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1.
AIDS Behav ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39307898

RESUMO

The articles in this special issue of AIDS and Behavior focus on the collision between HIV/AIDS and COVID-19 as intersecting pandemics that profoundly impacted communities globally. This editorial highlights the complex interplay between these two public health crises. The pandemic disrupted access to HIV prevention, testing, and treatment services, potentially jeopardizing decades of progress. Mental health challenges and social vulnerability among people living with HIV (PWH) were exacerbated, with preexisting health disparities amplified, disproportionately affecting marginalized populations. However, despite these challenges, the pandemic also spurred innovation and adaptation in HIV prevention and care, with increased use of telehealth and other modalities. The enduring and actionable lessons learned from the collision of HIV and COVID-19 pandemics can prepare us for the next public health challenge with two calls for action. First, we call for integrated and equitable responses that address the multifaceted challenges faced by individuals and communities affected by HIV in the post-COVID-19 era. Second, we call for a strengthened commitment to building resilient health systems and community-engaged interventions that can withstand future challenges.

2.
Front Nutr ; 11: 1453147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39315012

RESUMO

Background: Numerous observational studies and randomized controlled trials have recently revealed the associations between circulating antioxidants and the risk of endometriosis, while the underlying causal relationship remains unclear. This study aimed to investigate the causal association between genetically determined circulating antioxidants and the risk of endometriosis using Mendelian randomization (MR). Methods: A two-sample MR analysis was conducted using publicly available summary data from genome-wide association studies (GWAS) to investigate the causal impact of genetically determined absolute circulating antioxidants (such as ascorbate, retinol, ß-carotene, and lycopene) and their metabolites (including α-and γ-tocopherol, ascorbate, and retinol) on the risk of endometriosis. The study used inverse variance weighted (IVW) or Wald ratio analyses as the primary estimation method and also conducted sensitivity analyses to assess heterogeneity and pleiotropy. Results: No significant causality was observed for genetically determined circulating antioxidants and the risk of endometriosis. The pooled odds ratios (ORs) for absolute circulating antioxidants were 0.62 (95% CI: 0.32-1.18, retinol), 0.95 (95% CI: 0.79-1.15, ß-carotene), 1.01 (95% CI: 0.95-1.08, lycopene), and 1.00 (95% CI: 0.99-1.02, ascorbate, expressed as a Wald ratio). The pooled ORs indicating the EM risk per unit increase in circulating antioxidant metabolites were 1.04 (95% CI: 0.82-1.33, γ-tocopherol), 0.91 (95% CI: 0.57-1.46, α-tocopherol), 1.03 (95% CI: 0.99-1.07, retinol), and 0.96 (95% CI: 0.87-1.06, ascorbate). Conclusion: Our study demonstrated that increased levels of diet-derived circulating antioxidants were not significantly associated with a reduced risk of endometriosis.

3.
J Med Internet Res ; 26: e53171, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302713

RESUMO

BACKGROUND: According to the Morbidity and Mortality Weekly Report, polysubstance use among pregnant women is prevalent, with 38.2% of those who consume alcohol also engaging in the use of one or more additional substances. However, the underlying mechanisms, contexts, and experiences of polysubstance use are unclear. Organic information is abundant on social media such as X (formerly Twitter). Traditional quantitative and qualitative methods, as well as natural language processing techniques, can be jointly used to derive insights into public opinions, sentiments, and clinical and public health policy implications. OBJECTIVE: Based on perinatal polysubstance use (PPU) data that we extracted on X from May 1, 2019, to October 31, 2021, we proposed two primary research questions: (1) What is the overall trend and sentiment of PPU discussions on X? (2) Are there any distinct patterns in the discussion trends of PPU-related tweets? If so, what are the implications for perinatal care and associated public health policies? METHODS: We used X's application programming interface to extract >6 million raw tweets worldwide containing ≥2 prenatal health- and substance-related keywords provided by our clinical team. After removing all non-English-language tweets, non-US tweets, and US tweets without disclosed geolocations, we obtained 4848 PPU-related US tweets. We then evaluated them using a mixed methods approach. The quantitative analysis applied frequency, trend analysis, and several natural language processing techniques such as sentiment analysis to derive statistics to preview the corpus. To further understand semantics and clinical insights among these tweets, we conducted an in-depth thematic content analysis with a random sample of 500 PPU-related tweets with a satisfying κ score of 0.7748 for intercoder reliability. RESULTS: Our quantitative analysis indicates the overall trends, bigram and trigram patterns, and negative sentiments were more dominant in PPU tweets (2490/4848, 51.36%) than in the non-PPU sample (1323/4848, 27.29%). Paired polysubstance use (4134/4848, 85.27%) was the most common, with the combination alcohol and drugs identified as the most mentioned. From the qualitative analysis, we identified 3 main themes: nonsubstance, single substance, and polysubstance, and 4 subthemes to contextualize the rationale of underlying PPU behaviors: lifestyle, perceptions of others' drug use, legal implications, and public health. CONCLUSIONS: This study identified underexplored, emerging, and important topics related to perinatal PPU, with significant stigmas and legal ramifications discussed on X. Overall, public sentiments on PPU were mixed, encompassing negative (2490/4848, 51.36%), positive (1884/4848, 38.86%), and neutral (474/4848, 9.78%) sentiments. The leading substances in PPU were alcohol and drugs, and the normalization of PPU discussed on X is becoming more prevalent. Thus, this study provides valuable insights to further understand the complexity of PPU and its implications for public health practitioners and policy makers to provide proper access and support to individuals with PPU.


