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1.
Nephrology (Carlton) ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38716715

ABSTRACT

AIM: The aim of this study was to examine the clinical and pathological characteristics as well as the prognosis of immunoglobulin A nephropathy (IgAN) accompanied by renal thrombotic microangiopathy (rTMA) in paediatric patients. METHODS: After balancing epidemiological characteristics and pathological types between groups, 427 patients (rTMA group: 23, non-rTMA group: 46) were included. The clinical and pathological features, prognosis and clinical risk factors of the two groups were analysed. RESULTS: IgAN-rTMA children showed more severe clinical and pathological manifestations. The findings from the logistic regression analysis indicated that hypercellularity 1 (E1) (HR: 0.805, 95% CI: 0.763 ~ 1.452, P = .016), endocapillary proliferation (HR: 1.214, 95% CI: 0.093 ~ 4.815, P = .025) and C3 staining (HR: 7.554, 95% CI: 2.563 ~ 15.729, P = .037) were the risk factors for rTMA in children with IgAN. The renal survival in rTMA group was lower than non-rTMA group (χ2 = 18.467, P = .000). Cox regression analysis showed that E1 (HR: 7.441, 95% CI: 1.095 ~ 10.768, P = .037), C3 disposition (HR: 3.414, 95% CI: 0.834 ~ 11.578, P = .027) and rTMA (HR: 8.918, 95% CI: 1.032 ~ 16.754, P = .041) were identified as independent risk factors for the development of end-stage renal disease (ESRD). CONCLUSION: The presence of rTMA had a significant impact on the severity and prognosis of IgAN. And rTMA has been identified as an independent risk factor for the development of renal failure in children diagnosed with IgAN.

2.
Minerva Anestesiol ; 90(4): 263-270, 2024 04.
Article in English | MEDLINE | ID: mdl-38652449

ABSTRACT

BACKGROUND: Transaxillary endoscopic thyroidectomy (TAET) is favored for its favorable cosmetic outcomes and the preservation of anterior cervical function. Despite these benefits, postoperative analgesia has traditionally relied on pharmacological interventions, and regional anesthetic procedures may be an alternative method. This study aimed to evaluate the efficacy of an ultrasound-guided pectoserratus plane block (PSPB) combined with an intermediate cervical plexus block (ICPB) for TAET. METHODS: Forty patients undergoing TAET were randomized into two groups: the nerve block group (N.=20) received ultrasound guided PSPB with 20 ml of 0.375% ropivacaine and ICPB with 8 mL of 0.3% ropivacaine, while the control group (N.=20) received no block. The primary outcome was the Visual Analog Scale (VAS) scores for postoperative neck and axillary pain at different time points (1, 6, 12, 24 h) during rest and movement post-TAET. The secondary outcomes included intraoperative remifentanil consumption, incidence of postoperative nausea and vomiting (PONV), number of remedial analgesic requirements, and patient satisfaction postoperatively. RESULTS: Compared to the control group, patients in the nerve block had significantly lower VAS scores of the neck and axilla whether at rest or movement, and 1, 6, 12, and 24 h postoperatively (P<0.0125). The nerve block group showed higher patient satisfaction (P<0.001). No difference was observed in intraoperative remifentanil consumption, need for rescue analgesics, or other adverse effects 48 h postoperatively. CONCLUSIONS: Ultrasound-guided PSPB with ICPB significantly alleviated postoperative pain and improved patient satisfaction with TAET.


Subject(s)
Cervical Plexus Block , Nerve Block , Pain, Postoperative , Thyroidectomy , Humans , Thyroidectomy/methods , Female , Male , Adult , Pain, Postoperative/prevention & control , Pain, Postoperative/drug therapy , Prospective Studies , Nerve Block/methods , Cervical Plexus Block/methods , Middle Aged , Endoscopy/methods , Ultrasonography, Interventional , Axilla , Pain Measurement
3.
Cancer Lett ; 590: 216840, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38604311

