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Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

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Neural Regeneration Research 2025年第11期20卷 3095-3112页

作者： Fengcheng Deng Dan Yang Lingxi Qing Yifei Chen Jilian Zou Meiling Jia Qian Wang Runda Jiang Lihua Huang College of pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina State Key Laboratory of Southwestern Chinese medicine Resources Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain *** gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine ***,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host *** reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological *** coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological *** study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological *** pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional *** can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage *** findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

关键词： cyclic adenosine monophosphate emotional disorders gut microbiota neurodegenerative diseases neurological diseases protein kinase A reciprocal regulation signaling pathway strategy therapies

B2 adrenergic receptors and morphological changes of the enteric nervous system in colorectal adenocarcinoma

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World Journal of Gastroenterology 2017年第7期23卷 1250-1261页

作者： Raluca Niculina Ciurea Ion Rogoveanu Daniel Pirici Georgica-Costinel Tartea Costin Teodor Streba Cristina Florescu Bogdan Catalin Ileana Puiu Elena-Anca Tartea Cristin Constantin Vere Department of Pathology University of Medicine and Pharmacy of Craiova Department of Gastroenterology University of Medicine and Pharmacy of Craiova Department of Research Methodology University of Medicine and Pharmacy of Craiova Department of Internal medicine University of Medicine and Pharmacy of Craiova Department of Cardiology University of Medicine and Pharmacy of Craiova Department of Physiology University of Medicine and Pharmacy of Craiova Department of Pediatrics University of Medicine and Pharmacy of Craiova

To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal *** this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2A receptors as well as the morphological changes of the enteric nervous system (ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni’s post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson’s correlation ***2A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis (P 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2A area showed an inverse correlation with the Auerbach plexus areas [r(14) = -0.531, P < 0.05], while for G2 tumors, epithelial B2A areas showed an indirect variation with both the Auerbach plexus areas [r(14) = -0.453, P < 0.05] and the Meissner areas [r(14) = -0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) = -0.587, P < 0.05] and Meissner [r(14) = -0.934, P < 0.05] ***2A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer m

关键词： Beta-2 adrenergic receptors Enteric nervous system Colorectal adenocarcinoma Spectral unmixing immunohistochemistry Tumor grading

Nonalcoholic fatty liver disease, metabolic risk factors, and hepatocellular carcinoma: An open question

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World Journal of Gastroenterology 2015年第14期21卷 4103-4110页

作者： Letitia Adela Maria Streba Cristin Constantin Vere Ion Rogoveanu Costin Teodor Streba Internal medicine Medical SemiologyUniversity of Medicine and Pharmacy of Craiova Research Center of Gastroenterology and Hepatology of craiova University of Medicine and Pharmacy of Craiova Internal medicine GastroenterologyUniversity of Medicine and Pharmacy of Craiova

Non-alcoholic liver disease(NAFLD) defines liver abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis with or without cirrhosis development, occurring in the absence of significant alcohol consumption, use of teratogenic medication, or hereditary *** association between NAFLD and metabolic syndrome is well documented and widely ***, type 2 diabetes mellitus(T2DM), and dyslipidemia are the most common metabolic risk factors associated with *** the components of metabolic syndrome, current evidence strongly indicates obesity and diabetes as hepatocellular carcinoma(HCC) risk *** is also growing evidence that suggests an increased risk of HCC in NAFLD patients, even surpassing other etiologies in some high-income *** data demonstrate a parallel rise in prevalence of obesity, diabetes, NAFLD, and *** obesity and its related diseases have steadily afflicted larger populations, HCC incidence is expected to increase in the *** mechanisms that underlie NAFLD development and subsequent progression to nonalcoholic steatohepatitis and cirrhosis(insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell activation, cytokine/adipocytokine signaling pathways, and genetic and environmental factors) appear to play a significant role in the development of NAFLD-related ***, a comprehensive view of molecular mechanisms linking obesity, T2 DM, and NAFLD-related HCC, as well as the exact sequence of molecular events, is still not understood in its ***-quality data are still necessary, and efforts should continue towards better understanding the underlying carcinogenic mechanisms of NAFLD-related *** this paper, we aimed to centralize the most important links supporting these relationships, focusing on obesity, T2 DM, and NAFLD-related HCC, as well as point out the major gaps in knowledge regarding the underlying molecular mechanisms beh

