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1.
Materials (Basel) ; 17(11)2024 May 27.
Article in English | MEDLINE | ID: mdl-38893832

ABSTRACT

This research demonstrates changes in the behaviors and characteristics of sintered bricks while using industrial sludge ash (ISA) and waste glass (WG) as a replacement for clay in the brick manufacturing procedure. Owing to the limited amount of available land in Taiwan, it is becoming increasingly difficult to locate suitable sites for sanitary landfills, which is a common final disposal method for ash that is produced during thermal treatment in sludge factories. To meet the urgent need for land, the final waste disposal must convert this waste into a new resource. This research investigated the feasibility of using general industrial sludge ash waste, due to its abundance and high potential as a raw material in producing bricks. The result of this study shows that the bricks made from ISA and WG under a certain mixture proportion (ISA50%/WG40%/Clay10%) had excellent industrial potentials, such as compressive strength and water absorption rate. However, owing to the wide variety of components from different sources of ISA, the mixture proportion might vary accordingly. This study also analyzed the incineration index, proportion design, and process improvement, as well as investigating the possibility of increasing the total use of sludge ash as a resource. This study shows the potentials of utilizing wastes as raw materials in industrial manufacturing procedures. Therefore, more wastes can be tested and turned into resources in the future.

2.
Int J Biol Macromol ; 265(Pt 2): 130945, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38493818

ABSTRACT

INTRODUCTION: Immune checkpoint inhibitor therapy is a highly promising strategy for clinical treatment of cancer. Among these inhibitors, ipilimumab stands out for its ability to induce cytotoxic T cell proliferation and activation by binding to CTLA-4. However, ipilimumab also gives rise to systemic immune-related adverse effects and tumor immune evasion, limiting its effectiveness. OBJECTIVES: We developed IFNγ-ipilimumab and confirmed that the addition of INF-γ does not alter the fundamental properties of ipilimumab. RESULTS: IFNγ-ipilimumab can be activated by matrix metalloproteinases, thereby promoting the IFNγ signaling pathway and enhancing the cytotoxicity of T cells. In vivo studies demonstrated that IFNγ-ipilimumab enhances the therapeutic effect of ipilimumab against colorectal cancer by increasing CD8+ and CD4+ lymphocyte infiltration into the tumor area and inducing MHC-I expression in tumor cells. Mice treated with IFNγ-ipilimumab showed higher survival rates and body weight, as well as lower CD4+ and CD8+ lymphocyte activation rates in the blood and reduced organ damage. CONCLUSION: IFNγ-ipilimumab improved the effectiveness of ipilimumab while reducing its side effects. It is likely that future immunotherapies would rely on such antibodies to activate local cancer cells or immune cells, thereby increasing the therapeutic effectiveness of cancer treatments and ensuring their safety.


Subject(s)
Antineoplastic Agents , Neoplasms , Animals , Mice , Ipilimumab/pharmacology , Ipilimumab/therapeutic use , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , T-Lymphocytes, Cytotoxic
3.
J Virol ; 98(4): e0125823, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38546211

