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1.
Front Med (Lausanne) ; 11: 1389040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957305

RESUMO

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

2.
Ecotoxicol Environ Saf ; 282: 116703, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38986335

RESUMO

3-methyl-4-nitrophenol (PNMC), a degradation product of organophosphorus insecticides and a byproduct of fuel combustion, exerting endocrine-disrupting effects. However, its impact on the meiotic process of oocytes remains unclear. In the present study, we investigated the effects of PNMC on meiotic maturation of mouse oocytes in vitro and related mechanisms. Morphologically, PNMC-exposure affected germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Proteomic analysis suggested that PNMC-exposure altered oocyte protein expression that are associated with cytoskeleton, mitochondrial function and oxidative stress. Further studies demonstrated that PNMC-exposure disrupted spindle assembly and chromosome alignment, caused sustained activation of spindle assembly checkpoint (SAC), and arrested meiosis in oocytes. Specifically, PNMC-exposure interfered with the function of microtubule organizing centers (MTOCs) by significantly reducing phosphorylated mitogen activated protein kinase (p-MAPK) expression and disrupting the localization of Pericentrin and p-Aurora A, leading to spindle assembly failure. Besides, PNMC-exposure also increased α-tubulin acetylation, decreased microtubule stability. Moreover, PNMC-exposure impaired mitochondrial function, evidenced by abnormal mitochondrial distribution, decreased mitochondrial membrane potential and ATP levels, release of Cytochrome C into the cytoplasm, and elevated ROS levels. As a result, exposure to PNMC caused DNA damage and early apoptosis in oocytes. Fortunately, melatonin was able to promote oocyte maturation by removing the excessive ROS and enhancing mitochondrial function. These results highlight the adverse effects of PNMC on meiotic maturation, and underscore the protective role of melatonin against PNMC-induced damage.

3.
Nanomedicine (Lond) ; : 1-13, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016060

RESUMO

Aim: To evaluate a liposome complex conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for the treatment of pre-eclampsia (PE). Methods: In in vitro experiments, the transfection rate, silencing effect and cytotoxicity were determined. In the in vivo PE model, the siRNA distribution, mean arterial pressure, 24-h urine protein concentration, serum sFlt1 concentration, number of viable fetuses and placental weight were measured. Results: The nanomedicine effectively reduced the expression of sFIt1 and had a strong ability to target placental tissues. It could significantly reduce the symptoms of pre-eclampsia and improve pregnancy outcomes in PE model rats. Conclusion: The constructed nanomedicine can improve pregnancy outcomes in a rat model of pre-eclampsia and provides a new strategy for the treatment of pre-eclampsia.


[Box: see text].

4.
Front Pharmacol ; 15: 1339153, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841368

RESUMO

Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, Tripterygium wilfordii poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.

5.
Heliyon ; 10(11): e32466, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38933958

RESUMO

Sirtuin 5 (Sirt5), a member of the Sirtuin family, is involved in various intracellular biological processes. However, the function of Sirt5 in oocyte maturation has not been clearly elucidated. In this study, we observed that Sirt5 was persistently expressed during the meiotic division of mouse oocytes, with a notable decline in expression in aging oocytes. Sirt5 inhibition led to the failure of the first polar body extrusion and induced cell cycle arrest, indicative of unsuccessful oocyte maturation. Furthermore, Sirt5 inhibition was associated with the extrusion of abnormally large polar bodies, suggesting disrupted asymmetric oocyte division. Mechanistically, the inhibition of Sirt5 resulted in aberrant spindle assembly and disordered chromosome alignment in oocytes. Moreover, Sirt5 inhibition caused the spindle to be centrally located in the oocyte without migrating to the cortical region, consequently preventing the formation of the actin cap. Further investigation revealed that Sirt5 inhibition notably diminished the expression of phosphorylated cofilin and profilin1, while increasing cytoplasmic F-actin levels. These findings suggest that Sirt5 inhibition during oocyte maturation adversely affects spindle assembly and chromosome alignment and disrupts actin dynamics impairing spindle migration and contributing to the failure of symmetric oocyte division and maturation.

