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1.
IUBMB Life ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822621

ABSTRACT

MicroRNAs (miRNAs) are small non-coding RNAs that can actively participate in post-transcriptional regulation of genes. A number of studies have shown that miRNAs can serve as important regulators of cancer cell growth, differentiation, and apoptosis. They can also act as markers for the diagnosis and prognosis of certain cancers. To explore the potential prognosis-related miRNAs in liver cancer patients, to provide theoretical basis for early diagnosis and prognosis of liver cancer, as well as to provide a new direction for the targeted therapy of liver cancer. The miRNA expression profiles of liver cancer patients in the the Cancer Genome Atlas database were comprehensively analyzed and various prognostic-related miRNAs of liver cancer were screened out. The data was further subjected to survival analysis, prognostic analysis, gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis, microenvironment analysis, and drug sensitivity analysis by R Language version 4.2.0. Finally, the screened miRNAs were further validated by different experiments. Thus, miNRAs involved in liver cancer diagnosis and prognosis were identified. MiRNA-3680-3p was found to be significantly different in 10 different cancers, including liver cancer, and was significantly associated with the microenvironment, survival, and prognosis of liver cancer patients. In addition, drug sensitivity analysis revealed that miRNA-3680-3p can provide a useful reference for drug selection in targeted therapy for liver cancer. MiRNA-3680-3p can serve as a biomarker for the diagnosis and prognosis of liver cancer patients and down-regulation of miRNA-3680-3p could significantly inhibit both the proliferation and migration of liver cancer cells.

2.
Prev Med ; : 108026, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38844051

ABSTRACT

INTRODUCTION: This study explored the association between psoriasis and the weight-adjusted waist index (WWI), a newly developed measure of adiposity. The research was conducted among adults in the United States. METHODS: Utilizing survey data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2009 to 2014, the present study aimed to investigate the potential correlation between psoriasis and WWI within a sample of 15,920 adult participants. Employing multivariable logistic regression and nonlinear curve fitting techniques, we analyzed this plausible association. Additionally, a subgroup analysis was conducted to ascertain the consistency across diverse populations. RESULTS: A significant positive association was discovered between psoriasis and WWI in the investigated sample of 15,920 adults. After conducting a comprehensive adjustment of the model, it was observed that each incremental unit of WWI was significantly associated with an 14% elevated likelihood of developing psoriasis (OR = 1.16, 95% CI 1.01-1.36). Moreover, individuals belonging to the highest quartile of WWI exhibited a 47% higher risk of psoriasis compared to those in the lowest quartile (OR = 1.44, 95% CI 1.01-2.06). This positive correlation remained consistent across various subgroups. The study also compared WWI with BMI and waist circumference, finding that WWI is a more stable metric of obesity. CONCLUSIONS: Our study suggested that in US adults, there is a positive association between WWI and psoriasis. It also indicated that WWI showed potential as a valuable index of psoriasis among the general population.

3.
BMC Infect Dis ; 24(1): 560, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840046

ABSTRACT

BACKGROUND: China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy. METHODS: From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China). RESULTS: Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P < 0.0001). The positive rates and titers of anti-N/S1 IgG had no significant difference between boys and girls respectively. CONCLUSION: Vast majority of children were infected with SARS-CoV-2 shortly after ending zero-COVID-19 policy in China. Whether these unvaccinated infected children should receive COVID-19 vaccine merits further investigation.


Subject(s)
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Humans , COVID-19/prevention & control , COVID-19/immunology , COVID-19/epidemiology , China/epidemiology , Child, Preschool , Male , Female , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Child , Antibodies, Viral/blood , SARS-CoV-2/immunology , Infant , Cross-Sectional Studies , Immunoglobulin G/blood , Immunoglobulin M/blood , Vaccination/statistics & numerical data , Spike Glycoprotein, Coronavirus/immunology
4.
Cell Commun Signal ; 22(1): 314, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849885

