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1.
Sci Rep ; 14(1): 15429, 2024 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965381

RESUMEN

Associations between migraine and retinal vascular occlusion have been reported, but there is no large-scale and comprehensive study. Therefore, we aimed to determine risks of retinal vascular occlusion in patients with migraine. Using the Taiwan National Health Insurance Research Database from 2009 to 2020, we enrolled 628,760 patients with migraine and 628,760 matched individuals without migraine. Study outcomes were diagnoses of retinal vascular occlusion, including retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Adjusted hazard ratio (aHR) of retinal vascular occlusion related to migraine was estimated. The cumulative incidences of subsequent retinal vascular occlusion, RAO, and RVO were significantly higher in migraine patients compared with controls (0.31% vs. 0.21%; 0.09% vs. 0.05%; 0.22% vs. 0.17%; all p < 0.001). The hazards of retinal vascular occlusion, RAO, and RVO were significantly greater in the migraine group (aHR, 1.69 [95% CI, 1.57, 1.83], 2.13 [95% CI, 1.84, 2.48] and 1.53 [95% CI, 1.40, 1.68], respectively). Risks of retinal vascular occlusion were significantly higher in migraine both with aura (MA) and without aura (MO) (aHR, 1.77 [95% CI, 1.58, 1.98], and 1.92 [95% CI, 1.64, 2.25]). Among patients with migraine, nonsteroidal anti-inflammatory drugs, propranolol, and flunarizine significantly reduce their risks of retinal vascular occlusion (aHR, 0.19 [95% CI, 0.16, 0.22], 0.73 [95% CI, 0.62, 0.86], 0.84 [95% CI, 0.76, 0.93]). Migraine, MA and MO are independently associated with higher risks of retinal vascular occlusion, RAO, and RVO.


Asunto(s)
Trastornos Migrañosos , Oclusión de la Arteria Retiniana , Oclusión de la Vena Retiniana , Humanos , Masculino , Femenino , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/complicaciones , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Oclusión de la Vena Retiniana/tratamiento farmacológico , Oclusión de la Vena Retiniana/epidemiología , Oclusión de la Vena Retiniana/complicaciones , Oclusión de la Arteria Retiniana/epidemiología , Taiwán/epidemiología , Factores de Riesgo , Incidencia , Anciano , Bases de Datos Factuales , Modelos de Riesgos Proporcionales , Adulto Joven
2.
J Proteome Res ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949094

RESUMEN

Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide, causing significant health problems. Early diagnosis of the disease is quite inadequate. To screen urine biomarkers of DN and explore its potential mechanism, this study collected urine from 87 patients with type 2 diabetes mellitus (which will be classified into normal albuminuria, microalbuminuria, and macroalbuminuria groups) and 38 healthy subjects. Twelve individuals from each group were then randomly selected as the screening cohort for proteomics analysis and the rest as the validation cohort. The results showed that humoral immune response, complement activation, complement and coagulation cascades, renin-angiotensin system, and cell adhesion molecules were closely related to the progression of DN. Five overlapping proteins (KLK1, CSPG4, PLAU, SERPINA3, and ALB) were identified as potential biomarkers by machine learning methods. Among them, KLK1 and CSPG4 were positively correlated with the urinary albumin to creatinine ratio (UACR), and SERPINA3 was negatively correlated with the UACR, which were validated by enzyme-linked immunosorbent assay (ELISA). This study provides new insights into disease mechanisms and biomarkers for early diagnosis of DN.

