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1.
Sci Rep ; 14(1): 6542, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503819

RESUMO

Fatty acids (FAs) play important roles as membrane components and signal transduction molecules. Changes in short chain FA (SCFA) composition are associated with gut microbiota modifications. However, the effect of bacteria-driven changes on the detailed FA spectrum has not been explored yet. We investigated the effect of antibiotics (ABx) and/or probiotics, in four treatment groups on rat stool FA composition. Principal component analysis indicated that the chromatogram profiles of the treatment groups differ, which was also observed at different time points. Linear mixed effects models showed that in the parameters compared (sampling times, treatments. and their interactions), both the weight percentage and the concentration of FAs were affected by ABx and probiotic administration. This study found that the gut microbiome defines trans and branched saturated FAs, most saturated FAs, and unsaturated FAs with less carbon atoms. These results are among the first ones to demonstrate the restoring effects of a probiotic mixture on a substantial part of the altered total FA spectrum, and also revealed a previously unknown relationship between gut bacteria and a larger group of FAs. These findings suggest that intestinal bacteria produce not only SCFAs but also other FAs that may affect the host's physiological processes.


Assuntos
Ácidos Graxos , Probióticos , Ratos , Animais , Ácidos Graxos/análise , Antibacterianos/farmacologia , Fezes/microbiologia , Ácidos Graxos Insaturados/análise , Probióticos/farmacologia , Bactérias , Ácidos Graxos Voláteis
2.
Sci Rep ; 14(1): 2666, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302505

RESUMO

The socialist era postponed suburbanisation in Central and Eastern European countries. After 1990, the process became extremely intensive and transformed the compact form of cities into more decentralised and dispersed urban structures. Therefore, the study aims to identify the main trends in land-cover transformation caused by urban sprawl in peri-urban areas of three Central and Eastern European cities (NUTS 3 level: the Pest County, Bratislava Region, and Krakowski subregion). In addition, we identified various policy tools for green infrastructure protection. We further investigated the extent to which the presence of legal means of nature conservation affects the stability of natural and seminatural areas. The research used an original questionnaire and spatio-temporal analysis. It has been confirmed that after decades of socialism, a highly intensive urban sprawl process started in the analysed regions. It generally slowed down after 2000 except for the Krakowski subregion. The majority of new artificial areas replaced agricultural land. Despite the dynamic urban sprawl, almost one-third of the analysed Central and Eastern European peri-urban areas were stable natural and seminatural areas. The traditional nature conservation tools proved to be effective in preserving natural and seminatural areas, but the protection of landscapes exposed to urban sprawl needs specific tools. The effectiveness of urban sprawl control is hindered by the fact that spatial planning competences are dispersed. This research may influence monitoring urban sprawl and offer an innovative method because it combines spatial analysis (quantitative approach) with the impact of policy tools (qualitative approach).

3.
Molecules ; 29(2)2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38257318

RESUMO

The long time (2 h) required for measurement, expensive chemicals (Ag2SO4), and toxic reagents (K2Cr2O7, HgSO4) limit the application of the standard method for measuring the oxygen equivalent of organic content in wastewater (chemical oxygen demand, COD). In recent years, the COD has increasingly been replaced by the total organic carbon (TOC) parameter. Since the limit values of the pollution levels are usually given in terms of the COD, efforts are being made to find the correlation between these parameters. Several papers have published correlation analyses of COD and TOC for industrial and municipal wastewater, but the relationship has not been discussed for individual chemicals. Here, this relationship was investigated using 70 contaminants (laboratory chemicals, pharmaceuticals, and pesticides). The calculated COD values, in most cases, agreed, within ~10%, with the experimental ones; for tetracyclines and some chloroaromatic molecules, the measured values were 20-50% lower than the calculated values. The COD/TOC ratios were between 2 and 3: for macrolides, they were ~3; for fluoroquinolones and tetracyclines, they were ~2. The molecular structure dependence of the ratio necessitates the establishing of the correlation on an individual basis. In advanced oxidation processes (AOPs), the ratio changes during degradation, limiting the application of TOC instead of COD.