ABSTRACT

Dengue fever, an infectious disease prevalent in subtropical and tropical regions, currently lacks effective small-molecule drugs as treatment. In this study, we used a fluorescence peptide cleavage assay to screen seven compounds to assess their inhibition of the dengue virus (DENV) NS2B-NS3 protease. DV-B-120 demonstrated superior inhibition of NS2B-NS3 protease activity and lower toxicity compared to ARDP0006. The selectivity index of DV-B-120 was higher than that of ARDP0006. In vivo assessments of the antiviral efficacy of DV-B-120 against DENV replication demonstrated delayed mortality of suckling mice treated with the compound, with 60-80% protection against life-threatening effects, compared to the outcomes of DENV-infected mice treated with saline. The lower clinical scores of DENV-infected mice treated with DV-B-120 indicated a reduction in acute-progressive illness symptoms, underscoring the potential therapeutic impact of DV-B-120. Investigations of DV-B-120's ability to restore the antiviral type I IFN response in the brain tissue of DENV-infected ICR suckling mice demonstrated its capacity to stimulate IFN and antiviral IFN-stimulated gene expression. DV-B-120 not only significantly delayed DENV-2-induced mortality and illness symptoms but also reduced viral numbers in the brain, ultimately restoring the innate antiviral response. These findings strongly suggest that DV-B-120 holds promise as a therapeutic agent against DENV infection and highlight its potential contribution in addressing the current lack of effective treatments for this infectious disease.IMPORTANCEThe prevalence of dengue virus (DENV) infection in tropical and subtropical regions is escalating due to factors like climate change and mosquito vector expansion. With over 300 million annual infections and potentially fatal outcomes, the urgent need for effective treatments is evident. While the approved Dengvaxia vaccine has variable efficacy, there are currently no antiviral drugs for DENV. This study explores seven compounds targeting the NS2B-NS3 protease, a crucial protein in DENV replication. These compounds exhibit inhibitory effects on DENV-2 NS2B-NS3, holding promise for disrupting viral replication and preventing severe manifestations. However, further research, including animal testing, is imperative to assess therapeutic efficacy and potential toxicity. Developing safe and potent treatments for DENV infection is critical in addressing the rising global health threat posed by this virus.


Subject(s)
Dengue Virus , Dengue , Piperidines , Animals , Mice , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Communicable Diseases , Dengue/drug therapy , Dengue Virus/physiology , Endopeptidases/pharmacology , Mice, Inbred ICR , Piperidines/administration & dosage , Protease Inhibitors/pharmacology , Viral Nonstructural Proteins/chemistry
4.
Mediators Inflamm ; 2023: 3906043, 2023.
Article in English | MEDLINE | ID: mdl-37101595

ABSTRACT

This study is aimed at exploring whether curcumin can regulate the AKT pathway, promote the transfer of Nrf2 into the nucleus, and inhibit cell pyroptosis in diabetic cardiomyopathy. Diabetic rats and cardiomyocytes were treated with curcumin to study its effect on myocardial pyroptosis. Whether curcumin can promote the transfer of Nrf2 into the nucleus through AKT pathway regulation was assessed by western blotting and immunofluorescence. The Nrf2 knockout vector and ml385 were used to block the Nrf2 pathway, and the differences between the different groups in the expression of pyroptosis protein, cell activity, and incidence of apoptosis were evaluated to verify the relationship between the effect of curcumin on pyroptosis inhibition and the Nrf2 pathway. Curcumin promoted the transfer of Nrf2 into the nucleus through the AKT pathway and increased the expression of the antioxidant factors HO-1 and GCLC. These effects reduced reactive oxygen species accumulation and mitochondrial damage in diabetic myocardium and inhibited diabetes-induced pyroptosis. However, in cardiomyocytes with a blocked Nrf2 pathway, the ability of curcumin to inhibit pyroptosis was significantly reduced, and the protective effect on the cells was lost. Curcumin can reduce the accumulation of superoxide in the myocardium through AKT/Nrf2/ARE pathway activation and inhibit pyroptosis. It also has a role in diabetic cardiomyopathy treatment. This study provides new directions for evaluating the mechanism of diabetic cardiomyopathy and treating diabetic myocardium.


Subject(s)
Curcumin , Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Rats , Animals , Curcumin/pharmacology , Curcumin/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Pyroptosis , Diabetic Cardiomyopathies/drug therapy , NF-E2-Related Factor 2/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Oxidative Stress
5.
Br J Neurosurg ; 37(5): 1395-1397, 2023 Oct.
Article in English | MEDLINE | ID: mdl-33377403

ABSTRACT

We report a case of cholesteatoma that caused left facial pain with facial numbness. The tumour was located in the left cerebellopontine angle (CPA) and Meckel's cave. A balloon was first placed into Meckel's cave, and then, under electrophysiological monitoring, the tumour within the CPA cistern was resected via the retrosigmoid approach. The balloon was inflated in Meckel's cave to push the tumour out of Meckel's cave, and then, the tumour was completely removed under endoscopy. The symptoms, including pain and numbness, subsided after surgery.


