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1.
Appl Radiat Isot ; 212: 111439, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39111052

ABSTRACT

Abnormal levels of potassium are linked to several health conditions, including high blood pressure, cardiac dysfunction, kidney damage, and osteoporosis. Given the limited availability of in vivo measurement techniques, there is a need for novel methods to measure potassium to enhance the diagnosis and management of potassium metabolism related diseases. This study aimed to evaluate the feasibility of compact neutron generator based in vivo measurement system for quantification of potassium using rat carcasses. A cohort of thirty-nine rats (n = 20 males and 19 females, average weight 255 ± 15 and 163 ± 7 g) were sacrificed, and their carcasses were placed in polyethylene bottles. The rats were then positioned and irradiated in a carefully designed irradiation cave built alongside the neutron generator with an optimized thermal neutron flux and radiation dose ratio. The irradiation time was 10 min, followed by a 5-min decay and 2-h measurement using a high efficiency high purity germanium detector(HPGe). RESULTS: The average potassium concentration in male and female rats was found to be comparable (male 2874 ± 161 and female 2866 ± 144 µg/g). A marginally positive correlation between potassium concentration and weight was found in female rats only (male(20) = 0.07, P = 0.76 and female r(19) = 0.34, P = 0.15). We assessed the influence of manganese toxicity on potassium levels and observed no significant impact. These results were consistent with our previous study in mice. CONCLUSION: This study suggests that in vivo neutron activation analysis could serve as a promising method to quantify potassium and to investigate the storage and metabolism of potassium in human and in animals.

2.
Redox Biol ; 75: 103273, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39142180

ABSTRACT

Malic enzymes (MEs) are metabolic enzymes that catalyze the oxidation of malate to pyruvate and NAD(P)H. While researchers have well established the physiological metabolic roles of MEs in organisms, recent research has revealed a link between MEs and carcinogenesis. This review collates evidence of the molecular mechanisms by which MEs promote cancer occurrence, including transcriptional regulation, post-transcriptional regulation, post-translational protein modifications, and protein-protein interactions. Additionally, we highlight the roles of MEs in reprogramming energy metabolism, suppressing senescence, and modulating the tumor immune microenvironment. We also discuss the involvement of these enzymes in mediating tumor resistance and how the development of novel small-molecule inhibitors targeting MEs might be a good therapeutic approach. Insights through this review are expected to provide a comprehensive understanding of the intricate relationship between MEs and cancer, while facilitating future research on the potential therapeutic applications of targeting MEs in cancer management.


Subject(s)
Energy Metabolism , Malate Dehydrogenase , Neoplasms , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/genetics , Malate Dehydrogenase/metabolism , Malate Dehydrogenase/antagonists & inhibitors , Malate Dehydrogenase/genetics , Gene Expression Regulation, Neoplastic/drug effects , Tumor Microenvironment , Animals , Protein Processing, Post-Translational , Oxidation-Reduction
3.
BMC Pregnancy Childbirth ; 24(1): 420, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858685

ABSTRACT

BACKGROUND: Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years. CASE PRESENTATION: A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND. CONCLUSION: The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities.


Subject(s)
Agenesis of Corpus Callosum , Craniofacial Abnormalities , Face , Hydrocephalus , Imaging, Three-Dimensional , Limb Deformities, Congenital , Ultrasonography, Prenatal , Humans , Female , Adult , Pregnancy , Craniofacial Abnormalities/diagnostic imaging , Agenesis of Corpus Callosum/diagnostic imaging , Agenesis of Corpus Callosum/genetics , Limb Deformities, Congenital/diagnostic imaging , Limb Deformities, Congenital/genetics , Face/abnormalities , Face/diagnostic imaging , Hydrocephalus/diagnostic imaging , Heart Septal Defects, Ventricular/diagnostic imaging , Heart Septal Defects, Ventricular/genetics , Abnormalities, Multiple/diagnostic imaging , Abnormalities, Multiple/genetics
4.
Nutrients ; 16(11)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38892715

ABSTRACT

NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3-V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.