6.
Sci Rep ; 14(1): 14460, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914679

RESUMO

Genomic instability (GI) was associated with tumorigenesis. However, GI-related lncRNA signature (GILncSig) in lung adenocarcinoma (LUAD) is still unknown. In this study, the lncRNA expression data, somatic mutation information and clinical survival information of LUAD were downloaded from The Cancer Genome Atlas (TCGA) and performed differential analysis. Functional and prognosis analysis revealed that multiple GI-related pathways were enriched. By using univariate and multivariate Cox regression analysis, 5 GI-associated lncRNAs (AC012085.2, FAM83A-AS1, MIR223HG, MIR193BHG, LINC01116) were identified and used to construct a GILncSig model. Mutation burden analysis indicated that the high-risk GI group had much higher somatic mutation count and the risk score constructed by the 5 GI-associated lncRNAs was an independent predictor for overall survival (OS) (P < 0.05). Overall, our study provides valuable insights into the involvement of GI-associated lncRNAs in LUAD and highlights their potential as therapeutic targets.


Assuntos
Adenocarcinoma de Pulmão , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Instabilidade Genômica , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Prognóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Feminino , Perfilação da Expressão Gênica , Pessoa de Meia-Idade
7.
Int J Mol Sci ; 25(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38928291

RESUMO

The process of aging inevitably leads to an increase in age-related comorbidities, including chronic kidney disease (CKD). In many aspects, CKD can be considered a state of accelerated and premature aging. Aging kidney and CKD have numerous common characteristic features, ranging from pathological presentation and clinical manifestation to underlying mechanisms. The shared mechanisms underlying the process of kidney aging and the development of CKD include the increase in cellular senescence, the decrease in autophagy, mitochondrial dysfunction, and the alterations of epigenetic regulation, suggesting the existence of potential therapeutic targets that are applicable to both conditions. In this review, we provide a comprehensive overview of the common characteristics between aging kidney and CKD, encompassing morphological changes, functional alterations, and recent advancements in understanding the underlying mechanisms. Moreover, we discuss potential therapeutic strategies for targeting senescent cells in both the aging process and CKD.


Assuntos
Envelhecimento , Senescência Celular , Epigênese Genética , Rim , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/etiologia , Envelhecimento/patologia , Rim/patologia , Rim/metabolismo , Animais , Mitocôndrias/metabolismo , Mitocôndrias/genética , Mitocôndrias/patologia , Autofagia
8.
J Oral Microbiol ; 16(1): 2362313, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835338

RESUMO

Background: Burning mouth syndrome (BMS) is a chronic idiopathic facial pain with intraoral burning or dysesthesia. BMS patients regularly suffer from anxiety/depression, and the association of psychiatric symptoms with BMS has received considerable attention in recent years. The aims of this study were to investigate the potential interplay between psychiatric symptoms and BMS. Methods: Using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS) to evaluate the oral microbiota and saliva metabolism of 40 BMS patients [including 29 BMS patients with depression or anxiety symptoms (DBMS)] and 40 age matched healthy control (HC). Results: The oral microbiota composition in BMS exhibited no significant differences from HC, although DBMS manifested decreased α-diversity relative to HC. Noteworthy was the discernible elevation in the abundance of proinflammatory microorganisms within the oral microbiome of individuals with DBMS. Parallel findings in LC/MS analyses revealed discernible disparities in metabolites between DBMS and HC groups. Principal differential metabolites were notably enriched in amino acid metabolism and lipid metabolism, exhibiting associations with infectious and immunological diseases. Furthermore, the integrated analysis underscores a definitive association between the oral microbiome and metabolism in DBMS. Conclusions: This study suggests possible future modalities for better understanding the pathogenesis and personalized treatment plans of BMS.

9.
Opt Express ; 32(12): 21374-21388, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859492

RESUMO

To distinguish the contributions of electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) in their applications in precision laser spectroscopy, we propose a real-imaginary spectrum decomposition method to investigate the transparency spectra in a four-level microwave (MW) dressed Rydberg system. We show that the opening transparency windows in the absorption spectra of probe field is a prominent character by EIT, EIT-ATS crossover, and ATS when the MW field is turned off and the intensity of the control field is adjusted. When the MW field is turned on and gradually increased, the EIT is destroyed and disappears. In addition, the most prominent characters that open a transparency window are the EIT-ATS crossover and the ATS. Then, if we further increase the intensity of the MW field, we find that the transparency windows open mainly due to the ATS. Compared to the previous considerations of this issue, which were limited to three-level systems, our four-level scheme reported here is useful for understanding the features of quantum interference in multilevel atomic systems, and has potential applications to study enhanced sensitivity, measurement spectroscopic, quantum processing, quantum communication, and transmission.