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies, highlighting the urgent need to elucidate the underlying oncogenic mechanisms. VIRMA is a classic isoform of methyltransferases that participates in epigenetic transcriptomic modification in eukaryotic mRNAs. However, the exact roles of VIRMA in PDAC remain unclear. Here, we identified that VIRMA is highly expressed in PDAC, and histone modifications of the promoter may partly account for this dysregulation. Moreover, VIRMA is closely related to glycolysis and poor prognosis in PDAC. We further determined that STRA6 is a direct downstream target of VIRMA in PDAC by RNA sequencing (RNA-seq) and m6A sequencing (m6A-seq). VIRMA is involved in gene expression regulation via 3' UTR targeting of STRA6 mRNA. Furthermore, the m6A reader IGF2BP2 was shown to critically contribute to the stability of STRA6 mRNA. We describe the role of VIRMA in promoting signaling via the STRA6/STAT3 axis, which results in increased levels of HIF-1α, a key activator of glycolysis. In vivo and in vitro experiments reveal that the VIRMA-STRA6-STAT3-HIF-1α axis plays an instrumental role in glycolysis and tumor progression in PDAC. In conclusion, we demonstrate that VIRMA can increase glycolysis in PDAC by upregulating STRA6, a cell surface membrane protein that stimulates the STAT3 pathway, thereby activating HIF-1α and leading to pancreatic cancer malignancy. Overall, our data strongly suggest that the VIRMA-STRA6-STAT3-HIF-1α axis is a viable therapeutic target in PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Gene Expression Regulation, Neoplastic , Glycolysis , Pancreatic Neoplasms , Up-Regulation , Humans , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Glycolysis/genetics , Cell Line, Tumor , Animals , Disease Progression , Methyltransferases/genetics , Methyltransferases/metabolism , Mice , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism , Male , Mice, Nude , Signal Transduction
4.
Huan Jing Ke Xue ; 45(2): 802-812, 2024 Feb 08.
Article in Chinese | MEDLINE | ID: mdl-38471919

ABSTRACT

As an important water supply source in Beijing, karst groundwater has played an irreplaceable role in the security of urban water supply and ecological environment protection in the past 70 years. The Xishan karst groundwater system, located in the upper reaches of western Beijing, belongs to ecological conservation areas. There are several centralized water supply fields in this area. In this study, the Xishan karst groundwater system was taken as the research object. A total of 120 karst groundwater samples in this area were investigated by using statistical analysis, ion ratio, and principal component analysis (PCA) methods to explore the spatial distribution characteristics and formation mechanism of groundwater hydrochemistry. The research results showed that: ① the groundwater quality of the Xishan system was generally good, with the characteristics of neutral pH and low salinity. A total of 84.17% of the water samples were classified as hard water. The chemical type of groundwater was mainly HCO3-Ca·Mg. ② The chemical composition of groundwater was mainly affected by the water-rock interaction, and the weathering source of rock was mainly the dissolution of carbonate. ③ The results of principal component analysis showed that 34.41% of the chemistry formation of groundwater could be explained by carbonate dissolution, 27.33% by rock salt and evaporate dissolution, 11.76% by aquifer sediment dissolution, and 10.30% by domestic sewage discharge. From the recharge area to the runoff area and then to the discharge area, the TH and TDS gradually increased. Coal mining drainage and human activities were the main factors that caused groundwater degradation and variable hydrochemical types in the piedmont. In the future, it is necessary to further strengthen environmental governance, control point and non-point source pollution, and continuously monitor key areas to provide scientific support for ecological and environmental protection.