3.
Front Microbiol ; 15: 1343564, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855762

RESUMEN

Background: The main functional gastrointestinal disorders (FGIDs) include functional dyspepsia (FD) and irritable bowel syndrome (IBS), which often present overlapping symptoms with gastroesophageal reflux disease (GERD), posing a challenge for clinical diagnosis and treatment. The gut microbiota is closely associated with FGIDs and GERD, although the causal relationship has not been fully elucidated. Therefore, we aimed to investigate the potential causal relationship using bidirectional two-sample Mendelian randomization (MR) analysis. Materials and methods: The genetic data of the 211 gut microbiota were obtained from the MiBioGen consortium (N = 14,306, from phylum to genus level) and species level of gut microbiota were acquired from the Dutch Microbiome Project (N = 7,738). For FD and IBS, we utilized the FinnGen consortium, whereas, for GERD data analysis, we obtained the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was used as the primary method to calculate causal effect values. Sensitivity analyses were also performed to confirm the robustness of the primary findings of the MR analyses. Moreover, a reverse MR analysis was conducted to assess the likelihood of reverse causality. Results: Combining the results of the preliminary and sensitivity analyses, we identified that 8 gut microbial taxa were associated with FD. Genus Lachnospiraceae NK4A136 group (p = 3.63 × 10-3) and genus Terrisporobacter (p = 1.13 × 10-3) were strongly associated with FD. At the same time, we found that 8 gut microbial taxa were associated with IBS. Family Prevotellaceae (p = 2.44 × 10-3) and species Clostridium leptum (p = 7.68 × 10-3) display a robust correlation with IBS. In addition, 5 gut microbial taxa were associated with GERD using the IVW approach. In the reverse MR analysis, 2 gut microbial taxa were found to be associated with FD, 5 gut microbial taxa were found to be associated with IBS, and 21 gut microbial taxa were found to be associated with GERD. Conclusion: The study reveals the potential causal effects of specific microbial taxa on FD, IBS, and GERD and may offer novel insights into the diagnosis and treatment of these conditions.

4.
Ying Yong Sheng Tai Xue Bao ; 35(4): 1007-1015, 2024 Apr 18.
Artículo en Chino | MEDLINE | ID: mdl-38884235

RESUMEN

Soil matrix infiltration is an important pathway for plantations to obtain water, which affects ecological benefits and water conservation function of plantations. The changes of soil matrix infiltration and its influencing factors in different growth stages of Chinese fir plantations remain unclear. We measured soil matrix infiltration process using a tension infiltrometer in Chinese fir plantations (5, 8, 11, and 15 years old) of Beijiang River Forest Farm in Rongshui, Guangxi, and analyzed soil basic physicochemical properties to identify the dominant factors influencing soil matrix infiltration. The results showed that initial infiltration rate, stable infiltration rate, and cumulative infiltration increased with stand ages. The ranges of different stand ages were 141-180 mm·h-1, 109-150 mm·h-1, and 188-251 mm, respectively. The initial infiltration rate, stable infiltration rate, and cumulative infiltration were significantly positively correlated with soil capillary porosity, soil organic matter, soil water stable macroaggregate, sand content, and clay content, while negatively correlated with soil bulk density and silt content. Early thinning had a positive effect on soil matrix infiltration, but thinning measures after 11 years did not enhance soil matrix infiltration further. Philip model was optimal for describing soil matrix infiltration process in this region. In conclusion, soil matrix infiltration capacity of Chinese fir plantations gradually increased from young to middle-aged stands, but matrix infiltration capacity tended to stabilize after 11 years old. Silt content and water stable macroaggregate were the dominant factors influencing matrix infiltration.


Asunto(s)
Suelo , Suelo/química , China , Cunninghamia/crecimiento & desarrollo , Agua/análisis , Ecosistema , Factores de Tiempo , Abies/crecimiento & desarrollo
5.
Sci Rep ; 14(1): 14330, 2024 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-38906945

RESUMEN

This study aimed to investigate the association between obesity and herpes zoster (HZ) occurrence. This study used data covering 2 million people in Taiwan in 2000, which were obtained from the National Health Insurance Research Database. The cohort study observed aged 20-100 years with obesity from 2000 to 2017 (tracking to 2018). Obesity was indicated by the presence of two or more outpatient diagnoses or at least one admission record. And, obesity was categorized into non-morbid obesity and morbid obesity. Patients with HZ before the index date were excluded. The obesity cohort and control cohort were matched 1:1 according to age, sex, comorbidities, and index year. There were 18,855 patients in both the obesity and control cohorts. The obesity cohort [adjusted hazard ratio (aHR) 1.09] had a higher risk of HZ than the control cohort. Further analysis, the morbid obesity group (aHR 1.47), had a significantly higher risk of HZ than the non-morbid obesity group. Among the patients without any comorbidities, the patients with obesity had a significantly higher risk of developing HZ than the patients without obesity (aHR 1.18). Obese patients are at a higher risk of HZ development, especially in the patients with morbid obesity. Weight reduction is critical for preventing the onset of chronic diseases and decreasing the risk of HZ in patients with obesity.