ABSTRACT

BACKGROUND: Abnormally expressed BCR/ABL protein serves as the basis for the development of chronic myeloid leukaemia (CML). The F-actin binding domain (FABD), which is a crucial region of the BCR/ABL fusion protein, is also located at the carboxyl end of the c-ABL protein and regulates the kinase activity of c-ABL. However, the precise function of this domain in BCR/ABL remains uncertain. METHODS: The FABD-deficient adenovirus vectors Ad-BCR/ABL△FABD, wild-type Ad-BCR/ABL and the control vector Adtrack were constructed, and 32D cells were infected with these adenoviruses separately. The effects of FABD deletion on the proliferation and apoptosis of 32D cells were evaluated by a CCK-8 assay, colony formation assay, flow cytometry and DAPI staining. The levels of phosphorylated BCR/ABL, p73, and their downstream signalling molecules were detected by western blot. The intracellular localization and interaction of BCR/ABL with the cytoskeleton-related protein F-actin were identified by immunofluorescence and co-IP. The effect of FABD deletion on BCR/ABL carcinogenesis in vivo was explored in CML-like mouse models. The degree of leukaemic cell infiltration was observed by Wright‒Giemsa staining and haematoxylin and eosin (HE) staining. RESULTS: We report that the loss of FABD weakened the proliferation-promoting ability of BCR/ABL, accompanied by the downregulation of BCR/ABL downstream signals. Moreover, the deletion of FABD resulted in a change in the localization of BCR/ABL from the cytoplasm to the nucleus, accompanied by an increase in cell apoptosis due to the upregulation of p73 and its downstream proapoptotic factors. Furthermore, we discovered that the absence of FABD alleviated leukaemic cell infiltration induced by BCR/ABL in mice. CONCLUSIONS: These findings reveal that the deletion of FABD diminished the carcinogenic potential of BCR/ABL both in vitro and in vivo. This study provides further insight into the function of the FABD domain in BCR/ABL.


Subject(s)
Apoptosis , Cell Proliferation , Fusion Proteins, bcr-abl , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/metabolism , Animals , Humans , Mice , Apoptosis/genetics , Actins/metabolism , Carcinogenesis/genetics , Protein Domains , Cell Line, Tumor
5.
Front Oncol ; 14: 1359635, 2024.
Article in English | MEDLINE | ID: mdl-38725625

ABSTRACT

Background: Epithelial ovarian cancer (EOC) is a significant cause of mortality among gynecological cancers. While Olaparib, a PARP inhibitor, has demonstrated efficacy in EOC maintenance therapy, individual responses vary. This study aims to assess the prognostic significance of body composition and systemic inflammation markers in EOC patients undergoing initial Olaparib treatment. Methods: A retrospective analysis was conducted on 133 EOC patients initiating Olaparib therapy. Progression-free survival (PFS) was assessed through Kaplan-Meier analysis and Cox proportional hazards regression. Pre-treatment computed tomography images were utilized to evaluate body composition parameters including subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), skeletal muscle area index (SMI), and body mineral density (BMD). Inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), serum albumin, and hemoglobin levels, were also measured. Results: The median follow-up duration was 16 months (range: 5-49 months). Survival analysis indicated that high SATI, high VATI, high SMI, high BMD, low NLR, and low PLR were associated with decreased risk of disease progression (all p < 0.05). Multivariate analysis identified several factors independently associated with poor PFS, including second or further lines of therapy (HR = 2.16; 95% CI = 1.09-4.27, p = 0.027), low VATI (HR = 3.79; 95% CI = 1.48-9.70, p = 0.005), low SMI (HR = 2.52; 95% CI = 1.11-5.72, p = 0.027), low BMD (HR = 2.36; 95% CI = 1.22-4.54, p = 0.010), and high NLR (HR = 0.31; 95% CI = 0.14-0.69, p = 0.004). Subgroup analysis in serous adenocarcinoma patients revealed distinct prognostic capabilities of SATI, VATI, SMI, PLR, and NLR. Conclusion: Body composition and inflammation variables hold promise as predictors of therapeutic response to Olaparib in EOC patients. Understanding their prognostic significance could facilitate tailored treatment strategies, potentially improving patient outcomes.

6.
Gynecol Oncol ; 187: 64-73, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38733954

ABSTRACT

OBJECTIVE: We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes. METHODS: We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features. RESULTS: Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3-189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3-54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation. CONCLUSION: Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST.