10.
Vasc Med ; : 1358863X241252370, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860436

RESUMO

BACKGROUND: To date, PCSK9 inhibitors are well known for eliminating cardiac and cerebral artery ischemia events by lowering the serum lipid level. However, the pathophysiological value of in-plaque PCSK9 expression is still unclear. METHODS: Advanced plaques removed by carotid endarterectomy were sectioned and stained to identify the PCSK9 expression pattern and its co-expression with rupture-relevant markers. To investigate the correlation of PCSK9 expression with regional blood shear flow, hemodynamic characteristics were analyzed using computational fluid dynamics, and representative parameters were compared between PCSK9 positive and negative staining plaques. To explore this phenomenon in vitro, human aortic vascular smooth muscle cells were used to overexpress and knock down PCSK9. The impacts of PCSK9 modulations on mechanical sensor activity were testified by western blot and immunofluorescence. Real-time polymerase chain reaction was used to evaluate the transcription levels of downstream rupture-prone effectors. RESULTS: PCSK9 distribution in plaque preferred cap and shoulder regions, residing predominantly in smooth muscle actin-positive cells. Cap PCSK9 expression correlated with fibrous cap thickness negatively and co-expressed with MMP-9, both pointing to the direction of plaque rupture. A hemodynamic profile indicated a rupture-prone feature of cap PCSK9 expression. In vitro, overexpression and knockdown of PCSK9 in human aortic vascular smooth muscle cells has positive modulation on mechanical sensor Yes-associated protein 1 (YAP) activity and transcription levels of its downstream rupture-prone effectors. Serial section staining verified in situ colocalization among PCSK9, YAP, and downstream effectors. CONCLUSIONS: Cap PCSK9 possesses a biomarker for rupture risk, and its modulation may lead to a novel biomechanical angle for plaque interventions.

11.
Neurourol Urodyn ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860474

RESUMO

AIM: To develop a conceptual framework for proactive health behavior among middle-aged and older adult females with urinary incontinence. DESIGN: Qualitative grounded theory study. BACKGROUND: There is a growing body of research emphasizing the pivotal significance of proactive health behavior. Proactive health behavior can empower patients to actively manage their illnesses and facilitate disease recovery. Clearly defining patients' relevant beliefs and assumptions regarding proactive health behavior can effectively promote their adoption. However, there is currently a lack of relevant research in this area. METHODS: We conducted in-depth interviews with middle-aged and older adult females with urinary incontinence (n = 17) and nursing caregivers (n = 9). We used theoretical sampling, whlie conducting continuous comparative analysisi and data collection. RESULTS: The study has yielded a substantive theory to facilitate healthcare professionals' comprehension of proactive health behavior in middle-aged and older adult females with urinary incontinence. The foundation for middle-aged and older adult females to adopt proactive health behavior is having a certain level of health literacy regarding their conditions. Patients' internal motivation to engage in proactive health behavior includes a sense of health responsibility and health demands. Additionally, external support received by patients can also facilitate their adoption of proactive health behavior. The proactive health behavior practices of middle-aged and older adult females mainly include proactive medical care behavior and establishing a healthy lifestyle. CONCLUSIONS: The conceptual framework established in this study offers theoretical support for middle-aged and older adult females with urinary incontinence to adopt proactive health behavior. It provides a basis for future exploration of proactive health behavior among this demographic and informs the development of more effective health interventions and support measures tailored to their needs. IMPACT: The study specifically elucidates the mechanisms and manifestations of proactive health behavior adopted by middle-aged and older adult females with urinary incontinence, laying the foundation for clarifying the level of proactive health among patients and implementing corresponding intervention measures. Additionally, it can also serve as a reference for related research on other diseases.