Subject(s)
Gastrointestinal Microbiome , Gynostemma , Non-alcoholic Fatty Liver Disease , Plant Extracts , Animals , Gastrointestinal Microbiome/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Mice , Gynostemma/chemistry , Plant Extracts/pharmacology , Male , Inflammation/drug therapy , Liver/drug effects , Liver/metabolism , Mice, Inbred C57BL , Disease Models, Animal , Signal Transduction/drug effects , Anti-Inflammatory Agents/pharmacology
5.
Arch Gynecol Obstet ; 310(1): 609-614, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38836926

ABSTRACT

OBJECTIVE: To investigate the superiority of transrectal high-frequency ultrasound (TRUS) in precise assessment of middle compartment prolapse in comparison with routine transperineal ultrasound (TPUS). METHODS: Prospectively analyzed and compared detection rates of entire cervical length and uterine descent on TPUS and TRUS in 101 patients with pelvic organ prolapse (POP). RESULTS: Detection rates of entire cervix on TRUS were significantly higher than those on TPUS both at rest and during Valsalva maneuver (90.10% VS 49.50%, 92.08% VS 9.90% respectively, both p < 0.05). Uterine descent was able to be evaluated in 92.08% of patients by TRUS and in 5.94% of patients by TPUS, which was statistically significant (p < 0.05). The interobserver repeatability for the measurements of anterior lip, cervical canal and posterior lip on TRUS was excellent. The mean lengths of anterior lip, cervical canal and posterior lip were significantly increased during Valsalva maneuver than those measured at rest (p < 0.05). And mean length of anterior lip was longer than posterior lip both at rest and during Valsalva (p < 0.05). CONCLUSION: TRUS can significantly raise detection rates of entire cervix, and make the direct evaluation of uterine descent feasible. TRUS can be used as a complementary method to TPUS to attain more comprehensive and accurate presurgical imaging information in middle compartment prolapse patients.


Subject(s)
Pelvic Organ Prolapse , Ultrasonography , Valsalva Maneuver , Humans , Female , Middle Aged , Pelvic Organ Prolapse/diagnostic imaging , Ultrasonography/methods , Prospective Studies , Aged , Adult , Cervix Uteri/diagnostic imaging
6.
Article in English | MEDLINE | ID: mdl-38810897

ABSTRACT

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.


Subject(s)
Anura , Cathelicidins , Animals , Mice , Amino Acid Sequence , Immunologic Factors/pharmacology , Aeromonas hydrophila , Amphibian Proteins/pharmacology , Amphibian Proteins/genetics , Amphibian Proteins/isolation & purification , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/isolation & purification , RAW 264.7 Cells , Immunomodulating Agents/pharmacology , Immunomodulating Agents/isolation & purification , Skin/drug effects , Skin/metabolism , Skin/immunology , East Asian People
7.
Nanomaterials (Basel) ; 14(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38668156

ABSTRACT

In recent years, the phenomenon of optical second harmonic generation (SHG) has attracted significant attention as a pivotal nonlinear optical effect in research. Notably, in low-dimensional materials (LDMs), SHG detection has become an instrumental tool for elucidating nonlinear optical properties due to their pronounced second-order susceptibility and distinct electronic structure. This review offers an exhaustive overview of the generation process and experimental configurations for SHG in such materials. It underscores the latest advancements in harnessing SHG as a sensitive probe for investigating the nonlinear optical attributes of these materials, with a particular focus on its pivotal role in unveiling electronic structures, bandgap characteristics, and crystal symmetry. By analyzing SHG signals, researchers can glean invaluable insights into the microscopic properties of these materials. Furthermore, this paper delves into the applications of optical SHG in imaging and time-resolved experiments. Finally, future directions and challenges toward the improvement in the NLO in LDMs are discussed to provide an outlook in this rapidly developing field, offering crucial perspectives for the design and optimization of pertinent devices.

8.
Heliyon ; 10(5): e26552, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38434403

ABSTRACT

Objectives: There are many available pharmaceutical and surgical management for Coronary artery disease (CAD) patients. However, coronary artery bypass grafting (CABG) is the preferred treatment modality for CAD patients with low ejection fraction (EF) in view of the more favorable outcomes. This study aimed to determine the associated factors of poor outcomes post-CABG for heart failure patients with reduced left ventricular ejection fraction who underwent on-pump and off-pump CABG. Methods: A retrospective review of CAD patients who underwent isolated on-pump CABG (ONCAB) or off-pump CABG (OPCAB) in Beijing Anzhen Hospital Affiliated with Capital Medical University from January 2013 to March 2021. Only those with confirmed reduced left ventricular ejection fraction (LVEF) ≤40% on preoperative echocardiography were included. By analyzing the clinical and surgical data, postoperative mortality and morbidity, as well as major cardiovascular and cerebrovascular adverse events (MACCE) as endpoints, certain risk factors of the postoperative complications were identified. Results: Out of the 500 patients, 64 developed MACCE, of which 14 (13.6%) occurred in the ONCAB group and 50 (14.0%) in the OPCAB group. Univariate COX regression analysis showed that age ≥65 years, history of diabetes, and preoperative renal insufficiency were independent risk factors for postoperative primary endpoint events in CAD patients with heart failure with reduced ejection fraction (HFrEF). Following the multivariate COX regression analysis, in addition to the above three risk factors, a history of previous percutaneous coronary angiography (PCI) intervention was also a risk factor for the occurrence of the primary endpoints post-CABG. Conclusion: Based on the analysis, significant predictors of post-CABG MACCE in patients with HFrEF included being older than 65 years old, having diabetes, preoperative renal insufficiency, and having previous PCI.