Subject(s)
Cholesteatoma , Neoplasms , Neuroendoscopy , Humans , Cerebellopontine Angle/diagnostic imaging , Cerebellopontine Angle/surgery , Cholesteatoma/surgery , Hypesthesia/surgery , Female , Middle Aged
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-992523

ABSTRACT

Objective:To understand the genome sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spike protein variations during different epidemic periods in Wuxi City.Methods:Nucleic acid was extracted from the nasopharyngeal swab samples of six local cases of coronavirus disease 2019 (COVID-19) (from January to February, 2020) and 13 imported cases of COVID-19 (from March to September, 2021) in Wuxi City, and the whole genome was amplified to construct the sequencing library. The second-generation sequencer was used for sequencing. The CLC Genomics Workbench (21 version) software was used to analyze the offline data with NC_045512.2 as the reference strain, and MEGA 7.0 software was used to construct the phylogenetic tree.Identification of type was conducted by Nextstrain typing method and phylogenetic assignment of named global outbreak lineages (Pangolin) typing method.Results:There were five subtypes in Nextstrain and seven subtypes in Pangolin of the nineteen patients with COVID-19. Compared with NC_045512.2, the median nucleotide mutation sites were 29 (range 0 to 42) and amino acid mutation sites were 20 (range 0 to 34). The six local and 13 imported cases had no common nucleotide mutation sites and were in different evolutionary branches. The sequences of the six local cases were highly homologous with the reference strain sequences (NC_045512.2) at the early stage of the pandemic, and the evolutionary distance was close to that of the reference strain. The 13 imported cases were obviously divided into three evolutionary branches (Alpha, Beta, Delta variant).The four Beta variants shared eight amino acid mutation sites in spike protein, and the two Alpha variants shared eight amino acid mutation sites in spike protein, and the seven Delta variants shared five amino acid mutation sites in spike protein.Conclusions:New mutations of SARS-CoV-2 are constantly emerging during the epidemic. The increase of the nucleotide sites number may result in the change of spike protein amino acid. Therefore, the whole-genome sequencing analysis plays an important role in the accurate tracing of epidemic origin and adjustment of prevention and control measures.

7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-989661

ABSTRACT

Objective:To establish a method for the determination of four effective components in Paeoniae Radix Alba and evaluate its quality of Paeoniae Radix Alba by principal component analysis. Methods:The effective components of Paeoniae Radix Alba were extracted by ultrasonic extraction method with ethanol. Wondasil WR C18 chromatographic column (250 mm×4.6 mm,5 μm) was used, and the mobile phase was acetonitrile-water, the flow rate was set at 1 ml/min, the column temperature was set at 30 ℃, and the total operation time was 65 min. The mass score of active components was imported into SPSS for principal component analysis. Results:The linear ranges of Paeoniflorin, Paeoniflorin, Benzoyl Paeoniflorin and Pallyl Paeoniflorin were 0.020 1-3.820 0 μg ( r2=0.999 4), 0.015 9-2.850 0 μg ( r2=0.999 2), 0.008 2- 1.820 0 μg ( r2=0.999 1), 0.003 2-0.970 0 μg ( r2=0.999 5). The quality of the 10 batches of Paeoniae Radix Alba samples from Anhui province was the best, while that from Sichuan province was the worst. Conclusions:HPLC method was established for the determination of four effective components in Paeoniae Radix Alba, and principal component analysis and evaluation of 10 batches of Paeoniae Radix Alba. Bozhou, Anhui Province, was identified as the main production area of Paeoniae Radix Alba, which can provide reference for the quality control and preparation production of Paeoniae Radix Alba.

