Publications by authors named "Ping Li"

5,907 Publications

  • Page 1 of 1

Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes.

Cell 2022 Jun;185(13):2292-2308.e20

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building (BSB), 1105 N. University Ave, Ann Arbor, MI 48109, USA. Electronic address:

Lysosomes require an acidic lumen between pH 4.5 and 5.0 for effective digestion of macromolecules. This pH optimum is maintained by proton influx produced by the V-ATPase and efflux through an unidentified "H leak" pathway. Here we show that TMEM175, a genetic risk factor for Parkinson's disease (PD), mediates the lysosomal H leak by acting as a proton-activated, proton-selective channel on the lysosomal membrane (LyPAP). Acidification beyond the normal range potently activated LyPAP to terminate further acidification of lysosomes. An endogenous polyunsaturated fatty acid and synthetic agonists also activated TMEM175 to trigger lysosomal proton release. TMEM175 deficiency caused lysosomal over-acidification, impaired proteolytic activity, and facilitated α-synuclein aggregation in vivo. Mutational and pH normalization analyses indicated that the channel's H conductance is essential for normal lysosome function. Thus, modulation of LyPAP by cellular cues may dynamically tune the pH optima of endosomes and lysosomes to regulate lysosomal degradation and PD pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2022.05.021DOI Listing
June 2022

SWOLLEN TAPETUM AND STERILITY 1 Is Required for Tapetum Degeneration and Pollen Wall Formation in Rice.

Plant Physiol 2022 Jun 24. Epub 2022 Jun 24.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Rice Research Institute, Sichuan Agricultural University, Chengdu 611130, China.

The pollen wall is important for protecting the male gametophyte and for fertilization. The lipid components of the pollen wall are mainly synthesized and transported from the sporophytic tapetum. Although several factors related to lipid biosynthesis have been characterized, the molecular mechanisms underlying lipid biosynthesis during pollen development in rice (Oryza sativa L.) remain elusive. Here, we showed that mutation in the SWOLLEN TAPETUM AND STERILITY 1 (STS1) gene causes delayed tapetum degradation and aborted pollen wall formation in rice. STS1 encodes an endoplasmic reticulum (ER)-localized protein that contains domain of unknown function (DUF) 726 and exhibits lipase activity. Lipidomic and transcriptomic analyses showed that STS1 is involved in anther lipid homeostasis. Moreover, STS1 interacts with Polyketide Synthase 2 (OsPKS2) and Acyl-CoA Synthetase 12 (OsACOS12), two enzymes crucial in lipidic sporopollenin biosynthesis in pollen wall formation, suggesting a potentially lipidic metabolon for sporopollenin biosynthesis in rice. Collectively, our results indicate that STS1 is an important factor for lipid biosynthesis in reproduction, providing a target for the artificial control of male fertility in hybrid rice breeding and insight into the function of DUF726-containing protein in plants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/plphys/kiac307DOI Listing
June 2022

Luteolin suppresses TNF-α-induced inflammatory injury and senescence of nucleus pulposus cells via the Sirt6/NF-κB pathway.

Exp Ther Med 2022 Jul 26;24(1):469. Epub 2022 May 26.

College of Acupuncture and Bone Injury, Hubei University of Chinese Medicine, Wuhan, Hubei 430061, P.R. China.