9.
Cell Signal ; 116: 111064, 2024 04.
Article in English | MEDLINE | ID: mdl-38266744

ABSTRACT

Abnormal inflammation of vascular endothelial cells occurs frequently in diabetic retinopathy (DR). Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) is a lipid raft enzyme and plays an anti-inflammatory role in various diseases but its function in DR-related vascular endothelial dysfunction remains unknown. We first found that SMPDL3B expression was upregulated from week 10 to 18 in the retinal tissues of db/db mice. Particularly, the high expression of SMPDL3B was mainly observed in retinal vascular endothelium of DR mice. To interfere retinal SMPDL3B expression, adeno-associated viruses 2 (AAV-2) containing SMPDL3B specific shRNA (1233-1253 bp) were injected into the vitreous cavity of db/db mice. SMPDL3B silencing exacerbated the spontaneous DR by further activating the NF-κB/NLRP3 pro-inflammatory pathway. In vitro, human retinal microvascular endothelial cells (HRVECs) were infected with SMPDL3B-shRNA lentiviruses and then stimulated with 30 mM glucose (HG) for 24 h. SMPDL3B-silenced HRVECs secreted more interleukin-1ß and had enhanced nuclear p65 translocation. Notably, HG treatment induced the palmitoylation of SMPDL3B. Zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) is a palmitoyltransferase that catalyzes the palmitoylation of its substrates, HG exposure increased the interaction between ZDHHC5 and SMPDL3B in HRVECs. 2-BP, a palmitoylation inhibitor, accelerated the protein degradation of SMPDL3B, whereas palmostatin B, a depalmitoylation inhibitor, decreased its turnover rate in HRVECs. Collectively, the present study suggests a compensatory increase of SMPDL3B in HG-treated HRVECs and the retinal tissues of DR mice, indicating that SMPDL3B may be a potential target for DR treatment.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Animals , Humans , Mice , Diabetes Mellitus/metabolism , Diabetic Retinopathy/metabolism , Endothelial Cells/metabolism , Mice, Inbred Strains , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , RNA, Small Interfering/metabolism , Sphingomyelin Phosphodiesterase/metabolism
10.
ACS Appl Mater Interfaces ; 16(1): 907-914, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38146641

ABSTRACT

Entropy engineering is aneffective scheme to reduce the thermal conductivity of thermoelectric materials, but it inevitably deteriorates the carrier mobility. Here, we report the optimization of thermoelectric performance of PbTe by combining entropy engineering and nanoprecipitates. In the continuously tuned compounds of Pb0.98Na0.02Te(1-2x)SxSex, we show that the x = 0.05 sample exhibits an exceptionally low thermal conductivity relative to its configuration entropy. By introducing Mn doping, the produced temperature-dependent nanoprecipitates of MnSe cause the high-temperature thermal conductivity to be further reduced. A very low lattice thermal conductivity of 0.38 W m-1 K-1 is achieved at 825 K. Meanwhile, the carrier mobility of the samples is only slightly influenced, owing to the well-controlled configuration entropy and the size of nanoprecipitates. Finally, a high peak zT of ∼2.1 at 825 K is obtained in the Pb0.9Na0.04Mn0.06Te0.9S0.05Se0.05 alloy.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1018365