Assuntos
Mídias Sociais , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Gravidez , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Mídias Sociais/estatística & dados numéricos , Revelação/estatística & dados numéricos , Assistência Perinatal/estatística & dados numéricos
4.
Pestic Biochem Physiol ; 204: 106101, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277423

RESUMO

Riptortus pedestris (Hemiptera: Alydidae), a common agricultural pest, is the major causative agent of "soybean staygreen." However, the interactions between chemosensory proteins (CSPs) in R. pedestris and host plant volatiles have yet to be comprehensively studied. In this study, we performed real-time fluorescence quantitative polymerase chain reaction (PCR) to analyze the antennal expression of RpedCSP22 and subsequently analyzed the interactions between 21 soybean volatiles, five aggregation pheromones, and RpedCSP22 protein in vitro using a protein expression system, molecular docking, site-directed mutagenesis, and fluorescence competitive binding experiments. The RpedCSP22 protein showed binding affinity to three soybean volatiles (benzaldehyde, 4-ethylbenzaldehyde, and 1-octene-3-ol), with optimal binding observed under neutral pH conditions, and lost binding ability after site-directed mutagenesis. In subsequent RNA interference (RNAi) studies, gene silencing was more than 90 %, and in silenced insects, electroantennographic responses were reduced by more than 75 % compared to non-silenced insects. Moreover, Y-tube olfactory behavioral assessments revealed that the attraction of R. pedestris to the three soybean volatiles was significantly attenuated. These findings suggest that RpedCSP22 plays an important role in the recognition of host plant volatiles by R. pedestris andprovides a theoretical basis for the development of novel inhibitors targeting pest behavior.


Assuntos
Glycine max , Proteínas de Insetos , Compostos Orgânicos Voláteis , Animais , Glycine max/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/química , Compostos Orgânicos Voláteis/metabolismo , Mutagênese Sítio-Dirigida , Simulação de Acoplamento Molecular , Hemípteros/metabolismo , Hemípteros/genética , Antenas de Artrópodes/metabolismo , Feromônios/metabolismo , Heterópteros/metabolismo , Heterópteros/genética
5.
Medicine (Baltimore) ; 103(38): e39717, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39312325