8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-981696

ABSTRACT

OBJECTIVE@#To compare clinical efficacy of platelet-rich plasma (PRP) and extracorporeal shock wave in treating chronic insertional Achilles tendinopathy.@*METHODS@#From February 2019 to August 2021, 42 patients with chronic insertional Achilles tendinopathy were selected and divided into PRP group(20 patients, 28 feet) and shock wave group (22 patients, 29 feet). In PRP group, there were 12 males and 8 females, aged 47.00(28.00, 50.75) years old, and the courses of disease ranged 7.00(6.00, 7.00) months;PRP injection was performed in the Achilles tendon stop area of the affected side. In shock wave group, there were 16 males and 6 females, aged 42.00(35.75, 47.25) years old;and the courses of disease was 7.00(6.00, 8.00) months;shock wave was performed in Achilles tendon stop area of the affected side and triceps surae area. Visual analogue scale (VAS) and Victorian Institute of Sport Assessment-Achilles (VISA-A) were applied to evaluate clnical effect before treatment, 1, 3 and 6 months after treatment, and satisfaction of patients was investigated.@*RESULTS@#VAS and VISA-A score in both groups were significantly improved at 1, 3 and 6 months after treatment than before treatment (P<0.05), VAS and VISA-A score in PRP group at 6 months after treatment were significantly higher than those at 1 and 3 months after treatment, and VAS and VISA-A score in shock wave group were lower than those at 1 and 3 months after treatment (P<0.05). There was no significant difference in VAS and VISA-A score between two groups before treatment, 1 and 3 months after treatment(P>0.05), while VAS and VISA-A score in PRP group were better than those in shock wave group at 6 months after treatment(P<0.05), and the satisfaction survey in PRP group was better than that in shock wave group(P<0.05).@*CONCLUSION@#PRP injection has a good clinical effect on chronic insertional Achilles tendinopathy with high patient satisfaction, and medium-and long-term effect of PRP injection for the treatment of chronic insertional Achilles tendinopathy is better than that of extracorporeal divergent shock wave.


Subject(s)
Male , Female , Humans , Middle Aged , Achilles Tendon , Tendinopathy/therapy , Treatment Outcome , Exercise Therapy , Platelet-Rich Plasma
9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-985866

ABSTRACT

Triple-negative breast cancer (TNBC) accounts for approximately 15%–20% of all breast cancers. Patients with TNBC have a rapidly progressive clinical course, an earlier age of onset, faster distant recurrence, and more common visceral metastases as compared with other subtypes. However, treatment of TNBC is often limited to chemotherapy and has a poor prognosis. Therefore, developing the best treatment strategy for patients is essential to reduce the burden of disease caused by TNBC. Various potential available drug targets have been discovered, as well as precision treatment and classified treatment are changing the clinical practice of TNBC, thereby indicating a new therapeutic area for TNBC in addition to traditional chemotherapy. This article reviews the systemic treatment options for TNBC in recent years, including immunotherapy and targeted therapy.

10.
Chinese Journal of Surgery ; (12): 693-699, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-985800

ABSTRACT

Objective: To examine the feasibility, safety, and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with high-riding vertebral artery (HRVA). Methods: The clinical data of 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation in the Department of Neurosurgery, the First Affiliated Hospital of University of Science and Technology of China between January 2020 and November 2021 were retrospectively analyzed. All patients had high-riding vertebral artery on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 10 females aged (48.0±12.8) years (range: 17 to 67 years). After correction of vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including the anterior atlantodental interval (ADI), the distance of the odontoid tip above the Chamberlain line, the clivus-canal angle, were collected and compared by paired t-test. Results: Mobilization of the high-riding vertebral artery was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were achieved in all 12 patients. All patients achieved bone fusion 6 months after surgery. No looseness and shift in internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative ADI decreased from (6.1±1.9) mm to (2.0±1.2) mm (t=6.73, P<0.01), the distance of the odontoid tip above Chamberlain line decreased from (10.4±2.5) mm to (5.5±2.3) mm (t=7.12, P<0.01), the clivus-canal angle increased from (123.4±11.1) ° to (134.7±9.6) ° (t=2.50, P=0.032), the JOA score increased from 13.3±2.1 to 15.6±1.2 (t=6.99, P<0.01). Conclusion: The C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