8.
Biochem Pharmacol ; 225: 116267, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38723721

ABSTRACT

Acute liver failure (ALF) is a critical condition that can lead to substantial liver dysfunction. It is characterized by complex clinical manifestations and rapid progression, presenting significant challenges in diagnosis and treatment. We investigated the protective effect of mefunidone (MFD), a novel antifibrosis pyridone agent, on ALF in mice, and explored its potential mechanism of action. MFD pretreatment can alleviate lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced ALF, reduce hepatocyte apoptosis, and reduce inflammation and oxidative stress. Additionally, MFD alleviated LPS/D-GalN-stimulated reactive oxygen species (ROS) production and cell death in AML12 cells. RNA sequencing enrichment analysis showed that MFD significantly affected the Mitogen-Activated Protein Kinase (MAPK) pathway. In vivo and in vitro experiments showed that MFD inhibited MKK4 and JNK phosphorylation. JNK activation caused by MKK4 and JNK activators could eliminate the therapeutic effect of MFD on AML12. In addition, MFD pretreatment alleviated ConA-induced ALF, reduced inflammation and oxidative stress in mice, and reduced mouse mortality. These results suggest that MFD can potentially protect against ALF, partially by inhibiting the MKK4-JNK pathway, and is a promising new therapeutic drug for ALF.

9.
BMJ Open ; 14(5): e079474, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38719298

ABSTRACT

OBJECTIVE: This study aimed to investigate the caregiving behaviours and supportive needs of caregivers of patients with HIV/AIDS and provide a basis for healthcare institutions to carry out caregiver interventions. DESIGN: A purposive sampling method was used to select 11 caregivers of patients with HIV/AIDS in the Infectious Disease Department of a tertiary hospital in Nanjing, China, to conduct semistructured interviews. Colaizzi analysis was used to collate and analyse the interview data. SETTING: All interviews were conducted at a tertiary hospital specialising in infectious diseases in Nanjing, Jiangsu Province. PARTICIPANTS: We purposively sampled 11 caregivers of people with HIV/AIDS, including nine women and two men. RESULTS: Analysing the results from the perspective of iceberg theory, three thematic layers were identified: behavioural, value and belief. The behavioural layer includes a lack of awareness of the disease, physical and mental coping disorders, and an increased sense of stigma; the values layer includes a heightened sense of responsibility, the constraints of traditional gender norms, the influence of strong family values and the oppression of public opinion and morality and the belief layer includes the faith of standing together through storms and stress. CONCLUSION: Healthcare professionals should value the experiences of caregivers of patients with HIV/AIDS and provide professional support to improve their quality of life.


Subject(s)
Adaptation, Psychological , Caregivers , HIV Infections , Qualitative Research , Social Stigma , Humans , Caregivers/psychology , Male , Female , Adult , Middle Aged , HIV Infections/psychology , China , Acquired Immunodeficiency Syndrome/psychology , Social Support , Interviews as Topic
10.
Mol Phylogenet Evol ; 197: 108094, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38723792

ABSTRACT

Thermophilic unicellular cyanobacteria of the family Thermosynechococcaceae are essential primary producers and integral components of many microbial mats found in hot springs of Asia and North America. Historically, based on their simple morphology, these organisms, along with members of taxonomically unrelated thermophilic Thermostichaceae have been described with a generic term, "Synechococcus", used for elongated unicellular cyanobacteria. This has created significant misperception in the scientific literature regarding the taxonomic status of these essential thermophilic primary producers and their relationship with Synechococcus sensu stricto. In this manuscript, we attempted a genome-driven taxonomic reevaluation of the family Thermosynechococcaceae. Application of genomic analyses such as GTDB classification, ANI/AAI and phylogenomics support the delineation of eight species within genus Thermosynechococcus. Two subspecies were further identified within T. taiwanensis by dDDH and phylogenomics. Moreover, the results also suggest the presence of two putative new genera phylogenetically alongside genus Thermosynechococcus, a thermophilic genus Parathermosynechococcus represented by PCC 6715 and a non-thermophilic genus represented by PCC 6312. The proposed genospecies and new genera were further integrated with morphological and/or ecological information. Interestingly, the phylogeny of 16S-23S ITS achieved a better taxonomic relationship than that of 16S rRNA and supported the genome-based classification of Thermosynechococcus spp. Finally, the pan-genome analysis indicated a conserved pattern of genomic core among known members of Thermosynechococcus.

