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1.
Heliyon ; 10(10): e31322, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803874

ABSTRACT

College students are inevitably online and at risk of becoming addicted. Life history theory provides an explanatory framework for individual differences in Internet addiction, and childhood harshness and unpredictability may be important antecedents. However, it is unclear whether and how childhood harshness and/or unpredictability affect Internet addiction during college. In this study, we recruited 483 Chinese college students and assessed their childhood harshness, unpredictability, self-control, and Internet addiction. The results of path analysis showed that childhood unpredictability was positively associated with Internet addiction among college students and was partially mediated by self-control. The effect of harshness on Internet addiction showed a suppression effect, i.e., the direct effect of harshness on Internet addiction was negative and the indirect effect through self-control was positive. This suggests that the high risk of Internet addiction stems from harshness and unpredictability in childhood, but that the effects of these factors are independent and distinct. Self-control plays an important role in this process, but many internal mechanisms remain to be tested in future research.

2.
Heliyon ; 10(9): e30310, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38742080

ABSTRACT

Background: Methods for washed microbiota transplantation (WMT) through the mid-gut include transendoscopic enteral tubing (TET) and manual spiral nasojejunal tube (SNT) placement have not been studied. Methods: This prospective interventional study was performed at a single centre. Patients were divided into the SNT and mid-gut TET groups based on their conditions and wishes. In the SNT group, an SNT was passively inserted into the stomach, and abdominal X-rays were taken within 24 h to confirm tube placement in the small intestine. In the mid-gut TET group, mid-gut TET was placed in the small intestine for gastroscopy. Data on the clinical efficacy of WMT, intubation time, cost, overall comfort score, adverse reactions, etc., were collected from the two groups. Results: Sixty-three patients were included in the study (SNT group (n = 40) and mid-gut TET group (n = 23)). The clinical efficacy of WMT in the SNT and mid-gut TET groups was 90 % and 95.7 %, respectively (P = 0.644). Compared with the mid-gut TET group, the SNT group showed a shorter operation time (120 s vs. 258 s, P = 0.001) and a lower average cost (641.7 yuan vs. 1702.1 yuan, P = 0.001). There was no significant difference in the overall comfort score or the incidence of common discomfort symptoms between the two groups. Conclusion: The different implantation methods have different advantages; compared with mid-gut TET placement, manual SNT placement provides some benefits.

3.
J Vis Exp ; (207)2024 May 03.
Article in English | MEDLINE | ID: mdl-38767369

ABSTRACT

A total of five samples of Chrysomya megacephala samples - three fresh samples, one sample stored in alcohol for 2 years, and one sample stored in dry sealed storage for 2 years protected from light only - were selected to investigate whether a blood DNA extraction kit could extract DNA from necrophilous flies and to determine whether alcohol could prolong the preservation of necrophilous flies' DNA. First, the blood DNA extraction kit was used to extract DNA from their thorax tissues. Then, the DNA purity and concentration were examined using a microplate reader and a fluorometer. Finally, PCR amplification and electrophoresis of the extracted DNA were done with necrophilic fly-specific primers located in the mitochondrial CO I gene sequence. The results showed that the DNA purity of all samples was greater than 2.0. The DNA concentration was observed to be of the following order: fresh samples > alcohol-preserved old samples > untreated, old samples. All samples had specific electrophoretic bands after PCR amplification. In conclusion, a blood DNA extraction kit can be used to extract DNA from necrophilic flies successfully, and the DNA concentration of fresh fly samples is greater than that of old fly samples. The flies can be stored in alcohol for a long time.


Subject(s)
DNA , Polymerase Chain Reaction , Animals , DNA/isolation & purification , DNA/genetics , Polymerase Chain Reaction/methods , Calliphoridae/genetics , Calliphoridae/chemistry
5.
J Colloid Interface Sci ; 670: 486-498, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38772264

ABSTRACT

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from âˆ¼ 57.31 kPa to âˆ¼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of âˆ¼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.