RESUMO

RATIONALE: Hungry bone syndrome (HBS) is a forgotten and underdiagnosed cause. Postoperative HBS refers to patients with high bone turnover before surgery, but after surgery, the inhibition of osteoclast resorption by intact parathyroid hormone suddenly decreases, resulting in a sudden increase in the amount of calcium resorbed by the bone, and a rapid, severe and persistent hypocalcemia, which may be accompanied by hypophosphatemia and hypomagnesemia. We present a case with information about HBS and related complications after parathyroidectomy (PTX). PATIENT CONCERNS: The patient was a 57-year-old woman who presented to the hospital with "pain in both ankles for more than 3 years and in both knees for more than 2 years." DIAGNOSES: A parathyroid mass was found preoperative. Unilateral resection of the lesion was performed under general anesthesia. On gross examination, the mass was reddish brown in color, about 2.9 × 2.5 × 2.3 cm, with abundant blood supply. Postoperative pathology diagnosed parathyroid adenoma. INTERVENTIONS: The patient was diagnosed with HBS on day 3 post-PTX, which lasted for 9 days. OUTCOMES: After active calcium supplementation and other pharmacological interventions, her test parameters gradually returned to normal and she was discharged on the 13th day after surgery. LESSONS: Using the case of a patient with primary hyperparathyroidism with HBS lasting 9 days after PTX for diagnosis and management, we aimed to summarize possible predictors and perioperative management strategies to reduce the incidence, severity, and duration of postoperative HBS.


Assuntos
Hiperparatireoidismo Primário , Hipocalcemia , Paratireoidectomia , Complicações Pós-Operatórias , Humanos , Feminino , Pessoa de Meia-Idade , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico , Paratireoidectomia/efeitos adversos , Hipocalcemia/etiologia , Complicações Pós-Operatórias/etiologia , Síndrome , Cálcio/sangue , Neoplasias das Paratireoides/cirurgia , Neoplasias das Paratireoides/complicações
6.
Int Immunopharmacol ; 142(Pt B): 113255, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39332088

RESUMO

OBJECTIVE: Hemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H2S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H2S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl-d-Aspartate (NMDA) receptor function. METHODS: Mice were immediately administered dl-propargylglycine (PAG) intragastrically as an H2S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala. RESULTS: Within 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H2S-induced intestinal and cerebral injury. CONCLUSION: This experimental data suggests that H2S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR.

7.
Methods ; 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39349287

RESUMO

Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality. Studies have shown that histone modification plays an important regulatory role in the occurrence and development of HCC. However, the specific regulatory effects of histone modifications on gene expression in HCC are still unclear. This study focuses on HepG2 cell lines and hepatocyte cell lines. First, the distribution of histone modification signals in the two cell lines was calculated and analyzed. Then, using the random forest algorithm, we analyzed the effects of different histone modifications and their modified regions on gene expression in the two cell lines, four key histone modifications (H3K36me3, H3K4me3, H3K79me2, and H3K9ac) and five key regions that co-regulate gene expression were obtained. Subsequently, target genes regulated by key histone modifications in key regions were screened. Combined with clinical data, Cox regression analysis and Kaplan-Meier survival analysis were performed on the target genes, and four key target genes (CBX2, CEBPZOS, LDHA, and UMPS) related to prognosis were identified. Finally, through immune infiltration analysis and drug sensitivity analysis of key target genes, the potential role of key target genes in HCC was confirmed. Our results provide a theoretical basis for exploring the occurrence of HCC and propose potential biomarkers associated with histone modifications, which may be potential drug targets for the clinical treatment of HCC.

8.
Cell Mol Immunol ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39349742

RESUMO

The hypersecretion of cytokines triggers life-threatening systemic inflammatory response syndrome (SIRS), leading to multiple organ dysfunction syndrome (MODS) and mortality. Although both coagulopathy and necroptosis have been identified as important factors in the pathogenesis of SIRS, the specific cell types that undergo necroptosis and the interrelationships between coagulopathy and necroptosis remain unclear. In this study, we utilized visualization analysis via intravital microscopy to demonstrate that both anticoagulant heparin and nonanticoagulant heparin (NAH) pretreatment protect mice against TNF-α-induced mortality in SIRS. Moreover, the deletion of Mlkl or Ripk3 resulted in decreased coagulation and reduced mortality in TNF-α-induced SIRS. These findings suggest that necroptosis plays a key role upstream of coagulation in SIRS-related mortality. Furthermore, using a genetic lineage tracing mouse model (Tie2-Cre;Rosa26-tdT), we tracked endothelial cells (ECs) and verified that EC necroptosis is responsible for the vascular damage observed in TNF-α-treated mice. Importantly, Mlkl deletion in vascular ECs in mice had a similar protective effect against lethal SIRS by blocking EC necroptosis to protect the integrity of the endothelium. Collectively, our findings demonstrated that RIPK3-MLKL-dependent necroptosis disrupted vascular integrity, resulting in coagulopathy and multiorgan failure, eventually leading to mortality in SIRS patients. These results highlight the importance of targeting vascular EC necroptosis for the development of effective treatments for SIRS patients.