5.
Article in English | MEDLINE | ID: mdl-38518155

ABSTRACT

Objective: Maxillofacial-neck hyperplastic scars have long been a persistent concern among individuals in both Western and Eastern countries. These scars exhibit rapid growth within 3-6 months following wound healing, subsequently receding at a slower pace, leading to skin redness, tension, and potential itching. The lack of comprehensive understanding regarding the formation mechanism and biological attributes of these scars has made them a prominent subject of research both domestically and internationally. Methods: Research data from 2010 to 2023 was selected, and relevant literature on the efficacy of botulinum toxin in the treatment of facial and neck hypertrophic scars was searched until August 2023. The literature on the incidence of facial-neck hypertrophic scars included in PubMed, the Cochrane Library, EMbase, and Web of Science was searched. Two researchers independently screened and extracted the data according to strict inclusion and exclusion criteria.Risk bias in Review Manager 5.4, provided by the Cochrane Collaboration, was used for methodological quality assessment and meta-analysis of the included literature. In case of any disagreement, the decision shall be made through consultation with the third party. Scar width, patient satisfaction, and visual analogue scale (VAS) were evaluated. Weighted mean difference (WMD), odds ratio (OR), and 95% confidence interval (95%CI) were used for evaluation. Publication bias was intuitively determined by funnel plot, and sensitivity analysis was conducted by removing literatures one by one for risk assessment. Results: After reading the title, abstract, and full text, a total of 237 patients were included in 7 articles. Scar width was only studied in 6 literatures, and the heterogeneity test of the included studies (χ2 = 148.95, P < .001, I2 = 98%) showed significant heterogeneity among the studies. Therefore, the random effects model was used to merge the data. Combined effect value WMD =-2.85 [95% CI :(-6.51, 0.81), P < .001], the difference between the two groups was statistically significant. The combined OR of the random-effects model was 8.52 [95%CI: (7.96, 9.08), P < .001], and the difference between the two groups was statistically significant. Among them, the heterogeneity test (χ2 = 2.69, P = .44, I² = 0%) was carried out in two studies, indicating good homogeneity among the studies, so the combined WMD was 0.68 [95%CI: (0.38, 0.99), P < .001] by using the fixed-effect model. The median VAS was described in the other two literatures, and the mean scores in the experimental group were 8.9 and 8.25, respectively, while the mean scores in the control group were 7.2 and 6.28, respectively, indicating that local injection of botulinum A toxin at the early stage of wound healing can significantly improve scar quality. Sensitivity analysis suggested that the meta-analysis results were stable and reliable, and publication bias was not analyzed using funnel plots. Conclusion: Botulinum toxin has a positive effect on preventing hyperplastic scars in the maxillofacial and neck areas, and it can also help fade existing scars.

6.
Phytomedicine ; 128: 155365, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38552436

ABSTRACT

BACKGROUND: Ferroptosis, a form of regulated cell death (RCD) that relies on excessive reactive oxygen species (ROS) generation, Fe2+accumulation, abnormal lipid metabolism and is involved in various organ ischemia/reperfusion (I/R) injury, expecially in myocardium. Mitochondria are the powerhouses of eukaryotic cells and essential in regulating multiple RCD. However, the links between mitochondria and ferroptosis are still poorly understood. Salidroside (Sal), a natural phenylpropanoid glycoside isolated from Rhodiola rosea, has mult-bioactivities. However, the effects and mechanism in alleviating ferroptosis caused by myocardial I/R injury remains unclear. PURPOSE: This study aimed to investigate whether pretreated with Sal could protect the myocardium against I/R damage and the underlying mechanisms. In particular, the relationship between Sal pretreatment, AMPKα2 activity, mitochondria and ROS generation was explored. STUDY DESIGN AND METHODS: Firstly, A/R or I/R injury models were employed in H9c2 cells and Sprague-Dawley rats. And then the anti-ferroptotic effects and mechanism of Sal pretreatment was detected using multi-relevant indexes in H9c2 cells. Further, how does Sal pretreatment in AMPKα2 phosphorylation was explored. Finally, these results were validated by I/R injury in rats. RESULTS: Similar to Ferrostatin-1 (a ferroptosis inhibitor) and MitoTEMPO, a mitochondrial free radical scavenger, Sal pretreatment effectively alleviated Fe2+ accumulation, redox disequilibrium and maintained mitochondrial energy production and function in I/R-induced myocardial injury, as demonstrated using multifunctional, enzymatic, and morphological indices. However, these effects were abolished by downregulation of AMPKα2 using an adenovirus, both in vivo and in vitro. Moreover, the results also provided a non-canonical mechanism that, under mild mitochondrial ROS generation, Sal pretreatment upregulated and phosphorylated AMPKα2, which enhanced mitochondrial complex I activity to activate innate adaptive responses and increase cellular tolerance to A/R injury. CONCLUSION: Overall, our work highlighted mitochondria are of great impotance in myocardial I/R-induced ferroptosis and demonstrated that Sal pretreatment activated AMPKα2 against I/R injury, indicating that Sal could become a candidate phytochemical for the treatment of myocardial I/R injury.


