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1.
Immunity ; 57(10): 2296-2309.e5, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39353440

RESUMO

The surface of the skin is continually exposed to pro-inflammatory stimuli; however, it is unclear why it is not constantly inflamed due to this exposure. Here, we showed undifferentiated keratinocytes residing in the deep epidermis could trigger a strong inflammatory response due to their high expression of pattern recognition receptors (PRRs) that detect damage or pathogens. As keratinocytes differentiated, they migrated outward toward the surface of the skin and decreased their PRR expression, which led to dampened immune responses. ZNF750, a transcription factor expressed only in differentiated keratinocytes, recruited the histone demethylase KDM1A/LSD1 to silence genes coding for PRRs (TLR3, IFIH1/MDA5, and DDX58/RIG1). Loss of ZNF750 or KDM1A in human keratinocytes or mice resulted in sustained and excessive inflammation resembling psoriatic skin, which could be restored to homeostatic conditions upon silencing of TLR3. Our findings explain how the skin's surface prevents excessive inflammation through ZNF750- and KDM1A-mediated suppression of PRRs.


Assuntos
Histona Desmetilases , Inflamação , Queratinócitos , Receptores de Reconhecimento de Padrão , Pele , Fatores de Transcrição , Histona Desmetilases/metabolismo , Histona Desmetilases/genética , Humanos , Queratinócitos/metabolismo , Animais , Camundongos , Receptores de Reconhecimento de Padrão/metabolismo , Receptores de Reconhecimento de Padrão/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Pele/imunologia , Pele/patologia , Pele/metabolismo , Inflamação/imunologia , Diferenciação Celular/imunologia , Psoríase/imunologia , Psoríase/genética , Psoríase/metabolismo , Camundongos Knockout , Inativação Gênica , Camundongos Endogâmicos C57BL , Proteínas Supressoras de Tumor
2.
J Genet Genomics ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39389460

RESUMO

Phosphorus (P) is an essential nutrient for crop growth, making it important for maintaining food security as the global population continues to increase. Plants acquire P primarily via the uptake of inorganic phosphate (Pi) in soil through their roots. Pi, which is usually sequestered in soils, is not easily absorbed by plants and represses plant growth. Plants have developed a series of mechanisms to cope with P deficiency. Moreover, P fertilizer applications are critical for maximizing crop yield. Maize is a major cereal crop cultivated worldwide. Increasing its P-use efficiency is important for optimizing maize production. Over the past two decades, considerable progresses have been achieved in research aimed at adapting maize varieties to changes in environmental P supply. Here, we present an overview of the morphological, physiological, and molecular mechanisms involved in P acquisition, translocation, and redistribution in maize, and combine the advances in Arabidopsis and rice, to better elucidate the progress of P nutrition. Additionally, we summarize the correlation between P and abiotic stress responses. Clarifying the mechanisms relevant to improving P absorption and use in maize can guide future research on sustainable agriculture.

3.
Nano Lett ; 24(42): 13388-13396, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39383340

RESUMO

Polarization-sensitive optoelectronic detection has been achieved by an all-Si detector in the NIR range, based on plasmon hot electron generation/internal photoemission effect. An advanced architecture with a specially designed anisotropic metasurface was developed and structurally optimized for maximizing the internal quantum efficiency (IQE). Assisted by finite difference time domain (FDTD) simulations, the well-designed device exhibits a maximum optical absorption of 80% around 1.45 µm, corresponding to an optical discrimination ratio of 120. Optoelectronic measurements show the peak responsivity and detectivity of 51.2 mA/W and 8.05 × 1010 cm Hz1/2/W, respectively, at 1.45 µm. A high polarization photocurrent ratio of 35 nm is also achieved at 1.55 µm. Moreover, the optoelectronic response can be tuned by a back-gate bias. Last but not least, we built up a model for theoretically estimating the IQE, which provides instructive guidance for further enhancing the optoelectronic performance of hot electron detectors.