9.
Ecotoxicol Environ Saf ; 284: 117005, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39250859

RESUMO

Land Use/ Cover Change (LUCC) plays a crucial role in influencing hydrological processes, nutrient cycling, and sediment transport in watersheds, ultimately impacting water quality on both spatial and temporal scales. Accurately predicting changes in watershed water quality is beneficial for the sustainable management of water resources. Current models often lack the ability to effectively predict water quality changes in a dynamic spatio-temporal context, particularly in complex watershed environments. The overall purpose of the study is to establish a comprehensive and dynamic modeling framework that links LUCC with water quality, allowing for accurate predictions of future water quality under varying land use scenarios. The model, which uses water quality as the dependent variable and LUCC as the independent variable, was developed to quantitatively predict changes in watershed water quality. To achieve this, annual multi-period remote sensing images from Landsat-5, Landsat-8 or Sentinel-2 satellites spanning from 1992 to 2022 were analyzed. Random Forest (achieving a Kappa coefficient of 0.9468) were employed to classify land use within the watershed. Based on classification results, a Cellular Automata-Markov chain model (CA-Markov) was constructed to simulate and predict the spatio-temporal patterns of land use, incorporating driving factors such as proximity to water systems, roads, elevation, and slope. Validation of the model using LUCC data from 2020 yielded a high prediction accuracy with a Kappa coefficient of 0.9505. The CA-Markov model was further utilized to project LUCC under three different scenarios-natural development, ecological protection, and arable land protection-between 2023 and 2033. Based on these projections, the coupled water quality and LUCC model was employed to predict water quality changes in the watershed over the same period. Key findings indicate that water quality is likely to improve under ecological protection scenario, while deterioration is expected under natural development scenario and cropland protection scenario due to urban expansion, agricultural practices, and water diversion for irrigation. This study provides a robust framework for watershed management, offering scientific guidance for source management and water purification efforts, thereby contributing significantly to the sustainable development of water resources.


Assuntos
Monitoramento Ambiental , Lagos , Qualidade da Água , China , Monitoramento Ambiental/métodos , Lagos/química , Modelos Teóricos , Agricultura , Poluentes Químicos da Água/análise
10.
Front Plant Sci ; 15: 1433670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39228837

RESUMO

Aims: China is one of the countries in the world most seriously affected by typhoons, which pose a great threat to the eucalyptus plantation industry. However, few studies have comprehensively accounted for the impact of key traits on the wind damage/resistance of eucalyptus. Methods: To identify the key factors affecting the wind resistance of eucalyptus, 20 eucalyptus genotypes were selected; a total of 18 traits, including the wind damage index, growth traits, and wood traits, were measured, and the wind resistance was determined via the tree-pulling test. Results: Correlation, principal component, canonical correlation, and path analyses were performed to evaluate these traits. Correlation analysis revealed that the wind resistance of eucalyptus plants was related to the tree height, volume, and duration of stress wave propagation. Principal components and tree-pulling variables were further used for correlation and path analyses. Canonical correlation analysis and the PA-OV model showed that holocellulose and lignin contents and fiber width, as well as growth traits, were important factors affecting the stability of standing trees under typhoon conditions. The key traits influencing the wind resistance of Eucalyptus camaldulensis, which may provide a reference for evaluating the wind resistance of Eucalyptus varieties for forest management, were identified. Conclusion: This study provides a knowledge base for forest management and planning in typhoon-prone coastal areas, and provides a theoretical basis for the breeding and genetically improving eucalyptus stocks based on wind resistance characteristics.