Asunto(s)
Herpes Zóster , Obesidad Mórbida , Humanos , Herpes Zóster/epidemiología , Herpes Zóster/complicaciones , Masculino , Femenino , Obesidad Mórbida/complicaciones , Obesidad Mórbida/epidemiología , Persona de Mediana Edad , Anciano , Adulto , Taiwán/epidemiología , Factores de Riesgo , Anciano de 80 o más Años , Comorbilidad , Adulto Joven , Estudios de Cohortes , Obesidad/complicaciones , Obesidad/epidemiología
6.
mSystems ; : e0024324, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940525

RESUMEN

The Mariana Trench (MT) is the deepest part of the ocean on Earth. Previous studies have described the microbial community structures and functional potential in the seawater and surface sediment of MT. Still, the metabolic features and adaptation strategies of the microorganisms involved in nitrogen cycling processes are poorly understood. In this study, comparative metagenomic approaches were used to study microbial nitrogen cycling in three MT habitats, including hadal seawater [9,600-10,500 m below sea level (mbsl)], surface sediments [0-46 cm below seafloor (cmbsf) at a water depth between 7,143 and 8,638 mbsl], and deep sediments (200-306 cmbsf at a water depth of 8,300 mbsl). We identified five new nitrite-oxidizing bacteria (NOB) lineages that had adapted to the oligotrophic MT slope sediment, via their CO2 fixation capability through the reductive tricarboxylic acid (rTCA) or Calvin-Benson-Bassham (CBB) cycle; an anammox bacterium might perform aerobic respiration and utilize sedimentary carbohydrates for energy generation because it contains genes encoding type A cytochrome c oxidase and complete glycolysis pathway. In seawater, abundant alkane-oxidizing Ketobacter species can fix inert N2 released from other denitrifying and/or anammox bacteria. This study further expands our understanding of microbial life in the largely unexplored deepest part of the ocean. IMPORTANCE: The metabolic features and adaptation strategies of the nitrogen cycling microorganisms in the deepest part of the ocean are largely unknown. This study revealed that anammox bacteria might perform aerobic respiration in response to nutrient limitation or O2 fluctuations in the Mariana Trench sediments. Meanwhile, an abundant alkane-oxidizing Ketobacter species could fix N2 in hadal seawater. This study provides new insights into the roles of hadal microorganisms in global nitrogen biogeochemical cycles. It substantially expands our understanding of the microbial life in the largely unexplored deepest part of the ocean.

7.
Int J Med Sci ; 21(7): 1302-1306, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38818474

RESUMEN

Background: Hyperopia is a significant refractive error in children, often leading to vision impairment. This study aimed to investigate whether partial or full spectacle correction is benefit for hyperopia in preschool-aged children. Methods: A retrospective study was conducted on hyperopic children visited to teaching medical center outpatient clinic between October 2011 and October 2018, and were categorized into three groups: full correction, overcorrection, and undercorrection. The study was approved by the institutional ethical committee of Tri-Service General Hospital. Results: Following a minimum of one-year follow-up period, no statistically significant differences were observed in best-corrected visual acuity (BCVA) among children receiving full, over, or under spectacle correction. Notably, the overcorrection group exhibited a significant reduction in spherical equivalent (SE) compared to both the full and under correction groups, indicating a better SE with spectacle overcorrection. Conclusions: Spectacle overcorrection may offer potential benefits for enhancing SE in preschool children with hyperopia. Nevertheless, further investigation through randomized controlled trials is warranted to establish the validity of this approach and its impact on visual outcomes in this hyperopic pediatric population.