5.
J Affect Disord ; 367: 903-912, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39251093

RESUMO

Aberrant structural covariance (SC) in the medial prefrontal cortex (mPFC) is believed to play a crucial role in adolescent-onset major depressive disorder (AO-MDD). However, the effect of childhood abuse (CA) on SC in AO-MDD patients is still unknown. Here, we measured anomalous SC in the mPFC of AO-MDD patients and assessed the potential modulation of this feature by CA. We acquired T1-weighted structural images of AO-MDD patients (n = 93) and healthy controls (HCs, n = 81). Using voxel-based morphometry analysis, we calculated gray matter volumes for each subject. Subsequently, we classified abnormal SC in the mPFC into three subtypes according to overall CA. Compared with HCs, AO-MDD patients showed alterations in the structural covariance network of the mPFC, which is a central region in the default mode network (DMN). We also found an anterior-posterior dissociation in the structural covariance connectivity of the DMN. A history of CA modulated bilateral mPFC SC. These changes were primarily focused on the SC between the mPFC and the limbic system, indicating a gap in the rate of neural maturation between these regions. In summary, the DMN and frontal-limbic system, which are involved in emotional processing, appear to play a significant role in the development of AO-MDD. These findings highlight the crucial effects of CA on neurophysiological alterations in individuals with AO-MDD.


Assuntos
Maus-Tratos Infantis , Transtorno Depressivo Maior , Imageamento por Ressonância Magnética , Córtex Pré-Frontal , Humanos , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/patologia , Adolescente , Feminino , Masculino , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Maus-Tratos Infantis/psicologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Criança , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Sistema Límbico/fisiopatologia , Sistema Límbico/diagnóstico por imagem , Estudos de Casos e Controles
7.
Free Radic Res ; 58(6-7): 417-429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39079051

RESUMO

Ovarian cancer, marked by high rate of recurrence, novel therapeutic strategies are needed to improve patient outcome. One of the potential strategies is inducing ferroptosis in ovarian cancer cells. Ferroptosis is an iron-dependent, lipid peroxidation-driven mode of cell death primarily occurring on the cell membrane. PTRF, an integral component of the caveolae structures located on the cell membrane, is involved in a multitude of physiological processes, including but not limited to, endocytosis, signal transduction, and lipid metabolism. This study elucidates the relationship between PTRF and ferroptosis in ovarian cancer, offering a fresh perspective for the development of new therapeutic strategies. We knocked down PTRF employing siRNA in the ovarian cancer cell lines HEY and SKOV3, following which we stimulated ferroptosis with Erastin (Era). Our research indicates that the lack of PTRF sensitizes cancer cells to ferroptosis, likely by altering membrane stability and tension, thereby affecting signal pathways related to ferroptosis, such as lipid and atherosclerosis, fluid shear stress, and atherosclerosis. Our findings provide new insights for developing new treatments for ovarian cancer.


Assuntos
Ferroptose , Neoplasias Ovarianas , Humanos , Ferroptose/genética , Feminino , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Linhagem Celular Tumoral , Proteínas de Ligação a RNA
8.
Tob Induc Dis ; 222024.
Artigo em Inglês | MEDLINE | ID: mdl-38952782

RESUMO

INTRODUCTION: China is the largest tobacco consumer in the world, and tobacco poses a serious threat to the health of pregnant women. However, there are relatively few domestic studies on smoking during pregnancy and childbirth outcomes among pregnant women. The purpose of this study was to analyze the effect of active and passive smoking on pregnant women and their pregnancy outcomes, providing evidence and recommendations for intervention measures. METHODS: This was a cohort study in Shanghai from April 2021 to September 2023. According to the smoking status of pregnant women, they were divided into three groups: active smokers, passive smokers and non-smokers. A self-designed questionnaire was utilized to conduct the survey, and their pregnancy outcomes were tracked and followed up. RESULTS: A total of 3446 pregnant women were included in this study, among which 2.1% were active smokers, 43.5% were passive smokers, and 54.4% were non-smokers. The average age of the pregnant women was 29.9 years, and 41.2% had a university degree or higher. The education level of active smokers and passive smokers was significantly lower than that of non-smokers (p<0.05).The average gestational age of non-smokers was 38.6 weeks, and the birth weight was 3283.2 g, which was higher than those of active smokers and passive smokers (p<0.05). Logistic regression analysis showed that passive smoking increased the likelihood of preterm birth (AOR=1.38; 95% CI: 1.05-1.81), low birth weight (AOR=1.53; 95% CI: 1.10-2.12), and intrauterine growth restriction (AOR=1.35; 95% CI: 1.02-1.79), while active smoking increased the likelihood of preterm birth (AOR=2.98; 95% CI: 1.50-5.90), low birth weight (AOR=4.29; 95% CI: 2.07-8.88), intrauterine growth restriction (AOR=2.70; 95% CI: 1.37-5.33) , and birth defects (AOR=2.66; 95% CI: 1.00-6.97). CONCLUSIONS: Our findings illustrate that active and passive smoking can lead to adverse pregnancy outcomes. This study provides data on the relationship between smoking during pregnancy and delivery outcomes among pregnant women. In the future, we need more effective strategies to protect pregnant women from the harm of tobacco.