Luteolin (3',4',5,7-tetrahydroxy flavone) is a flavonoid, which is widely distributed in various plants including flowers, vegetables, and medicinal herbs and spices. Luteolin can be applied in the treatment of various diseases due to its multiple biological activities, such as anti-inflammatory, anticancer, and antioxidative activity. However, its role in intervertebral disc degeneration has not been previously reported. Therefore, the purpose of the present study was to explore the effects of luteolin on Tumor necrosis factor (TNF)-α-induced inflammatory injury and senescence of human nucleus pulposus cells (HNPCs), as well as the underlying mechanisms of action of this compound. Cell viability and apoptosis were assessed by MTT assay and TUNEL staining, respectively. ELISA kits were applied to detect the levels of inflammatory cytokines and the activity of telomerase. Senescence β-galactosidase staining was used to detect the activity levels of β-galactosidase in the cells. Cell transfection was performed to achieve interference of sirtuin 6 (Sirt6). The protein expression levels were detected by western blot analysis. TUNEL staining and western blot analysis were performed to assess the expression levels of apoptosis-related proteins. The results indicated that TNF-α induced a significant decrease in HNPC viability and an increase in inflammatory factor levels, while the application of luteolin effectively increased cell viability and decreased intracellular interleukin (IL)-1β and IL-6 expression levels. Furthermore, luteolin decreased apoptosis compared with the TNF-α groups in a dose-dependent manner. In addition, the results of the detection kits suggested that luteolin reversed TNF-α-induced senescence. Notably, interference with Sirt6 partially reduced the protective effect of luteolin on TNF-α-induced HNPC senescence via the Sirt6/NF-κB pathway. In summary, the data indicated that luteolin suppresses TNF-α-induced inflammatory injury and senescence of HNPCs via the Sirt6/NF-κB pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2022.11396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204575PMC
July 2022

Upregulation of osteoprotegerin inhibits -butyl hydroperoxide-induced apoptosis of human chondrocytes.

Exp Ther Med 2022 Jul 26;24(1):470. Epub 2022 May 26.

Department of Joint Surgery, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China.

Necrosis of the femoral head (NFH) is an orthopedic disease characterized by a severe lack of blood supply to the femoral head and a marked increase in intraosseous pressure. NFH is associated with numerous factors, such as alcohol consumption and hormone levels. The present study focused on the expression levels of osteoprotegerin (OPG) in NFH and the effect of overexpression on chondrocyte apoptosis. The results demonstrated that expression was markedly decreased in the femoral head of patients with NFH compared with normal femoral heads. Lentivirus-mediated overexpression of in human chondrocytes reversed the decrease in cell viability and the increase in reactive oxygen species production induced by an oxidative stress-inducing factor, -butyl hydroperoxide. Flow cytometry and TUNEL assays revealed that overexpression inhibited the apoptosis of chondrocytes. In addition, it was revealed that exerted its anti-apoptotic effect mainly by promoting Bcl-2 expression and Akt phosphorylation and inhibiting caspase-3 cleavage and Bax expression. The present study revealed that may be an important regulator of NFH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2022.11397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204554PMC
July 2022

Simultaneous fluorescence imaging of Golgi O and Golgi HO in mice with hypertension.

Biosens Bioelectron 2022 Jun 17;213:114480. Epub 2022 Jun 17.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Minis-try of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University, Jinan, 250014, People's Republic of China. Electronic address:

Hypertensive cardiovascular disease is a persistent threat to public health. Elucidating the pathogenesis of hypertension is expected to provide more highly targeted therapies for patients. To date, reactive oxygen species (ROS) induced endothelial nitric oxide synthase (eNOS) uncoupling are generally considered to be common phenomena in hypertension. However, the critical factor contribute to persistent eNOS uncoupling remains poorly understood. Herein, we established a fluorescence probe, Gol, for the multicolored and simultaneous detection of Golgi O and HO in situ. We successfully detected increases in Golgi ROS levels in hypertensive mice and evaluated the pharmaceutical effects of various antihypertensive drugs. More importantly, we identified the ROS post-transcriptional modification sites on dihydrofolate reductase (DHFR). Altogether, we propose a novel therapeutic target for hypertension, which will promote the development of new antihypertensive drugs, and also developed an ideal fluorescence probe to study in situ Golgi O and HO changes in various biochemical processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2022.114480DOI Listing
June 2022

Identification and Characterization of and Causing Anthracnose on Luffa Sponge Gourd in China.

Plants (Basel) 2022 Jun 8;11(12). Epub 2022 Jun 8.

Hunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Nongda Road 1, Furong District, Changsha 410128, China.