Asunto(s)
Anteojos , Hiperopía , Agudeza Visual , Humanos , Hiperopía/terapia , Hiperopía/fisiopatología , Estudios Retrospectivos , Preescolar , Femenino , Masculino , Refracción Ocular/fisiología , Niño , Resultado del Tratamiento , Estudios de Seguimiento
8.
Int J Biol Sci ; 20(7): 2698-2726, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38725864

RESUMEN

Pancreatic cancer is a malignancy with high mortality. In addition to the few symptoms until the disease reaches an advanced stage, the high fatality rate is attributed to its rapid development, drug resistance and lack of appropriate treatment. In the selection and research of therapeutic drugs, gemcitabine is the first-line drug for pancreatic cancer. Solving the problem of gemcitabine resistance in pancreatic cancer will contribute to the progress of pancreatic cancer treatment. Long non coding RNAs (lncRNAs), which are RNA transcripts longer than 200 nucleotides, play vital roles in cellular physiological metabolic activities. Currently, our group and others have found that some lncRNAs are aberrantly expressed in pancreatic cancer cells, which can regulate the process of cancer through autophagy and Wnt/ß-catenin pathways simultaneously and affect the sensitivity of cancer cells to therapeutic drugs. This review presents an overview of the recent evidence concerning the node of lncRNA for the cross-talk between autophagy and Wnt/ß-catenin signaling in pancreatic cancer, together with the practicability of lncRNAs and the core regulatory factors as targets in therapeutic resistance.


Asunto(s)
Autofagia , Resistencia a Antineoplásicos , Neoplasias Pancreáticas , ARN Largo no Codificante , Vía de Señalización Wnt , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , Humanos , Autofagia/efectos de los fármacos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Resistencia a Antineoplásicos/genética , Animales
9.
Hepatology ; 79(6): 1324-1336, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38758104

RESUMEN

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.


Asunto(s)
Neoplasias del Sistema Biliar , Café , , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Sistema Biliar/epidemiología , Neoplasias del Sistema Biliar/etiología , Anciano , Incidencia , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias de la Vesícula Biliar/etiología , Neoplasias de la Vesícula Biliar/prevención & control , Factores de Riesgo , Adulto , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/etiología
10.
Biometals ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38568319

RESUMEN

Arsenic (As) is a widespread environmental metalloid and human carcinogen, and its exposure is associated with a wide range of toxic effects, leading to serious health hazards. As poisoning is a complex systemic multi-organ and multi-system damage disease. In this study, a rat model of As poisoning was established to investigate the levels of trace elements in the blood of rats and sex differences in the effect of As on every trace elements in rat blood. Twenty 6-week-old SD (Sprague Dawley) rats were randomly divided into the control group and the As-exposed group. After 3 months, the contents of 19 elements including As in the blood were detected in these two groups by inductively coupled plasma mass spectrometry (ICP-MS). As levels in the blood of As-exposed rats were significantly higher than those in the control group, with increased levels of Rb, Sr, Cs and Ce, and decreased levels of Pd. As showed a significant positive correlation with Rb. There were significant sex differences in blood Se, Pd, Eu, Dy, Ho, and Au levels in the As-exposed group. The results showed that As exposure can lead to an increase of As content in blood and an imbalance of some elements. There were sex differences in the concentration and the correlation between elements of some elements. Elemental imbalances may affect the toxic effects of As and play a synergistic or antagonistic role in As toxicity.