4.
Biometals ; 37(2): 461-475, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38110781

RESUMO

Citric acid plays an ubiquitous role in the complexation of essential metals like iron and thus it has a key function making them biologically available. For this, iron(III) citrate complexes are considered among the most significant coordinated forms of ferric iron that take place in biochemical processes of all living organisms. Although these systems hold great biological relevance, their coordination chemistry has not been fully elucidated yet. The current study aimed to investigate the speciation of iron(III) citrate using Mössbauer and electron paramagnetic resonance spectroscopies. Our aim was to gain insights into the structure and nuclearity of the complexes depending on the pH and iron to citrate ratio. By applying the frozen solution technique, the results obtained directly reflect the iron speciation present in the aqueous solution. At 1:1 iron:citrate molar ratio, polynuclear species prevailed forming most probably a trinuclear structure. In the case of citrate excess, the coexistence of several monoiron species with different coordination environments was confirmed. The stability of the polynuclear complexes was checked in the presence of organic solvents.


Assuntos
Compostos Férricos , Ferro , Ferro/química , Compostos Férricos/química , Ácido Cítrico/química , Citratos/química
5.
Int J Mol Sci ; 24(23)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38069185

RESUMO

The ionic environment within the nucleoplasm might diverge from the conditions found in the cytoplasm, potentially playing a role in the cellular stress response. As a result, it is conceivable that interactions of nuclear actin and actin-binding proteins (ABPs) with apoptosis factors may differ in the nucleoplasm and cytoplasm. The primary intracellular stress response is Ca2+ influx. The junctional mediating and regulating Y protein (JMY) is an actin-binding protein and has the capability to interact with the apoptosis factor p53 in a Ca2+-dependent manner, forming complexes that play a regulatory role in cytoskeletal remodelling and motility. JMY's presence is observed in both the cytoplasm and nucleoplasm. Here, we show that ex vivo ectocervical squamous cells subjected to electroporation with JMY protein exhibited varying morphological alterations. Specifically, the highly differentiated superficial and intermediate cells displayed reduced nuclear size. In inflamed samples, nuclear enlargement and simultaneous cytoplasmic reduction were observable and showed signs of apoptotic processes. In contrast, the less differentiated parabasal and metaplastic cells showed increased cytoplasmic activity and the formation of membrane protrusions. Surprisingly, in severe inflammation, vaginosis or ASC-US (Atypical Squamous Cells of Undetermined Significance), JMY appears to influence only the nuclear and perinuclear irregularities of differentiated cells, and cytoplasmic abnormalities still existed after the electroporation. Our observations can provide an appropriate basis for the exploration of the relationship between cytopathologically relevant morphological changes of epithelial cells and the function of ABPs. This is particularly important since ABPs are considered potential diagnostic and therapeutic biomarkers for both cancers and chronic inflammation.


Assuntos
Actinas , Proteínas Nucleares , Humanos , Actinas/metabolismo , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Células Epiteliais/metabolismo , Eletroporação , Inflamação
6.
Sci Rep ; 13(1): 22451, 2023 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-38105266

RESUMO

Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo in a murine colitis model. We induced colitis with dextran sulfate sodium (DSS), with the co-administration of liposome-encapsulated clodronate (L-clodronate) to simultaneously deplete blood monocytes contributing to macrophage infiltration in the inflamed muscularis of experimental mice. DSS-treated animals receiving concurrent L-clodronate injection showed significantly decreased blood monocyte numbers and colon muscularis macrophage (MM) density compared to DSS-treated control (DSS-vehicle). DSS-clodronate-treated mice exhibited significantly slower whole gut transit time than DSS-vehicle-treated animals and comparable to that of controls. Experiments with oral gavage-fed Evans-blue dye showed similar whole gut transit times in DSS-clodronate-treated mice as in control animals. Furthermore, qPCR-analysis and immunofluorescence on colon muscularis samples revealed that factors associated with neuroinflammation and neurodegeneration, including Bax1, Hdac4, IL-18, Casp8 and Hif1a are overexpressed after DSS-treatment, but not in the case of concurrent L-clodronate administration. Our findings highlight that MM-infiltration in the muscularis layer is responsible for colitis-associated dysmotility and enteric neuronal dysfunction along with the release of mediators associated with neurodegeneration in a murine experimental model.