9.
JMIR Serious Games ; 12: e55785, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083796

RESUMO

BACKGROUND: Serious games (SGs) are nonpharmacological interventions that are widely applied among older adults. To date, no evidence has been published regarding the effect of digital SGs on cognitive ability, daily behavioral capacity, or depression in older adults with Alzheimer's disease (AD) and mild cognitive impairment (MCI). OBJECTIVE: This study aimed to assess the effect of SGs on older adults with AD and MCI by summarizing and pooling the results of previous studies. METHODS: This meta-analysis examined the effectiveness of digital SGs in improving cognitive ability, enhancing daily behavioral capacity, and alleviating depression in older adults with AD and MCI. We searched the following databases up to December 31, 2023, to identify relevant high-quality randomized controlled trials (RCTs): PubMed, Embase, Web of Science, Scopus, and Cochrane Library. Stata 15.1 and Review Manager 5.3 were used to screen the 14 studies, extract data, code the data, and perform meta-analysis. Mean differences and standardized mean differences (SMDs) with 95% CIs were used to calculate continuous variables. The Cochrane risk-of-bias assessment tool was used to evaluate the risk of bias. Eligibility criteria were developed in accordance with the Population, Intervention, Comparison, Outcomes, and Study Design framework: (1) population (older adults with AD and MCI), (2) intervention (digital SG intervention), (3) comparison (digital SG intervention vs routine health care), (4) outcomes (cognitive ability, daily behavioral capacity, and depression), and (5) study or research design (RCT). Sensitivity analysis was performed, and a funnel plot was constructed. RESULTS: From January 2017 to December 2023, we enrolled 714 individuals across 14 RCTs, with 374 (52.4%) in the severe game group using digital SGs and 340 (47.6%) in the control group using traditional methods. The results of our meta-analysis indicated that using digital SGs in older adults with AD and MCI is more effective than traditional training methods in several key areas. Specifically, digital SG therapy significantly increased cognitive ability, as found in the Mini-Mental State Examination (SMD 2.11, 95% CI 1.42-2.80; P<.001) and the Montreal Cognitive Assessment (SMD 2.75, 95% CI 1.98-3.51; P<.001), significantly increased daily behavioral capacity (SMD 0.53, 95% CI 0.06-0.99; P=.03), and significantly reduced depression (SMD -2.08, 95% CI -2.94 to -1.22; P<.001) in older adults with AD and MCI. No publication bias was detected based on the results of Begg and Egger tests. CONCLUSIONS: Digital SGs offer a viable and effective nonpharmacological approach for older adults with AD and MCI, yielding better results compared to traditional formats. However, caution is warranted in interpreting these findings due to limited RCTs, small sample sizes, and low-quality meta-analyzed evidence. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews: CRDCRD42023486090; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=486090.

