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1.
Front Public Health ; 12: 1413492, 2024.
Article in English | MEDLINE | ID: mdl-39091524

ABSTRACT

Background: There are limited studies exploring the relationship between physical activity (PA), cognitive function, and the brain processing characteristics in healthy older adults. Methods: A total of 41 participants (42.7 ± 20.5 years, 56.1% males) were included in the data analysis. The International Physical Activity Questionnaire Short Form was used to assess PA levels, and the Chinese version of the Montreal Cognitive Assessment-Basic and the Flanker task were employed to evaluate cognitive function. Furthermore, fMRI technology was utilized to examine brain activation patterns. Results: The cognitive function of the older adults was found to be significantly lower compared to the young adults. Within the older adults, those with high levels of PA exhibited significantly higher cognitive function than those with low and medium PA levels. The fMRI data showed significant differences in brain activation patterns among young adults across the different PA levels. However, such difference was not observed among older adults. Conclusion: A decline in cognitive function was observed among older adults. There was a significant correlation between the levels of PA and cognitive function in healthy older adults. The study demonstrated significant effects of PA levels on brain activation patterns in inhibitory control-related regions among young adults, while not significant among older adults. The findings suggest that neurological mechanisms driving the relationship between PA and cognitive function may differ between older and young adults.


Subject(s)
Cognition , Exercise , Magnetic Resonance Imaging , Humans , Male , Female , Cognition/physiology , Pilot Projects , Exercise/physiology , Adult , Middle Aged , Aged , Brain/physiology , Brain/diagnostic imaging , Surveys and Questionnaires , Young Adult , Age Factors
2.
J Cancer ; 15(14): 4656-4667, 2024.
Article in English | MEDLINE | ID: mdl-39006076

ABSTRACT

Objective: So far, there have been no reports of coumestrol inhibiting colorectal cancer (CRC) through the ferroptosis pathway. This study is to investigate the mechanism of the traditional Chinese medicine monomer coumestrol in the treatment of CRC. Methods: Data on CRC transcriptome sequencing was obtained from the GEO database and TCGA database. Bioinformatics analyses were conducted to screen for CRC prognostic-related key genes and their potential binding monomers in traditional Chinese medicine. The inhibitory effect of coumestrol on CRC cell lines (COLO 205 & HCT 116) was determined using the CCK-8 assay, and cell apoptosis was assessed by flow cytometry. The content of ferrous ions was measured using the Ferrous Ion Content Assay Kit. The expression of ferroptosis pathway-related genes SLC39A8, NCOA4, VDAC2, and NOX2 before and after small interference RNA (siRNA) was examined through real-time PCR and Western blotting. Results: SLC39A8 was found to be associated with CRC clinical progression staging, and its encoded protein ZIP8 may bind to coumestrol. KEGG enrichment analysis suggested that ZIP8 plays a role in iron transmembrane transport and may affect the expression of ferroptosis pathway-related genes NCOA4, VDAC2, and NOX2. Coumestrol was found to induce apoptosis in CRC cell lines by upregulating the expression of ferroptosis pathway-related genes SLC39A8, NCOA4, VDAC2, and NOX2. However, coumestrol was unable to upregulate the expression of ferroptosis pathway-related genes in CRC cell lines after SLC39A8 interference. Conclusion: Coumestrol facilitates apoptosis in CRC cells by interacting with ZIP8 protein via the ferroptosis pathway.

3.
Int Urol Nephrol ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012583

ABSTRACT

PURPOSE: The potential benefits of caffeine intake are currently receiving much attention and exploration. Urine flow rate (UFR) is an objective index to comprehensively reflect bladder function. The aim of this study was to investigate the association between caffeine intake and UFR using the National Health and Nutrition Examination Survey (NHANES) database. METHODS: 14,142 participants were enrolled in this study. Weighted multivariate adjusted regression models were used to explore the relationship between caffeine intake and UFR. The dose-response relationships were explored using a restricted cubic spline (RCS) and a threshold effect analysis was conducted based on the inflection points identified by the two-segment linear regression model. In addition, subgroup analysis and sensitivity analysis were applied. RESULTS: The findings suggested that the intake of caffeine was correlated with improved UFR [Model 3: 0.091 (0.057, 0.126), P value < 0.001]. In addition, the RCS supported a nonlinear relationship between them. The analysis of threshold effect further revealed a specific level of caffeine intake (34.51 mg/day) that exhibited a significant enhancement in UFR. Finally, through re-analyzing the data set obtained after multiple imputation (MI), we obtained similar results. CONCLUSION: This study found a nonlinear beneficial relationship between caffeine intake and UFR, and revealed the recommended intake of caffeine. The values varied by gender, race, education, and smoking status.