Subject(s)
Dendrimers , Hydrogels , Meloxicam , Nylons , Polyglutamic Acid , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Polyglutamic Acid/chemistry , Polyglutamic Acid/pharmacology , Polyglutamic Acid/analogs & derivatives , Nylons/chemistry , Tissue Adhesions/prevention & control , Dendrimers/chemistry , Dendrimers/pharmacology , Meloxicam/chemistry , Meloxicam/pharmacology , Meloxicam/administration & dosage , Mice , Inflammation/prevention & control , Inflammation/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Rats , Rats, Sprague-Dawley , Fibrinolysis/drug effects , Postoperative Complications/prevention & control , Particle Size , Injections , Drug Carriers/chemistry
6.
Nat Cell Biol ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714852

ABSTRACT

Upon endoplasmic reticulum (ER) stress, activation of the ER-resident transmembrane protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) initiates a key branch of the unfolded protein response (UPR) through unconventional splicing generation of the transcription factor X-box-binding protein 1 (XBP1s). Activated IRE1 can form large clusters/foci, whose exact dynamic architectures and functional properties remain largely elusive. Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs). In response to different stressors, IRE1α clusters are dynamically tethered to SGs at the ER. The cytosolic linker portion of IRE1α possesses intrinsically disordered regions and is essential for its condensation with SGs. Furthermore, disruption of SG assembly abolishes IRE1α clustering and compromises XBP1 mRNA splicing, and such IRE1α-SG coalescence engenders enrichment of the biochemical components of the pro-survival IRE1α-XBP1 pathway during ER stress. Our findings unravel a phase transition mechanism for the spatiotemporal assembly of IRE1α-SG condensates to establish a more efficient IRE1α machinery, thus enabling higher stress-handling capacity.

7.
Int J Biol Macromol ; 271(Pt 2): 132713, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815944

ABSTRACT

The hydrophilicity of gelatin films obviously limits their application. In this work, novel protonated chitin nanofiber was prepared with green methods, surficial deacetylation combined with acidic and mechanical treatment. Composite films with excellent water and oxygen barrier properties were successfully prepared by blending O/W Pickering emulsions stabilized by chitin nanofibers with gelatin substrates. The films were characterized by Fourier-transform infrared, X-ray diffraction, mechanical properties, water and oxygen permeability, moisture content, water solubility, water contact angle and optical properties. The results demonstrated that the amino groups of chitin nanofibers bound to the carboxyl groups of gelatin via electrostatic interactions, which contributing to the excellent mechanical and barrier properties of composite films. The elongation at break of composite film (the concentration of chitin nanofiber was 0.2 wt%) was 2.66 times of gelatin film. And the water vapor and oxygen permeability of composite films lowered to 65.9 % and 52.9 %, respectively. The introduction of O/W Pickering emulsion significantly enhanced the hydrophobicity of gelatin-based film and the chitin nanofibers played a positive role in stabilizing the gelatin chains to a certain extent. This study expands the application fields of gelatin-based films and provides valuable technical route for the preparation of barrier films.

8.
Sensors (Basel) ; 24(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38610355

ABSTRACT

Sensing data from vessel operations are of great importance in reflecting operational performance and facilitating proper decision-making. In this paper, statistical analyses of vessel operational data are first conducted to compare manual noon reports and autolog data from sensors. Then, new indicators to identify data aberrations are proposed, which are the errors between the reported values from operational data and the expected values of different parameters based on baseline models and relevant sailing conditions. A method to detect aberrations based on the new indicators in terms of the reported power is then investigated, as there are two independent measured power values. In this method, a sliding window that moves forward along time is implemented, and the coefficient of variation (CV) is calculated for comparison. Case studies are carried out to detect aberrations in autolog and noon data from a commercial vessel using the new indicator. An analysis to explore the source of the deviation is also conducted, aiming to find the most reliable value in operations. The method is shown to be effective for practical use in detecting aberrations, having been initially tested on both autolog and noon report from four different commercial vessels in 14 vessel years. Approximately one triggered period per vessel per year with a conclusive deviation source is diagnosed by the proposed method. The investigation of this research will facilitate a better evaluation of operational performance, which is beneficial to both the vessel operators and crew.