10.
Fish Shellfish Immunol ; 151: 109750, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38969153

RESUMO

The largemouth bass has become one of the economically fish in China, according to the latest China Fishery Statistical Yearbook. The farming scale is constantly increasing. Salidroside has been found in past studies to have oxidative stress reducing and immune boosting properties. In this study, the addition of six different levels of salidroside supplements were 0、40、80、120、160 and 200 mg/kg. A 56-day feeding trial was conducted to investigate the effects of salidroside on the intestinal health, immune parameters and intestinal microbiota composition of largemouth bass. Dietary addition of salidroside significantly affected the Keap-1ß/Nrf-2 pathway as well as significantly increased antioxidant enzyme activities resulting in a significant increase in antioxidant capacity of largemouth bass. Dietary SLR significantly reduced feed coefficients. The genes related to tight junction proteins (Occludin, ZO-1, Claudin-4, Claudin-5) were found to be significantly upregulated in the diet supplemented with salidroside, indicating that salidroside can improve the intestinal barrier function (p < 0.05). The dietary administration of salidroside was found to significantly reduce the transcription levels of intestinal tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) (p < 0.05). Furthermore, salidroside was observed to reduce the transcription levels of intestinal apoptosis factor Bcl-2 associated death promoter (BAD) and recombinant Tumor Protein p53 (P53) (p < 0.05). Concomitantly, the beneficial bacteria, Fusobacteriota and Cetobacterium, was significantly increased in the SLR12 group, while that of pathogenic bacteria, Proteobacteria, was significantly decreased (p < 0.05). In conclusion, the medium-sized largemouth bass optimal dosage of salidroside in the diet is 120mg/kg-1.


Assuntos
Ração Animal , Bass , Dieta , Suplementos Nutricionais , Microbioma Gastrointestinal , Glucosídeos , Fenóis , Animais , Bass/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Ração Animal/análise , Dieta/veterinária , Suplementos Nutricionais/análise , Glucosídeos/administração & dosagem , Glucosídeos/farmacologia , Fenóis/administração & dosagem , Fenóis/farmacologia , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Intestinos/microbiologia , Imunidade Inata/efeitos dos fármacos , Relação Dose-Resposta a Droga , Distribuição Aleatória
11.
Langmuir ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034851

RESUMO

The guiding pattern in the chemoepitaxially directed self-assembly (DSA) of block copolymers is often fabricated by periodically functionalizing homogeneously random copolymer brushes tethered on a substrate. The prepatterned copolymer brushes constitute a soft penetrable surface, and their two components can in principle locally segregate in response to the overlying self-assembly process of block copolymers. To reveal how the self-responsive behavior of the copolymer brushes affects the directing effect, we develop a dissipative particle dynamics model to explicitly include the prepatterned polymer brushes and implement it to simulate the DSA of a cylinder-forming diblock copolymer melt on the sparse pattern of polymer brushes. Through large-scale dynamic simulations, we identify the windows of the content of the random copolymer, the film thickness, and the diameter of the patterned spot, for the formation of perfectly ordered hexagonal patterns composed of perpendicular cylinders. Our dynamic simulations reveal that the random copolymer brushes grafted on the unpatterned area exhibit a remarkable self-responsive ability with respect to the self-assembly of the diblock copolymers overlying them, which may widen the effective window of the content of the random copolymer. Within the processing windows of these key parameters, defect-free patterns are successfully achieved both in simulations and in experiments with sizes as large as a few micrometers for 4-fold density multiplications. This work demonstrates that highly efficient computer simulations based on an effective model can provide helpful guidance for experiments to optimize the critical parameters and even may promote the application of DSA.

12.
Plant Biotechnol J ; 22(11): 3085-3098, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39037027

RESUMO

As an essential macronutrient, phosphorus (P) is often a limiting nutrient because of its low availability and mobility in soils. Drought is a major environmental stress that reduces crop yield. How plants balance and combine P-starvation responses (PSRs) and drought resistance is unclear. In this study, we identified the transcription factor ZmPHR1 as a major regulator of PSRs that modulates phosphate (Pi) signaling and homeostasis. We found that maize zmphr1 mutants had reduced P concentration and were sensitive to Pi starvation, whereas ZmPHR1-OE lines displayed elevated Pi concentration and yields. In addition, 57% of PSR genes and nearly 70% of ZmPHR1-regulated PSR genes in leaves were transcriptionally responsive to drought. Under moderate and early drought conditions, the Pi concentration of maize decreased, and PSR genes were up-regulated before drought-responsive genes. The ZmPHR1-OE lines exhibited drought-resistant phenotypes and reduced stomatal apertures, whereas the opposite was true of the zmphr1 mutants. ZmPT7-OE lines and zmspx3 mutants, which had elevated Pi concentration, also exhibited drought resistance, but zmpt7 mutants were sensitive to drought. Our results suggest that ZmPHR1 plays a central role in integrating Pi and drought signals and that Pi homeostasis improves the ability of maize to combat drought.