11.
Chem Sci ; 15(17): 6583-6588, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38699248

ABSTRACT

The adsorptive separation of ternary propyne (C3H4)/propylene (C3H6)/propane (C3H8) mixtures is of significant importance due to its energy efficiency. However, achieving this process using an adsorbent has not yet been accomplished. To tackle such a challenge, herein, we present a novel approach of fine-regulation of the gradient of gate-opening in soft nanoporous crystals. Through node substitution, an exclusive gate-opening to C3H4 (17.1 kPa) in NTU-65-FeZr has been tailored into a sequential response of C3H4 (1.6 kPa), C3H6 (19.4 kPa), and finally C3H8 (57.2 kPa) in NTU-65-CoTi, of which the gradient framework changes have been validated by in situ powder X-ray diffractions and modeling calculations. Such a significant breakthrough enables NTU-65-CoTi to sieve the ternary mixtures of C3H4/C3H6/C3H8 under ambient conditions, particularly, highly pure C3H8 (99.9%) and C3H6 (99.5%) can be obtained from the vacuum PSA scheme. In addition, the fully reversible structural change ensures no loss in performance during the cycling dynamic separations. Moving forward, regulating gradient gate-opening can be conveniently extended to other families of soft nanoporous crystals, making it a powerful tool to optimize these materials for more complex applications.

12.
Front Surg ; 11: 1379769, 2024.
Article in English | MEDLINE | ID: mdl-38817944

ABSTRACT

Purpose: Thoracolumbar fascia injury is often associated with poor early pain relief after percutaneous vertebroplasty (PVP). This study will evaluate the effects of thoracolumbar fascia injury on early pain relief and time to get out of bed after PVP. Methods: A total of 132 patients treated with PVP for osteoporotic vertebral compression fractures (OVCF) were included and divided into injured group (52 cases) and non-injured group (80 cases) according to the existence of thoracolumbar fascia injury. Before surgery, 1 day, 3 days, 1 week, 1 month, and 3 months after surgery, and at the last follow-up, the primary patient-reported outcome measures (PROMs) were the visual analogue scale (VAS) of pain while rolling over and standing, and the secondary PROMs was the Oswestry disability index (ODI). Meanwhile, the achieved rate of minimal clinically important differences (MCID) and patient acceptable symptom states (PASS) of the above measures in both groups was evaluated at the last follow-up. Results: Except for the postoperative 3 months and the last follow-up, there were statistically significant differences in VAS-standing and ODI between the two groups at other time points after surgery (P < 0.05), and the non-injured group was significantly better than the injured group. At the last follow-up, there was no statistically significant difference in the MCID and PASS achievement rates of the above measures between the two groups (P > 0.05). In addition, the proportion of patients who got out of bed 1 and 3 days after surgery in the non-injury group was significantly higher than that in the injury group (P = 0.000 for both). Conclusion: Thoracolumbar fascia injury significantly affected early pain relief and extended time of getting out of bed after PVP. Attention should be paid to preoperative evaluation of thoracolumbar fascial injury in order to better predict the postoperative efficacy of PVP.

13.
Plant Physiol Biochem ; 211: 108694, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38714131

ABSTRACT

Using natural clinoptilolite (NCP) as a carrier and alginate (Alg)-calcium as an active species, the porous silicon calcium alginate nanocomposite (Alg-Ca-NCP) was successfully fabricated via adsorption-covalence-hydrogen bond. Its structural features and physicochemical properties were detailed investigated by various characterizations. The results indicated that Alg-Ca-NCP presented the disordered lamellar structures with approximately uniform particles in size of 300-500 nm. Specially, their surface fractal evolutions between the irregular roughness and dense structures were demonstrated via the SAXS patterns. The results elucidated that the abundant micropores of NCP were beneficial for unrestricted diffusing of Alg-Ca, which was conducive to facilitate a higher loading and sustainable releasing. The Ca content of leaf mustard treated with Alg-Ca-NCP-0.5 was 484.5 mg/100g on the 21st day, higher than that by water (CK) and CaCl2 solution treatments, respectively. Meanwhile, the prepared Alg-Ca-NCPs presented the obvious anti-aging effects on peroxidase drought stress of mustard leaves. These demonstrations provided a simple and effective method to synthesize Alg-Ca-NCPs as delivery nanocomposites, which is useful to improve the weak absorption and low utilization of calcium alginate by plants.