9.
CNS Neurosci Ther ; 30(4): e14703, 2024 04.
Article in English | MEDLINE | ID: mdl-38572816

ABSTRACT

INTRODUCTION: Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated. METHODS: In this study, we used high-fat diet/low-dose streptozotocin-induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real-time PCR, western blot, and immunofluorescence were performed to investigate the mechanism. RESULTS: We found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD+-dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV-SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a-PINK1-Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected. CONCLUSION: These results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a-PINK1-Parkin-mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Neuropathies , Sirtuin 3 , Animals , Rats , Adenosine Triphosphate/pharmacology , Hyperalgesia , Mitophagy , Protein Kinases/metabolism , Signal Transduction , Sirtuin 3/genetics , Sirtuin 3/metabolism , Ubiquitin-Protein Ligases/genetics
10.
J Urol ; 211(6): 743-753, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38620056

ABSTRACT

PURPOSE: We assessed the effect of prophylactic biologic mesh on parastomal hernia (PSH) development in patients undergoing cystectomy and ileal conduit (IC). MATERIALS AND METHODS: This phase 3, randomized, controlled trial (NCT02439060) included 146 patients who underwent cystectomy and IC at the University of Southern California between 2015 and 2021. Follow-ups were physical exam and CT every 4 to 6 months up to 2 years. Patients were randomized 1:1 to receive FlexHD prophylactic biological mesh using sublay intraperitoneal technique vs standard IC. The primary end point was time to radiological PSH, and secondary outcomes included clinical PSH with/without surgical intervention and mesh-related complications. RESULTS: The 2 arms were similar in terms of baseline clinical features. All surgeries and mesh placements were performed without any intraoperative complications. Median operative time was 31 minutes longer in patients who received mesh, yet with no statistically significant difference (363 vs 332 minutes, P = .16). With a median follow-up of 24 months, radiological and clinical PSHs were detected in 37 (18 mesh recipients vs 19 controls) and 16 (8 subjects in both arms) patients, with a median time to radiological and clinical PSH of 8.3 and 15.5 months, respectively. No definite mesh-related adverse events were reported. Five patients (3 in the mesh and 2 in the control arm) required surgical PSH repair. Radiological PSH-free survival rates in the mesh and control groups were 74% vs 75% at 1 year and 69% vs 62% at 2 years. CONCLUSIONS: Implementation of biologic mesh at the time of IC construction is safe without significant protective effects within 2 years following surgery.


Subject(s)
Cystectomy , Surgical Mesh , Urinary Diversion , Humans , Surgical Mesh/adverse effects , Male , Female , Urinary Diversion/methods , Aged , Middle Aged , Cystectomy/methods , Cystectomy/adverse effects , Incisional Hernia/prevention & control , Urinary Bladder Neoplasms/surgery , Follow-Up Studies , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prophylactic Surgical Procedures/methods
11.
J Cancer Res Clin Oncol ; 150(5): 222, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38687350

ABSTRACT

PURPOSE: The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy. METHODS: This retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression. RESULTS: The PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than -15% had significantly longer OS. CONCLUSION: CT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis.


Subject(s)
Peritoneal Neoplasms , Stomach Neoplasms , Tomography, X-Ray Computed , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/drug therapy , Stomach Neoplasms/diagnostic imaging , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/diagnostic imaging , Female , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed/methods , Aged , Prognosis , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
12.
Nutr Metab Cardiovasc Dis ; 34(6): 1407-1415, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38664127

ABSTRACT

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.


Subject(s)
Aortic Aneurysm , Aortic Dissection , Ascorbic Acid , Protective Factors , Vitamin E , Humans , Male , Prospective Studies , Middle Aged , Female , Ascorbic Acid/administration & dosage , Ascorbic Acid/adverse effects , Vitamin E/administration & dosage , Risk Factors , Aged , Incidence , Aortic Dissection/epidemiology , Aortic Dissection/prevention & control , Aortic Aneurysm/epidemiology , Aortic Aneurysm/prevention & control , Risk Assessment , United Kingdom/epidemiology , Time Factors , Diet/adverse effects , Adult
13.
Cell Cycle ; 23(4): 435-447, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38626328