Assuntos
Secas , Regulação da Expressão Gênica de Plantas , Homeostase , Fosfatos , Proteínas de Plantas , Zea mays , Zea mays/genética , Zea mays/metabolismo , Zea mays/fisiologia , Fosfatos/metabolismo , Fosfatos/deficiência , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Mutação , Estresse Fisiológico/genética , Folhas de Planta/metabolismo , Folhas de Planta/genética , Folhas de Planta/fisiologia , Resistência à Seca
13.
Nutrients ; 16(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38892543

RESUMO

Long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of omega-3 fatty acid levels on CHD risk remains a subject of debate. Here, we aimed to investigate the association between n-3 PUFA levels and the risk of CHD, with particular reference to the subtypes of n-3 PUFA. METHODS: Prospective studies and retrospective case-control studies analyzing n-3 PUFA levels in CHD, published up to 30 July 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n-3 PUFA exposure interval on the CHD subtype variables of the study. RESULTS: We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n-3 PUFAs were measured. Higher levels of n-3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n-3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n-3 PUFA levels compared to healthy controls (p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n-3 PUFA (EPA + DHA) levels. Also, the link between n-3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools. CONCLUSIONS: n-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n-3 PUFAs on CHD.


Assuntos
Doença das Coronárias , Ácidos Graxos Ômega-3 , Estudos Observacionais como Assunto , Humanos , Ácidos Graxos Ômega-3/sangue , Doença das Coronárias/sangue , Doença das Coronárias/prevenção & controle , Doença das Coronárias/epidemiologia , Feminino , Estudos Retrospectivos , Masculino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Estudos Prospectivos , Suplementos Nutricionais , Idoso , Fatores de Risco
14.
Int J Mol Sci ; 25(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38791445

RESUMO

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it is reported that Westernized diet and lifestyle play a significant role in its higher incidence and rapid progression. The intake of high amounts of omega-6 (n - 6) PUFAs and low levels of omega-3 (n - 3) PUFAs has an important role in chronic inflammation and cancer progression, which could be associated with the increase in CRC prevalence. Oxylipins generated from PUFAs are bioactive lipid mediators and have various functions, especially in inflammation and proliferation. Carcinogenesis is often a consequence of chronic inflammation, and evidence has shown the particular involvement of n - 6 PUFA arachidonic acid-derived oxylipins in CRC, which is further described in this review. A deeper understanding of the role and metabolism of PUFAs by their modifying enzymes, their pathways, and the corresponding oxylipins may allow us to identify new approaches to employ oxylipin-associated immunomodulation to enhance immunotherapy in cancer. This paper summarizes oxylipins identified in the context of the initiation, development, and metastasis of CRC. We further explore CRC chemo-prevention strategies that involve oxylipins as potential therapeutics.


Assuntos
Neoplasias Colorretais , Inflamação , Oxilipinas , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/patologia , Oxilipinas/metabolismo , Inflamação/metabolismo , Animais , Ácidos Graxos Ômega-6/metabolismo , Ácidos Graxos Ômega-6/uso terapêutico
16.
Opt Express ; 32(4): 5022-5030, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439239

RESUMO

Metasurfaces, composed by metals and dielectrics in periodical order with subwavelength pitches, are of great importance for their unique ability to abruptly manipulate optical fields. So far, all the reported metasurfaces are constructed by thermally deposited metals and dielectric films, based on semiconductor processes which are expensive and time-consuming. Inspired by the outstanding dry etch property of spin-on-carbon (SOC) as the interlayer material in CMOS technology, this paper proposes to utilize the SOC as the dielectric layer in a chessboard metasurface with dual layer of gold to form an array of local surface plasmonic resonators (localized surface plasmon resonance). Finite difference and time domain (FDTD) method is used to investigate the spectral characteristics in reflectance of the metasurface in both visible and short wavelengths of infrared light. Electron beam lithography is applied to generate the nanoscale chessboard pattern on ZEP520A, followed by a conventional oxygen-based plasma etch to form high aspect ratio nanopillar arrays in SOC with the feature width under 50 nm, and ended by a thermal deposition of gold to form self-aligned dual layer local surface plasmonic resonators (LSPRs). The measured reflectance spectra agree with the simulated. A wealth of optical properties, such as coupling induced modulations of spectra by LSPRs, are revealed and analyzed. These special modes result in tunable structural colors and wavelength-selective antireflection ability. To the best of our knowledge, this is the first time that SOC is applied in the construction of metasurfaces, which has great potential for next generation nanophotonic devices.