关键词： Diabetes mellitus Hepatocellular carcinoma Metabol

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher J.O’Connell Matthew J.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA James L.Winkle College of pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

Focus on alcoholic liver disease:From nosography to treatment

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World Journal of Gastroenterology 2014年第25期20卷 8040-8047页

作者： Letitia Adela Maria Streba Cristin Constantin Vere Costin Teodor Streba Marius Eugen Ciurea Internal medicine-Medical Semiology University of Medicine and Pharmacy of Craiova 200639 Craiova Romania Research Center of Gastroenterology and Hepatology of craiova University of Medicine and Pharmacy of Craiova200639 CraiovaRomania university of medicine and pharmacy of craiova 200639 Craiova Romania

Abusive alcohol intake currently ranks as a major cause of liver disease, and is associated with significant mortality worldwide. Alcoholic liver disease(ALD) generically defines liver abnormalities ranging from liver steatosis to the end-stages of disease such as liver cirrhosis. Information regarding the precise incidence and prevalence of ALD is still limited by a lack of large population-based studies and by the absence of large systematic reviews of all epidemiological data available. However, existing collected data show an overall increase in the number of alcohol abusers and alcoholrelated liver disease. The burden exerted on medical systems worldwide is significant, with hospitalization and management costs rising constantly over the years. A great number of all cirrhosis-related deaths in Europe and a significant percentage worldwide areassociated with alcohol consumption. The main possible risk factors for ALD are the amount and duration of alcohol abuse, patterns of drinking and the type of alcoholic beverage consumed. However, ALD does not progress to cirrhosis in all patients, therefore a series of additional factors are implicated. Even though insufficiently studied, genetic factors are generally regarded as highly important, and the presence of comorbidities and dietary habits seem to play a role in disease onset and progression. This lack of clear pathophysiological data further translates in the absence of definite treatment for ALD and shall prove challenging in the coming years. In this article, we aimed to briefly review epidemiologic data on the burden of ALD, risk factors, clinical and nosographic as well as therapeutic aspects of this disease. Without attempting to be exhaustive, this short topic highlight emphasizes each point and may serve as a general guidance tool in the complicated literature related to ALD.

关键词： Alcoholic liver disease Epidemiology Risk factors Diagnosis Treatment

Contrast-enhanced ultrasonography parameters in neural network diagnosis of liver tumors

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World Journal of Gastroenterology 2012年第32期18卷 4427-4434页

作者： Costin Teodor Streba Mihaela Ionescu Dan Ionut Gheonea Larisa Sandulescu Tudorel Ciurea Adrian Saftoiu Cristin Constantin Vere Ion Rogoveanu Research Center of Gastroenterology and Hepatology University of Medicine and Pharmacy of Craiova200349 CraiovaRomania Department of Bioinformatics and Statistics University of Medicine and Pharmacy Craiova200349 CraiovaRomania

AIM:To study the role of time-intensity curve(TIC) analysis parameters in a complex system of neural networks designed to classify liver ***:We prospectively included 112 patients with hepatocellular carcinoma(HCC)(n = 41),hypervascular(n = 20) and hypovascular(n = 12) liver metastases,hepatic hemangiomas(n = 16) or focal fatty changes(n = 23) who underwent contrast-enhanced ultrasonography in the Research Center of Gastroenterology and Hepatology,craiova,*** recorded full length movies of all contrast uptake phases and post-processed them offline by selecting two areas of interest(one for the tumor and one for the healthy surrounding parenchyma) and consecutive TIC *** difference in maximum intensities,the time to reaching them and the aspect of the late/portal phase,as quantified by the neural network and a ratio between median intensities of the central and peripheral areas were analyzed by a feed forward back propagation multi-layer neural network which was trained to classify data into five distinct classes,corresponding to each type of liver ***:The neural network had 94.45% training accuracy(95% CI:89.31%-97.21%) and 87.12% testing accuracy(95% CI:86.83%-93.17%).The automatic classification process registered 93.2% sensitivity,89.7% specificity,94.42% positive predictive value and 87.57% negative predictive *** artificial neural networks(ANN) incorrectly classified as hemangyomas three HCC cases and two hypervascular metastases,while in turn misclassifying four liver hemangyomas as HCC(one case) and hypervascular metastases(three cases).Comparatively,human interpretation of TICs showed 94.1% sensitivity,90.7% specificity,95.11% positive predictive value and 88.89% negative predictive *** accuracy and specificity of the ANN diagnosis system was similar to that of human interpretation of the TICs(P = 0.225 and P = 0.451,respectively).Hepatocellular carcinoma cases showed contrast uptake during the arterial phase