Subject(s)
AMP-Activated Protein Kinases , Ferroptosis , Glucosides , Myocardial Reperfusion Injury , Phenols , Rats, Sprague-Dawley , Reactive Oxygen Species , Rhodiola , Ferroptosis/drug effects , Phenols/pharmacology , Animals , Glucosides/pharmacology , Myocardial Reperfusion Injury/drug therapy , Rats , Male , Rhodiola/chemistry , AMP-Activated Protein Kinases/metabolism , Reactive Oxygen Species/metabolism , Cell Line , Mitochondria/drug effects , Mitochondria/metabolism , Myocytes, Cardiac/drug effects
7.
CNS Neurosci Ther ; 30(2): e14573, 2024 02.
Article in English | MEDLINE | ID: mdl-38421101

ABSTRACT

AIMS: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. AD pathology involves protein acetylation. Previous studies have mainly focused on histone acetylation in AD, however, the roles of nonhistone acetylation in AD are less explored. METHODS: The protein acetylation and expression levels were detected by western blotting and co-immunoprecipitation. The stoichiometry of acetylation was measured by home-made and site-specific antibodies against acetylated-CaM (Ac-CaM) at K22, K95, and K116. Hippocampus-dependent learning and memory were evaluated by using the Morris water maze, novel object recognition, and contextual fear conditioning tests. RESULTS: We showed that calmodulin (CaM) acetylation is reduced in plasma of AD patients and mice. CaM acetylation and its target Ca2+ /CaM-dependent kinase II α (CaMKIIα) activity were severely impaired in AD mouse brain. The stoichiometry showed that Ac-K22, K95-CaM acetylation were decreased in AD patients and mice. Moreover, we screened and identified that lysine deacetylase 9 (HDAC9) was the main deacetylase for CaM. In addition, HDAC9 inhibition increased CaM acetylation and CaMKIIα activity, and hippocampus-dependent memory in AD mice. CONCLUSIONS: HDAC9-mediated CaM deacetylation induces memory impairment in AD, HDAC9, or CaM acetylation may become potential therapeutic targets for AD.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Mice , Humans , Animals , Alzheimer Disease/metabolism , Calmodulin , Mice, Transgenic , Memory Disorders/etiology , Hippocampus/metabolism , Disease Models, Animal , Histone Deacetylases/metabolism , Repressor Proteins/metabolism
8.
J Cell Biol ; 223(3)2024 03 04.
Article in English | MEDLINE | ID: mdl-38349334

ABSTRACT

The cell cycle is a highly regulated process in which proteins involved in cell cycle progression exhibit periodic expression patterns, controlled by specific mechanisms such as transcription, translation, and degradation. However, the precise mechanisms underlying the oscillations of mRNA levels in cell cycle regulators are not fully understood. In this study, we observed that the stability of cyclin D1 (CCND1) mRNA fluctuates during the cell cycle, with increased stability during interphase and decreased stability during the M phase. Additionally, we identified a key RNA binding protein, positive coactivator 4 (PC4), which plays a crucial role in stabilizing CCND1 mRNA and regulating its periodic expression. Moreover, the binding affinity of PC4 to CCND1 mRNA is modulated by two cell cycle-specific posttranslational modifications: ubiquitination of K68 enhances binding and stabilizes the CCND1 transcript during interphase, while phosphorylation of S17 inhibits binding during the M phase, leading to degradation of CCND1 mRNA. Remarkably, PC4 promotes the transition from G1 to S phase in the cell cycle, and depletion of PC4 enhances the efficacy of CDK4/6 inhibitors in hepatocellular carcinoma, suggesting that PC4 could serve as a potential therapeutic target. These findings provide valuable insights into the intricate regulation of cell cycle dynamics.