4.
Drug Metab Dispos ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960734

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world. Inadequate efficacy of 5-fluorouracil (5-FU) on HCC could be related to low expression of human organic anion transporter 2 (OAT2). However, the knowledge of down-regulation of OAT2 in HCC remains limited. We explored the underlying mechanism focusing on protein expression regulation and attempted to design a strategy to sensitize HCC cells to 5-FU. In this study, we revealed that 1 bp to 300 bp region of OAT2 mRNA 3' untranslated region (UTR) reduced its protein expression and uptake activity in Li-7 and PLC/PRF/5 cells. Mechanistically, it was demonstrated that staphylococcal nuclease and Tudor domain containing 1 (SND1) bound at 1 bp to 300 bp region of OAT2 mRNA 3' UTR, leading to a decrease in OAT2 protein expression. Enrichment analysis results indicated reduction of OAT2 might be mediated by translational inhibition. Furthermore, the knockdown of SND1 up-regulated OAT2 protein expression and uptake activity. Based on it, decreasing SND1 expression enhanced 5-FU-caused G1/S phase arrest in Li-7 and PLC/PRF/5 cells, resulting in suppression of cell proliferation. Besides, the knockdown of SND1 augmented the inhibitory effect of 5-FU on PLC/PRF/5 xenograft tumor growth in vivo by increasing OAT2 protein expression and accumulation of 5-FU in the tumor. Collectively, a combination of inhibition of SND1 with 5-FU might be a potential strategy to sensitize HCC cells to 5-FU from the perspective of restoring OAT2 protein level. Significance Statement We investigated the regulatory mechanism of OAT2 protein expression in HCC cells and designed a strategy to sensitize them to 5-FU (OAT2 substrate) via restoring OAT2 protein level. It found that SND1, an RNA binding protein, regulated OAT2 protein expression by interacting with OAT2 mRNA 3' UTR 1-300bp region. Through decreasing SND1, the anti-tumor effect of 5-FU on HCC was enhanced in vitro and in vivo, indicating that SND1 could be a potential target for sensitizing HCC cells to 5-FU.

5.
Front Public Health ; 12: 1367818, 2024.
Article in English | MEDLINE | ID: mdl-38966706

ABSTRACT

Background: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019. Methods: Data on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0-4, 5-9, 10-14 and 15-19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC. Results: The global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0-4, 5-9, 10-14 and 15-19 years were also associated with the incidences, particularly for the exposures at ages 15-19 years. Conclusion: The global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.


Subject(s)
Colorectal Neoplasms , Global Health , Humans , Incidence , Colorectal Neoplasms/epidemiology , Adolescent , Child , Infant , Child, Preschool , Young Adult , Global Health/statistics & numerical data , Risk Factors , Infant, Newborn , Female , Male , Global Burden of Disease/trends , Age of Onset , Adult
6.
IEEE Trans Biomed Eng ; PP2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968024

ABSTRACT

OBJECTIVE: Brain dynamic effective connectivity (dEC), characterizes the information transmission patterns between brain regions that change over time, which provides insight into the biological mechanism underlying brain development. However, most existing methods predominantly capture fixed or temporally invariant EC, leaving dEC largely unexplored. METHODS: Herein we propose a deep dynamic causal learning model specifically designed to capture dEC. It includes a dynamic causal learner to detect time-varying causal relationships from spatio-temporal data, and a dynamic causal discriminator to validate these findings by comparing original and reconstructed data. RESULTS: Our model outperforms established baselines in the accuracy of identifying dynamic causalities when tested on the simulated data. When applied to the Philadelphia Neurodevelopmental Cohort, the model uncovers distinct patterns in dEC networks across different age groups. Specifically, the evolution process of brain dEC networks in young adults is more stable than in children, and significant differences in information transfer patterns exist between them. CONCLUSION: This study highlights the brain's developmental trajectory, where networks transition from undifferentiated to specialized structures with age, in accordance with the improvement of an individual's cognitive and information processing capability. SIGNIFICANCE: The proposed model consists of the identification and verification of dynamic causality, utilizing the spatio-temporal fusing information from fMRI. As a result, it can accurately detect dEC and characterize its evolution over age.