11.
Opt Express ; 30(23): 42347-42361, 2022 Nov 07.
Article in English | MEDLINE | ID: mdl-36366690

ABSTRACT

In this paper, we employ the atomic arrays in one-dimensional optical waveguides to simulate topological phases, where the waveguide is modeled as a one-dimensional infinitely long coupled cavity array. Under the Markov approximation, the coherent and dissipative coupling between atoms is established by eliminating waveguide modes. When the detuning between atoms and cavity fields lies in the band gap, the dynamics of the system is completely dominated by the coherent interaction. Under this condition, we designed three atomic arrays with different geometries and show that the topologically trivial and non-trivial phases of atomic arrays can be simulated. Furthermore, by introducing periodic atomic driving, the topological phase transition can be induced by adjusting the driving parameters. Finally, we investigate the effect of next-nearest neighbor interactions on topological state transfer and find that the next-nearest neighbor interactions break the degenerated bandgap state and establish a topological state transfer channel.

12.
Opt Express ; 30(11): 20135-20148, 2022 May 23.
Article in English | MEDLINE | ID: mdl-36221770

ABSTRACT

The simultaneous cooling of multiple mechanical oscillators in the cavity optomechanical system has aroused people's attention and may be applicable in the quantum information process. In this paper, a scheme to realize the simultaneous ground-state cooling of two identical mechanical oscillators is proposed, where the frequency of one of the oscillators is designed according to Lyapunov control. By this method, the dark mode can effectively couple with the bright mode so that the two identical oscillators can be simultaneously cooled to their ground state. Extending this scheme into multiple identical mechanical oscillators, we show that simultaneous cooling can also be achieved.

13.
Cardiovasc Ther ; 2022: 3159717, 2022.
Article in English | MEDLINE | ID: mdl-35909950

ABSTRACT

Diabetes causes lipid peroxide to accumulate within cardiomyocytes. Furthermore, lipid peroxide buildup is a risk factor for ferroptosis. This study is aimed at examining whether curcumin can ameliorate ferroptosis in the treatment of diabetic cardiomyopathy. Hematoxylin and eosin and Masson sections were used to examine the morphology, arrangement, and degree of fibrosis of the myocardium of diabetic rabbit models. The expression levels of nuclear Nrf2, Gpx4, Cox1, and Acsl4 in diabetic animal and cell models were quantitatively analyzed using immunofluorescence and western blotting. Nrf2-overexpression lentivirus vectors were transfected into cardiomyocytes, and the protective effects of curcumin and Nrf2 on cardiomyocytes under high glucose stimulation were assessed using terminal deoxynucleotidyl transferase dUTP nick-end labelling and reactive oxygen species probes. Diabetes was found to disorder myocardial cell arrangement and significantly increase the degree of myocardial fibrosis and collagen expression in myocardial cells. Curcumin treatment can increase nuclear transfer of Nrf2 and the expression of Gpx4 and HO-1, reduce glucose induced myocardial cell damage, and reverse myocardial cell damage caused by the ferroptosis inducer erastin. This study confirmed that curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy.


Subject(s)
Curcumin , Diabetes Mellitus , Diabetic Cardiomyopathies , Ferroptosis , Animals , Apoptosis , Curcumin/pharmacology , Diabetic Cardiomyopathies/prevention & control , Glucose/toxicity , Lipid Peroxides/pharmacology , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Rabbits
14.
Anal Cell Pathol (Amst) ; 2022: 2376288, 2022.
Article in English | MEDLINE | ID: mdl-35757013

ABSTRACT

Gliosarcoma (GSM), a histologic variant of glioblastoma (GBM), carries a poor prognosis with less than one year of median survival. Though GSM is similar with GBM in most clinical and pathological symptoms, GBM has unique molecular and histological features. However, as the rarity of GSM samples, the genetic information of this tumor is still lacking. Here, we take a comprehensive analysis of DNA copy number variations (CNV) in GBM and GSM. Whole genome sequencing was performed on 21 cases of GBM and 15 cases of GSM. CNVKIT is used for CNV calling. Our data showed that chromosomes 7, 8, 9, and 10 were the regions where CNV frequently happened in both GBM and GSM. There was a distinct CNV signal in chromosome 2 especially in GSM. The pathway enrichment of genes with CNV was suggested that the GBM and GSM shared the similar mechanism of tumor development. However, the CNV of some screened genes displayed a disparate form between GBM and GSM, such as AMP, BEND2, HDAC6, FOXP3, ZBTB33, TFE3, and VEGFD. It meant that GSM was a distinct subgroup possessing typical biomarkers. The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.