Luffa sponge gourd () is an important cucurbitaceous vegetable and is known as the source of loofah. From 2020 to 2021, a leaf disease occurred on luffa leaves in the Hunan Province of China. Symptoms were displayed as oval to irregular chlorotic lesions surrounded by yellow halos. The pathogens were isolated from the affected leaves. According to morphological characterization and molecular identification using multi-locus phylogenetic analysis of the internal transcribed spacer (ITS), actin (), chitin synthase (), glyceraldehyde-3-phosphate dehydrogenase (), β-tubulin (), and partial mating type (Mat1-2) gene () regions, the pathogens were identified as two species: and . Koch's postulates were identified by a pathogenicity test and re-confirmation. To the best of our knowledge, and are two new species associated with luffa sponge gourd anthracnose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/plants11121537DOI Listing
June 2022

Biodegradable Zn-Cu-Fe Alloy as a Promising Material for Craniomaxillofacial Implants: An Investigation into Degradation Behavior, Cytotoxicity, and Hemocompatibility.

Front Chem 2022 6;10:860040. Epub 2022 Jun 6.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Zinc-based nanoparticles, nanoscale metal frameworks and metals have been considered as biocompatible materials for bone tissue engineering. Among them, zinc-based metals are recognized as promising biodegradable materials thanks to their moderate degradation rate ranging between magnesium and iron. Nonetheless, materials' biodegradability and the related biological response depend on the specific implant site. The present study evaluated the biodegradability, cytocompatibility, and hemocompatibility of a hot-extruded zinc-copper-iron (Zn-Cu-Fe) alloy as a potential biomaterial for craniomaxillofacial implants. Firstly, the effect of fetal bovine serum (FBS) on degradation behavior was evaluated. Furthermore, an extract test was used to evaluate the cytotoxicity of the alloy. Also, the hemocompatibility evaluation was carried out by a modified Chandler-Loop model. The results showed decreased degradation rates of the Zn-Cu-Fe alloy after incorporating FBS into the medium. Also, the alloy exhibited acceptable toxicity towards RAW264.7, HUVEC, and MC3T3-E1 cells. Regarding hemocompatibility, the alloy did not significantly alter erythrocyte, platelet, and leukocyte counts, while the coagulation and complement systems were activated. This study demonstrated the predictable degradation behavior, acceptable cytotoxicity, and appropriate hemocompatibility of Zn-Cu-Fe alloy; therefore, it might be a candidate biomaterial for craniomaxillofacial implants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2022.860040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208203PMC
June 2022

Effects of lidocaine administration via the perforated outer cuff of a dual-cuff endotracheal tube and remifentanil administration on recovery from general anaesthesia for female patients undergoing thyroidectomy: a single centre, double-blind, randomised study.

BMC Anesthesiol 2022 Jun 22;22(1):194. Epub 2022 Jun 22.

Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine: Guangdong Provincial Hospital of Chinese Medicine, Guangzhou City, Guangdong Province, 510120, People's Republic of China.

Background: Cough caused by endotracheal tube (ETT) placement is ubiquitous and correlates with adverse outcomes. Remifentanil administration via target-controlled infusion (TCI) is one of the cough prevention measures used during recovery. In a pilot study, lidocaine administered via the perforated outer cuff of a dual-cuff endotracheal tube was also found to prevent cough due to ETT placement. We therefore compared these two cough prevention approaches during recovery after thyroidectomy in a single-centre, double-blind, randomised study conducted in China during the period from 09/10/2020 to 30/04/2021.

Methods: Ninety-eight female patients aged 18-65 years with American Society of Anaesthesiologists Physical Status scores of I and II were scheduled to undergo thyroidectomy. The ETT contained an internal cuff covered by a perforated outer cuff to allow for lidocaine delivery. Patients were randomised to receive either 4 ml of saline solution (Group R, n = 49) or 4 ml of 2% lidocaine in the outer cuff (Group L, n = 49) at the beginning of skin suturing. Remifentanil (2 ng/ml) was maintained in Group R until extubation, while remifentanil was maintained in Group L until the end of skin suturing. The primary outcome was cough during patient transfer, at 1 min before extubation, and at extubation. The secondary outcomes were haemodynamics and other recovery parameters.