ABSTRACT

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1021658

ABSTRACT

BACKGROUND:Mesenchymal stem cells are pluripotent stromal cells isolated from a variety of tissues,which can differentiate into osteoblasts under certain conditions.Photobiomodulation,as an external stimulus,can promote osteogenic differentiation combined with other inducers or alone,providing new ideas for solving a series of bone diseases. OBJECTIVE:To review the relevant literature and mechanisms of photobiomodulation-induced osteogenic differentiation of mesenchymal stem cells,which will lay a theoretical foundation for bone tissue engineering using mesenchymal stem cells as seed cells and may offer some suggestions for future studies. METHODS:Relevant articles were searched on CNKI,PubMed and Wed of Science databases with Chinese search terms of"photobiomodulation,low power laser,low level laser,light-emitting diode,mesenchymal stem cells,osteogenic differentiation,biomaterials"and English search terms of"photobiomodulation,low level laser(light),light-emitting diode(LED),mesenchymal stem cell,osteogenic differentiation,biomaterials".Finally,88 articles were included for analysis. RESULTS AND CONCLUSION:(1)Photobiomodulation represented by low level laser and diode laser has a positive effect on promoting the proliferation and differentiation of mesenchymal stem cells.(2)Photobiomodulation can induce osteogenic differentiation of mesenchymal stem cells,whose feasibility has been verified in cell and animal experiments.On one hand,photobiomodulation can promote the expansion and differentiation of stem cells in vitro by activating related signaling pathways and up-regulating the expression of osteogenic molecules.On the other hand,photobiomodulation can improve the survival rate of stem cells in vivo,promote homing effect and shorten the healing time of bone defects after stem cells are injected into the body.However,photobiomodulation has a biphasic dose effect,whose laser parameters,experimental environment,cell type and other factors in various studies are different,making the research results lack consistency and difficult to apply in the clinic.(3)Combined with biological materials,other physical factors and drugs,photobiomodulation can also accelerate osteogenic differentiation.(4)In conclusion,photobiomodulation has been used increasingly widely in the medical field with its advantages of non-invasive,efficient and less-side reactions,and its role in bone tissue engineering has gradually become prominent,which provides a new method for the treatment of bone defects and related diseases.Further exploration should be focused on the standardized treatment parameters of photobiomodulation.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1028731

ABSTRACT

AIM To explore the effects of Shiquan Dabu Decoction on the synaptic function and cognitive impairment in a mouse model of Alzheimer's disease(AD).METHODS Sixty mice were randomly divided into the control group,the model group,the memantine group(5 mg/kg)and the high,medium and low dose Shiquan Dabu Decoction groups(6.24,3.12 and 1.56 g/kg),with 10 mice in each group.Except for those of the control group,the mice of other groups underwent their 70-day AD models induction by intraperitoneal injection of D-galactose and gavage feeding of AlCl3,followed by 42-day corresponding dosing of drugs by gavage on the 29th day.The mice had their spatial learning and associative memory detected by Morris water maze test and conditioned fear test;their morphological changes of hippocampal neurons observed by HE staining;their serum SOD activity,MDA level,and SOD,AChE activities and MDA,ACh,TNF-α and IL-1β levels in hippocampus detected by kits;and their PSD-95,Shank3,NR1,NR2A,NR2B,AMPK and p-AMPK protein expressions in hippocampus detected by Western blot.RESULTS Compared with the model group,the high-dose Shiquan Dabu Decoction group displayed improved spatial learning and memory ability and associative memory(P<0.05,P<0.01);reduced pathological damage of hippocampal neurons,decreased levels of oxidative stress and inflammation(P<0.05,P<0.01);enhanced cholinergic transmission(P<0.05,P<0.01),and increased protein expressions of PSD-95,Shank3,NR1,NR2A,NR2B,and p-AMPK in hippocampal tissue(P<0.05,P<0.01).CONCLUSION Shiquan Dabu Decoction can improve the cognitive impairment of in the mouse model of AD,and its mechanism may be related to AMPK activation and synaptic function restoration.

14.
Polymers (Basel) ; 15(17)2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37688224

ABSTRACT

Silicone rubber insulators are widely used in power grids because of their excellent performance, but aging has been an inevitable problem of silicone rubber, especially in extreme conditions, such as acidic conditions. In order to clarify the performance changes in silicone rubber in an acidic environment, this paper uses the developed acid-resistant silicone rubber sheet and common silicone rubber samples as the research objects, and conducts an aging comparison test on them in a natural acidic environment. The electrical properties, physical properties, and chemical properties of the two types of silicone rubber specimens with different aging times are analyzed to obtain the performance characteristics of silicone rubber under a natural acidic environment. The research results show that the dry flash voltage and pollution flashover voltage of the acid-resistant silicone rubber after one year of aging are greater than those of the common type; the water repellency of both types of silicone rubber remains in good condition. The silicone rubber produced by our team according to the self-developed acid-resistant silicone rubber formula has indeed played a role in delaying aging in an acidic environment compared with the common-type silicone rubber.

