviate the symptoms of several psychiatric illnesses. Post-traumatic stress disorder (PTSD) is a mental disorder that results after experiencing a serious physical or psychological injury. The currently used drugs are not satisfactory for the treatment of PTSD. However, it has been reported that TSA can improve PTSD-like symptoms like learning and memory, cognitive disorder, and depression through multi-target regulation. PURPOSE: This paper discusses the ameliorative effects of TSA on PTSD-like symptoms and the possible mechanisms of action in terms of inhibition of neuronal apoptosis, anti-neuroinflammation, and anti-oxidative stress. Based on the pathological changes and clinical observations of PTSD, we hope to provide some reference for the clinical transformation of Chinese medicine in treating PTSD. METHODS: A large number of literatures on tanshinone in the treatment of neurological diseases and PTSD were retrieved from online electronic PubMed and Web of Science databases. CONCLUSION: TSA is a widely studied natural active ingredient against mental illness. This review will contribute to the future development of TSA as a new clinical candidate drug for improving PTSD-like symptoms.


Subject(s)
Salvia miltiorrhiza , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/drug therapy , Abietanes/pharmacology , Apoptosis , Oxidative Stress
6.
J Therm Biol ; 114: 103570, 2023 May.
Article in English | MEDLINE | ID: mdl-37344028

ABSTRACT

With the outbreak of the Ukrainian crisis, extremely cold environment warfare has once again become the focus of international attention. People exposed to extremely cold environments may suffer from cold damage, further aggravate trauma, trigger high disability and mortality rates, and even cause serious sequelae. To declare the effects and mechanisms of the extremely cold environment on the body after trauma, this paper reviews, firstly, physiological reaction of human body in an extremely cold environment. Then, the post-traumatic body response in an extremely cold environment was introduced, and finally, the sequelae of trauma in extremely cold environment was further summarized in the paper. The results indicated that extremely cold environment can cause a series of damage to the body, especially the body after trauma. The extremely cold factor is a double-edged sword, showing a favorable and unfavorable side in different aspects. Moreover, in addition to the trauma suffered by the body, the subsequent sequelae such as cognitive dysfunction, anxiety, depression and even post-traumatic stress disorder may also be induced. The paper summarizes the human body's physiological response in an extremely cold environment, and declares the effects and mechanisms of the extremely cold environment on the body after trauma, which may provide a theoretical basis for effectively improving the level of combat trauma treatment in extremely cold regions.


Subject(s)
Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/psychology , Stress Disorders, Post-Traumatic/therapy , Anxiety
7.
Biochim Biophys Acta Mol Cell Res ; 1870(7): 119506, 2023 10.
Article in English | MEDLINE | ID: mdl-37263298

ABSTRACT

Alternative pre-mRNA splicing, which produces various mRNA isoforms with distinct structures and functions from a single gene, is regulated by specific RNA-binding proteins and is an essential method for regulating gene expression in mammals. Recent studies have shown that abnormal change during neuronal development triggered by splicing mis-regulation is an important feature of various neurological diseases. Polypyrimidine tract binding protein 1 (PTBP1) is a kind of RNA-binding proteins with extensive biological functions. As a well-known splicing regulator, it affects the neuronal development process through its involvement in axon formation, synaptogenesis, and neuronal apoptosis, according to the most recent studies. Here, we summarized the mechanism of alternative splicing, structure and function of PTBP1, and the latest research progress on the role of alternative splicing events regulated by PTBP1 in axon formation, synaptogenesis and neuronal apoptosis, to reveal the mechanism of PTBP1-regulated changes in neuronal development process.


Subject(s)
Nervous System Diseases , Neurogenesis , Polypyrimidine Tract-Binding Protein , RNA , Animals , Mammals/genetics , Mammals/metabolism , Polypyrimidine Tract-Binding Protein/genetics , Polypyrimidine Tract-Binding Protein/metabolism , RNA/metabolism , RNA Splicing , RNA Splicing Factors/genetics , RNA Splicing Factors/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Nervous System Diseases/genetics , Neurogenesis/genetics
8.
J Drug Target ; 31(7): 685-692, 2023 08.
Article in English | MEDLINE | ID: mdl-37358358

ABSTRACT

Mitochondria are a crucial energy source for maintaining neuronal growth and synaptic function. Neurons possess unique morphological characteristics, which make the proper regulation of mitochondrial transport essential for meeting their energy demands. Syntaphilin (SNPH) is capable of specifically targeting the outer membrane of axonal mitochondria, anchoring them to microtubules, and thereby preventing their transport. SNPH also interacts with other mitochondrial proteins to regulate mitochondrial transport. The regulation of mitochondrial transport and anchoring mediated by SNPH is indispensable for axonal growth during neuronal development, maintenance of ATP levels during neuronal synaptic activity, and regeneration of mature neurons following damage. Precise blocking of SNPH may be an effective therapeutic strategy for neurodegenerative diseases and related mental disorders.