Subject(s)
Brain Neoplasms , Glioblastoma , Gliosarcoma , Brain Neoplasms/genetics , Brain Neoplasms/pathology , DNA Copy Number Variations/genetics , Genomics , Glioblastoma/genetics , Glioblastoma/pathology , Gliosarcoma/genetics , Gliosarcoma/pathology , Gliosarcoma/therapy , Humans
15.
Front Endocrinol (Lausanne) ; 13: 797121, 2022.
Article in English | MEDLINE | ID: mdl-35321334

ABSTRACT

Objective: Elective single embryo transfer (eSET) has been increasingly advocated to achieve the goal of delivering a single healthy baby. A novel endometrial preparation approach down-regulation ovulation-induction (DROI) proposed by our team was demonstrated in an RCT that DROI could significantly improve the reproductive outcome compared with modified natural cycle. We aimed to evaluate whether DROI improved clinic pregnancy rate in this single frozen-thawed blastocyst transfer RCT compared with hormone replace treatment (HRT). Method: Eligible participants were recruited and randomized into one of two endometrial preparation regimens: DROI or HRT between March 15, 2019 and March 12, 2021. The primary outcome was clinical pregnancy rate (CPR). The secondary endpoints included ongoing pregnancy rate (OPR), biochemical miscarriage and first trimester pregnancy loss. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR2000039804. Result s: A total of 330 women were randomized in a 1:1 ratio between two groups and 289 women received embryo transfer and completed the study (142 DROI; 147HRT). Pregnancy outcomes were significantly different between the two groups. The CPR and OPR in the DROI group were significantly higher than those of the HRT group (64.08% versus 46.94%, P<0.01; 56.34% versus 38.78%,P<0.01). The biochemical miscarriage and first trimester pregnancy loss were comparable between the two groups. Conclusion s: The findings of this RCT support the suggestion that the DROI might be a more efficient and promising alternative endometrial preparation approach for FET. Moreover, DROI could play a critical role in promoting uptake of single embryo transfer strategies in FET.


Subject(s)
Abortion, Spontaneous , Abortion, Spontaneous/epidemiology , Cryopreservation , Down-Regulation , Embryo Transfer , Female , Humans , Male , Ovulation , Pregnancy
16.
J Diabetes Res ; 2022: 9723632, 2022.
Article in English | MEDLINE | ID: mdl-36624860

ABSTRACT

The present study investigated whether quercetin promotes the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) to inhibit pyroptosis progression and ameliorate diabetic cardiomyopathy. We evaluated the protective effects of quercetin against diabetic cardiomyopathy by analyzing the expression of pyroptosis pathway proteins, myocardial cell apoptosis rate, degree of myocardial fibrosis, and serum inflammatory indices in the hearts of model rats with diabetes. We evaluated the expression of Nrf2 in the nucleus of cardiomyocytes and H9C2 cells to clarify the role of quercetin in promoting the nuclear translocation of Nrf2. In addition, we coincubated cardiomyocytes with the Nrf2 inhibitor ML385 to confirm that quercetin inhibits the diabetes-induced cardiomyocyte pyroptosis via the Nrf2 pathway. We found that quercetin promoted the nuclear translocation of Nrf2 in cardiac cells of diabetic rats, increased the expression of the antioxidant proteins HO-1, GCLC, and SOD, reduced the accumulation of ROS and the degree of cardiomyocyte apoptosis, and alleviated diabetes-induced cardiac fibrosis. The therapeutic effects of quercetin were further validated in H9C2 cardiomyocytes. Interestingly, ML385 prevented the beneficial effects of quercetin on diabetic cardiomyopathy, further indicating that the quercetin-mediated inhibition of pyroptosis requires the participation of the Nrf2 pathway. In conclusion, quercetin promoted the nuclear translocation of Nrf2, increased the expression of antioxidant factors in cells, and inhibited the progression of cell pyroptosis, thereby alleviating diabetic cardiomyopathy.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Rats , Animals , Quercetin/pharmacology , Quercetin/therapeutic use , Antioxidants/pharmacology , Antioxidants/metabolism , Pyroptosis , NF-E2-Related Factor 2/metabolism , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Cell Line , Oxidative Stress , Myocytes, Cardiac
17.
Chinese Journal of Burns ; (6): 549-554, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-940958