Assuntos
Ácido Clodrônico , Colite , Camundongos , Animais , Ácido Clodrônico/farmacologia , Colite/induzido quimicamente , Inflamação , Macrófagos , Colo , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
7.
Pathol Oncol Res ; 29: 1611547, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38146588

RESUMO

Introduction: The role of p16 and p53 immunohistochemistry in the diagnosis of rare and aggressive uterine carcinosarcoma (UCS) has been well established. However, enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a member of the polycomb group family is a relatively new biomarker, with limited published data on its significance in this tumor type. The goal of this study was to examine EZH2 expression in UCS and its components, in correlation with morphological features, and p16 and p53 staining patterns. Methods: Twenty-eight UCSs were included in the study. EZH2, p16 and p53 immunoreactivity were assessed independently by two pathologists in both tumor components (epithelial and mesenchymal). EZH2 and p16 immunostains were scored semiquantitatively: based on the percentage and intensity of tumor cell staining a binary staining index ("high- or low-expressing") was calculated. The p53 staining pattern was evaluated as wild-type or aberrant (diffuse nuclear, null, or cytoplasmic expression). Statistical tests were used to evaluate the correlation between staining patterns for all three markers and the different tumor components and histotypes. Results: High EZH2 and p16 expression and aberrant p53 patterns were present in 89.3% 78.6% and 85.7% of the epithelial component and in 78.6%, 62.5% and 82.1% of the mesenchymal component, respectively. Differences among these expression rates were not found to be significant (p > 0.05). Regarding the epithelial component, aberrant p53 pattern was found to be significantly (p = 0.0474) more frequent in the serous (100%) than in endometrioid (66.6%) histotypes. Within the mesenchymal component, p53 null expression pattern occurred significantly (p = 0.0257) more frequently in heterologous sarcoma components (71.4%) compared to the homologous histotype (18.8%). Conclusion: In conclusion, EZH2, p16 and p53 seem to play a universal role in the pathogenesis of UCS; however, a distinctive pattern of p53 expression appears to exist between the serous and endometrioid carcinoma components and also between the homologous and heterologous sarcoma components.


Assuntos
Carcinossarcoma , Inibidor p16 de Quinase Dependente de Ciclina , Proteína Potenciadora do Homólogo 2 de Zeste , Regulação Neoplásica da Expressão Gênica , Proteína Supressora de Tumor p53 , Neoplasias Uterinas , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/fisiopatologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/genética , Carcinossarcoma/fisiopatologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
8.
Front Oncol ; 13: 1207295, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37860193

RESUMO

Objective: The approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database. Methods: This retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology. Results: In total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1-66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011-2012 (28.7% [95% CI: 26.4%-30.9%] vs. 14.45% [95% CI: 13.21%-15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%-25.2%) and 13.37% (95% CI: 11.8%-15.0%) in 2019 and 2011-2012, respectively, the change was statistically significant. Compared to 2011-2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015-2016, 2017-2018, and 2019, respectively (p<0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p<0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020-2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period. Conclusion: 3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic.