11.
J Acquir Immune Defic Syndr ; 97(2): 107-116, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39250644

RESUMO

OBJECTIVES: This study aims to identify COVID-19 breakthrough infections among people with HIV (PWH) across different phases of the pandemic and explore whether differential immune dysfunctions are associated with breakthrough infections. DESIGN AND METHODS: This retrospective population-based cohort study used data from an integrated electronic health record (EHR) database in South Carolina (SC). Breakthrough infection was defined as the first COVID-19 diagnosis documented in the state agency after the date an individual was fully vaccinated (ie, 2 doses of Pfizer/BNT162b2 or Moderna/mRNA-1273, or 1 dose of Janssen/Ad26.COV2.S) through June 14, 2022. We analyzed the risk and associated factors of the outcome using Cox proportional hazards models. RESULTS: Among 7596 fully vaccinated PWH, the overall rate of breakthrough infections was 118.95 cases per 1000 person-years. When compared with the alpha-dominant period, the breakthrough infection rate was higher during both delta-dominant (HR: 1.50; 95% CI: 1.25 to 1.81) and omicron-dominant (HR: 2.86; 95% CI: 1.73 to 4.73) periods. Individuals who received a booster dose had a lower likelihood of breakthrough infections (HR: 0.19; 95% CI: 0.15 to 0.24). There was no association of breakthrough infections with degree of HIV viral suppression, but a higher CD4 count was significantly associated with fewer breakthroughs among PWH (>500 vs <200 cells/mm3: HR: 0.68; 95% CI: 0.49 to 0.94). CONCLUSIONS: In our PWH population, the incidence of breakthrough infections was high (during both delta-dominant and omicron-dominant periods) and mainly associated with the absence of a booster dose in patients older than 50 years, with comorbidities and low CD4 count.


Assuntos
COVID-19 , Infecções por HIV , SARS-CoV-2 , Humanos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Masculino , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/complicações , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , SARS-CoV-2/imunologia , South Carolina/epidemiologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Estudos de Coortes , Contagem de Linfócito CD4 , Infecções Irruptivas
13.
Quant Imaging Med Surg ; 14(9): 6413-6424, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39281170

RESUMO

Background: Viral pneumonia (VP) often leads to the development of deep vein thrombosis (DVT) in hospitalized patients. The aim of the study was to investigate the incidence of DVT in discharged patients with VP, and whether new and old DVT differ in transverse relaxation time. Methods: In this prospective cohort study in Wuhan, China, 338 consecutive discharged VP patients from February 2021 to March 2023 who underwent T2 weighted Sampling Perfection with Application Optimized Contrast Evolution (SPACE) were recruited to detect DVT. T2 mapping and T2* mapping were performed for the patients with DVT detected by magnetic resonance imaging (MRI). The minimum, maximum, mean of T2 time and T2* time of DVT were recorded as T2min, T2max, T2mean, T2*min, T2*max, and T2*mean, respectively. Clinical data and laboratory findings were compared between new and old DVT cases, which were defined based on the examination results before and after discharge. A Mann-Whitney test was used to compare transverse relaxation time parameters between new and old DVT. Results: Twelve percent of VP patients (40/338) developed new DVT after discharge. Thirty-three out of 104 DVTs did not resolve after discharge. Compared with patients with new DVT, patients with old DVT were older (67 vs. 59 years, P=0.003); and had a higher proportion of bedridden time >72 hours (72.7% vs. 37.0%, P<0.001). Patients with old DVT had a lower lymphocyte count (0.67×109/L vs. 0.97×109/L, P=0.01), higher C-reactive protein (59 vs. 35 mg/L, P=0.019), and higher levels of D-dimer (6.7 vs. 0.9 µg/mL, P<0.001) than patients with new DVT. Patients with old DVT received more invasive mechanical ventilation (30.3% vs. 7.4%, P<0.001) and had a higher proportion of acute respiratory distress syndrome (75.8% vs. 51.9%, P<0.001), and a higher proportion of cardiac injury (39.4% vs. 14.8%, P=0.033) than patients with new DVT. T2min, T2max, T2mean, and T2*max of new DVT were significantly greater than old DVT (17.6±10.4 vs. 13.2±5.9 ms, 94.9±44.9 vs. 42.3±23.6 ms, 46.8±24.0 vs. 25.0±12.6 ms, 22.5±12.4 vs. 10.7±3.5 ms, P<0.05 for all). There was no significant difference in T2*min or T2*mean between new and old DVT (3.2±0.4 vs. 3.1±0.4 ms, 8.2±4.9 vs. 5.5±1.5 ms, P>0.05 for both). Conclusions: T2 weighted SPACE magnetic resonance (MR) is valuable in the follow-up of thrombosis of discharged VP patients. T2 mapping distinguishes between new and old DVT.