Subject(s)
Alginates , Mustard Plant , Zeolites , Alginates/chemistry , Alginates/pharmacology , Zeolites/chemistry , Zeolites/pharmacology , Mustard Plant/metabolism , Mustard Plant/drug effects , Mustard Plant/chemistry , Plant Leaves/metabolism , Plant Leaves/drug effects , Plant Leaves/chemistry , Porosity , Brassica/metabolism , Brassica/drug effects , Brassica/growth & development , Glucuronic Acid/chemistry , Nanocomposites/chemistry , X-Ray Diffraction , Hexuronic Acids/chemistry , Hexuronic Acids/metabolism
15.
Food Res Int ; 183: 114202, 2024 May.
Article in English | MEDLINE | ID: mdl-38760133

ABSTRACT

Pixian broad bean paste is a renowned fermented seasoning. The fermentation of broad bean is the most important process of Pixian broad bean paste. To enhance the flavor of tank-fermented broad bean paste, salt-tolerant Bacillus amyloliquefaciens strain was inoculated, resulting in an increase in total amount of volatile compounds, potentially leading to different flavor characteristics. To investigate the fermentation mechanism, monoculture simulated fermentation systems were designed. Metabolomics and transcriptomics were used to explore Bacillus amyloliquefaciens' transcriptional response to salt stress and potential aroma production mechanisms. The results highlighted different metabolite profiles under salt stress, and the crucial roles of energy metabolism, amino acid metabolism, reaction system, transportation system in Bacillus amyloliquefaciens' hypersaline stress response. This study provides a scientific basis for the industrial application of Bacillus amyloliquefaciens and new insights into addressing the challenges of poor flavor quality in tank fermentation products.


Subject(s)
Bacillus amyloliquefaciens , Fermentation , Metabolomics , Bacillus amyloliquefaciens/metabolism , Bacillus amyloliquefaciens/genetics , Transcriptome , Food Microbiology , Fermented Foods/microbiology , Volatile Organic Compounds/analysis , Volatile Organic Compounds/metabolism , Gene Expression Profiling , Taste , Fabaceae/microbiology
16.
Int J Mol Sci ; 25(10)2024 May 14.
Article in English | MEDLINE | ID: mdl-38791398

ABSTRACT

Chimeric antigen receptor (CAR)-T cell immunotherapy represents a cutting-edge advancement in the landscape of cancer treatment. This innovative therapy has shown exceptional promise in targeting and eradicating malignant tumors, specifically leukemias and lymphomas. However, despite its groundbreaking successes, (CAR)-T cell therapy is not without its challenges. These challenges, particularly pronounced in the treatment of solid tumors, include but are not limited to, the selection of appropriate tumor antigens, managing therapy-related toxicity, overcoming T-cell exhaustion, and addressing the substantial financial costs associated with treatment. Nanomedicine, an interdisciplinary field that merges nanotechnology with medical science, offers novel strategies that could potentially address these limitations. Its application in cancer treatment has already led to significant advancements, including improved specificity in drug targeting, advancements in cancer diagnostics, enhanced imaging techniques, and strategies for long-term cancer prevention. The integration of nanomedicine with (CAR)-T cell therapy could revolutionize the treatment landscape by enhancing the delivery of genes in (CAR)-T cell engineering, reducing systemic toxicity, and alleviating the immunosuppressive effects within the tumor microenvironment. This review aims to explore how far (CAR)-T cell immunotherapy has come alone, and how nanomedicine could strengthen it into the future. Additionally, the review will examine strategies to limit the off-target effects and systemic toxicity associated with (CAR)-T cell therapy, potentially enhancing patient tolerance and treatment outcomes.