Results: Primary outcomes were compared between remifentanil vs. lidocaine application, namely, the incidence of cough during patient transfer (0% in Group R vs. 0% in Group L), at 1 min before extubation (22.45% in Group R vs. 4.08% in Group L; P = 0.015), and at extubation (61.22% in Group R vs. 20.41% in Group L; P < 0.001). Compared with remifentanil, lidocaine more effectively decreased heart rate elevation and hypoxemia at 5 min after extubation, the spontaneous respiration recovery time, the extubation time, the duration of post-anaesthesia care unit (PACU) stay, Richmond Agitation-Sedation Scale scores in the agitated range and Critical-Care Pain Observation Tool scores.

Conclusion: Lidocaine administered via the perforated outer cuff of the ETT significantly improved recovery from general anaesthesia compared to remifentanil in female patients after thyroidectomy.

Trial Registration: Chinese Clinical Trial Registry (No. ChiCTR2000038653), registered on 27/09/2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12871-022-01734-1DOI Listing
June 2022

Hyperoside ameliorates TNF‑α‑induced inflammation, ECM degradation and ER stress‑mediated apoptosis via the SIRT1/NF‑κB and Nrf2/ARE signaling pathways .

Mol Med Rep 2022 Aug 22;26(2). Epub 2022 Jun 22.

College of Acupuncture and Bone Injury, Hubei University of Chinese Medicine, Wuhan, Hubei 430061, P.R. China.

Intervertebral disc degeneration (IDD) is the main pathogenesis of numerous cases of chronic neck and back pain, and has become the leading cause of spinal‑related disability worldwide. Hyperoside is an active flavonoid glycoside that exhibits anti‑inflammation, anti‑oxidation and anti‑apoptosis effects. The purpose of the present study was to investigate the effect of hyperoside on tumor necrosis factor (TNF)‑α‑induced IDD progression in human nucleus pulposus cells (NPCs) and its potential mechanism. The activity and apoptosis of NPCs were detected by Cell Counting Kit‑8 and flow cytometry analyses, respectively. The expression of interleukin (IL)‑6 and IL‑1β was detected with ELISA kits. Western blotting was used to detect the expression levels of proteins. The results showed that hyperoside effectively alleviated TNF‑α‑induced NPC apoptosis, and hyperoside treatment inhibited the upregulation of inducible nitric oxide synthase, cyclooxygenase‑2, IL‑1β and IL‑6 in TNF‑α‑stimulated NPCs. Compared with the findings in the TNF‑α group, the intervention of hyperoside attenuated the upregulated expression of aggrecan and collagen II, and downregulated the expressions of matrix metalloproteinase (MMP) 3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 5. In addition, hyperoside upregulated sirtuin‑1 (SIRT1) and nuclear factor E2‑related factor 2 (Nrf2) protein expression, and inhibition of SIRT1 or Nrf2 signaling reversed the protective effect of hyperoside on TNF‑α‑induced NPCs. In summary, hyperoside ameliorated TNF‑α‑induced inflammation, extracellular matrix degradation, and endoplasmic reticulum stress‑mediated apoptosis, which may be associated with the regulation of the SIRT1/NF‑κB and Nrf2/antioxidant responsive element signaling pathways by hyperoside.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2022.12776DOI Listing
August 2022

17β-Estradiol nongenomically induces vasodilation is enhanced by promoting phosphorylation of endophilin A2.

Gynecol Endocrinol 2022 Jun 22:1-7. Epub 2022 Jun 22.

Department of Gynecology and Obstetrics, Guangzhou First People's Hospital, South China University of Technology, Guang zhou, Guangdong, China.

Objective: A previous study found that the tyrosine phosphorylation of endophilin A2 (Endo II) was responsible for increase surface expression of MT1-MMP and ECM degradation; however, there is little information about whether Endo II could influence membrane estrogen receptors (mERs) and its functions.

Materials And Methods: In the present study, Human umbilical vein endothelial cells (HUVECs) were treated with E2, PPT, DPN, ICI 182780, Endo siRNA or negative control siRNA, and the biological behavior of the treated cells was observed. The mice were randomly divided into AAV-control-shRNA + Ach, AAV-Endo II-shRNA + Ach, AAV-control-shRNA + E2, AAV-Endo II-shRNA + E2 groups and the thoracic aorta were isolated, cut into 2-mm rings, then the wall tension was detected.