14.
Artigo em Inglês | MEDLINE | ID: mdl-39286872

RESUMO

Dihydroartemisinin (DHA), an artemisinin derivative, can influence certain malignancies' inflammatory response and growth. This study used Cell Counting Kit-8 and Transwell assays to show that DHA suppressed the growth, migration, and invasion of medullary thyroid cancer cells. Furthermore, the authors used enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence to confirm the expression of the transcriptional coactivators Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding domain (TAZ) downstream of the Hippo pathway and changes in the expression of the epithelial-mesenchymal transition (EMT) process markers E-cadherin and N-cadherin. These results demonstrate that DHA effectively reduced the expression of interleukin (IL)-6 in medullary thyroid carcinoma (MTC) cells and hindered the EMT process by regulating the Hippo pathway. This regulation was achieved by promoting YAP phosphorylation and inhibiting YAP/TAZ protein expression. Additional activation of the Hippo pathway by GA-017 alleviated the inhibitory effect of DHA on IL-6. Hippo pathway activation led to an increase in the expression of E-cadherin, a marker of EMT. In conclusion, DHA was demonstrated to regulate the Hippo pathway by inhibiting IL-6 secretion, leading to the inhibition of EMT in MTC. These findings provide a theoretical foundation for further exploration of the anticancer mechanisms of DHA and offer valuable insights into its potential clinical application as a combinatorial drug.

15.
Front Pharmacol ; 15: 1450238, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39295935

RESUMO

Objective: This study aims to investigate the inhibitory effect of Polydatin (PD) on endoplasmic reticulum (ER) stress following subarachnoid hemorrhage (SAH) and to elucidate the underlying mechanisms. Methods: A standard intravascular puncture model was established to mimic SAH in mice. Neurological functions were assessed using neurological scoring, Grip test, and Morris water maze. Brain edema and Evans blue extravasation were measured to evaluate blood-brain barrier permeability. Western blot and quantitative real-time polymerase chain reaction (PCR) analyses were performed to examine protein and mRNA expressions related to ER stress. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was used to detect cell apoptosis, and transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum. Results: The results indicated that PD significantly reduced brain edema and Evans blue extravasation after SAH, improving neurological function. Compared to the SAH group, the expression levels of ER stress-related proteins including glucose-regulated protein 78 (GRP78), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were significantly lower in the PD-treated group. Moreover, PD significantly enhances the protein expression of Sirtuin 1 (SIRT1). Validation with sh-SIRT1 confirmed the critical role of SIRT1 in ER stress, with PD's inhibitory effect on ER stress being dependent on SIRT1 expression. Additionally, PD attenuated ER stress-mediated neuronal apoptosis and SAH-induced ferroptosis through upregulation of SIRT1. Conclusion: PD alleviates ER stress following SAH by upregulating SIRT1 expression, thereby mitigating early brain injury. The protective effects of PD are mediated through SIRT1, which inhibits ER stress and reduces neuronal apoptosis and ferroptosis.

16.
Heliyon ; 10(17): e37434, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39295993

RESUMO

Background: Distinguishing nontuberculous mycobacteria pulmonary disease (NTM-PD) from pulmonary tuberculosis (PTB) is a challenge especially in patients with positive sputum smear of acid-fast bacilli (AFB). This study aimed to compare and identify the clinical characteristics between the two diseases among patients with positive sputum AFB. Methods: From February 2017 through March 2021, patients with positive sputum AFB were reviewed in two hospitals of China. Among them, clinical data of NTM-PD and PTB patients was collected and compared. Results: 76 cases of NTM-PD and 92 cases of PTB were included in our study. When compared with PTB, NTM-PD patients were older (59.2 ± 11.4 vs 44.2 ± 19.5 years, P < 0.001) and manifested more hemoptysis and dyspnea (28.9 % vs 14.1 %, P < 0.05; 48.7 % vs 17.4 %, P < 0.001 respectively). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for Xpert were 85.9 %, 96.1 %, 96.3 %, 84.9 %, respectively, compared to 94.2 %, 81.1 %, 83.1 %, 93.5 %, respectively for T-spot in diagnosing PTB. In radiological features, NTM-PD affected more lobes (4.53 ± 0.89 vs 3.61 ± 1.41, P < 0.001) and showed more consolidation (50 % vs 32.6 %, P < 0.05), destroyed lung (22.7 % vs 9.8 %, P < 0.05), honeycomb lung (26.7 % vs 6.5 %, P < 0.001) but less nodules (80.3 % vs 95.7 %, P < 0.05), tree-in-bud sign (49.3 % vs 87 %, P < 0.001), and satellite nodules (14.5 % vs 90.2 %, P < 0.001) than PTB. Age (odds ratio [OR], 1.043; 95 % confidence interval [CI], 1.018-1.069, P < 0.05), hemoptysis (OR, 3.552; 95%CI, 1.421-8.729, P < 0.05), and dyspnea (OR, 2.631; 95%CI, 1.151-6.016, P < 0.05) were independently correlated with NTM infection. Conclusions: NTM-PD and PTB share similar clinical manifestations. Among them, advanced age, hemoptysis, and dyspnea are the independent predictors for NTM infection. Xpert is an efficiency analysis in discriminating between NTM-PD and PTB in patients with positive sputum AFB.