Subject(s)
Microtubule-Associated Proteins , Neurodegenerative Diseases , Humans , Microtubule-Associated Proteins/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Axons/metabolism , Neurons/metabolism , Mitochondria/metabolism
9.
Wiley Interdiscip Rev RNA ; 14(2): e1740, 2023 03.
Article in English | MEDLINE | ID: mdl-35574699

ABSTRACT

Central nervous system injury diseases can cause the loss of many neurons, and it is difficult to regenerate. The field of regenerative medicine believes that supplementing the missing neurons may be an ideal method for nerve injury repair. Recent studies have found that down-regulation of polypyrimidine tract binding protein 1 (PTBP1) expression can make glial cells transdifferentiate into different types of neurons, which is expected to be an alternative therapy to restore neuronal function. This article summarized the research progress on the structure and biological function of the PTBP family, the mutual regulation of PTBP1 and PTBP2, their role in neurogenesis, and the latest research progress in targeting PTBP1 to mediate the transdifferentiation of glial cells into neurons, which may provide some new strategies and new ideas for the future treatment of central nervous system injury and neurodegenerative diseases. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing.


Subject(s)
Cell Transdifferentiation , Polypyrimidine Tract-Binding Protein , RNA Splicing Factors/metabolism , Polypyrimidine Tract-Binding Protein/genetics , Polypyrimidine Tract-Binding Protein/chemistry , Polypyrimidine Tract-Binding Protein/metabolism , Neurons/metabolism , Alternative Splicing , Neuroglia/metabolism , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Heterogeneous-Nuclear Ribonucleoproteins/metabolism
10.
Neuropharmacology ; 224: 109365, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36462635

ABSTRACT

Abscisic acid (ABA), a conserved hormone existing in plants and animals, not only regulates blood glucose and inflammation but also has good therapeutic effects on obesity, diabetes, atherosclerosis and inflammatory diseases in animals. Studies have shown that exogenous ABA can pass the blood-brain barrier and inhibit neuroinflammation, promote neurogenesis, enhance synaptic plasticity, improve learning, memory and cognitive ability in the central nervous system. At the same time, ABA plays a crucial role in significant improvement of Alzheimer's disease, depression, and anxiety. Here we review the previous research progress of ABA on the physiological effects and clinical application in the related diseases. By summarizing the biological functions of ABA, we aim to reveal the possible mechanisms of ameliorative function of ABA on learning and memory, to provide a theoretical basis that ABA as a novel and safe drug improves learning memory and cognitive impairment in central system diseases such as aging, neurodegenerative diseases and traumatic brain injury.


Subject(s)
Abscisic Acid , Alzheimer Disease , Animals , Abscisic Acid/pharmacology , Learning , Cognition
11.
Exp Ther Med ; 24(6): 746, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36561974

ABSTRACT

Evodiamine (EVO) is one of the main components extracted from Evodia rutaecarpa and has been reported to inhibit tumor growth by inhibiting proliferation and inducing apoptosis. Although the anticancer activity of evodiamine has been confirmed, the exact mechanism remains to be elucidated. In the present study, cancer stem-like cells (CSCs) were successfully enriched from A549 cells by being cultured in serum-free medium and characterized by detecting stemness markers. Expectedly, the addition of EVO inhibited proliferation, migration and invasion in A549 cells, demonstrating its inhibitory effects on the malignant behaviors of A549 cells. In CSCs derived from A549 cells, EVO treatment promoted cell proliferation while inhibiting migration and invasion. By detecting the hallmarks of the epithelial-mesenchymal transition (EMT), including E-cadherin, Vimentin, Slug and Snail via western blotting, it was revealed that EVO treatment inactivated the EMT process and potentially led to the loss of self-renewal capacity of CSCs and promoted proliferation. By activating the EMT using TGF-ß pretreatment, EVO treatment downregulated the hallmarks of the EMT and led to inactivation of the EMT, indicating its potential mechanism of regulating CSCs via the EMT pathway. The findings suggested that modulation of the self-renewal capacity of CSCs may affect malignant cancer behaviors following surgery. EVO exerts inhibitory effects not only on cancer cells but also on CSCs in non-small-cell lung cancer, and therefore could be used as a promising drug targeting CSCs.