7.
Mol Diagn Ther ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967864

ABSTRACT

BACKGROUND: There is no consensus regarding the specific genes included in the homologous recombination repair (HRR) gene panel for identifying the HRR deficiency (HRD) status and predicting the prognosis of epithelial ovarian cancer (EOC) patients. OBJECTIVE: We aimed to explore a 15-gene panel involving the HRR pathway as a predictive prognostic indicator in Chinese patients newly diagnosed with EOC. PATIENTS AND METHODS: We reviewed the previously published reports about different HRR gene panels and prespecified the 15-gene panel. The genetic testing results in a 15-gene panel from 308 EOC patients diagnosed between 2014 and 2022 from six centers were collected. The association of clinicopathologic characteristics, the use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and progression-free survival (PFS) with 15-gene panel HRR mutations (HRRm) status was assessed. RESULTS: 43.2% (133/308) of patients were determined to carry 144 deleterious HRRm, among which 68.1% (98/144) were germline mutations and 32.8% (101/308) were BRCA1/2 gene lethal mutations. The hazard ratio (HR) (95% confidence interval, CI) for PFS (HRRm v HRR wild type, HRRwt) using the 15-gene panel HRRm was 0.42 (0.28-0.64) at all stages and 0.42 (0.27-0.65) at stages IIIC-IV. However, a prognostic difference was observed only between the BRCA mutation group and the HRRwt group, not between the non-BRCA HRRm group and the HRRwt group. For the subgroups of patients not using PARPis, the HR (95% CI) was 0.41 (0.24-0.68) at stages IIIC-IV. CONCLUSIONS: This study provides evidence that 15-gene panel HRRm can predict the prognosis of EOC, of these only the BRCA1/2 mutations, not non-BRCA HRRm, contribute to prognosis prediction. Among patients without PARPis, the HRRm group presented a better PFS. This is the first study of this kind in the Chinese population.

8.
Medicine (Baltimore) ; 103(27): e38595, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968523

ABSTRACT

To observe of the effect of electrical stimulation at the back-shu acupoint with extrinsic diaphragmatic pacing (EDP) mode on respiratory function and extubation success rate in tracheostomized stroke patients. A total of 200 patients who underwent tracheostomy after a stroke from January 2022 to February 2023 were included in this study. They were divided into 2 groups based on whether electroacupuncture was used: the EDP + electroacupuncture group and the EDP group. We assessed the differences in cough reflex scores and clinical lung infection scores between the 2 groups, and measured levels of blood gas analysis indicators, diaphragmatic function, lung function, maximum inspiratory pressure, and maximum expiratory pressure in both groups. The total effective rate in the EDP + electroacupuncture group was 91.00% (91/100), which was higher than the EDP group's 80.00% (80/100) (P < .05). After treatment, both groups showed a decrease in clinical lung infection scores and cough reflex scores compared to before treatment, with the EDP + electroacupuncture group having lower scores than the EDP group (P < .05). After treatment, the pH value, arterial oxygen pressure, and oxygenation index all increased compared to before treatment, with the EDP + electroacupuncture group showing higher values than the EDP group (P < .05). After treatment, both groups showed a decrease in arterial carbon dioxide pressure compared to before treatment, with the EDP + electroacupuncture group having lower PaCO2 levels than the EDP group (P < .05). After treatment, both groups showed an increase in forced vital capacity as a percentage of predicted value (FVC%), diaphragm thickness, diaphragm mobility, maximum inspiratory pressure, maximum expiratory pressure, forced expiratory volume in the first second as a percentage of predicted value (FEV1%), and diaphragm contraction speed compared to before treatment. Additionally, the EDP + electroacupuncture group had higher values in these parameters compared to the EDP group (P < .05). The EDP + electroacupuncture group had a shorter average extubation time and a higher extubation success rate compared to the EDP group (P < .05). The combination of EDP mode and electroacupuncture at the back-shu acupoint appears to be effective in improving lung function and diaphragmatic function in tracheostomized stroke patients. It also leads to a shorter extubation time and higher extubation success rates.