11.
Biomed Pharmacother ; 173: 116425, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38490155

RESUMEN

Depression is a common mental health disorder, and in recent years, the incidence of various forms of depression has been on the rise. Most medications for depression are highly dependency-inducing and can lead to relapse upon discontinuation. Therefore, novel treatment modalities and therapeutic targets are urgently required. Traditional Chinese medicine (TCM) offers advantages in the treatment of depression owing to its multi-target, multi-dimensional approach that addresses the root cause of depression by regulating organ functions and balancing Yin and Yang, with minimal side effects. Cynaroside (CNS), an extract from the traditional Chinese herb honeysuckle, is a flavonoid compound with antioxidant properties. In this study, network pharmacology identified 44 potential targets of CNS associated with depression and several highly correlated inflammatory signaling pathways. CNS alleviated LPS-induced M1 polarization and the release of inflammatory factors in BV-2 cells. Transcriptomic analysis and validation revealed that CNS reduced inflammatory polarization, lipid peroxidation, and ferroptosis via the IRF1/SLC7A11/GPX4 signaling pathway. In vivo experiments showed that CNS treatment had effects similar to those of fluoxetine (FLX). It effectively ameliorated anxiety-, despair-, and anhedonia-like states in chronic unpredictable mild stress (CUMS)-induced mice and reduced microglial activation in the hippocampus. Thus, we conclude that CNS exerts its therapeutic effect on depression by inhibiting microglial cells from polarizing into the M1 phenotype and reducing inflammation and ferroptosis levels. This study provides further evidence that CNS is a potential antidepressant, offering new avenues for the treatment of depression.


Asunto(s)
Depresión , Ferroptosis , Glucósidos , Luteolina , Ratones , Animales , Depresión/tratamiento farmacológico , Depresión/metabolismo , Microglía/metabolismo , Hipocampo , Conducta Animal , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Estrés Psicológico/tratamiento farmacológico , Modelos Animales de Enfermedad
12.
Inflammation ; 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38460093

RESUMEN

The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects modulating Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.

13.
Cancer Cell ; 42(3): 474-486.e12, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38402610

RESUMEN

Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increases lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly alters the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolishes stress-induced metastasis. Chronic stress shifts normal circadian rhythm of neutrophils and causes increased neutrophil extracellular trap (NET) formation via glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress fails to increase NETs and metastasis. Furthermore, digesting NETs with DNase I prevents chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease.


Asunto(s)
Trampas Extracelulares , Neoplasias Pulmonares , Humanos , Animales , Ratones , Neutrófilos/patología , Neoplasias Pulmonares/patología , Pulmón/patología , Microambiente Tumoral
14.
Clin Gastroenterol Hepatol ; 22(6): 1275-1285.e2, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38365094

RESUMEN

BACKGROUND & AIMS: The impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the development of cirrhosis and hepatocellular carcinoma (HCC) by chronic hepatitis B (CHB) or C infection and antiviral treatment statuses is not well-known. METHODS: A total of 336,866 adults aged ≥30 years were prospectively enrolled in a health screening program between 1997-2013. MASLD was identified by abdominal ultrasonography and cardiometabolic profiles. Data linkage was performed using 3 nationwide databases-National Health Insurance, Cancer Registry, and Death Certification System-to obtain information on antiviral treatment, vital status, and newly diagnosed cirrhosis and HCC. Follow-up was conducted until December 31, 2019. RESULTS: In the total population, 122,669 (36.4%) had MASLD. Over a mean follow-up of 15 years, 5562 new cases of cirrhosis and 2273 new cases of HCC were diagnosed. Although MASLD significantly increased the cumulative risks of cirrhosis or HCC (P < .0001), the associated risk was more pronounced when comparing CHB or C infection with the presence of MASLD. Stratifying the participants based on their MASLD and CHB or C statuses, hazard ratios (HRadj) with 95% confidence intervals for HCC were 8.81 (7.83-9.92) for non-steatotic liver disease (SLD) with CHB or C, 1.52 (1.32-1.74) for MASLD without CHB or C, and 8.86 (7.76-10.12) for MASLD with CHB or C, compared with non-SLD without CHB or C (all P < .0001). Among CHB or C patients who received antivirals during follow-up, MASLD was associated with increased risks of cirrhosis and HCC, with HRadj of 1.23 (1.01-1.49) and 1.32 (1.05-1.65), respectively. CONCLUSIONS: These findings underscore the need to prioritize treatment of chronic viral hepatitis before addressing MASLD.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Hepatitis C Crónica , Cirrosis Hepática , Neoplasias Hepáticas , Humanos , Masculino , Hepatitis B Crónica/complicaciones , Persona de Mediana Edad , Femenino , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/epidemiología , Adulto , Hepatitis C Crónica/complicaciones , Estudios Prospectivos , Anciano , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Factores de Riesgo , Antivirales/uso terapéutico , Taiwán/epidemiología , Medición de Riesgo
15.
J Pharm Anal ; 14(1): 52-68, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38352949