Subject(s)
Cell Cycle , Cyclin D1 , RNA Stability , RNA-Binding Proteins , Cell Cycle/genetics , Cell Division , Cyclin D1/genetics , Cyclin-Dependent Kinase Inhibitor Proteins , RNA Stability/genetics , RNA, Messenger/genetics , Male , Animals , Mice , Mice, Inbred BALB C , Humans , Cell Line, Tumor , RNA-Binding Proteins/genetics , Phosphorylation , Ubiquitination
9.
Cell Death Dis ; 15(2): 167, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38396027

ABSTRACT

Neuronal nitric oxide synthase (nNOS, gene name Nos1) orchestrates the synthesis of nitric oxide (NO) within neurons, pivotal for diverse neural processes encompassing synaptic transmission, plasticity, neuronal excitability, learning, memory, and neurogenesis. Despite its significance, the precise regulation of nNOS activity across distinct neuronal types remains incompletely understood. Erb-b2 receptor tyrosine kinase 4 (ErbB4), selectively expressed in GABAergic interneurons and activated by its ligand neuregulin 1 (NRG1), modulates GABA release in the brain. Our investigation reveals the presence of nNOS in a subset of GABAergic interneurons expressing ErbB4. Notably, NRG1 activates nNOS via ErbB4 and its downstream phosphatidylinositol 3-kinase (PI3K), critical for NRG1-induced GABA release. Genetic removal of nNos from Erbb4-positive neurons impairs GABAergic transmission, partially rescued by the NO donor sodium nitroprusside (SNP). Intriguingly, the genetic deletion of nNos from Erbb4-positive neurons induces schizophrenia-relevant behavioral deficits, including hyperactivity, impaired sensorimotor gating, and deficient working memory and social interaction. These deficits are ameliorated by the atypical antipsychotic clozapine. This study underscores the role and regulation of nNOS within a specific subset of GABAergic interneurons, offering insights into the pathophysiological mechanisms of schizophrenia, given the association of Nrg1, Erbb4, Pi3k, and Nos1 genes with this mental disorder.


Subject(s)
ErbB Receptors , Phosphatidylinositol 3-Kinases , Animals , Humans , Mice , ErbB Receptors/metabolism , gamma-Aminobutyric Acid , Hippocampus/metabolism , Neuregulin-1/genetics , Neurons/metabolism , Nitric Oxide Synthase Type I/genetics , Receptor, ErbB-4/genetics , Receptor, ErbB-4/metabolism
10.
J Biol Chem ; 300(3): 105671, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38272222

ABSTRACT

Poly(ADP-ribosyl)ation (PARylation) is a critical posttranslational modification that plays a vital role in maintaining genomic stability via a variety of molecular mechanisms, including activation of replication stress and the DNA damage response. The nudix hydrolase NUDT16 was recently identified as a phosphodiesterase that is responsible for removing ADP-ribose units and that plays an important role in DNA repair. However, the roles of NUDT16 in coordinating replication stress and cell cycle progression remain elusive. Here, we report that SETD3, which is a member of the SET-domain containing protein (SETD) family, is a novel substrate for NUDT16, that its protein levels fluctuate during cell cycle progression, and that its stability is strictly regulated by NUDT16-mediated dePARylation. Moreover, our data indicated that the E3 ligase CHFR is responsible for the recognition and degradation of endogenous SETD3 in a PARP1-mediated PARylation-dependent manner. Mechanistically, we revealed that SETD3 associates with BRCA2 and promotes its recruitment to stalled replication fork and DNA damage sites upon replication stress or DNA double-strand breaks, respectively. Importantly, depletion of SETD3 in NUDT16-deficient cells did not further exacerbate DNA breaks or enhance the sensitivity of cancer cells to IR exposure, suggesting that the NUDT16-SETD3 pathway may play critical roles in the induction of tolerance to radiotherapy. Collectively, these data showed that NUDT16 functions as a key upstream regulator of SETD3 protein stability by reversing the ADP-ribosylation of SETD3, and NUDT16 participates in the resolution of replication stress and facilitates HR repair.