9.
Front Oncol ; 13: 1182170, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795445

RESUMO

Background: This nationwide study examined breast cancer (BC) incidence and mortality rates in Hungary between 2011-2019, and the impact of the Covid-19 pandemic on the incidence and mortality rates in 2020 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Methods: Our nationwide, retrospective study included patients who were newly diagnosed with breast cancer (International Codes of Diseases ICD)-10 C50) between Jan 1, 2011 and Dec 31, 2020. Age-standardized incidence and mortality rates (ASRs) were calculated using European Standard Populations (ESP). Results: 7,729 to 8,233 new breast cancer cases were recorded in the NHIF database annually, and 3,550 to 4,909 all-cause deaths occurred within BC population per year during 2011-2019 period, while 2,096 to 2,223 breast cancer cause-specific death was recorded (CSO). Age-standardized incidence rates varied between 116.73 and 106.16/100,000 PYs, showing a mean annual change of -0.7% (95% CI: -1.21%-0.16%) and a total change of -5.41% (95% CI: -9.24 to -1.32). Age-standardized mortality rates varied between 26.65-24.97/100,000 PYs (mean annual change: -0.58%; 95% CI: -1.31-0.27%; p=0.101; total change: -5.98%; 95% CI: -13.36-2.66). Age-specific incidence rates significantly decreased between 2011 and 2019 in women aged 50-59, 60-69, 80-89, and ≥90 years (-8.22%, -14.28%, -9.14%, and -36.22%, respectively), while it increased in young females by 30.02% (95%CI 17,01%- 51,97%) during the same period. From 2019 to 2020 (in first COVID-19 pandemic year), breast cancer incidence nominally decreased by 12% (incidence rate ratio [RR]: 0.88; 95% CI: 0.69-1.13; 2020 vs. 2019), all-cause mortality nominally increased by 6% (RR: 1.06; 95% CI: 0.79-1.43) among breast cancer patients, and cause-specific mortality did not change (RR: 1.00; 95%CI: 0.86-1.15). Conclusion: The incidence of breast cancer significantly decreased in older age groups (≥50 years), oppositely increased among young females between 2011 and 2019, while cause-specific mortality in breast cancer patients showed a non-significant decrease. In 2020, the Covid-19 pandemic resulted in a nominal, but not statistically significant, 12% decrease in breast cancer incidence, with no significant increase in cause-specific breast cancer mortality observed during 2020.

10.
Front Cell Neurosci ; 17: 1277375, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841285

RESUMO

Hypoxia causes structural and functional changes in several brain regions, including the oxygen-concentration-sensitive hippocampus. We investigated the consequences of mild short-term hypoxia on rat hippocampus in vivo. The hypoxic group was treated with 16% O2 for 1 h, and the control group with 21% O2. Using a combination of Gallyas silver impregnation histochemistry revealing damaged neurons and interneuron-specific immunohistochemistry, we found that somatostatin-expressing inhibitory neurons in the hilus were injured. We used 32-channel silicon probe arrays to record network oscillations and unit activity from the hippocampal layers under anaesthesia. There were no changes in the frequency power of slow, theta, beta, or gamma bands, but we found a significant increase in the frequency of slow oscillation (2.1-2.2 Hz) at 16% O2 compared to 21% O2. In the hilus region, the firing frequency of unidentified interneurons decreased. In the CA3 region, the firing frequency of some unidentified interneurons decreased while the activity of other interneurons increased. The activity of pyramidal cells increased both in the CA1 and CA3 regions. In addition, the regularity of CA1, CA3 pyramidal cells' and CA3 type II and hilar interneuron activity has significantly changed in hypoxic conditions. In summary, a low O2 environment caused profound changes in the state of hippocampal excitatory and inhibitory neurons and network activity, indicating potential changes in information processing caused by mild short-term hypoxia.