Subject(s)
Acupuncture Points , Airway Extubation , Diaphragm , Electroacupuncture , Stroke , Tracheostomy , Humans , Male , Female , Middle Aged , Electroacupuncture/methods , Aged , Airway Extubation/methods , Diaphragm/physiopathology , Stroke/therapy , Tracheostomy/methods , Treatment Outcome , Respiratory Function Tests
9.
Am J Gastroenterol ; 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39051647

ABSTRACT

BACKGROUND AND AIMS: Linear-array endoscopic ultrasound (EUS) and narrow-banding imaging (NBI) are both used to estimate the invasion depth of nonpedunculated rectal lesions (NPRLs). However, it is unclear which procedure is more accurate. This randomized controlled trial aimed to compare the diagnostic accuracy of linear EUS and NBI for estimating the invasion depth of NPRLs. METHODS: This study is a single-center, randomized, tandem trial. Eligible patients with NPRLs were randomly assigned to A group (Assessment with EUS followed by NBI) or B group (Assessment with NBI followed by EUS). The invasion depth of each lesion was independently measured by each procedure and categorized as mucosal to slight submucosal (M-SMs, invasion depth <1000 µm) or deep submucosal (SMd, invasion depth ≥1000 µm) invasion, with postoperative pathology as standard measurement. The primary outcome was diagnostic accuracy, and secondary outcomes included sensitivity, specificity, and procedure time. RESULTS: 86 patients with NPRLs were enrolled and 79 patients were finally analyzed, including 39 cases in the A group and 40 cases in the B group. Comparable diagnostic accuracies were observed between EUS and NBI (96.2% vs. 93.7%, P = 0.625). EUS identified lesions with deep submucosal invasion with 81.8% sensitivity, while that of NBI was 63.6% (P = 0.500). The specificity of both EUS and NBI was 98.5%. The procedure time was also similar between EUS and NBI (5.90 ± 3.44 vs. 6.4 ± 3.94 minutes, P = 0.450). Furthermore, the combined use of EUS and NBI did not improve diagnostic accuracy compared to EUS or NBI alone (94.9% vs 96.2% vs 93.7%, P = 0.333). CONCLUSIONS: Linear EUS and NBI measure the invasion depth of NPRLs with comparable accuracy. The combination of the two methods does not improve the diagnostic accuracy. Single NBI should be preferred, considering its simplicity and convenience in clinical practice.

10.
Reprod Toxicol ; 129: 108671, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39038764

ABSTRACT

Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5 % O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.

11.
Phytomedicine ; 132: 155868, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39032278

ABSTRACT

BACKGROUND: Linderae Radix (LR), the dried root of Lindera aggregata (Sims) Kosterm., is a traditional Chinese herbal medicine that has been used for thousands of years for promoting Qi circulation, soothing the liver, and treating diarrhea and dysentery. Previous studies have found that ethanol extract of LR plays an anti-ulcerative colitis (UC) role by regulating Th17/ Treg balance. Water extract is the classic clinical application form of LR, but the effect of water extract of LR (LRWE) on UC and its underlying mechanism is still unclear. PURPOSE: Purpose: UC is a gastrointestinal disease characterized by intestinal inflammation, mucosal injury, and fibrosis, and it is one of the high-risk factors for colon cancer. However, there is still a lack of remedies with satisfactory effects. This study aimed to investigate the efficacy and the potential mechanism of LRWE against UC. METHODS: LRWE samples were prepared using a reflux extraction method. Colitis in mice was induced by administering 2.5 % DSS water solution to evaluate the therapeutic effect of LRWE by assessing disease activity score, colon length, and fecal morphology. H&E staining, TEM, Masson staining, and AB-PAS staining were applied to observe histopathological changes in the colon tissues. Differentially expressed genes in colon tissues were analyzed by transcriptomics. Cell apoptosis was detected by TUNEL staining. The expression of inflammatory factors such as IL-6 and IL-1ß, as well as the expression of p-STAT1, p-JAK2, p-STAT3, Bax, and Bcl-2, were detected by immunofluorescence and immunohistochemistry. The expression of occludin, Bcl-2, Bax, and JAK/STAT signaling pathway-related vital proteins were quantified by Western blot (WB). RESULTS: LRWE alleviated body weight loss, colon shortening, DAI scores, pathological changes, and ultrastructural features of colon tissue in mice with colitis. It also inhibited the increase of pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1ß) and increased IL-10 levels. Additionally, it protected the intestinal barrier by upregulating the expression of Occludin and Mucin-2. Mechanistically, LRWE could inhibit the activation of JAK-STAT signaling pathway by reducing the protein expression of p-JAK2, p-STAT3, p-STAT1, Bcl2, and Bax, thus reducing the inflammatory responses and inhibiting cell apoptosis. CONCLUSION: LRWE has a protective effect on DSS-induced UC. This effect is related to the inhibition of the JAK-STAT signaling pathway, the improvement of intestinal inflammation, and the reduction of intestinal epithelial cell apoptosis.