Subject(s)
ADP-Ribosylation , Neoplasms , DNA Breaks, Double-Stranded , DNA Damage , DNA Repair , Neoplasms/genetics , Neoplasms/radiotherapy , Poly (ADP-Ribose) Polymerase-1/genetics , Protein Processing, Post-Translational , Humans , Cell Line , Pyrophosphatases/genetics , Pyrophosphatases/metabolism , Histone Methyltransferases/genetics , Histone Methyltransferases/metabolism
11.
J Burn Care Res ; 45(3): 644-654, 2024 05 06.
Article in English | MEDLINE | ID: mdl-38236154

ABSTRACT

Diabetic wound is one of the serious complications of diabetes, and the wound is persistent and easily recurring, which seriously endangers the health and life of patients. How to effectively promote the healing of diabetic wounds has been a hot spot and difficult area of clinical research. Some previous studies have shown that dihydromyricetin has the effects of regulating blood glucose, controlling the severity, and inhibiting scarring. In the present study, we used polylactic-co-glycolic acid nanoparticles as a carrier to load dihydromyricetin to make drug-loaded nanoparticles and applied them dropwise (200 µL) to diabetic mice wounds by topical application to observe the healing and scar formation of diabetic wounds. We found that the healing rate of the diabetic mice was faster and the scar formation was less obvious. In addition, the elevated blood glucose level and weight loss of the mice in the treatment group were also reduced. Therefore, nanoparticle-mediated dihydromyricetin may be an effective treatment for diabetic wounds.


Subject(s)
Diabetes Mellitus, Experimental , Flavonols , Nanoparticles , Wound Healing , Animals , Flavonols/pharmacology , Flavonols/therapeutic use , Wound Healing/drug effects , Mice , Diabetes Mellitus, Experimental/complications , Male , Blood Glucose/metabolism , Lactic Acid , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry
12.
J Perianesth Nurs ; 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38219078

ABSTRACT

PURPOSE: To evaluate the efficacy of dexamethasone in reducing pain and accelerating recovery after total hip arthroplasty (THA). DESIGN: A prospective randomized controlled trial. METHODS: A total of 98 patients who underwent THA received either low-dose (10 mg) dexamethasone (dexa group) or isotonic saline (placebo group). C-reactive protein and interleukin-6 levels were recorded at 24, 48, and 72 hours after surgery. Pain visual analog scale (VAS) score at rest and walking, the incidence of postoperative nausea and vomiting (PONV), nausea VAS score, postoperative identity-consequence fatigue scale rating, antiemetic use, postoperative length of stay (PLOS), and complications were also recorded and compared. FINDINGS: Inflammatory marker (C-reactive protein and interleukin-6) levels at 24, 48, and 72 hours postoperatively in the dexa group were lower than that in the placebo group (P < .05). After 24 hours of rest, the dynamic pain VAS scores in the dexa group were lower than those in the placebo group (P < .05). The incidence of PONV, nausea VAS score, and identity-consequence fatigue scale score in the dexa group were lower than those in the placebo group (P < .05), and the dosages of analgesics and antiemetics were also lower (P < .05). In addition, PLOS in the dexa group was shorter than that in the placebo group (P < .05). No significant difference in perioperative complications between the two groups was observed (P > .05). CONCLUSIONS: Low-dose dexamethasone in the THA perioperative period can effectively reduce inflammatory marker levels, pain, nausea, postoperative fatigue, opioid analgesic use, and shorten PLOS without increasing complications.

14.
J Burn Care Res ; 45(1): 85-92, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37526062

ABSTRACT

This study evaluated the effects of topical use of caffeine hydrogel on hypertrophic scar in a rabbit ear wound model. Nine rabbits were randomly divided into three groups: control group, caffeine hydrogel group, and matrix group. Punched defects were established on each rabbit's ear which resulted in a hypertrophic scar. When the wound epithelialization and scar hyperplasia could be seen, control group did not do any treatment, while caffeine hydrogel group and matrix group were treated with caffeine hydrogel and hydrogel matrix, respectively. After 3 weeks of administration, the general morphological changes of scar were observed, and the scar tissue of rabbit ears was stained with HE and Masson. The relative expressions of TGF ß-1, α-SMA, type I collagen, and type III collagen in scar tissue were detected by Western blot. In all three groups, findings showed that caffeine hydrogel can inhibit scar growth by reducing the expression of TGF ß-1, reducing the proliferation of fibroblasts, improving collagen arrangement and reducing collagen deposition. The overall study shows efficacy and mechanism of caffeine. It concluded that caffeine could be an effective therapeutic agent for hypertrophicscars.