ABSTRACT

Objective: To investigate the incidence and risk factors of deep venous thrombosis (DVT) of lower extremity in patients with stage Ⅲ and Ⅳ pressure ulcer on admission. Methods: A retrospective case series study was conducted. A total of 241 patients with stage Ⅲ and Ⅳ pressure ulcers who met the inclusion criteria and were discharged from the Department of Wound Repair of the First People's Hospital of Zhengzhou from January 1, 2015 to December 31, 2019 were enrolled in this study, including 134 males and 107 females, aged 22 to 93 years, with a median age of 68 years; 37 patients were with stage Ⅲ pressure ulcers and 204 patients were with stage Ⅳ pressure ulcers. The DVT occurrence of patients was recorded. According to whether DVT of lower extremity veins was diagnosed by color Doppler ultrasound within 48 h after admission or not, the patients were divided into DVT group (n=37) and non-DVT group (n=204). Data of patients in the two groups were collected and compared, including gender, age, duration of pressure ulcer, time in bed, and combination with diabetes, hypertension, coronary heart disease, cerebral infarction, pneumonia, sepsis/septic shock, and paraplegia, and the plasma D-dimer level and Caprini score within 24 h after admission. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test, and Fisher's exact probability test. The indicators with statistically significant differences between the two groups were analyzed with multivariate logistic regression analysis to screen the independent risk factors influencing the DVT of lower extremity in 241 patients with stage Ⅲ and Ⅳ pressure ulcers on admission. Results: The incidence of DVT of lower extremity was 15.4% (37/241), of which 86.5% (32/37) were asymptomatic DVT. Among the DVT of 46 lower limbs, only 29 involved the inferior genicular veins, accounting for 63.0%. There were no statistically significant differences in gender, duration of pressure ulcer, combination with diabetes, hypertension, coronary heart disease, cerebral infarction, pneumonia, and sepsis/septic shock of patients between the two groups (P>0.05), while there were statistically significant differences in age, time in bed, combination with paraplegia, the plasma D-dimer level and Caprini score of patients between the two groups(t=-3.19, Z=-2.04, χ2=4.44, Z=-3.89, t=-2.14, respectively, P<0.05 or P<0.01). Multivariate logistic regression analysis showed that age and plasma D-dimer level were independent risk factors influencing the DVT of lower extremity in 241 patients with stage Ⅲ and Ⅳ pressure ulcers on admission (with odds ratios of 1.03 and 1.18, respectively, with 95% confidence intervals of 1.00-1.06 and 1.05-1.33, respectively, P<0.05 or P<0.01). Conclusions: The patients with stage Ⅲ and Ⅳ pressure ulcers have a higher incidence of DVT on admission, with age and plasma D-dimer level being the independent risk factors for DVT of lower extremity. It is necessary to pay attention to the targeted screening of DVT and education of its prevention.


Subject(s)
Aged , Female , Humans , Male , Hypertension , Lower Extremity , Paraplegia , Pressure Ulcer/epidemiology , Prevalence , Retrospective Studies , Risk Factors , Shock, Septic , Venous Thrombosis/epidemiology
18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1015725