12.
Eur J Oncol Nurs ; 71: 102651, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38950499

ABSTRACT

PURPOSE: Fear of cancer recurrence (FCR) is a psychological problem often faced by breast cancer patients in the rehabilitation period. The aim of this study was to identify FCR subgroups of Chinese breast cancer patients in rehabilitation and to analysis the factors affecting each subgroup. The effects of the subgroups on quality of life (QoL) were also explored. METHODS: Cross-sectional data were collected from 300 breast cancer patients in a rehabilitation setting. The researchers invited the subjects to complete questionnaires on FCR, fatigue, anxiety depression, perception of illness and QoL. The researchers conducted a latent profile analysis. The factors influencing the subgroups of FCR were identified using ANOVA and multinomial logistic regression analyses. Linear regression analyses were used to explore the effect of subgroups on QoL. RESULTS: There were three subgroups of FCR: profile 1 'Low FCR Group' (42.3%), profile 2 'Moderate FCR Group' (45.6%), and profile 3 'High FCR Group' (12.1%). Cancer stage II was a protective factor for FCR patients (OR = 0.107, P < 0.01) and was more likely to be categorized among the low FCR group. Anxiety depression was a risk factor for FCR patients and was more likely to be categorized in the medium FCR group (OR = 1.764, P < 0.001) and in the high FCR group (OR = 2.911, P < 0.001). In addition, patients subjected to a high perception of illness were more likely to be considered in the medium FCR group (OR = 1.041, P < 0.05), a risk factor affecting patients with FCR. Linear regression analysis showed that subgroups with higher FCR had a stronger negative predictive effect on their QoL (all P < 0.001). CONCLUSIONS: The FCR was identified as three subgroups among breast cancer patients in rehabilitation, which suggests that healthcare professionals should give full consideration to the impact of cancer stage, anxiety and depression, and illness perceptions on the FCR subgroups in order to improve their QoL.


Subject(s)
Breast Neoplasms , Fear , Neoplasm Recurrence, Local , Quality of Life , Humans , Female , Breast Neoplasms/psychology , Middle Aged , Cross-Sectional Studies , Neoplasm Recurrence, Local/psychology , Adult , China/epidemiology , Surveys and Questionnaires , Aged , Anxiety/epidemiology , Depression/epidemiology , East Asian People
13.
Langmuir ; 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39066716

ABSTRACT

We investigated the surface orthogonal patterning and bidirectional self-assembly of binary hairy nanoparticles (NPs) constructed by uniformly tethering a single NP with multiple V-shaped AB diblock copolymers using Brownian dynamics simulations in a poor solvent. At low concentration, the chain collapse and microphase separation of binary polymer brushes can lead to the patterning of the NP surface into A- and B-type orthogonal patches with various numbers of domains (valency), n = 1-6, that adopt spherical, linear, triangular, tetrahedral, square pyramidal, and pentagonal pyramidal configurations. There is a linear relationship between the valency and the average ratio of NP diameter to the polymers' unperturbed root-mean-square end-to-end distance for the corresponding valency. The linear slope depends on the grafting density and is independent of the interaction parameters between polymers. At high concentration, the orthogonal patch NPs serve as building blocks and exhibit directional attractions by overlapping the same type of domains, resulting in self-assembly into a series of fascinating architectures depending on the valency and polymer length. Notably, the 2-valent orthogonal patch NPs have the bidirectional bonding ability to form the two-dimensional (2D) square NP arrays by two distinct pathways. Simultaneously patching A and B blocks enables the one-step formation of 2D square arrays via bidirectional growth, whereas step-by-step patching causes the directional formation of 1D chains followed by 2D square arrays. Moreover, the gap between NPs in the 2D square arrays is related to the polymer length but independent of the NP diameter. These 2D square NP arrays are of significant value in practical applications such as integrated circuit manufacturing and nanotechnology.