12.
J Int Adv Otol ; 18(6): 537-540, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36349677

ABSTRACT

Heterotopic pancreas is the congenital presence of pancreatic tissue outside its normal location in the absence of vascular and anatomical connection with the main pancreas. To our knowledge, no case of heterotopic pancreas cyst in the middle ear has been reported to date. In this study, we report the first case of a 6-year-old boy with ectopic pancreas in the area of middle ear. The patient underwent canal wall down mastoidectomy with tympanoplasty. It was finally diagnosed as ectopic pancreas (left middle ear). During the 6-year follow-up, no evidence of recurrence or residual disease in the middle ear cleft or mastoid was found. Heterotopic pancreas in the middle ear is an uncommon condition and may present with otorrhea or aural fullness. Diagnosis is usually straightforward on the histologic evaluation of resection specimen, complemented with immun ohist ochem istry . Total excision with such lesion is preferred to avoid some complications. Regular follow-up is necessary due to the potential risk of recurrence and malignant transformation.


Subject(s)
Cholesteatoma, Middle Ear , Mastoid , Male , Humans , Child , Treatment Outcome , Mastoid/surgery , Tympanoplasty , Ear, Middle/surgery , Pancreas , Cholesteatoma, Middle Ear/surgery , Retrospective Studies , Ear Canal/surgery
13.
Front Genet ; 13: 910556, 2022.
Article in English | MEDLINE | ID: mdl-35774506

ABSTRACT

Preeclampsia is the leading cause of morbidity and mortality for mothers and newborns worldwide. Despite extensive efforts made to understand the underlying pathology of preeclampsia, there is still no clinically useful effective tool for the early diagnosis of preeclampsia. In this study, we conducted a retrospectively multicenter discover-validation study to develop and validate a novel biomarker for preeclampsia diagnosis. We identified 38 differentially expressed genes (DEGs) involved in preeclampsia in a case-control study by analyzing expression profiles in the discovery cohort. We developed a 5-mRNA signature (termed PE5-signature) to diagnose preeclampsia from 38 DEGs using recursive feature elimination with a random forest supervised classification algorithm, including ENG, KRT80, CEBPA, RDH13 and WASH9P. The PE5-signature showed high accuracy in discriminating preeclampsia from controls with a receiver operating characteristic area under the curve value (AUC) of 0.971, a sensitivity of 0.842 and a specificity of 0.950. The PE5-signature was then validated in an independent case-control study and achieved a reliable and robust predictive performance with an AUC of 0.929, a sensitivity of 0.696, and a specificity of 0.946. In summary, we have developed and validated a five-mRNA biomarker panel as a risk assessment tool to assist in the detection of preeclampsia. This gene panel has potential clinical value for early preeclampsia diagnosis and may help us better understand the precise mechanisms involved.

14.
Gynecol Endocrinol ; 37(11): 1020-1026, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34282706

ABSTRACT

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease in reproductive women, and the endocrine levels are also affected by diseases. The aim of this study was to determine the effect of thrombospondin-1 (TSP-1) on PCOS rat model. METHODS: We established the PCOS rat model, the serum hormones including TSP-1 expression were determined and morphological characteristics were investigated to evaluate the model. These above endocrine and morphological features were investigated again to evaluate the effect of TSP-1 treatment. RESULTS: In the PCOS model group, the serum hormones change (higher luteinizing hormone, testosterone and estrogen) and decreased TSP-1 expression levels were found compared with the control group. Besides, the morphological characteristics of PCOS were also observed in the model group. After TSP-1 treatment, the higher TSP-1, ANGPT2, PDGFB and PDGFD expression levels, the lower LH and T levels, decreased vessel density as well as VEGFA and ANGPT1 expression levels were found compared with the control group, and the ovary morphological changes were also observed in the TSP-1 experimental group. CONCLUSIONS: TSP-1 delivery system might be an alternative therapy for PCOS treatment.