11.
Heliyon ; 9(9): e20029, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809425

RESUMO

While sponge cake is one of the most well-liked cookies in the world, mint and cocoa have both been shown to be excellent sources of antioxidant compounds. Therefore, the aim of the study was to create functional sponge cakes with the addition of Dutch cocoa powder and different types of mint, with proven increased total antioxidant and polyphenol content. Additionally, made an effort to produce functional sponge cakes enhanced with cocoa powder and dried, ground mint leaves. To accomplish this, the cakes with cocoa addition were also added 1, 3, and 5% of the ground mint variety, and then the changes in their antioxidant and polyphenol content were assessed. To prove the functionality of cakes, total polyphenol content was detected by Folin-Ciocalteu, while all antioxidant content was measured by the FRAP method. The spectrophotometric analysis supported the functionality of sponge cakes and the baking losses of identified components. The total polyphenol content of baked goods ranged from 1.37 to 1.66 mg GAE/g for peppermint cakes, from 1.66 to 1.87 mg GAE/g for spearmint cakes, and from 1.20 to 1.68 mg GAE/g for strawberry mint sponge cakes. The total antioxidant content of the functional cakes changed between 1.84 and 2.82 mg AAE/g for peppermint cakes, from 1.84 to 4.00 mg AAE/g for spearmint cakes, and from 1.56 to 2.94 mg GAE/g for strawberry mint sponge cakes. The natural control samples, and control sponge cakes made without mint addition with only cocoa powder always had lower levels of polyphenols and antioxidants. All samples had baking loss (control samples had the highest in all cases), but strawberry mint samples had the least of it when it came to antioxidant content and spearmint samples had the least in the case of polyphenol content. Overall, mints and Dutch cocoa powder are appropriate for the production of functional bakery goods because they give the final product a tasty flavor and provide a significant amount of antioxidants and polyphenols despite baking.

12.
Int J Mol Sci ; 24(14)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37511494

RESUMO

Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamic nucleus (PVH) are in the position to integrate stress-related information and initiate adaptive neuroendocrine-, autonomic-, metabolic- and behavioral responses. In addition to hypophyseotropic cells, CRH is widely expressed in the CNS, however its involvement in the organization of the stress response is not fully understood. In these experiments, we took advantage of recently available Crh-IRES-Cre;Ai9 mouse line to study the recruitment of hypothalamic and extrahypothalamic CRH neurons in categorically distinct, acute stress reactions. A total of 95 brain regions in the adult male mouse brain have been identified as containing putative CRH neurons with significant expression of tdTomato marker gene. With comparison of CRH mRNA and tdTomato distribution, we found match and mismatch areas. Reporter mice were then exposed to restraint, ether, high salt, lipopolysaccharide and predator odor stress and neuronal activation was revealed by FOS immunocytochemistry. In addition to a core stress system, stressor-specific areas have been revealed to display activity marker FOS. Finally, activation of CRH neurons was detected by colocalization of FOS in tdTomato expressing cells. All stressors resulted in profound activation of CRH neurons in the hypothalamic paraventricular nucleus; however, a differential activation of pattern was observed in CRH neurons in extrahypothalamic regions. This comprehensive description of stress-related CRH neurons in the mouse brain provides a starting point for a systematic functional analysis of the brain stress system and its relation to stress-induced psychopathologies.


Assuntos
Hormônio Liberador da Corticotropina , Hipotálamo , Camundongos , Masculino , Animais , Hormônio Liberador da Corticotropina/metabolismo , Hipotálamo/metabolismo , Encéfalo/metabolismo , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo
13.
Materials (Basel) ; 16(9)2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37176465

RESUMO

Photonic nanoarchitectures of butterfly wings can serve as biotemplates to prepare semiconductor thin films of ZnO by atomic layer deposition. The resulting biotemplated ZnO nanoarchitecture preserves the structural and optical properties of the natural system, while it will also have the features of the functional material. The ZnO-coated wings can be used directly in heterogeneous photocatalysis to decompose pollutants dissolved in water upon visible light illumination. We used the photonic nanoarchitectures of different Morpho butterflies with different structural colors as biotemplates and examined the dependence of decomposition rates of methyl orange and rhodamine B dyes on the structural color of the biotemplates and the thickness of the ZnO coating. Using methyl orange, we measured a ten-fold increase in photodegradation rate when the 20 nm ZnO-coated wings were compared to similarly coated glass substrates. Using rhodamine B, a saturating relationship was found between the degradation rate and the thickness of the deposited ZnO on butterfly wings. We concluded that the enhancement of the catalytic efficiency can be attributed to the slow light effect due to a spectral overlap between the ZnO-coated Morpho butterfly wings reflectance with the absorption band of dyes, thus the photocatalytic performance could be changed by the tuning of the structural color of the butterfly biotemplates. The photodegradation mechanism of the dyes was investigated by liquid chromatography-mass spectroscopy.