16.
Exp Cell Res ; 430(2): 113735, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37517590

ABSTRACT

Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovary morphology, affecting more and more women of reproductive age. Our study aimed to explore the molecular mechanism and effect of exosomal miR-4449 on granulosa cells (GCs). Two immortalized human ovarian granulosa cells (KGN and COV434 cells) were used for in vitro functional studies. Our study found that follicular fluid (FF) derived exosomal miR-4449 was significantly decreased in women with PCOS compared with the control patients. And exosomal miR-4449 could alleviate GCs oxidative stress (OS) and promote GCs proliferation, while the opposite trend was observed after inhibiting the expression of miR-4449. In addition, we demonstrated that Kelch-like ECH-associated protein 1(KEAP1) was a direct target of miR-4449 through dual-luciferase reporter assay, and the expression patterns of KEAP1 and miR-4449 in PCOS FF-derived exosomes were exactly opposite. In addition, KEAP1/NRF2 signaling pathway may play an important role in GCs proliferation and OS. Our results demonstrated that the decreased FF-derived exosomal miR-4449 expression in PCOS might aggravate the OS of GCs and inhibit GCs proliferation via KEAP1/NRF2 signaling pathway. Exosomal miR-4449 might be a potential biomarker for the diagnosis of PCOS. Our study contributes to a new understanding of the pathogenesis of PCOS.


Subject(s)
MicroRNAs , Polycystic Ovary Syndrome , Humans , Female , MicroRNAs/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/pathology , Follicular Fluid/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Granulosa Cells , Cell Proliferation/genetics , Apoptosis
17.
Opt Express ; 31(6): 9481-9495, 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-37157518

ABSTRACT

Multi-mode converters, which can achieve spatial mode conversion in multimode waveguide, play a key role in multi-mode photonics and mode-division multiplexing (MDM). However, rapid design of high-performance mode converters with ultra-compact footprint and ultra-broadband operation bandwidth is still a challenge. In this work, through combining adaptive genetic algorithm (AGA) and finite element simulations, we present an intelligent inverse design algorithm and successfully designed a set of arbitrary-order mode converters with low excess losses (ELs) and low crosstalk (CT). At the communication wavelength of 1550 nm, the footprint of designed TE0-n (n = 1, 2, 3, 4) and TE2-n (n = 0, 1, 3, 4) mode converters are only 1.8 × 2.2 µm2. The maximum and minimum conversion efficiency (CE) is 94.5% and 64.2%, and the maximum and minimum ELs/CT are 1.92/-10.9 dB and 0.24/-20 dB, respectively. Theoretically, the smallest bandwidth for simultaneously achieving ELs ≤ 3 dB and CT ≤ -10 dB exceeds 70 nm, which can be as large as 400 nm for the case of low-order mode conversion. Moreover, the mode converter in conjunction with a waveguide bend allows for mode-conversion in ultra-sharp waveguide bends, significantly increasing the density of on-chip photonic integration. This work provides a general platform for the realization of mode converters and has good prospect in application of multimode silicon photonics and MDM.

18.
Nanomedicine ; 51: 102686, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37121459

ABSTRACT

Sonodynamic therapy (SDT) can noninvasively focus sound energy to deep tumor tissues and activate sonosensitizer (such as chlorin e6(Ce6)) to produce antitumor effects. However, due to the hypoxic microenvironment of the tumor, the effect of sonodynamic therapy is limited. In this work, we successfully synthesized Platinum-Boron-Phosphorus ternary nanoparticles (Pt-B-P NPs) for the first time to efficiently catalyze the decomposition of hydrogen peroxide (H2O2) in tumor tissues to produce sufficient oxygen (O2) and improve the effect of sonodynamic treatment of ovarian cancer. In vitro studies, we found that compared with Platinum nanoparticles (Pt NPs), Pt-B-P NPs have the significantly increased ability to catalyze the decomposition of H2O2 to produce oxygen and thus the hypoxic environment of tumor cells could be improved efficiently. Meanwhile, the bio-distribution, therapeutic effect and bio-safety of Pt-B-P NPs in vivo were evaluated using BALB/c-nu mouse model of ovarian cancer and the desired result had been achieved.