Results: We found that 17β-Estradiol (E2) enhanced mERα protein level, which was further increased after knocking down Endo II, the mechanism maybe involved in E2-induced tyrosine phosphorylation of Endo II. In addition, we also observed that Endo II blocked the activation of Akt, ERK1/2 and eNOS signaling in HUVECs treated with E2. E2 induced vasodilation was significantly increased by silencing of Endo II expression.

Conclusion: Our study provided a sound basis to selective modulate Endo II for E2's nongenomic pathway, which can be benefit for cardiovascular system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09513590.2022.2088731DOI Listing
June 2022

Small molecules as modulators of regulated cell death against ischemia/reperfusion injury.

Med Res Rev 2022 Jun 21. Epub 2022 Jun 21.

Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.

Ischemia/reperfusion (IR) injury contributes to disability and mortality worldwide. Due to the complicated mechanisms and lack of proper therapeutic targets, few interventions are available that specifically target the pathogenesis of IR injury. Regulated cell death (RCD) of endothelial and parenchymal cells is recognized as the promising intervening target. Recent advances in IR injury suggest that small molecules exhibit beneficial effects on various RCD against IR injury, including apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, and parthanatos. Here, we describe the mechanisms behind these novel promising therapeutic targets and explain the machinery powering the small molecules. These small molecules exert protection by targeting endothelial or parenchymal cells to alleviate IR injury. Therapies of the ideal combination of small molecules targeting multiple cell types have shown potent synergetic therapeutic effects, laying the foundation for novel strategies to attenuate IR injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/med.21917DOI Listing
June 2022

Crucial Roles of a Pendant Imidazole Ligand of a Cobalt Porphyrin Complex in the Stoichiometric and Catalytic Reduction of Dioxygen.

Angew Chem Int Ed Engl 2022 Jun 21. Epub 2022 Jun 21.

Ewha Womans University, Department of Chemistry and Nanoscience, KOREA, REPUBLIC OF.

A cobalt porphyrin complex with a pendant imidazole base ([(L1)CoII]) is an efficient catalyst for the homogeneous catalytic two-electron reduction of dioxygen by 1,1'-dimethylferrocene (Me2Fc) in the presence of triflic acid (HOTf), as compared with a cobalt porphyrin complex without a pendant imidazole base ([(L2)CoII]). The pendant imidazole ligand plays a crucial role not only to provide an imidazolinium proton for proton-coupled electron transfer (PCET) from [(L1)CoII] to O2 in the presence of HOTf but also to facilitate electron transfer (ET) from [(L1)CoII] to O2 in the absence of HOTf. The kinetics analysis and the detection of intermediates in the stoichiometric and catalytic reduction of O2 have provided clues to clarify the crucial roles of the pendant imidazole ligand of [(L1)CoII] for the first time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202208143DOI Listing
June 2022

Self-template synthesis of mesoporous vanadium oxide nanospheres with intrinsic peroxidase-like activity and high antibacterial performance.

J Colloid Interface Sci 2022 Jun 13;625:435-445. Epub 2022 Jun 13.

Institute of Analytical Chemistry and Instrument for Life Science, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China. Electronic address:

Mesoporous vanadium oxide nanospheres are a very promising nanozyme for antibacterial and chemical sensing. However, controllable synthesis of mesoporous vanadium oxide nanospheres with uniform structure and small diameter (<200 nm) remains challenging. Herein, mesoporous vanadium oxide nanospheres (MVONs) with a small, uniform and adjustable particle size (52-105 nm), large mesopore size (5.1-5.8 nm), and high specific surface area (up to 63.7 m g) are constructed via a self-template strategy using tannic acid, formaldehyde and vanadium compounds as a polymerizable ligand, cross-linking agent and metal source, respectively. The relationships between synthesis conditions and material nanostructure are systematically investigated. The particle size and peroxidase-like activity of MVONs can be easily changed by adding different amounts of Pluronic block copolymer F127. Owing to the mesoporous structure, high specific surface area and small particle size, MVONs can effectively convert HO into extremely toxic reactive oxygen species, and further kill Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). This research establishes a universal, reliable method for synthesizing mesoporous vanadium oxide nanospheres, which might be used in catalysis, biosensors, and antibacterial treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2022.06.049DOI Listing
June 2022

Association of Polycystic Ovary Syndrome Phenotypes With Adverse Pregnancy Outcomes After Fertilization/Intracytoplasmic Sperm Injection.