12.
Small ; : e2401681, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38923771

RESUMO

Perovskite is an emerging material with immense potential in the field of optoelectronics. 1D perovskite nanowires are crucial building blocks for the development of optoelectronic devices. However, producing perovskite nanowires with high quality and controlled alignment is challenging. In this study, the direct epitaxial growth of perovskite on oriented carbon nanotube (CNT) templates is presented through a chemical vapor deposition method. The deposition process of lead iodide and methylammonium iodide is systematically investigated, and a layer plus island growth mechanism is proposed to interpret the experimental observations. The aligned long CNTs serve as 1D templates and allow the growth of CNT@perovskite core-shell heterostructure with a high aspect ratio to withstand large deformation. The obtained 1D perovskite materials can be easily manipulated and transferred, enabling the facile preparation of microscale flexible devices. For proof of concept, a photodetector based on an individual CNT@methylammonium lead iodide heterostructure is fabricated. This work provides a new approach to prepare 1D hetero-nanostructure and may inspire the design of novel flexible nanophotodetectors.

13.
Colloids Surf B Biointerfaces ; 241: 114053, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38924849

RESUMO

The integration of immunotherapy and standard chemotherapy holds great promise for enhanced anticancer effects. In this study, we prepared a pH- and glutathione (GSH)-sensitive manganese-doped mesoporous silicon (MMSNs) based drug delivery system by integrating paclitaxel (PTX) and anti-programmed cell death-ligand 1 antibody (aPD-L1), and encapsulating with polydopamine (PDA) for chemoimmunosynergic treatment of ovarian cancer cells. The nanosystem was degraded in response to the tumor weakly acidic and reductive microenvironment. The Mn2+ produced by degradation can be used as a contrast agent for magnetic resonance (MR) imaging to provide visual exposure to tumor tissue. The released PTX can not only kill tumor cells directly, but also induce immunogenic death (ICD) of tumor cells, which can play a synergistic therapeutic effect with aPD-L1. Therefore, our study is expected to provide a promising strategy for improving the efficacy of cancer immunotherapy and the detection rate of cancer.

14.
PLoS One ; 19(6): e0305980, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917102

RESUMO

BACKGROUND: Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general anesthesia in patients with PIH undergoing laparoscopic cholecystectomy. METHODS: This prospective study included 557 adult patients who underwent laparoscopic cholecystectomy under general anesthesia. PIH was defined as a greater than 20% decrease in systolic blood pressure from the pre-induction value, a systolic arterial pressure of less than 90 mmHg, or both. Plasma concentrations of epinephrine and norepinephrine during the induction of general anesthesia were determined using enzyme-linked immunosorbent assay. Multivariate logistic regression analysis evaluated the association between the clinical factors and PIH. RESULTS: Of the 557 patients, 390 had PIH, and the remaining 167 were allocated to the non-PIH group. Changes in blood adrenaline, noradrenaline levels, or both were more pronounced in the PIH than in the non-PIH group (p<0.05). Age, body mass index, a history of hypertension, preoperative systolic blood pressure, and propofol or sufentanil dose were independent predictors of PIH. CONCLUSION: The changes of blood catecholamines in patients with more stable hemodynamics during the induction of general anesthesia are smaller than that in patients with post-induction hypotension. TRIAL REGISTRATION: ChiCTR2200055549, 12/01/2022.


Assuntos
Anestesia Geral , Catecolaminas , Colecistectomia Laparoscópica , Hipotensão , Humanos , Colecistectomia Laparoscópica/efeitos adversos , Masculino , Feminino , Anestesia Geral/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Hipotensão/sangue , Hipotensão/etiologia , Adulto , Catecolaminas/sangue , Pressão Sanguínea , Idoso , Norepinefrina/sangue , Epinefrina/sangue
15.
Drug Des Devel Ther ; 18: 2215-2225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882049