ABSTRACT

The precise mechanisms underlying the inhibitory effects of SIRT3, a mitochondrial sirtuin protein, on hepatocellular carcinoma (HCC) development, as well as its impact on mitochondrial respiration, remain poorly understood. We assessed sirtuins 3 (SIRT3) levels in HCC tissues and Huh7 cells cultured under hypoxic condition. We investigated the effects of SIRT3 on cell proliferation, glycolytic metabolism, mitochondrial respiration, mitophagy, and mitochondrial biogenesis in Huh7 cells. Besides, we explored the potential mechanisms regulating SIRT3 expression in hypoxically cultured Huh7 cells. Gradual reduction in SIRT3 expressions were observed in both adjacent tumor tissues and tumor tissues. Similarly, SIRT3 expressions were diminished in Huh7 cells cultured under hypoxic condition. Forced expression of SIRT3 attenuated the growth of hypoxically cultured Huh7 cells. SIRT3 overexpression led to a decrease in extracellular acidification rate while increasing oxygen consumption rate. SIRT3 downregulated the levels of hexokinase 2 and pyruvate kinase M2. Moreover, SIRT3 enhanced mitophagy signaling, as indicated by mtKeima, and upregulated key proteins involved in various mitophagic pathways while reducing intracellular reactive oxygen species levels. Furthermore, SIRT3 increased proxisome proliferator-activated receptor-gamma coactivator 1α levels and the amount of mitochondrial DNA in Huh7 cells. Notably, ß-catenin expressions were elevated in Huh7 cells cultured under hypoxic condition. Antagonists and agonists of ß-catenin respectively upregulated and downregulated SIRT3 expressions in hypoxically cultured Huh7 cells. The modulationsof glycolysis and mitochondrial respiration represent the primary mechanism through which SIRT3, suppressed by ß-catenin, inhibits HCC cell proliferation.


Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Glycolysis , Liver Neoplasms , Mitochondria , Sirtuin 3 , beta Catenin , Humans , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Sirtuin 3/metabolism , Sirtuin 3/genetics , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Cell Line, Tumor , beta Catenin/metabolism , Mitochondria/metabolism , Mitophagy/drug effects , Signal Transduction , Cell Hypoxia , Hexokinase/metabolism , Hexokinase/genetics , Reactive Oxygen Species/metabolism , Gene Expression Regulation, Neoplastic
14.
J Alzheimers Dis ; 99(1): 53-84, 2024.
Article in English | MEDLINE | ID: mdl-38640155

ABSTRACT

Background: Alzheimer's disease (AD), the most common form of dementia, remains long-term and challenging to diagnose. Furthermore, there is currently no medication to completely cure AD patients. Rapamycin has been clinically demonstrated to postpone the aging process in mice and improve learning and memory abilities in animal models of AD. Therefore, rapamycin has the potential to be significant in the discovery and development of drugs for AD patients. Objective: The main objective of this systematic review and meta-analysis was to investigate the effects and mechanisms of rapamycin on animal models of AD by examining behavioral indicators and pathological features. Methods: Six databases were searched and 4,277 articles were retrieved. In conclusion, 13 studies were included according to predefined criteria. Three authors independently judged the selected literature and methodological quality. Use of subgroup analyses to explore potential mechanistic effects of rapamycin interventions: animal models of AD, specific types of transgenic animal models, dosage, and periodicity of administration. Results: The results of Morris Water Maze (MWM) behavioral test showed that escape latency was shortened by 15.60 seconds with rapamycin therapy, indicating that learning ability was enhanced in AD mice; and the number of traversed platforms was increased by 1.53 times, indicating that the improved memory ability significantly corrected the memory deficits. CONCLUSIONS: Rapamycin therapy reduced age-related plaque deposition by decreasing AßPP production and down-regulating ß-secretase and γ-secretase activities, furthermore increased amyloid-ß clearance by promoting autophagy, as well as reduced tau hyperphosphorylation by up-regulating insulin-degrading enzyme levels.


Subject(s)
Alzheimer Disease , Disease Models, Animal , Sirolimus , Animals , Alzheimer Disease/drug therapy , Sirolimus/pharmacology , Sirolimus/therapeutic use , Cognitive Dysfunction/drug therapy , Mice , Humans
16.
Polymers (Basel) ; 16(7)2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38611126