ABSTRACT

Salvia miltiorrhiza is widely used in the treatment of the angina pectoris, coronary heart disease and myocardial infarction. CYP76AH3 is the key P450 enzyme, locating at the branch point of the tanshinone synthesis pathway. The crystal structural study and key amino acid analysis are of great significance for synthetic biology study on tanshinone. But it is always a challenge for scientists to carry out protein purification, crystallization and crystal structural studies on transmembrane type Ⅱ P450 enzymes. In this study, the prokaryotic expression plasmid was generated, and the high-purity target protein was purified. CYP76AH3 was successfully crystallized, and the crystal structure was solved.After docking range was determined by Cavityplus analysis, molecular docking with Discovery Studio was conducted. The docking result indicated that Gly298 and Asp294 had hydrogen bond interaction with the substrate, while Phe479, Leu367 and Leu293 had hydrophobic interaction with the substrate.In addition, the effect of mutations at the key amino acids on the protein structure stability was predicted throung point mutation simulation. This study would provide a target for protein engineering of CYP76AH3 and lay a foundation for the study of synthesis biology on tanshinones.

19.
Front Endocrinol (Lausanne) ; 12: 730059, 2021.
Article in English | MEDLINE | ID: mdl-34616363

ABSTRACT

Background: In recent years frozen-thawed embryo transfer (FET) has played an increasingly important role in ART, but there is limited consensus on the most effective method of endometrial preparation (EP) for FET. Inspired by significantly higher implantation rate and clinical pregnancy rate of the depot GnRH-a protocol, we proposed a novel EP protocol named down-regulation ovulation-induction (DROI) aimed to improve pregnancy outcomes of FET. Methods: This was a single-center, randomized controlled pilot trial. A total of 307 patients with freeze-all strategy scheduled for first FET were enrolled in the study. A total 261 embryos were transferred in DROI-FET group including 156 patients and 266 embryos were transferred in mNC-FET group including 151 patients. Reproductive outcomes were compared between the two groups. Results: The basic characteristics of patients, and the average number, quality and stage of embryos transferred were comparable between the two groups. Our primary outcome, implantation rate(IR) in DROI-FET group, was significantly higher than that of the mNC-FET group (54.41% versus 35.71%, P<0.01). The clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in DROI-FET group was also higher than that in mNC-FET group (69.87% versus 50.33%, P<0.01; 64.10% versus 42.38%, P<0.01). Conclusions: Compared to existing endometrial preparation methods, the DROI protocol might be the more efficient and promising protocol.


Subject(s)
Cryopreservation/methods , Embryo Implantation , Embryo Transfer/methods , Endometrium/physiology , Ovulation Induction/methods , Pregnancy Rate , Adult , Endometrium/drug effects , Female , Follow-Up Studies , Gonadotropin-Releasing Hormone/administration & dosage , Humans , Male , Pregnancy , Pregnancy Outcome , Prospective Studies
20.
PeerJ ; 9: e11410, 2021.
Article in English | MEDLINE | ID: mdl-34221708

ABSTRACT

Polar auxin transport in plant is mediated by influx and efflux transporters, which are encoded by AUX/LAX, PIN and PILS genes, respectively. The auxin transporter gene families have been characterized in several species from monocots and eudicots. However, a genome-wide overview of auxin transporter gene families in pineapple is not yet available. In this study, we identified a total of threeAcAUX genes, 12 AcPIN genes, and seven AcPILS genes in the pineapple genome, which were variably located on 15 chromosomes. The exon-intron structure of these genes and properties of deduced proteins were relatively conserved within the same family. Most protein motifs were widespread in the AUX, PIN or PILS proteins, whereas a few motifs were absent in only one or two proteins. Analysis of the expression profiles of these genes elucidated that several genes exhibited either preferential or tissue-specific expression patterns in vegetative and/or reproductive tissues. AcAUX2 was specifically expressed in the early developmental ovules, while AcPIN1b and AcPILS2 were strongly expressed in stamens and ovules. AcPIN9b, AcPILS1, AcPILS6a, 6b and 6c were abundantly expressed in stamens. Furthermore, qRT-PCR results showed that several genes in these families were responsive to various abiotic stresses. Comparative analysis indicated that the genes with close evolutionary relationships among pineapple, rice and Arabidopsis exhibited similar expression patterns. Overexpression of the AcAUX1 in Arabidopsis rescued the phenotype in aux1-T, and resulted in increased lateral roots in WT. These results will provide new insights into auxin transporter genes of pineapple and facilitate our understanding of their roles in pineapple growth and development.

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