14.
J Neurosci ; 43(5): 846-862, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36564184

RESUMO

Stress disorders impair sleep and quality of life; however, their pathomechanisms are unknown. Prolactin-releasing peptide (PrRP) is a stress mediator; we therefore hypothesized that PrRP may be involved in the development of stress disorders. PrRP is produced by the medullary A1/A2 noradrenaline (NA) cells, which transmit stress signals to forebrain centers, and by non-NA cells in the hypothalamic dorsomedial nucleus. We found in male rats that both PrRP and PrRP-NA cells innervate melanin-concentrating hormone (MCH) producing neurons in the dorsolateral hypothalamus (DLH). These cells serve as a key hub for regulating sleep and affective states. Ex vivo, PrRP hyperpolarized MCH neurons and further increased the hyperpolarization caused by NA. Following sleep deprivation, intracerebroventricular PrRP injection reduced the number of REM sleep-active MCH cells. PrRP expression in the dorsomedial nucleus was upregulated by sleep deprivation, while downregulated by REM sleep rebound. Both in learned helplessness paradigm and after peripheral inflammation, impaired coping with sustained stress was associated with (1) overactivation of PrRP cells, (2) PrRP protein and receptor depletion in the DLH, and (3) dysregulation of MCH expression. Exposure to stress in the PrRP-insensitive period led to increased passive coping with stress. Normal PrRP signaling, therefore, seems to protect animals against stress-related disorders. PrRP signaling in the DLH is an important component of the PrRP's action, which may be mediated by MCH neurons. Moreover, PrRP receptors were downregulated in the DLH of human suicidal victims. As stress-related mental disorders are the leading cause of suicide, our findings may have particular translational relevance.SIGNIFICANCE STATEMENT Treatment resistance to monoaminergic antidepressants is a major problem. Neuropeptides that modulate the central monoaminergic signaling are promising targets for developing alternative therapeutic strategies. We found that stress-responsive prolactin-releasing peptide (PrRP) cells innervated melanin-concentrating hormone (MCH) neurons that are crucial in the regulation of sleep and mood. PrRP inhibited MCH cell activity and enhanced the inhibitory effect evoked by noradrenaline, a classic monoamine, on MCH neurons. We observed that impaired PrRP signaling led to failure in coping with chronic/repeated stress and was associated with altered MCH expression. We found alterations of the PrRP system also in suicidal human subjects. PrRP dysfunction may underlie stress disorders, and fine-tuning MCH activity by PrRP may be an important part of the mechanism.


Assuntos
Hormônios Hipotalâmicos , Privação do Sono , Ratos , Masculino , Humanos , Animais , Hormônio Liberador de Prolactina/farmacologia , Hormônio Liberador de Prolactina/metabolismo , Privação do Sono/metabolismo , Transtornos do Humor/etiologia , Qualidade de Vida , Ratos Wistar , Hormônios Hipotalâmicos/metabolismo , Sono/fisiologia , Neurônios/fisiologia , Norepinefrina/metabolismo
15.
NanoImpact ; 29: 100444, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36470408