ABSTRACT

To investigate the optimal delivery system of quercetin, in this paper, cellulose nanocrystals (CNCs) extracted from rice bran were used to stabilize the Pickering emulsion and Pickering emulsion gels (PEGs) with quercetin. To compare the emulsion properties, stability, antioxidation activity, encapsulation rate, and bioaccessibility of the quercetin, four emulsions of CNC Pickering emulsion (C), CNC Pickering emulsion with quercetin (CQ), CNC Pickering gel emulsion (CG), and CNC Pickering gel emulsions with quercetin (CQG) were prepared. All four emulsions exhibited elastic gel network structure and good stability. The quercetin significantly reduced the particle size, increased the stability, and improved the antioxidant capacity of CQ and CQG. Compared to C and CG, the ABTS+ radical scavenging capacities of CQ and CQG were respectively enhanced by 46.92% and 3.59%. In addition, CQG had a higher encapsulation rate at 94.57% and higher bioaccessibility (16.17) compared to CQ. This study not only indicated that CNC from rice bran could be exploited as an excellent stabilization particle for Pickering emulsions, but also provided a highly stable and bioaccessible delivery system for water-insoluble functional active factors.

17.
Antioxidants (Basel) ; 13(3)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38539822

ABSTRACT

The role of hypoxia in terms of affecting mammary epithelial cells (MECs) proliferation is closely associated with the milk synthesis of lactating mammals. Primary bovine MECs were cultured at 1, 6, 11, 16, and 21% O2 for 24 h. The results showed that cell proliferation decreased linearly, and hypoxic inducible factor (HIF)-1α expression increased linearly along with the declining O2. The linear increase in oxidative stress resulted in the accumulation of malondialdehyde and reactive oxygen species and decreased antioxidant enzyme activities following the reduced O2. Concerning mitochondria, the dynamin-related protein 1 showed improved expression, and optin atrophy protein 1 decreased along with the decreasing O2 gradient, which led to decreased mitochondrial mass and mitophagy emerging under 1% O2. Oxygen concentration-trend RNA-seq analysis was conducted. Specifically, HIF-1-MAPK (1% O2), PI3K-Akt-MAPK (6% O2), and p53-Hippo (11 and 16% O2) were found to primarily regulate cell proliferation in response to hypoxia compared with normoxia (21%), respectively. In conclusion, our study suggests that bMEC proliferation is suppressed in low-oxygen conditions, and is exacerbated following the reduced oxygen supply. The cross-oxygen gradient comparisons suggest that MAPK and Hippo, which are core pathways of mammary cell proliferation, are repressed by hypoxia via oxidative-stress-dependent signals.

18.
J Transl Med ; 22(1): 297, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38515161

ABSTRACT

BACKGROUND: The aberrant secretion and excessive deposition of type I collagen (Col1) are important factors in the pathogenesis of myocardial fibrosis in dilated cardiomyopathy (DCM). However, the precise molecular mechanisms underlying the synthesis and secretion of Col1 remain unclear. METHODS AND RESULTS: RNA-sequencing analysis revealed an increased HtrA serine peptidase 1 (HTRA1) expression in patients with DCM, which is strongly correlated with myocardial fibrosis. Consistent findings were observed in both human and mouse tissues by immunoblotting, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunofluorescence analyses. Pearson's analysis showed a markedly positive correlation between HTRA1 level and myocardial fibrosis indicators, including extracellular volume fraction (ECV), native T1, and late gadolinium enhancement (LGE), in patients with DCM. In vitro experiments showed that the suppression of HTRA1 inhibited the conversion of cardiac fibroblasts into myofibroblasts and decreased Col1 secretion. Further investigations identified the role of HTRA1 in promoting the formation of endoplasmic reticulum (ER) exit sites, which facilitated the transportation of Col1 from the ER to the Golgi apparatus, thereby increasing its secretion. Conversely, HTRA1 knockdown impeded the retention of Col1 in the ER, triggering ER stress and subsequent induction of ER autophagy to degrade misfolded Col1 and maintain ER homeostasis. In vivo experiments using adeno-associated virus-serotype 9-shHTRA1-green fluorescent protein (AAV9-shHTRA1-GFP) showed that HTRA1 knockdown effectively suppressed myocardial fibrosis and improved left ventricular function in mice with DCM. CONCLUSIONS: The findings of this study provide valuable insights regarding the treatment of DCM-associated myocardial fibrosis and highlight the therapeutic potential of targeting HTRA1-mediated collagen secretion.