14.
J Transl Med ; 22(1): 709, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080766

ABSTRACT

BACKGROUND: Chemokine (C-C motif) receptor 8 (CCR8) is a chemokine receptor selectively expressed on tumor-infiltrating regulatory T cells (Tregs). Strong immunosuppression mediated by CCR8+ Tregs observed in breast and lung malignancies suggest for their functional significance in cancer therapy. To date, detailed characterization of tumor-infiltrating CCR8+ Tregs cells in colorectal cancer (CRC) is limited. METHODS: To study the presence and functional involvement of CCR8+ Tregs in CRC, we analyzed the proportions of CCR8-expressing T cells in different T cell subsets in tumor and adjacent normal tissues and peripheral blood mononuclear cells (PBMCs) from CRC patients by Flow cytometry. Also, we compared the distribution of CCR8+ T cells in malignant tissues and peripheral lymphoid organs from a subcutaneous CRC murine model. Bioinformatic analysis was performed to address the significance of CCR8 expression levels in CRC prognosis, immune regulatory gene expression profiles and potential molecular mechanisms associated with CCR8+ Tregs in CRC tumors. Further, we administrated an anti-CCR8 monoclonal antibody to CT26 tumor-bearing mice and examined the antitumor activity of CCR8-targeted therapy both in vivo and in an ex vivo confirmative model. RESULTS: Here, we showed that Tregs was predominantly presented in the tumors of CRC patients (13.4 ± 5.8, p < 0.0001) and the CRC subcutaneous murine model (35.0 ± 2.6, p < 0.0001). CCR8 was found to be preferentially expressed on these tumor-infiltrating Tregs (CRC patients: 63.6 ± 16.0, p < 0.0001; CRC murine model: 65.3 ± 9.5, p < 0.0001), which correlated with poor survival. We found that majority of the CCR8+ Tregs expressed activation markers and exhibited strong suppressive functions. Treatment with anti-CCR8 antibody hampered the growth of subcutaneous CRC tumor through effectively restoring the anti-tumor immunity of CD4+ conventional T cells (CD4+ Tconvs) and CD8+ T cells, which was confirmed in the ex vivo examinations. CONCLUSIONS: Collectively, these findings illustrate the importance of CCR8+ Tregs for an immunosuppressive microenvironment in CRC tumors by functional inhibition of CD4+ Tconvs and CD8+ T cells, and suggest for the applicable value of CCR8-targeted therapy for CRC.


Subject(s)
CD8-Positive T-Lymphocytes , Colorectal Neoplasms , Lymphocytes, Tumor-Infiltrating , Receptors, CCR8 , T-Lymphocytes, Regulatory , Animals , Female , Humans , Male , Mice , Middle Aged , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Immunity , Lymphocytes, Tumor-Infiltrating/immunology , Mice, Inbred BALB C , T-Lymphocytes, Regulatory/immunology , Aged
15.
Cereb Cortex ; 34(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39077917

ABSTRACT

Trauma exposure may precipitate a cascade of plastic modifications within the intrinsic activity of brain regions, but it remains unclear which regions could be responsible for the development of post-traumatic stress disorder based on intrinsic activity. To elucidate trauma-related and post-traumatic stress disorder-related alterations in cortical intrinsic activity at the whole-brain level, we recruited 47 survivors diagnosed with post-traumatic stress disorder, 64 trauma-exposed controls from a major earthquake, and 46 age- and sex-matched healthy controls. All subjects were scanned with an echo-planar imaging sequence, and 5 parameters including the amplitude of low-frequency fluctuations, fractional amplitude of low-frequency fluctuations, regional homogeneity, degree centrality, and voxel-mirrored homotopic connectivity were calculated. We found both post-traumatic stress disorder patients and trauma-exposed controls exhibited decreased amplitude of low-frequency fluctuations in the bilateral posterior cerebellum and inferior temporal gyrus, decreased fractional amplitude of low-frequency fluctuation and regional homogeneity in the bilateral anterior cerebellum, and decreased fractional amplitude of low-frequency fluctuation in the middle occipital gyrus and cuneus compared to healthy controls, and these impairments were more severe in post-traumatic stress disorder patients than in trauma-exposed controls. Additionally, fractional amplitude of low-frequency fluctuation in left cerebellum was positively correlated with Clinician-Administered PTSD Scale scores in post-traumatic stress disorder patients. We identified brain regions that might be responsible for the emergence of post-traumatic stress disorder, providing important information for the treatment of this disorder.