RESUMO

Nanoscale Fe containing particles can penetrate the root apoplast. Nevertheless, cell wall size exclusion questions that for Fe mobilisation, a close contact between the membrane integrating FERRIC REDUCTASE OXIDASE (FRO) enzymes and Fe containing particles is required. Haematite nanoparticle suspension, size of 10-20 nm, characterized by 57Fe Mössbauer spectroscopy, TEM, ICP and SAED was subjected to Fe utilisation by the flavin secreting model plant cucumber (Cucumis sativus). Alterations in the structure and distribution of the particles were revealed by 57Fe Mössbauer spectroscopy, HRTEM and EDS element mapping. Biological utilisation of Fe resulted in a suppression of Fe deficiency responses (expression of CsFRO 1, 2 & 3 and RIBOFLAVIN A1; CsRIBA1 genes and root ferric chelate reductase activity). Haematite nanoparticles were stacked in the middle lamella of the apoplast. Fe mobilisation is evidenced by the reduction in the particle size. Fe release from nanoparticles does not require a contact with the plasma membrane. Parallel suppression in the CsFRO 1&3 and CsRIBA1 transcript amounts support that flavin biosynthesis is an inclusive Fe deficiency response involved in the reduction-based Fe utilisation of Cucumis sativus roots. CsFRO2 is suggested to play a role in the intracellular Fe homeostasis.


Assuntos
Cucumis sativus , Ferro , Ferro/metabolismo , Oxirredutases/metabolismo , Transporte Biológico , Flavinas/metabolismo
16.
Front Oncol ; 12: 1032366, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505881

RESUMO

Objective: The Hungarian Undiagnosed Lung Cancer (HULC) study aimed to explore the potential reasons for missed LC (lung cancer) diagnosis by comparing healthcare and socio-economic data among patients with post-mortem diagnosed LC with those who were diagnosed with LC during their lives. Methods: This nationwide, retrospective study used the databases of the Hungarian Central Statistical Office (HCSO) and National Health Insurance Fund (NHIF) to identify patients who died between January 1, 2019 and December 31, 2019 and were diagnosed with lung cancer post-mortem (population A) or during their lifetime (population B). Patient characteristics, socio-economic factors, and healthcare resource utilization (HCRU) data were compared between the diagnosed and undiagnosed patient population. Results: During the study period, 8,435 patients were identified from the HCSO database with LC as the cause of death, of whom 1,203 (14.24%) had no LC-related ICD (International Classification of Diseases) code records in the NHIF database during their lives (post-mortem diagnosed LC population). Post-mortem diagnosed LC patients were significantly older than patients diagnosed while still alive (mean age 71.20 vs. 68.69 years, p<0.001), with a more pronounced age difference among female patients (difference: 4.57 years, p<0.001), and had significantly fewer GP (General Practitioner) and specialist visits, X-ray and CT scans within 7 to 24 months and 6 months before death, although the differences in GP and specialist visits within 7-24 months did not seem clinically relevant. Patients diagnosed with LC while still alive were more likely to be married (47.62% vs. 33.49%), had higher educational attainment, and had more children, than patients diagnosed with LC post-mortem. Conclusions: Post-mortem diagnosed lung cancer accounts for 14.24% of total lung cancer mortality in Hungary. This study provides valuable insights into patient characteristics, socio-economic factors, and HCRU data potentially associated with a high risk of lung cancer misdiagnosis.