RESUMEN

The occurrence of benign prostate hyperplasia (BPH) was related to disrupted sex steroid hormones, and metformin (Met) had a clinical response to sex steroid hormone-related gynaecological disease. However, whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear. Here, our clinical study showed that along with prostatic epithelial cell (PEC) proliferation, sex steroid hormones were dysregulated in the serum and prostate of BPH patients. As the major contributor to dysregulated sex steroid hormones, elevated dihydrotestosterone (DHT) had a significant positive relationship with the clinical characteristics of BPH patients. Activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor (AR)-mediated Yes-associated protein (YAP1)-TEA domain transcription factor (TEAD4) heterodimers. Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells. Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

16.
Br J Pharmacol ; 181(11): 1596-1613, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38124222

RESUMEN

BACKGROUND AND PURPOSE: Oat ß-glucan could ameliorate epidermal hyperplasia and accelerate epidermal barrier repair. Dectin-1 is one of the receptors of ß-glucan and many biological functions of ß-glucan are mediated by Dectin-1. Dectin-1 promotes wound healing through regulating the proliferation and migration of skin cells. Thus, this study aimed to investigate the role of oat ß-glucan and Dectin-1 in epidermal barrier repair. EXPERIMENTAL APPROACH: To investigate the role of Dectin-1 in the epidermal barrier, indicators associated with the recovery of a damaged epidermal barrier, including histopathological changes, keratinization, proliferation, apoptosis, differentiation, cell-cell junctions and lipid content were compared between WT and Dectin-1-/- mice. Further, the effect of oat ß-glucan on the disruption of the epidermal barrier was also compared between WT and Dectin-1-/- mice. KEY RESULTS: Dectin-1 deficiency resulted in delayed recovery and marked keratinization, as well as abnormal levels of keratinocyte differentiation, cell-cell junctions and lipid synthesis during the restoration of the epidermal barrier. Oat ß-glucan significantly reduces epidermal hyperplasia, promotes epidermal differentiation, increases cell-cell junction expression, promotes lipid synthesis and ultimately accelerates the recovery of damaged epidermal barriers via Dectin-1. Oat ß-glucan could promote CaS receptor expression and activate the PPAR-γ signalling pathway via Dectin-1. CONCLUSION AND IMPLICATIONS: Oat ß-glucan promote the recovery of damaged epidermal barriers through promoting epidermal differentiation, increasing the expression of cell-cell junctions and lipid synthesis through Dectin-1. Dectin-1 deficiency delay the recovery of epidermal barriers, which indicated that Dectin-1 may be a potential target in epidermal barrier repair.


Asunto(s)
Diferenciación Celular , Epidermis , Lectinas Tipo C , Regulación hacia Arriba , beta-Glucanos , Animales , Lectinas Tipo C/metabolismo , beta-Glucanos/farmacología , Epidermis/metabolismo , Epidermis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ratones , Regulación hacia Arriba/efectos de los fármacos , Ratones Noqueados , Ratones Endogámicos C57BL , Uniones Intercelulares/efectos de los fármacos , Uniones Intercelulares/metabolismo , Masculino , Cicatrización de Heridas/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos
17.
Appl Environ Microbiol ; 90(1): e0125023, 2024 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-38112479