17.
HIV Med ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39252604

RESUMO

BACKGROUND: People with HIV might be at an increased risk of long COVID (LC) because of their immune dysfunction and chronic inflammation and alterations in immunological responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]). This systematic review aimed to evaluate the association between HIV infection and LC and the prevalence and characteristics of and risk factors for LC among people with HIV. METHODS: Multiple databases, including Embase, PubMed, PsycINFO, Web of Science, and Sociological Abstracts, were searched to identify articles published before June 2023. Published articles were included if they presented at least one LC outcome measure among people with HIV and used quantitative or mixed-methods study designs. For effects reported in three or more studies, meta-analyses using random-effects models were performed using R software. RESULTS: We pooled 39 405 people with HIV and COVID-19 in 17 eligible studies out of 6158 publications in all the databases. It was estimated that 52% of people with HIV with SARS-CoV-2 infection developed at least one LC symptom. Results from the random-effects model showed that HIV infection was associated with an increased risk of LC (odds ratio 2.20; 95% confidence interval 1.25-3.86). The most common LC symptoms among people with HIV were cough, fatigue, and asthenia. Risk factors associated with LC among people with HIV included a history of moderate-severe COVID-19 illness, increased interferon-gamma-induced protein 10 or tumour necrosis factor-α, and decreased interferon-ß, among others. CONCLUSIONS: The COVID-19 pandemic continues to exacerbate health inequities among people with HIV because of their higher risk of developing LC. Our review is informative for public health and clinical communities to develop tailored strategies to prevent aggravated LC among people with HIV.

18.
Nat Commun ; 15(1): 7728, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39231981

RESUMO

To ensure survival, animals must sometimes suppress fear responses triggered by potential threats during feeding. However, the mechanisms underlying this process remain poorly understood. In the current study, we demonstrated that when fear-conditioned stimuli (CS) were presented during food consumption, a neural projection from lateral hypothalamic (LH) GAD2 neurons to nucleus incertus (NI) relaxin-3 (RLN3)-expressing neurons was activated, leading to a reduction in CS-induced freezing behavior in male mice. LHGAD2 neurons established excitatory connections with the NI. The activity of this neural circuit, including NIRLN3 neurons, attenuated CS-induced freezing responses during food consumption. Additionally, the lateral mammillary nucleus (LM), which received NIRLN3 projections, along with RLN3 signaling in the LM, mediated the decrease in freezing behavior. Collectively, this study identified an LHGAD2-NIRLN3-LM circuit involved in modulating fear responses during feeding, thereby enhancing our understanding of how animals coordinate nutrient intake with threat avoidance.