17.
Antibiotics (Basel) ; 11(10)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36289984

RESUMO

Strict anaerobes have been reported to account for 0.5-13% of episodes of bacteremia in the adult population, with a growing awareness among clinicians regarding anaerobic bacteremia, especially in patients with specific predisposing factors. The aim of our present study was to assess the incidence and clinical characteristics of anaerobic bacteremia during a 5-year period (2016-2020) at a tertiary care teaching hospital, and to compare our findings with other studies in Hungary. Overall, n = 160 strict anaerobes were detected, out of which, 44.4% (n = 71; 0.1% of positive blood cultures, 0.1/1000 hospitalizations, 3.3/100,000 patient days) were clinically significant, while Cutibacterium spp. accounted for 55.6% (n = 89) of isolates. Among relevant pathogens, the Bacteroides/Parabacteroides spp. group (32.4%; n = 23), Clostridium spp. (22.5%; n = 16) and Gram-positive anaerobic cocci (15.5%; n = 11) were the most common. The mean age of patients was 67.1 ± 14.1 years, with a male majority (59.2%; n = 42). A total of 38.0% of patients were affected by a malignancy or immunosuppression, while an abscess was identified in 15.5% of cases. A total of 74.7% (n = 53) of patients received antibiotics prior to blood culture sampling; in instances where antimicrobials were reported, anaerobic coverage of the drugs was appropriate in 52.1% (n = 37) of cases. The 30-day crude mortality rate was 39.4% (n = 28); age ≥ 75 years was a significant predictor of 30-day mortality (OR: 5.0; CI: 1.8-14.4; p = 0.003), while malignancy and immunosuppression, lack of anti-anaerobic coverage or female sex did not show a significant relationship with the mortality of these patients. Early recognition of the role played by anaerobes in sepsis and timely initiation of adequate, effective antimicrobial treatment have proven efficient in reducing the mortality of patients affected by anaerobic bacteremia.

18.
Front Psychol ; 13: 955232, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033062

RESUMO

The present study explored the types of stressors faced by rhythmic gymnastics athletes, their parents, and coaches. Semi-structured interviews with 12 participants-four gymnasts, five coaches, and three parents-were analyzed using reflexive thematic analysis in a theory-driven framework. The categorizations of sport-related stressors for the parents, coaches, and gymnasts were based on existing theories. The results showed that both the gymnasts and the coaches predominantly noted mastery-avoidance goals in terms of performance, while the interviews with parents mostly indicated performance-avoidance goals. All three groups of participants consistently reported a detrimental atmosphere in rhythmic gymnastics. For instance, they emphasized the stress related to inadequate communication between the concerned parties. Moreover, all parties believed that having a lean body was linked to success in the competitive world of rhythmic gymnastics. The present study provides insight into some of the potential major stressors and the related subjective experiences affecting athletes socializing in the same sporting environment.

19.
iScience ; 25(8): 104693, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35880047

RESUMO

There is a strong relationship between stress and metabolism. Because acute traumatic- and chronic stress events are often accompanied with metabolic pathophysiology, it is important to understand the details of the metabolic stress response. In this study we directly compared metabolic effects of acute stress with chronic repeated- and chronic unpredictable stress in mouse models. All types of adversities increased energy expenditure, chronic stress exposure decreased body weight gain, locomotor activity and differentially affected fuel utilization. During chronic exposure to variable stressors, carbohydrates were the predominant fuels, whereas fatty acids were catabolized in acutely and repeatedly restrained animals. Chronic exposure to variable stressors in unpredictable manner provoked anxiety. Our data highlight differences in metabolic responses to acute- repeated- and chronic stressors, which might affect coping behavior and underlie stress-induced metabolic and psychopathologies.

20.
Artigo em Inglês | MEDLINE | ID: mdl-35805673

RESUMO

(1) Background: Although parental behavior is known to be an important source of influence, relatively few studies have examined the factors possibly contributing parental stressors as being directly related to their children's sport socialization. The present study explored the relative importance of related parental stressors and the associations between these stressors and various types of parental involvement. (2) Method: A total of 1260 parents completed an online form including demographic questions, questions on their children's sport participation, and three self-report measures (PSSS, PISQ, and PASSES). (3) Results: The results revealed that the multiple linear regression models for overall parental stress were statistically significant. The significant predictors were the parent's educational level, the child's current stage of sports participation, and the child's sport injury (or the lack thereof). Furthermore, the stressors perceived by parents were positively associated with parental direct behavior and pressure. (4) Conclusions: Parents are under more stress as their child's stages of sport development increases, if their child has already had a sports injury, and the parents' directive behavior and experienced stress were significantly associated. The obtained results expand the existing knowledge of the complexity of parents' importance in children's sports careers.


Assuntos
Relações Pais-Filho , Esportes , Criança , Humanos , Autorrelato , Socialização , Inquéritos e Questionários
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