Subject(s)
Polycystic Ovary Syndrome/drug therapy , Thrombospondin 1/therapeutic use , Angiogenic Proteins/metabolism , Animals , Disease Models, Animal , Drug Evaluation, Preclinical , Female , Ovary/drug effects , Polycystic Ovary Syndrome/metabolism , Rats, Sprague-Dawley , Thrombospondin 1/metabolism , Thrombospondin 1/pharmacology
15.
Curr Neuropharmacol ; 19(12): 2180-2187, 2021.
Article in English | MEDLINE | ID: mdl-33430733

ABSTRACT

Chlorogenic acid (CGA) is a kind of traditional Chinese medicine, abundant in honeysuckle and eucommia, and has a wide range of biological activities, and pharmacological effects. Previous studies have shown that CGA can regulate learning, memory, cognitive ability, coupled with improvement to anxiety, depression, and other post-traumatic stress disorder (PTSD)-like symptoms. This article explores the protective effects of CGA on neurons through its anti-apoptotic effect, inhibition of neuroinflammation and oxidative stress, which may be the mechanisms of its improvement of PTSD-like symptoms. It may provide a new therapeutic strategy for the treatment of PTSD and its comorbidities.


Subject(s)
Stress Disorders, Post-Traumatic , Anxiety , Anxiety Disorders , Chlorogenic Acid/pharmacology , Chlorogenic Acid/therapeutic use , Humans , Neuroinflammatory Diseases , Stress Disorders, Post-Traumatic/drug therapy
16.
Curr Pharm Des ; 27(4): 531-539, 2021.
Article in English | MEDLINE | ID: mdl-32938344

ABSTRACT

Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its proapoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or proapoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.


Subject(s)
Hippocampus , Receptors, Nerve Growth Factor , Apoptosis , Hippocampus/metabolism , Humans , Nerve Tissue Proteins , Neuronal Plasticity , Receptor, Nerve Growth Factor/metabolism , Receptors, Nerve Growth Factor/metabolism , Signal Transduction
17.
Front Endocrinol (Lausanne) ; 11: 527592, 2020.
Article in English | MEDLINE | ID: mdl-33716949

ABSTRACT

Recently, a growing body of evidence has suggested that abnormal ovarian angiogenesis, secondary to the imbalance between various angiogenic markers, is involved in the pathogenesis of PCOS, and this has led to the use of various interventions (such as Diane-35) to restore the normal ovarian angiogenesis. Therefore, we conducted the current investigation to determine the role of such markers (endothelial growth factor (VEGF), endostatin (ES), and thrombospondin-1 (TSP-1)) in the pathogenesis of PCOS along with the associated changes in ovarian blood flow in patients with PCOS compared to healthy controls, both before and after a course of oral contraception. A total of 381 patients with PCOS and 98 healthy females of childbearing age were recruited from July 2014 to June 2017 at the Reproductive Center of the Second Affiliated Hospital of Harbin Medical University. The serum levels of VEGF, ES, and TSP-1 were determined by enzyme-linked immunosorbent assay, while ovarian perfusion was measured by the pulsatility index (PI) and resistance index (RI) by using transvaginal color Doppler ultrasound. Repeated analyses were carried out after 3 months of Diane-35 treatment. Post-treatment serum levels of luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio of patients with PCOS decreased significantly (P <0.05). The RI values of most PCOS patients increased after treatment (P<0.05), while PI was significantly increased in all patients (P<0.05). However, variable changes in the serum levels of TSP-1, VEGF, and ES after treatment were observed. Serum VEGF levels showed a negative correlation with serum LH/FSH ratio, T concentration, and ES (P <0.05), while ES levels were negatively correlated with serum T concentrations only (P<0.05). The markers of angiogenesis (VEGF, ES, and TSP-1) were expressed differently among PCOS patients, who also responded differently to the same course of Diane-35 treatment. This field still warrants further investigation to reach a more definitive conclusion.


Subject(s)
Contraceptive Agents, Hormonal/therapeutic use , Endostatins/blood , Polycystic Ovary Syndrome/blood , Thrombospondin 1/blood , Vascular Endothelial Growth Factor A/blood , Adult , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Polycystic Ovary Syndrome/drug therapy , Treatment Outcome , Young Adult
18.
Front Med ; 13(6): 680-689, 2019 Dec.
Article in English | MEDLINE | ID: mdl-30820805

ABSTRACT

Anti-ß2 glycoprotein I (anti-ß2GPI) antibodies are important contributors to the development of thrombosis. Anti-ß2GPI antibody complexes with ß2GPI are well known to activate monocytes and endothelial cells via the intracellular NF-kB pathway with prothrombotic implications. By contrast, the interaction of anti- ß2GPI/ß2GPI complexes with platelets has not been extensively studied. The p38 mitogen-activated protein kinase (MAPK) pathway has been recognized to be an important intracellular signaling pathway in the coagulation cascade and an integral component of arterial and venous thrombosis. The present study reveals that levels of anti- ß2GPI/ß2GPI complexes in sera are positively associated with p38MAPK phosphorylation of platelets in thrombotic patients. Furthermore, SB203580 inhibits anti-ß2GPI/ß2GPI complex-induced platelet activation. Thrombus formation decreased in p38MAPK-/- mice after treatment with anti-ß2GPI/ß2GPI complexes. In conclusion, p38MAPK may be a treatment target for anti-ß2GPI antibody-associated thrombotic events.