RESUMEN

Valorization of microalgae into high-value products and drop-in chemicals can reduce our dependence on non-renewable fossil fuels in an environmentally sustainable way. Among the valuable products, medium-chain carboxylic acids (MCCAs) and alcohols are attractive building blocks as fuel precursors. However, the biosynthetic mechanisms of MCCAs and alcohols in anaerobic microalgae fermentation and the regulating role of pH on the microbial structure and metabolism interaction among different functional groups have never been documented. In this work, we systematically investigated the roles of pH (5, 7, and 10) on the production of MCCAs and alcohols in anaerobic microalgae fermentation. The gene-centric and genome-centric metagenomes were employed to uncover the dynamics and metabolic network of the key players in the microbial communities. The results indicated that the pH significantly changed the product spectrum. The maximum production rate of alcohol was obtained at pH 5, while pH 7 was more beneficial for MCCA production. Metagenomic analysis reveals that this differential performance under different pH is attributed to the transformation of microbial guild and metabolism regulated by pH. The composition of various functional groups for MCCA and alcohol production also varies at different pH levels. Finally, a metabolic network was proposed to reveal the microbial interactions at different pH levels and thus provide insights into bioconversion of microalgae to high-value biofuels.IMPORTANCECarboxylate platforms encompass a biosynthesis process involving a mixed and undefined culture, enabling the conversion of microalgae, rich in carbohydrates and protein, into valuable fuels and mitigating the risks associated with algae blooms. However, there is little known about the effects of pH on the metabolic pathways of chain elongation and alcohol production in anaerobic microalgae fermentation. Moreover, convoluted and interdependent microbial interactions encumber efforts to characterize how organics and electrons flow among microbiome members. In this work, we compared metabolic differences among three different pH levels (5, 7, and 10) in anaerobic microalgae fermentation. In addition, genome-centric metagenomic analysis was conducted to reveal the microbial interaction for medium-chain carboxylic acid and alcohol production.


Asunto(s)
Ácidos Carboxílicos , Microalgas , Fermentación , Ácidos Carboxílicos/metabolismo , Microalgas/metabolismo , Anaerobiosis , Etanol/metabolismo , Concentración de Iones de Hidrógeno
18.
Anticancer Res ; 44(1): 287-300, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38159982

RESUMEN

BACKGROUND/AIM: Lung adenocarcinoma (LUAD) is the deadliest cancer, and approximately 20% of stage I LUAD cases recur after surgical resection due to its high intratumor heterogeneity. Reactive oxygen species (ROS) have been detected in LUAD and are involved in carcinogenesis and tumor progression. Here, a comprehensive analysis was performed to evaluate the effects of antioxidants on the prognosis of LUAD. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) database was used to study the relationship of gene expression of different ROS-scavenging enzymes with the progression and prognosis of LUAD. RESULTS: Using TCGA LUAD datasets, we found that catalase (CAT) expression was significantly down-regulated in LUAD tissues compared to normal tissues, CAT down-regulation differed significantly between different grades of LUAD, low CAT expression was independently correlated with a worse prognosis in LUAD, and the expression of the CAT gene was associated with an inhibition of the "cell cycle". A panel of LUAD cells (CL1-0, CL1-1, CL1-3, and CL1-5), which harbored mutated p53 (R248W), with gradually increasing invasiveness showed a gradual decrease in CAT expression. Silencing of CAT upregulated cell growth in A549 cells, which harbor wild-type p53 and show high CAT expression and was associated with an increase in the expression of BUB1B, PLK1, and PKMYT1. Finally, over 38% (186/490) of LUAD cases with a p53 mutation exhibited significantly lower CAT expression than those with wild-type p53. CONCLUSION: CAT expression is a potent favorable prognostic marker for LUAD and may represent a drug target.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Pronóstico , Catalasa/genética , Catalasa/metabolismo , Proteína p53 Supresora de Tumor , Especies Reactivas de Oxígeno/metabolismo , Recurrencia Local de Neoplasia , Adenocarcinoma del Pulmón/patología , Proteínas de la Membrana/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo
19.
Proc Natl Acad Sci U S A ; 120(51): e2303641120, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38096410