RESUMO

Objective: While the role of aldosterone in bone metabolism is well established, the specific effects of the widely used aldosterone antagonist, spironolactone, on bone health are not fully understood. This study aimed to investigate the effects of spironolactone on osteoporosis and future fracture risk in middle-aged and elderly hypertensive patients, revealing its potential benefits for bone health. Methods: Propensity score matching was employed in this study to create matched groups of spironolactone users and non-users at a 1:4 ratio. We investigated the association between spironolactone use and the risk of osteoporosis using multivariate logistic regression analysis. Furthermore, we conducted multivariate linear regression analysis to explore the relationship between cumulative dosage and the FRAX score. Subgroup analysis was also performed to assess the effects under different stratification conditions. Results: In both pre-match and post-match analyses, multivariable logistic regression revealed a significant reduction in the risk of osteoporosis in the spironolactone usage group (pre-match: odds ratios [OR] 0.406, 95% confidence interval [CI], 0.280-0.588; post-match: OR 0.385, 95% CI, 0.259-0.571). Furthermore, post-match multivariable linear regression demonstrated a clear negative correlation between cumulative spironolactone dosage and the FRAX score. Subgroup analyses consistently supported these findings. Conclusion: This study offers evidence supporting the significant positive impact of the antihypertensive drug spironolactone on bone health, resulting in a substantial reduction in the risk of osteoporosis and future fractures in hypertensive patients. Future research should consider conducting large-scale, multicenter, randomized controlled trials to further investigate the long-term effects of spironolactone on bone health in hypertensive patients.


Assuntos
Hipertensão , Osteoporose , Espironolactona , Humanos , Espironolactona/uso terapêutico , Espironolactona/farmacologia , Espironolactona/efeitos adversos , Hipertensão/tratamento farmacológico , Osteoporose/tratamento farmacológico , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Fraturas Ósseas/prevenção & controle , Fatores de Risco
16.
Ying Yong Sheng Tai Xue Bao ; 35(4): 1123-1130, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38884247

RESUMO

China has complex natural conditions and is rich in biodiversity. Based on the geographical distribution and species composition of terrestrial mammals, we explored the characteristics and geographic partitioning of mammal populations in different regions of China. We used a clustering algorithm, combined with the spatial distribution data and taxonomic characteristics of mammals, to geographically partition the terrestrial mammals in China. We found 10 zoogeographic regions of terrestrial mammals in China: Northeast region, North China region, Eastern grassland region, Western region, Northwest region, Qiangtang plateau region, Eastern Qinghai-Tibet Plateau region, Himalayan region, South China region, and Taiwan-Hainan region. We found a new geographical zoning pattern for terrestrial mammals in China, examined the variability and characteristics of species composition among different regions, and quantified the association between species distribution and environmental factors. We proposed a method of incorporating taxonomic information into cluster analysis, which provided a new idea for zoogeographic region studies, a new perspective for understanding species diversity, and a scientific basis for animal conservation and habitat planning.


Assuntos
Biodiversidade , Ecossistema , Mamíferos , China , Animais , Mamíferos/classificação , Geografia , Análise por Conglomerados , Conservação dos Recursos Naturais
17.
Artigo em Inglês | MEDLINE | ID: mdl-38852918

RESUMO

BACKGROUND: The sex differences were co-shaped by innate biological differences and social environment, and were frequently observed in human emotional neural responses. Oral administration of oxytocin, as an alternative and noninvasive intake method, has been demonstrated to produce sex-dependent effects on emotional face processing. However, it is unclear whether oral oxytocin produces similar sex-dependent effects on processing continuous emotional scenes. METHODS: Current randomized, double-blind, placebo-controlled neuro-psychopharmacological fMRI experiment was conducted in 147 healthy participants (oxytocin=74, male/female=37/37; placebo=73, male/female=36/37) to examine the oral oxytocin effect on plasma oxytocin concentrations and neural response to emotional scenes in both sexes. RESULTS: At the neuroendocrine level, females showed lower endogenous oxytocin concentrations than males, but oral oxytocin equally increased the oxytocin concentrations in both sexes. Regarding neural activity, emotional scenes evoked opposite valence-independent effects on right amygdala activation (females>males) and its functional connectivity with the insula (males>females) in two sexes in the placebo group. This sex difference were either attenuated (amygdala response) or even completely eliminated (amygdala-insula functional connectivity) in the oxytocin group. The multivariate pattern analysis confirmed these findings by developing an accurate sex-predictive neural pattern that including the amygdala and the insula under the placebo but not oxytocin condition. CONCLUSION: Present study suggests a pronounced sex-difference in neural responses to emotional scenes which is abolished by oral oxytocin, with it having opposite modulatory effects in two sexes. Possibly this may reflect oral OXT enhancing emotional regulation to continuous emotional stimuli in both sexes by facilitating appropriate changes in sex-specific amygdala-insula circuitry.