Assuntos
Medo , Animais , Medo/fisiologia , Masculino , Camundongos , Hipotálamo/fisiologia , Hipotálamo/metabolismo , Relaxina/metabolismo , Neurônios/fisiologia , Neurônios/metabolismo , Camundongos Endogâmicos C57BL , Vias Neurais/fisiologia , Ingestão de Alimentos/fisiologia , Condicionamento Clássico/fisiologia , Região Hipotalâmica Lateral/fisiologia , Região Hipotalâmica Lateral/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-39306641

RESUMO

PURPOSE: This investigation aimed to examine the mediating effect of inflammatory biomarkers on the relationship between dust exposure and lung function levels among steelworkers. METHODS: The study comprised 2,315 front-line workers employed at an iron and steel company in Tangshan, who underwent occupational health assessments through cluster sampling. Demographic and lifestyle data were collected via a self-administered questionnaire, while physical examinations measured parameters such as height and weight. Lung function was assessed using a portable pulmonary function tester (CHEST). Blood cell counts were uniformly analyzed using a Mindray fully automated biochemistry analyzer (BS-800). Inflammatory biomarkers, including leukocyte count, neutrophil count, lymphocyte count, and platelet count, were assessed, and the neutrophil-to-lymphocyte ratio and systemic immune inflammation index were computed. Generalized linear models and Spearman rank correlation analyses were employed to explore the interplay among dust exposure, inflammatory biomarkers, and alterations in lung function. A mediation analysis model was constructed to elucidate how inflammatory biomarkers mediate the relationship between dust exposure and lung function levels. RESULTS: After adjusting for covariates, dust exposure was significantly associated with reduced lung function levels, with statistically significant differences observed between dust-exposed and non-exposed groups across various lung function indicators (P < 0.001). In the dust-exposed group, inflammatory biomarkers were elevated, showing significant correlations with FVC and FEV1 (P < 0.05). However, the correlation between FEV1/FVC and various inflammatory biomarkers was insignificant (P > 0.05). Mediation analysis revealed that white blood cells and neutrophils partially mediated the association between dust exposure and FVC, with proportions of 1.75% and 1.09%, respectively. Similarly, white blood cells, neutrophils, and the systemic immune inflammation index partially mediated the association between dust exposure and FEV1, with proportions of 1.15%, 0.82%, and 0.82%, respectively. CONCLUSION: In conclusion, dust exposure poses a risk for decreased lung function levels. Inflammatory biomarkers derived from blood cells offer a valuable and easily obtainable means of identifying changes in lungfunction levels. Among these biomarkers, white blood cells, neutrophils, and the systemic immune inflammation index significantly mediate the association between dust exposure and lung function levels, although further exploration is needed to understand their underlying mechanisms.

20.
J Control Release ; 374: 154-170, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39127448

RESUMO

To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NH2 nanoparticles (NPs) into a sodium alginate/hydroxyapatite/polyvinyl alcohol hydrogel loaded with PDGF-BB, allowing for the sequential release of angiogenic and osteogenic growth factors (GFs) during bone repair. ZIF-8 served as a protective host for BMP-2 from degradation, ensuring high encapsulation efficiency and long-term bioactivity. The SHPP-ZB hydrogel exhibited enhanced mechanical strength and injectability, making it suitable for complex bone defects. It provided a swelling interface for tissue interlocking and the early release of Zn2+ and tannin acid (TA) to exert antioxidant and antibacterial effects, followed by the sequential release of angiogenic and osteogenic GFs to promote high-quality vascularized bone regeneration. In vitro experiments demonstrated the superior angiogenic and osteogenic properties of SHPP-ZB compared to other groups. In vivo experiments indicated that the sequential delivery of GFs via SHPP-ZB hydrogel could improve vascularized bone regeneration. Further, RNA sequencing analysis of regenerative bone tissue revealed that SHPP-ZB hydrogel promoted vascularized bone regeneration by regulating JUN, MAPK, Wnt, and calcium signaling pathways in vivo. This study presented a promising approach for efficient vascularized bone regeneration in large-scale bone defects.


Assuntos
Alginatos , Becaplermina , Proteína Morfogenética Óssea 2 , Regeneração Óssea , Hidrogéis , Osteogênese , Regeneração Óssea/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/administração & dosagem , Osteogênese/efeitos dos fármacos , Proteína Morfogenética Óssea 2/administração & dosagem , Alginatos/química , Becaplermina/administração & dosagem , Nanopartículas/química , Durapatita/química , Durapatita/administração & dosagem , Indutores da Angiogênese/administração & dosagem , Indutores da Angiogênese/farmacologia , Indutores da Angiogênese/química , Masculino , Álcool de Polivinil/química , Polietilenoglicóis/química , Taninos/química , Taninos/administração & dosagem , Taninos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Humanos , Ratos Sprague-Dawley , Camundongos
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