Subject(s)
Burns , Cicatrix, Hypertrophic , Animals , Rabbits , Cicatrix, Hypertrophic/pathology , Caffeine/pharmacology , Caffeine/metabolism , Caffeine/therapeutic use , Hydrogels/therapeutic use , Burns/metabolism , Collagen/metabolism , Fibroblasts/metabolism
15.
Cardiol J ; 31(1): 32-44, 2024.
Article in English | MEDLINE | ID: mdl-37853822

ABSTRACT

BACKGROUND: Lipoprotein(a) [Lp(a)] was positively associated with recurrent ischemic events in patients with acute coronary syndrome (ACS). This study was performed to investigate the effect of Lp(a) levels on outcomes of dual antiplatelet therapy (DAPT) > 1 year versus DAPT ≤ 1 year after percutaneous coronary intervention (PCI) in this population. METHODS: A total of 4,357 ACS patients who were event-free at 1 year after PCI were selected from the Fuwai PCI Registry, and patients were stratified into four groups according to DAPT duration (≤ 1 year vs. > 1 year) and Lp(a) levels (≤ 30 mg/dL vs. > 30 mg/dL). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of cardiac death, myocardial infarction or stroke. RESULTS: After 2.4-year follow-up, the incidence of MACCE (HRadjusted 0.284, 95% CI 0.115-0.700; HRIPTW 0.351, 95% CI 0.164-0.751) were significantly reduced in DAPT > 1 year group than that in DAPT ≤ 1 year group in individuals with elevated Lp(a) levels. However, in individuals with normal Lp(a) levels, no statistically difference was found between these two groups in terms of MACCE, although the risks of all-cause death and definite/probable stent thrombosis were lower in DAPT > 1 year group. Notably, the risk of clinically relevant bleeding did not statistically differ between these two groups in individuals with different Lp(a) levels. CONCLUSIONS: This study firstly demonstrated that extended DAPT (> 1 year) was statistically associated with lower risk of ischemic events in ACS patients with elevated Lp(a) levels after PCI, whereas this association was not found in individuals with normal Lp(a) levels.


Subject(s)
Acute Coronary Syndrome , Drug-Eluting Stents , Percutaneous Coronary Intervention , Humans , Platelet Aggregation Inhibitors/adverse effects , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/drug therapy , Percutaneous Coronary Intervention/adverse effects , Lipoprotein(a) , Drug Therapy, Combination , Treatment Outcome
16.
Fitoterapia ; 172: 105779, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38104910

ABSTRACT

Six new compounds, including two depsidones garciculendepsidones A and B (1 and 2), one prenylated xanthone garciculenxanthone (3) and three dimeric xanthones bigarciculenxanthones A-C (4-6), were isolated from the twigs and leaves of Garcinia esculenta Y. H. Li. Their structures were elucidated based on comprehensive analyses of spectral data, including HRESIMS, 1D and 2D NMR, and ECD calculation. All the isolates were tested for their cytotoxicity against five human cancer cell lines (myeloid leukemia HL-60, lung cancer A-549 cells, hepatocellular carcinoma SMMC-7721, breast cancer MDA-MB-231 and colon cancer SW480), among them, compounds 3-5 displayed cytotoxic potential, especially garciculenxanthone (3) had the lowest IC50 value of 8.2 µm for lung cancer A-549 cells.


Subject(s)
Antineoplastic Agents, Phytogenic , Antineoplastic Agents , Depsides , Garcinia , Lactones , Lung Neoplasms , Xanthones , Humans , Molecular Structure , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Garcinia/chemistry , Xanthones/pharmacology , Xanthones/chemistry , Lung Neoplasms/drug therapy
17.
Adv Sci (Weinh) ; 11(9): e2305508, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38145957

ABSTRACT

Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post-surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti-recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti-recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Humans , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Blood Loss, Surgical , Hydrogels/therapeutic use , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/pathology , Nanoparticles/therapeutic use , Tumor Microenvironment
18.
Circ J ; 2023 Dec 23.
Article in English | MEDLINE | ID: mdl-38143084