Subject(s)
Metal Nanoparticles , Nanoparticles , Ovarian Neoplasms , Humans , Mice , Animals , Female , Metal Nanoparticles/therapeutic use , Platinum/pharmacology , Hydrogen Peroxide , Ovarian Neoplasms/drug therapy , Oxygen , Mice, Inbred BALB C , Reactive Oxygen Species , Cell Line, Tumor , Tumor Microenvironment
19.
BMJ Open ; 13(3): e069465, 2023 03 08.
Article in English | MEDLINE | ID: mdl-36889830

ABSTRACT

OBJECTIVES: The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA). DESIGN: Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III). SETTING: We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China. PARTICIPANTS: 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was a new stroke, LDL-C goal (LDL-C<1.8mmol/L and LDL-C<1.4mmol/L, respectively) achievement rates, and LLT compliance within 3, 6, and 12 months. The secondary outcomes included major adverse cardiovascular events (MACE) and all caused death at 3 and 12 months. RESULTS: Among the 15,166 patients, over 90% of patients received LLT during hospitalization and 2 weeks after discharge; the LLT compliance was 84.5% at 3 months, 75.6% at 6 months, and 64.8% at 12 months. At 12 months, LDL-C goal achievement rate for 1.8mmol/L and 1.4mmol/L was 35.4% and 17.6%, respectively. LLT at discharge was associated with reduced risk of ischemic stroke recurrence (HR=0.69, 95% CI: 0.48-0.99, p=0.04) at 3 months. The rate of LDL-C reduction from baseline to 3-month follow-up was not associated with a reduced risk of stroke recurrence or major adverse cardiovascular events (MACE) at 12 months. Patients with baseline LDL-C ≤1.4mmol/L had a numerically lower risk of stroke, ischemic stroke and MACE at both 3 months and 12 months. CONCLUSIONS: The LDL-C goal achievement rate has increased mildly in the stroke and TIA population in mainland China. Lowered baseline LDL-C level was significantly associated with a decreased short- and long-term risk of ischemic stroke among stroke and TIA patients. LDL-C<1.4mmol/L might be a safe standard for this population.


Subject(s)
Brain Ischemia , Ischemic Attack, Transient , Ischemic Stroke , Stroke , Humans , Stroke/therapy , Ischemic Attack, Transient/epidemiology , Ischemic Attack, Transient/therapy , Cholesterol, LDL , Registries , China/epidemiology
20.
Sci Rep ; 13(1): 4081, 2023 03 11.
Article in English | MEDLINE | ID: mdl-36906716

ABSTRACT

Phosphoserine aminotransferase 1 (PSAT1) has been associated with the occurrence and development of various carcinomas; however, its function in uterine corpus endometrial carcinoma (UCEC) is unknown. We aimed to explore the relationship between PSAT1 and UCEC using The Cancer Genome Atlas database and functional experiments. PSAT1 expression levels in UCEC were employed using the paired sample t-test, Wilcoxon rank-sum test, the Clinical Proteomic Tumor Analysis Consortium database, and the Human Protein Atlas database, while survival curves were constructed using the Kaplan-Meier plotter. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the possible functions and related pathways of PSAT1. Furthermore, single-sample gene set enrichment analysis was performed to detect the relationship between PSAT1 and tumor immune infiltration. StarBase and quantitative PCR were used to predict and verify the interactions between miRNAs and PSAT1. The Cell Counting Kit-8, EdU assay, clone formation assay, western blotting and flow cytometry were used to evaluate cell proliferation. Finally, Transwell and Wound healing assays were used to assess cell invasion and migration. Our study found that PSAT1 was significantly overexpressed in UCEC, and this high expression was associated with a worse prognosis. A high level of PSAT1 expression was associated with a late clinical stage and, histological type. In addition, the results of GO and KEGG enrichment analysis showed that PSAT1 was mainly involved in the regulation of cell growth, immune system and cell cycle in UCEC. In addition, PSAT1 expression was positively correlated with Th2 cells and negatively correlated with Th17 cells. Furthermore, we also found that miR-195-5P negatively regulated the expression of PSAT1 in UCEC. Finally, the knockdown of PSAT1 resulted in the inhibition of cell proliferation, migration, and invasion in vitro. Overall, PSAT1 was identified as a potential target for the diagnosis and immunotherapy of UCEC.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Transaminases , Female , Humans , Carcinoma, Endometrioid/genetics , Cell Proliferation , Databases, Protein , Down-Regulation , Endometrial Neoplasms/genetics , Proteomics , Transaminases/genetics
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