RESUMEN

When threatened by dangerous or harmful stimuli, animals engage in diverse forms of rapid escape behaviors. In Drosophila larvae, one type of escape response involves C-shaped bending and lateral rolling followed by rapid forward crawling. The sensory circuitry that promotes larval escape has been extensively characterized; however, the motor programs underlying rolling are unknown. Here, we characterize the neuromuscular basis of rolling escape behavior. We used high-speed, volumetric, Swept Confocally Aligned Planar Excitation (SCAPE) microscopy to image muscle activity during larval rolling. Unlike sequential peristaltic muscle contractions that progress from segment to segment during forward and backward crawling, muscle activity progresses circumferentially during bending and rolling escape behavior. We propose that progression of muscular contraction around the larva's circumference results in a transient misalignment between weight and the ground support forces, which generates a torque that induces stabilizing body rotation. Therefore, successive cycles of slight misalignment followed by reactive aligning rotation lead to continuous rolling motion. Supporting our biomechanical model, we found that disrupting the activity of muscle groups undergoing circumferential contraction progression leads to rolling defects. We use EM connectome data to identify premotor to motor connectivity patterns that could drive rolling behavior and perform neural silencing approaches to demonstrate the crucial role of a group of glutamatergic premotor neurons in rolling. Our data reveal body-wide muscle activity patterns and putative premotor circuit organization for execution of the rolling escape response.


Asunto(s)
Drosophila , Neuronas , Animales , Drosophila/fisiología , Neuronas/fisiología , Larva/fisiología , Reacción de Fuga/fisiología , Contracción Muscular , Drosophila melanogaster/fisiología
20.
BMC Vet Res ; 19(1): 259, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38057808

RESUMEN

BACKGROUND: Avian bornavirus (ABV) is a neurotropic virus, it has been established as the primary causative agent of proventricular dilatation disease (PDD). However, substantial international trade and transnational trafficking of wild birds occur, potentially enabling these birds to harbor and transmit pathogens to domestic poultry, adversely affecting their well-being. Real-time RT-PCR was employed to detect the presence of PaBV-4 in parrots imported to China in 2022. RESULTS: In 2022, a total of 47 cloacal swabs from 9 distinct species of parrots were collected at the Wildlife Rescue Monitoring Center in Guangdong, China. The purpose of this collection was to detect the presence of PaBV-4. Using real-time PCR techniques, it was determined that the positive rate of PaBV-4 was 2.12% (1 out of 47) in parrots. The PaBV-4 virus was detected in a Amazona aestiva that had been adopted for one month. Conversely, all other species tested negative for the virus. Subsequently, the whole genome of the PaBV-4 GD2207 strains was sequenced, and the homology and genetic evolution between these strains and previously published PaBV-4 strains on GenBank were analyzed using DNAStar and MEGA7.0 software. The findings revealed that the full-length genome of PaBV-4 consisted of 8915 nucleotides and encoded six proteins. Additionally, it exhibited the highest nucleotide similarity (99.9%) to the GZ2019 strain, which causes death and severe clinical symptoms in Aratinga solstitialis. Furthermore, when compared to other strains of PaBV-4, the GD2207 strain demonstrated the highest amino acid homology with GZ2019. The phylogenetic analysis demonstrated that the GD2207 strain clustered with various strains found in Japanese, American, and German parrots, indicating a close genetic relationship with PaBV-4, but it revealed a distant relationship with PaBV-5 Cockg5 from America. Notably, the GD2207 was closely associated with the GZ2019 strain from Aratinga solstitialis in China. CONCLUSION: This study presents the preliminary identification of PaBV-4 in Amazona aestiva parrots, emphasizing its importance as the predominant viral genotype linked to parrot infections resulting from trade into China. Through genetic evolution analysis, it was determined that the GD2207 strain of PaBV-4 exhibits the closest genetic relationship with GZ 2019 (Aratinga solstitialis, China), M14 (Ara macao, USA), AG5 (Psittacus erithacus, USA) and 6758 (Ara ararauna, Germany) suggesting a shared ancestry.


Asunto(s)
Enfermedades de las Aves , Bornaviridae , Infecciones por Mononegavirales , Loros , Animales , Bornaviridae/genética , Filogenia , Comercio , Infecciones por Mononegavirales/veterinaria , Internacionalidad , Animales Salvajes
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