Subject(s)
Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/physiopathology , Stress Disorders, Post-Traumatic/diagnostic imaging , Stress Disorders, Post-Traumatic/psychology , Female , Male , Adult , Middle Aged , Cerebral Cortex/physiopathology , Cerebral Cortex/diagnostic imaging , Echo-Planar Imaging , Earthquakes , Magnetic Resonance Imaging , Young Adult , Brain Mapping
16.
Front Med (Lausanne) ; 11: 1428431, 2024.
Article in English | MEDLINE | ID: mdl-39050533

ABSTRACT

Background: The objective of this study was to conduct a systematic review and meta-analysis of the clinical application effects of transnasal high flow nasal cannula compared to other conventional modalities for oxygen therapy devices in patients undergoing bronchoscopy. Methods: A comprehensive literature search was conducted in multiple English databases, including PubMed, Web of Science, and Cochrane Library, to collect relevant studies on the application of high flow nasal cannula in patients undergoing bronchoscopy, and conducted a meta-analysis utilizing RevMan 5.4 software, following the predetermined inclusion and exclusion criteria. Results: A total of 12 studies meeting the inclusion criteria were included, involving 1,631 patients (HFNC group: n = 811, other oxygen therapy group: n = 820). The meta-analysis results demonstrated that HFNC significantly reduced the incidence of hypoxemia and improved the minimum oxygen saturation compared to conventional oxygen therapy (RR = 0.27, 95% CI: 0.18-0.41, p < 0.00001; MD = 6.09, 95% CI: 3.73-8.45, p < 0.00001). Furthermore, HFNC showed statistically significant differences when compared to non-invasive ventilation in terms of hypoxemia incidence (RR = 3.52, 95% CI: 1.13-10.97, p = 0.03) and minimum oxygen saturation (MD = -1.97, 95% CI: -2.97--0.98, p < 0.0001). In addition, HFNC resulted in significantly shorter surgical time and higher PaO2 at the end of the procedure compared to conventional oxygen therapy (MD = 1.53, 95% CI: 0.66-2.40, p = 0.0006; MD = 15.52, 95% CI: 10.12-20.92, p < 0.00001). However, there were no statistically significant differences observed in PaCO2, EtCO2, and MAP at the end of the procedure (MD = 1.23, 95% CI: -0.74-3.20, p = 0.22; MD = -0.35, 95% CI: -3.77-3.06, p = 0.84; MD = -0.54, 95% CI: -2.44-1.36, p = 0.58). Conclusion: When HFNC or NIV is utilized during the examination and treatment of bronchoscopy patients, both oxygenation modalities enhance oxygenation function and reduce the incidence of hypoxemia compared to conventional oxygen therapy. HFNC can be regarded as a viable alternative to NIV for specific high-risk patients undergoing bronchoscopy. It decreases the duration of bronchoscopy and improves the PaO2 levels at the end of the procedure, but does not significantly impact the PaCO2, EtCO2, and mean arterial pressure. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier 1414374462@qq.com.