17.
Int J Mol Med ; 53(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38390952

RESUMO

Calcium overload, a notable instigator of acute pancreatitis (AP), induces oxidative stress and an inflammatory cascade, subsequently activating both endogenous and exogenous apoptotic pathways. However, there is currently lack of available pharmaceutical interventions to alleviate AP by addressing calcium overload. In the present study, the potential clinical application of liposome nanoparticles (LNs) loaded with 1,2­bis(2­aminophenoxy)ethane­N,N,N',N'­tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA­AM), a cell­permeant calcium chelator, was investigated as a therapeutic approach for the management of AP. To establish the experimental models in vitro, AR42J cells were exposed to high glucose/sodium oleate (HGO) to induce necrosis, and in vivo, intra­ductal taurocholate (TC) infusion was used to induce AP. The findings of the present study indicated that the use of BAPTA­AM­loaded LN (BLN) effectively and rapidly eliminated excessive Ca2+ and reactive oxygen species, suppressed mononuclear macrophage activation and the release of inflammatory cytokines, and mitigated pancreatic acinar cell apoptosis and necrosis induced by HGO. Furthermore, the systemic administration of BLN demonstrated promising therapeutic potential in the rat model of AP. Notably, BLN significantly enhanced the survival rates of rats subjected to the TC challenge, increasing from 37.5 to 75%. This improvement was attributed to the restoration of pancreatic function, as indicated by improved blood biochemistry indices and alleviation of pancreatic lesions. The potential therapeutic efficacy of BLN in rescuing patients with AP is likely attributed to its capacity to inhibit oxidative stress, prevent premature activation of zymogens and downregulate the expression of TNF­α, IL­6 and cathepsin B. Thus, BLN demonstrated promising value as a novel therapeutic approach for promptly alleviating the burden of intracellular Ca2+ overload in patients with AP.


Assuntos
Ácido Egtázico/análogos & derivados , Pancreatite , Humanos , Ratos , Animais , Pancreatite/metabolismo , Lipossomos/metabolismo , Cálcio/metabolismo , Doença Aguda , Células Acinares/patologia , Necrose/metabolismo
18.
J Affect Disord ; 351: 211-219, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38244793

RESUMO

OBJECTIVE: Childhood trauma (CT) is a major environmental risk factor for an adverse course and treatment outcome of major depressive disorder (MDD). Evidence suggests that an altered regional brain activity may play a crucial role in the relationship between CT and MDD. This study aimed to clarify the relationship between CT, regional brain activity, and depression severity. METHODS: In this study, 96 patients with MDD and 82 healthy controls (HCs) participated. Regional brain activity was measured using the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). These measures were compared between the MDD and HC groups, and the values of different brain regions were extracted as moderators. RESULTS: Increased fALFF and ReHo values were observed in the left middle temporal gyrus in the MDD group compared with the HC group (p < 0.001). Furthermore, the fALFF and ReHo values moderated the positive correlation between the Childhood Trauma Questionnaire (CTQ) score, 17-item Hamilton Depression Rating Scale (HAMD-17) total score, and retardation factor score in the MDD group (all, p < 0.05). Finally, as the fALFF and ReHo values increased, the positive correlations between CTQ, HAMD-17 total, and retardation dimension scores became stronger. CONCLUSION: Our study highlighted the crucial role of altered brain function in connecting childhood maltreatment with depressive symptoms. Our findings indicate that an altered regional brain activity could explain the potential neurobiological mechanisms of MDD symptoms, offering the opportunity to function as a powerful diagnostic biomarker.