ABSTRACT

BACKGROUND: The clinical impact of relative improvements in coronary physiology in patients receiving percutaneous coronary intervention (PCI) for coronary artery disease (CAD) remains undetermined.Methods and Results: The quantitative flow ratio (QFR) recovery ratio (QRR) was calculated in 1,424 vessels in the PANDA III trial as (post-PCI QFR-pre-PCI QFR)/(1-pre-PCI QFR). The primary endpoint was the 2-year vessel-oriented composite endpoint (VOCE; a composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization). Study vessels were dichotomously stratified according to the optimal QRR cut-off value. During the 2-year follow-up, 41 (2.9%) VOCEs occurred. Low (<0.86) QRR was associated with significantly higher rates of 2-year VOCEs than high (≥0.86) QRR (6.6% vs. 1.4%; adjusted hazard ratio [aHR] 5.05; 95% confidence interval [CI] 2.53-10.08; P<0.001). Notably, among vessels with satisfactory post-procedural physiological results (post-PCI QFR >0.89), low QRR also conferred an increased risk of 2-year VOCEs (3.7% vs. 1.4%; aHR 3.01; 95% CI 1.30-6.94; P=0.010). Significantly better discriminant and reclassification performance was observed after integrating risk stratification by QRR and post-PCI QFR to clinical risk factors (area under the curve 0.80 vs. 0.71 [P=0.010]; integrated discrimination improvement 0.05 [P<0.001]; net reclassification index 0.64 [P<0.001]). CONCLUSIONS: Relative improvement of coronary physiology assessed by QRR showed applicability in prognostication. Categorical classification of coronary physiology could provide information for risk stratification of CAD patients.

19.
Biomed Environ Sci ; 36(11): 1068-1078, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-38098326

ABSTRACT

Objective: To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of "people with the five elements in traditional Chinese medicine (TCM)." Methods: Data collected from the literature review, two sessions of brainstorming of experts with related experience in "people with the five elements in TCM" from October 2020 to December 2020, and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed. Triangulation was used in this study, and theming and synthesizing were used to analyze the data. Results: A total of 31 experts and 30 interviewees participated in this study. The median age of the experts and interviewees were 48.0 and 38.5 years, respectively; 51.66% and 54.8% of experts and interviewees, respectively, were men. The descriptors of facial diagrams of "people with the five elements in TCM" were complexion, shape, distribution state of facial bones, convergence trend of facial muscles, and facial expression. A theoretical model of "people with the five elements in TCM" was shaped based on these findings. Conclusion: The study suggests a possibility for bridging the gap between personality and bodily state, identifying an avenue for personality research from the perspective of TCM.


Subject(s)
Medicine, Chinese Traditional , Projective Techniques , Female , Humans , Male , Medicine, Chinese Traditional/methods , Adult , Middle Aged , Diagnosis
20.
Sci Rep ; 13(1): 19582, 2023 11 09.
Article in English | MEDLINE | ID: mdl-37950063

ABSTRACT

This study aimed to evaluate the optimal frequency of dexamethasone (DEX) administration and the efficacy of DEX with aggressive warming in total hip arthroplasty (THA), which remains unclear. A total of 150 patients were treated with DEX (10 mg) once before and once or twice after surgery with or without intraoperative aggressive warming. On postoperative day 3, the dynamic visual analogue scale scores and C-reactive protein (CRP) and interleukin-6 (IL-6) levels in participants administered with DEX twice after surgery were significantly lower than those who did not receive the second dose. The range of motion (ROM), postoperative fatigue based on Identity-Consequence-Fatigue Scale, average temperature at different stages, intraoperative blood loss, and postoperative drainage volume in patients who were subjected to warming were significantly higher than those who were not. The degree of satisfaction was also higher in the patients who received both second dose and warming than those who received neither. No differences in complications were observed based on the treatments. An additional dose of DEX at 48 h post-surgery has short-term advantages in terms of analgesia, anti-inflammatory effects, and accelerated rehabilitation after THA. DEX combined with aggressive warming further optimises short-term ROM and fatigue and improves the degree of satisfaction.Clinical trial was registered in the International Clinical Trial Registry, and the date of registration is 2/12/2020 (ChiCTR2000040560).


Subject(s)
Arthroplasty, Replacement, Hip , Humans , Arthroplasty, Replacement, Hip/adverse effects , Pain Management , Dexamethasone , Pain/etiology , Fatigue/etiology
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