17.
Front Med (Lausanne) ; 11: 1419635, 2024.
Article in English | MEDLINE | ID: mdl-38994339

ABSTRACT

Purpose: This study aimed to systematically evaluate the clinical effects of using transnasal high-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) in patients undergoing gastrointestinal endoscopy. Methods: A comprehensive literature search was conducted from 2004 to April 2024 to collect relevant studies on the application of HFNC in patients undergoing gastrointestinal endoscopy. Multiple Chinese and English databases, including China National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, PubMed, and Cochrane Library, were searched systematically for randomized controlled trials (RCTs). Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. RevMan 5.4 software was utilized for conducting the network meta-analysis. Results: A total of 12 RCTs involving 3,726 patients were included. Meta-analysis results showed that HFNC reduced the incidence of hypoxemia and improved the minimum oxygen saturation (SpO2) compared with COT [odds ratio (OR) = 0.39, 95% confidence interval (CI): 0.29-0.53], [mean difference (MD) = 4.07, 95% CI: 3.14-5.01], and the difference was statistically significant. However, the baseline SpO2 levels and incidence of hypercapnia were not statistically significantly different between the HFNC and COT groups [MD = -0.21, 95% CI: -0.49-0.07]; [OR = 1.43, 95% CI: 0.95-2.15]. In terms of procedure time, the difference between HFNC and COT was not statistically significant, and subgroup analyses were performed for the different types of studies, with standard deviation in the gastroscopy group (MD = 0.09, 95% CI: -0.07-0.24) and the endoscopic retrograde cholangiopancreatography group (MD = 0.36, 95% CI: -0.50-1.23). The results demonstrated a significant reduction in the adoption of airway interventions in the HFNC group compared to the COT group (OR = 0.16, 95% CI: 0.05-0.53), with a statistically significant difference; this result was consistent with those of the included studies. Conclusion: The application of HFNC improves the incidence of hypoxemia, enhances oxygenation, and reduces airway interventions during gastrointestinal endoscopy. However, HFNC does not significantly affect baseline SpO2, hypercapnia, or procedure time. The limitations of this study must be acknowledged, and further high-quality studies should be conducted to validate these findings.

18.
Antonie Van Leeuwenhoek ; 117(1): 92, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949726

ABSTRACT

Biological control is a promising approach to enhance pathogen and pest control to ensure high productivity in cash crop production. Therefore, PGPR biofertilizers are very suitable for application in the cultivation of tea plants (Camellia sinensis) and tobacco, but it is rarely reported so far. In this study, production of a consortium of three strains of PGPR were applied to tobacco and tea plants. The results demonstrated that plants treated with PGPR exhibited enhanced resistance against the bacterial pathogen Pseudomonas syringae (PstDC3000). The significant effect in improving the plant's ability to resist pathogen invasion was verified through measurements of oxygen activity, bacterial colony counts, and expression levels of resistance-related genes (NPR1, PR1, JAZ1, POD etc.). Moreover, the application of PGPR in the tea plantation showed significantly reduced population occurrences of tea green leafhoppers (Empoasca onukii Matsuda), tea thrips (Thysanoptera:Thripidae), Aleurocanthus spiniferus (Quaintanca) and alleviated anthracnose disease in tea seedlings. Therefore, PGPR biofertilizers may serve as a viable biological control method to improve tobacco and tea plant yield and quality. Our findings revealed part of the mechanism by which PGPR helped improve plant biostresses resistance, enabling better application in agricultural production.


Subject(s)
Nicotiana , Pest Control, Biological , Plant Diseases , Pseudomonas syringae , Animals , Plant Diseases/microbiology , Plant Diseases/prevention & control , Nicotiana/microbiology , Pseudomonas syringae/physiology , Pest Control, Biological/methods , Camellia sinensis/microbiology , Camellia sinensis/growth & development , Insecta/microbiology , Thysanoptera/microbiology , Disease Resistance , Plant Development , Biological Control Agents , Hemiptera/microbiology
19.
Commun Biol ; 7(1): 824, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971948

ABSTRACT

The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.


Subject(s)
Brain Neoplasms , DNA Copy Number Variations , DNA Methylation , Gene Expression Regulation, Neoplastic , Glioma , MicroRNAs , Humans , Glioma/genetics , Glioma/immunology , Glioma/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Epigenomics , Genomics , Gene Regulatory Networks , Cell Line, Tumor , Immune Evasion/genetics , Epigenesis, Genetic , Female , Male , Prognosis , Neoplasm Grading
20.
Zool Res ; 45(4): 937-950, 2024 07 18.
Article in English | MEDLINE | ID: mdl-39021082

ABSTRACT

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.


Subject(s)
Autophagy-Related Proteins , Autophagy , Neural Stem Cells , Animals , Neural Stem Cells/physiology , Neural Stem Cells/metabolism , Mice , Autophagy/physiology , Autophagy-Related Proteins/genetics , Autophagy-Related Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Mice, Knockout , Sequestosome-1 Protein/metabolism , Sequestosome-1 Protein/genetics , Gene Expression Regulation , Neoplasm Proteins
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