Subject(s)
Immunotherapy, Adoptive , Neoplasms , Receptors, Chimeric Antigen , Humans , Receptors, Chimeric Antigen/immunology , Neoplasms/therapy , Neoplasms/immunology , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Nanotechnology/methods , Nanomedicine/methods , Animals , Tumor Microenvironment/immunology , T-Lymphocytes/immunology , Antigens, Neoplasm/immunology
18.
Biomed Pharmacother ; 175: 116689, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703508

ABSTRACT

Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD+ synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD+ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway.


Subject(s)
Apoptosis , Myocardial Reperfusion Injury , Niacinamide , Oxidative Stress , Pyridinium Compounds , Rats, Sprague-Dawley , Signal Transduction , Sirtuin 3 , Superoxide Dismutase , Animals , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/prevention & control , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Sirtuin 3/metabolism , Signal Transduction/drug effects , Male , Niacinamide/pharmacology , Niacinamide/analogs & derivatives , Superoxide Dismutase/metabolism , Rats , Apoptosis/drug effects , Oxidative Stress/drug effects , Pyridinium Compounds/pharmacology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Reactive Oxygen Species/metabolism , Cell Line , Cardiotonic Agents/pharmacology , Sirtuins
19.
Acta Physiol (Oxf) ; 240(7): e14163, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38752665

ABSTRACT

AIM: To reveal the contribution of Irisin in the beneficial effects of resistance exercise on myocardial fibrosis (MF) and cardiac function in the mice with myocardial infarction (MI). METHODS: The MI model was built by ligating the left anterior descending coronary artery in Fndc5 knockout mice (Fndc5-/-). Resistance exercise was started one week after surgery and continued for four weeks. In addition, H2O2, AICAR, recombinant human Irisin protein (rhIRISIN), and Sirt1 shRNA lentivirus (LV-Sirt1 shRNA) were used to intervene primary isolated cardiac fibroblasts (CFs). MF was observed through Masson staining, and apoptosis was assessed using TUNEL staining. MDA and T-SOD contents were detected by biochemical kits. The expression of proteins and genes was detected by Western blotting and RT-qPCR. RESULTS: Resistance exercise increased Fndc5 mRNA level, inhibited the activation of TGFß1-TGFßR2-Smad2/3 pathway, activated AMPK-Sirt1 pathway, reduced the levels of oxidative stress, apoptosis, and MF in the infarcted heart, and promoted cardiac function. However, Fndc5 knockout attenuated the protective effects of resistance exercise on the MI heart. Results of the in vitro experiments showed that AICAR and rhIRISIN intervention activated the AMPK-Sirt1 pathway and inactivated the TGFß1-Smad2/3 pathway, and promoted apoptosis in H2O2-treated CFs. Notably, these effects of rhIRISIN intervention, except for the TGFßR2 expression, were attenuated by LV-Sirt1 shRNA. CONCLUSION: Resistance exercise upregulates Fndc5 expression, activates AMPK-Sirt1 pathway, inhibits the activation of TGFß1-Smad2/3 pathway, attenuates MF, and promotes cardiac function after MI.


Subject(s)
AMP-Activated Protein Kinases , Fibronectins , Fibrosis , Mice, Knockout , Myocardial Infarction , Sirtuin 1 , Transforming Growth Factor beta1 , Animals , Myocardial Infarction/metabolism , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Sirtuin 1/metabolism , Sirtuin 1/genetics , Fibronectins/metabolism , Fibronectins/genetics , Mice , Fibrosis/metabolism , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Transforming Growth Factor beta1/metabolism , Smad2 Protein/metabolism , Up-Regulation , Resistance Training , Male , Myocardium/metabolism , Myocardium/pathology , Smad3 Protein/metabolism , Smad3 Protein/genetics , Physical Conditioning, Animal/physiology , Mice, Inbred C57BL , Signal Transduction
20.
J Org Chem ; 89(11): 7848-7858, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38809686

ABSTRACT

A CuH-catalyzed reductive coupling of nitroarenes with phosphine oxides is developed, which produces a series of phosphamides in moderate to excellent yields with good functional group tolerance. Gram-scale synthesis and late-stage modification of nitro-aromatic functional molecule niclosamide are also successfully conducted. The mechanism study shows that the nitro group is transformed after being reduced to nitroso and a nucleophilic addition procedure is involved during the reaction.

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