18.
Vet Parasitol ; 330: 110237, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878462

RESUMO

Cryptosporidium parvum is an important zoonotic pathogen that is studied worldwide. MicroRNAs (miRNAs) act as post-transcriptional regulators and may play a key role in modulating host epithelial responses following Cryptosporidium infection. Our previous study has shown that C. parvum downregulates the expression of miR-181d through the p50-dependent TLRs/NF-κB pathway. However, the mechanism by which miR-181d regulates host cells in response to C. parvum infection remains unclear. The present study found that miR-181d downregulation inhibited cell apoptosis and increased parasite burden in HCT-8 cells after C. parvum infection. Bioinformatics analysis and luciferase reporter assays have shown that BCL2 was a target gene for miR-181d. Moreover, BCL2 overexpression and miR-181d downregulation had similar results. To further investigate the mechanism by which miR-181d regulated HCT-8 cell apoptosis during C. parvum infection, the expression of molecules involved in the intrinsic apoptosis pathway was detected. Bax, caspase-9, and caspase-3 expression was decreased at 4, 8, 12, and 24 hpi and upregulated at 36 and 48 hpi. Interfering with the expression of miR-181d or BCL2 significantly affected the expression of molecules in the intrinsic apoptosis pathway. These data indicated that miR-181d targeted BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to C. parvum infection via the intrinsic apoptosis pathway. These results allowed us to further understand the regulatory mechanisms of host miRNAs during Cryptosporidium infection, and provided a theoretical foundation for the design and development of anti-cryptosporidiosis drugs.

19.
Pestic Biochem Physiol ; 202: 105945, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879302

RESUMO

With the widespread utilization of the sanitizing product benzethonium chloride (BEC) throughout the coronavirus pandemic, concerns have emerged regarding its potential hazards. Nevertheless, the long-term and multigenerational toxic effects of BEC on aquatic organisms remains unexplored. This study investigates acute and chronic toxicity, oxidative stress, mitochondrial membrane potential, ATP concentrations, and gene expression using Daphnia carinata as the model organism. Meanwhile, hierarchical clustering analysis was utilized to investigate phenotypic effects among different treatment groups. The integrated biomarker response index version 2 (IBRv2) was employed to estimate the deviation in toxic effects over two generations. These results indicated that D. carinata in the second generation exhibited higher survival rate and lower levels of oxidative stress than the first generation. However, the higher sublethal effects were found in the second generation as follows, the weakened growth performance, mitochondrial membrane potential depolarization, reduced ATP concentrations, and down-regulated gene expression. The mitochondrial toxicity induced by BEC may account for the distinct toxic effects exhibited in two generations. The findings here can assist with the evaluation of potential risk for BEC on aquatic organisms, and provide new insight into the cross-generational toxicity mechanisms of pollutants in aquatic ecosystems.


Assuntos
Daphnia , Potencial da Membrana Mitocondrial , Estresse Oxidativo , Animais , Daphnia/efeitos dos fármacos , Daphnia/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Poluentes Químicos da Água/toxicidade
20.
J Cell Mol Med ; 28(12): e18440, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38890792

RESUMO

Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.


Assuntos
Vírus da Hepatite B , Hepatite B Crônica , Mitocôndrias , Humanos , Hepatite B Crônica/virologia , Hepatite B Crônica/patologia , Masculino , Feminino , Vírus da Hepatite B/patogenicidade , Adulto , Mitocôndrias/metabolismo , Pessoa de Meia-Idade , Contagem de Leucócitos , Leucócitos/metabolismo , DNA Viral/sangue , Potencial da Membrana Mitocondrial , Monócitos/metabolismo , Monócitos/imunologia , Monócitos/virologia , Monócitos/patologia , Neutrófilos/metabolismo , Neutrófilos/imunologia
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