关键词： Hepatocellular carcinoma Liver tumors Contrast enhanced ultrasound Time-intensity curve Artificial neural network Computer-aided diagnosis system

Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

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Neural Regeneration Research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang Feng Miao Peifeng Wei College of pharmacy and First Clinical Medical College Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National Drug Clinical Trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

Testosterone,cardiomyopathies,and heart failure:a narrative review

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Asian Journal of Andrology 2021年第4期23卷 348-356页

作者： Rodica Diaconu Ionuţ Donoiu Oana Mirea Tudor Adrian Bălşeanu Department of Cardiology University of Medicine and PharmacyCraiova 200349Romania Department of Physiology University of Medicine and PharmacyCraiova 200349Romania

Testosterone exerts an important regulation of cardiovascular function through genomic and nongenomic pathways. It produces several changes in cardiomyocytes, the main actor of cardiomyopathies, which are characterized by pathological remodeling, eventually leading to heart failure. Testosterone is involved in contractility, in the energy metabolism of myocardial cells, apoptosis, and the remodeling process. In myocarditis, testosterone directly promotes the type of inflammation that leads to fibrosis, and influences viremia with virus localization. At the same time, testosterone exerts cardioprotective effects that have been observed in different studies. There is increasing evidence that low endogenous levels of testosterone have a negative impact in some cardiomyopathies and a protective impact in others. This review focuses on the interrelationships between testosterone and cardiomyopathies and heart failure.

关键词： androgens cardiomyocytes heart disease myocardial prognosis

Real-time sono-elastography in the diagnosis of diffuse liver diseases

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World Journal of Gastroenterology 2010年第14期16卷 1720-1726页

作者： Dan Ionut Gheonea Adrian S ǎftoiu Tudorel Ciurea Florin Gorunescu Sevastita Iordache Gabriel Lucian Popescu Smaranda Belciug Marina Gorunescu Larisa Sǎndulescu Research Center of Gastroenterology and Hepatology University of Medicine and Pharmacy Craiova 200349 Romania Department of Biostatistics and Informatics University of Medicine and Pharmacy Craiova 200349 Romania IT Department University of Medicine and Pharmacy Craiova 200349 Romania Faculty of Mathematics of Computer Science University of Craiova Craiova 200585 Romania

AIM: To analyze whether computer-enhanced dynamic analysis of elastography movies is able to better characterize and differentiate between different degrees of liver fibrosis. METHODS: The study design was prospective. A total of 132 consecutive patients with chronic liver diseases and healthy volunteers were examined by transabdominal ultrasound elastography. All examinations were done by two ***: Due to the limitations of the method, we obtained high-quality elastography information in only 73.48% of the patients. The κ-means clustering method was applied to assess the inter-observer diagnosis varia- bility, which showed good variability values in accordance with the experience of ultrasound examination of every observer. Cohen’sκ test indicated a moderate agreement between the study observers (κ = 0.4728). Furthermore, we compared the way the two observers clustered the patients, using the test for comparing two proportions (t value, two-sided test). There was no statistically significant difference between the two physicians, regardless of the patients’ real status. CONCLUSION: Transabdominal real-time elastography is certainly a very useful method in depicting liver hard- ness, although it is incompletely tested in large multicenter studies.

关键词： Elastography Ultrasonography Liver steato- sis Viral hepatitis Liver cirrhosis