Subject(s)
Antigen-Antibody Complex/immunology , Imidazoles/pharmacology , MAP Kinase Signaling System , Platelet Activation/physiology , Pyridines/pharmacology , Thrombosis/immunology , beta 2-Glycoprotein I/immunology , Adult , Animals , Autoantibodies/immunology , Endothelial Cells/metabolism , Female , Humans , Male , Mice , Mice, Knockout , Middle Aged , Monocytes/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
19.
Neurotherapeutics ; 16(2): 381-393, 2019 04.
Article in English | MEDLINE | ID: mdl-30843154

ABSTRACT

Nogo-66 receptor (NgR) and paired immunoglobulin-like receptor B (PirB) are two common receptors of various myelin-associated inhibitors (MAIs) and, thus, play an important role in MAIs-induced inhibitory signalling of regeneration following spinal cord injury (SCI). Based on the concept of protective autoimmunity, vaccine approaches could induce the production of antibodies against inhibitors in myelin, such as using purified myelin, spinal cord homogenates, or MAIs receptor NgR, in order to block the inhibitory effects and promote functional recovery in SCI models. However, due to the complication of the molecules and the mechanisms involved in MAIs-mediated inhibitory signalling, these immunotherapy strategies have yielded inconsistent outcomes. Therefore, we hypothesized that the choice and modification of self-antigens, and co-regulating multiple targets, may be more effective in repairing the injured spinal cord and improving functional recovery. In this study, NgR and PirB were selected to construct a double-targeted granulocyte-macrophage colony stimulating factor-NgR-PirB (GMCSF-NgR-PirB) nucleic acid vaccine, and investigate the efficacy of this immunotherapy in a spinal cord injury model in rats. The results showed that this vaccination could stimulate the production of antibodies against NgR and PirB, block the inhibitory effects mediated by various MAIs, and promote nerve regeneration and functional recovery after spinal cord injury. These findings suggest that nucleic acid vaccination against NgR and PirB can be a promising therapeutic strategy for SCI and other central nervous system diseases and injuries.


Subject(s)
Immunotherapy/methods , Nerve Regeneration/immunology , Nogo Receptor 1/immunology , Spinal Cord Injuries/therapy , Vaccines, DNA/therapeutic use , Animals , Female , Rats , Rats, Sprague-Dawley , Recovery of Function/immunology , Spinal Cord Injuries/immunology , Vaccination
20.
Curr Pharm Des ; 24(34): 4051-4059, 2018.
Article in English | MEDLINE | ID: mdl-30457048

ABSTRACT

The studying of synaptic plasticity, the ability of synaptic connections between neurons to be weakened or strengthened and specifically long-term potentiation (LTP) and long-term depression (LTD), is one of the most active areas of research in neuroscience. The process of synaptic connections playing a crucial role in improving cognitive processes is important to the processing of information in brain. In general, the dysfunction of synaptic plasticity was involved in a wide spectrum of central nervous system (CNS) disorders, including some neurodegenerative disorders. Thus, synaptic plasticity which is a dysfunction reported in neurodegenerative disorders may also be involved in posttraumatic stress disorder (PTSD), an anxiety and/or memory disorder developed after experiencing natural disasters, domestic violence or combat-related trauma. In this review, we mainly focus on discussing the biological function and mechanism for diagnostics and therapy of synaptic plasticity in PTSD and associated comorbidities, such as schizophrenia, depression, sleep disturbances and alcohol dependence, and further studying the molecular mechanisms of PTSD with a particular focus on the LTP/LTD, glutamatergic ligand-receptor systems, voltage-gated calcium channels (VGCCs) and brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB). The summarized function and mechanism of synaptic plasticity in PTSD and its comorbidities may help us further understand PTSD and provide insight into novel neuroplasticity modifying for diagnostics and treatment for PTSD.


Subject(s)
Neuronal Plasticity , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/therapy , Animals , Humans , Neuronal Plasticity/drug effects , Neuroprotective Agents/pharmacology , Stress Disorders, Post-Traumatic/complications , Stress Disorders, Post-Traumatic/physiopathology
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