Assuntos
Experiências Adversas da Infância , Transtorno Depressivo Maior , Testes Psicológicos , Autorrelato , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Depressão , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem
19.
J Affect Disord ; 349: 394-399, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38211748

RESUMO

BACKGROUND: There have been many studies on the benefits of repeated ketamine infusions on patients' depression but few on the impact of ketamine on patients' long-term quality of life (QoL). This study investigated long-term QoL in individuals with depression, both anxious and nonanxious. METHODS: A total of 107 individuals with a diagnosis of depression were included in the study. The patients were evaluated on Days 0, 13 and 26 and Months 6 and 9, and they received six ketamine infusions over the course of two weeks. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) Scale and the Patient Health Questionnaire-9 (PHQ-9) Scale were used to measure depressive symptoms and QoL. Linear mixed models were used to evaluate depressive symptoms and QoL during ketamine treatment. RESULTS: A total of 67.2 % of patients were diagnosed with anxious depression. In the long term, there were no significant differences in the time-by-group interactions for general QoL (F = 0.510; P = 0.676), physical QoL (F = 2.092; P = 0.102), psychological QoL (F = 0.102; P = 0.959), social QoL (F = 2.180; P = 0.091), or environmental QoL (F = 1.849; P = 0.139) between the two groups. LIMITATIONS: The main limitation of this study is its open-label design. CONCLUSION: The improvement in depression symptoms and QoL following ketamine treatment was not impacted by the presence or absence of anxiety in patients who were depressed prior to treatment. Only occasionally did depressed individuals with anxiety experience a worsening of their quality of life compared to those without anxiety.


Assuntos
Ketamina , Humanos , Ketamina/efeitos adversos , Depressão/tratamento farmacológico , Qualidade de Vida/psicologia , Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Infusões Intravenosas
20.
Front Public Health ; 11: 1259250, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38146476

RESUMO

Introduction: We aimed to estimate the effect of mindfulness therapy on mental health. Methods: Two researchers searched 12 databases to identify relevant trials that were published from 1 January 2018 to 1 May 2023. We performed a meta-analysis to determine the effect of mindfulness therapy on depression, which was measured by the Beck Depression Inventory (BDI), Patient Health Questionnaire-9 (PHQ-9), Quick Inventory of Depressive Symptomatology (QIDS), Hamilton Depression Rating Scale (HDRS), Patient-Reported Outcomes Measurement Information System (PROMIS), Hospital Anxiety and Depression Scale (HADS), and Depression Anxiety Stress Scales (DASS); anxiety, which was measured by the Beck Anxiety Inventory (BAI), PROMIS, and DASS, Generalized Anxiety Disorder-7 (GAD-7); stress, which was measured by the Perceived Stress Scale (PSS), DASS, and GAD-7; mindfulness, which was measured by the GAD-7, Five Facet Mindfulness Questionnaire (FFMQ), Mindful Attention Awareness Scale (MAAS), Short Form-12 Mental Component Score (SF-12 MCS) and Short Form-12 Physical Component Score (SF-12 PCS); and sleep quality, which was measured by the Pittsburgh Sleep Quality Index (PSQI). After screening studies based on the inclusion and exclusion criteria, 11 randomized controlled trials (RCTs) involving 1,824 participants were ultimately included. Results: All these studies demonstrated positive effects of mindfulness therapy on depression (SMD = -0.33, 95% CI: [-0.44, -0.22], p < 0.00001, I2 = 29%), anxiety (SMD = -0.35, 95% CI: [-0.46, -0.25], p < 0.00001, I2 = 40%), stress (SMD = -0.39, 95% CI: [-0.48, -0.29], p < 0.00001, I2 = 69%) and sleep quality scores (SMD = -0.81, 95% CI: [-1.54, -0.09], p = 0.03, I2 = 0%). However, there was no significant difference in mindfulness (SMD = -0.12, 95% CI: [-0.36, -0.12], p = 0.34, I2 = 34%) between the mindfulness therapy group and the control group. Discussion: In future studies, it is necessary to consider the investigation on whether the strategies of improving the mindfulness therapy in adherence and fidelity can work on the improvement of the outcomes in mental health. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42023469301].


Assuntos
Atenção Plena , Humanos , Saúde Mental , Universidades , Depressão/terapia , Estudantes , Ensaios Clínicos Controlados Aleatórios como Assunto
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