Subject(s)
Cardiomyopathies , Cardiomyopathy, Dilated , Animals , Humans , Mice , Collagen Type I , Contrast Media , Fibrosis , Gadolinium , Myocardium/pathology
19.
J Glob Health ; 14: 04069, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38515427

ABSTRACT

Background: China's fertility policy has dramatically changed in the past decade with the successive promulgation of the partial two-child policy, universal two-child policy and three-child policy. The trajectories of maternal and neonatal health accompanied the changes in fertility policy are unknown. Methods: We obtained data of 280 203 deliveries with six common pregnancy complications and thirteen perinatal outcomes between 2010 and 2021 in eastern China. The average annual percent change (AAPC) was calculated to evaluated the temporal trajectories of obstetric characteristics and adverse outcomes during this period. Then, the autoregressive integrated moving average (ARIMA) models were constructed to project future trend of obstetric characteristics and outcomes until 2027. Results: The proportion of advanced maternal age (AMA), assisted reproduction technology (ART) treatment, gestational diabetes mellitus (GDM), anaemia, thrombocytopenia, thyroid dysfunction, oligohydramnios, placental abruption, small for gestational age (SGA) infants, and congenital malformation significantly increased from 2010 to 2021. However, the placenta previa, large for gestational age (LGA) infants and stillbirth significantly decreased during the same period. The AMA and ART treatment were identified as independent risk factors for the uptrends of pregnancy complications and adverse perinatal outcomes. The overall caesarean section rate remained above 40%. Importantly, among multiparas, a previous caesarean section was found to be associated with a significantly reduced risk of hypertensive disorders of pregnancy (HDP), premature rupture of membranes (PROM), placenta previa, placental abruption, perinatal asphyxia, LGA infants, stillbirths, and preterm births. In addition, the ARIMA time series models predicted increasing trends in the ART treatment, GDM, anaemia, thrombocytopenia, postpartum haemorrhage, congenital malformation, and caesarean section until 2027. Conversely, a decreasing trend was predicted for HDP, PROM, and placental abruption premature, LGA infants, SGA infants, perinatal asphyxia, and stillbirth. Conclusions: Maternal and neonatal adverse outcomes became more prevalent from 2010 to 2021 in China. Maternal age and ART treatment were independent risk factors for adverse obstetric outcomes. The findings offered comprehensive trajectories for monitoring pregnancy complications and perinatal outcomes in China, and provided robust intervention targets in obstetric safety. The development of early prediction models and the implementation of prevention efforts for adverse obstetric events are necessary to enhance obstetric safety.


Subject(s)
Abruptio Placentae , Anemia , Placenta Previa , Pregnancy Complications , Premature Birth , Thrombocytopenia , Female , Humans , Infant, Newborn , Pregnancy , Asphyxia , Cesarean Section , Cross-Sectional Studies , Infant Health , Placenta , Placenta Previa/epidemiology , Pregnancy Complications/epidemiology , Pregnancy Outcome/epidemiology , Retrospective Studies , Stillbirth
20.
Infect Drug Resist ; 17: 1011-1019, 2024.
Article in English | MEDLINE | ID: mdl-38505250

ABSTRACT

Purpose: Plastic bronchitis (PB), a rare complication of respiratory infection characterized by the formation of casts in the tracheobronchial tree, can lead to airway obstruction and severe condition. Adenovirus is one of the common pathogens of PB caused by infection. This study aimed to evaluate the clinical features and risk factors for PB in children with severe adenovirus pneumonia. Methods: A retrospective study of children with severe adenovirus pneumonia with bronchoscopy results at Guangzhou Women and Children's Hospital between January 2018 and January 2020 was performed. Based on bronchoscopy, we divided children with severe adenovirus pneumonia into two groups: PB and non-PB. Binary logistic regression analysis was used to identify independent risk factors for PB in patients with severe adenovirus pneumonia after univariate analysis. Results: Our study examined 156 patients with severe adenovirus pneumonia with bronchoscopy results in hospital. Among them, 18 developed PB and 138 did not. On multivariate analysis, the independent risk factors of PB in children with severe adenovirus pneumonia were history of allergies (OR 10.147, 95% CI 1.727-59.612; P=0.010), diminished breath sounds (OR 12.856, 95% CI 3.259-50.713; P=0.001), and increased proportion of neutrophils (>70%; OR 8.074, 95% CI 1.991-32.735; P=0.003). Conclusion: Children with severe adenovirus pneumonia with a history of allergies, diminished breath sounds, and increased the proportion of neutrophils >70% may show higher risk of PB.

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