Front Endocrinol (Lausanne) 2022 3;13:889029. Epub 2022 Jun 3.

Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China.

Objective: This study aims to evaluate the association between polycystic ovary syndrome (PCOS) phenotypes and adverse perinatal outcomes, comparing the characteristics, ovarian response, and assisted reproductive outcomes in patients with various PCOS phenotypes after fertilization (IVF)/intracytoplasmic sperm injection (ICSI).

Methods: This study comprised 6,732 patients who underwent the first cycle of IVF/ICSI treatment in our outpatient department from January 2017 to July 2018. Propensity score matching (PSM) was used in PCOS and non-PCOS groups to balance the influence of intergroup confounding factors. After the PSM procedure, 1,186 patients were included in the two groups, and the PCOS patients were further divided into four PCOS phenotype groups based on the Rotterdam criteria.

Results: Patients with various PCOS phenotypes had similar rates of biochemical pregnancy, clinical pregnancy, and live birth (all -values > 0.05). The overall incidence of adverse pregnancy outcomes (including ectopic pregnancy, miscarriage, preterm birth) was significantly higher in PCOS phenotype A and D groups than in the control group (44% and 46.4% vs. 28.7%,  = 0.027). The rates of hypertensive disorder of pregnancy (HDP) were significantly higher in PCOS phenotype A and C groups than in the control group (9.3% and 12.5% vs. 3.1%,  = 0.037). After adjustment for potential confounders, the differences in adverse pregnancy outcomes persisted ( = 0.025).

Conclusions: The overall incidence of adverse pregnancy outcomes is higher in women with PCOS phenotypes A and D than in women with non-PCOS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2022.889029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203834PMC
June 2022

LC-MS-based metabolomics reveals metabolic changes in short- and long-term administration of Compound Danshen Dripping Pills against acute myocardial infarction in rats.

Phytomedicine 2022 Jun 12;104:154269. Epub 2022 Jun 12.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Background: Mild and systematically improving multiple metabolic disorders was a focused view for Compound Danshen Dripping Pills playing synergistic effects through multiple components and multiple targets. The difference in overall therapeutic effects and endogenous metabolic regulation between short- and long-term administration was still unclear.

Purpose: This study aimed to explore the difference in endogenous metabolic regulation between short- and long-term Compound Danshen Dripping Pills (CDDP) administration against acute myocardial infarction (AMI).

Methods: The model of AMI was induced by ligating the left anterior descending coronary artery. The cardiac protection effects of CDDP were investigated by echocardiography, 1- or 2-week were defined as short- and long-term based on desirable efficacy variability. The entire metabolic changes between short- and long-term administration of CDDP were profiled by UPLC-Q-TOF-MS. In addition, the metabolic regulatory network of CDDP administration against myocardial infarction rats was also compared with those of a typical chemical drug isosorbide 5-mononitrate (ISMN).

Results: After 1- or 2-week continuous oral administration, CDDP could significantly alleviate AMI-induced cardiac dysfunction. By using LC-MS-based metabolomics analyses, we systematically investigated the metabolic profiles of plasma and heart tissue samples at fixed exposure time-points (2 h, 24 h) from AMI rats with CDDP treatment. Most interestingly, global endogenous metabolic changes were observed in cardiac samples collected at different stages post consecutive CDDP administration, fluctuating at 2 and 24 h after 1 week but stabilizing after 2 weeks. The disrupted metabolic pathways such as glycerophospholipid, amino acids, fatty acids, and arachidonic acid metabolism were reconstructed after both short- and long-term CDDP treatment, while taurine and hypotaurine metabolism and purine metabolism contributed to the whole efficacy after long-term CDDP administration.

Conclusion: Long-term CDDP treatment plays prolonged and stable efficacy against AMI compared with short-term treatment by specifically regulating purine and taurine and hypotaurine metabolism and systematically redressing metabolic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2022.154269DOI Listing
June 2022

An mTOR and DNA-PK dual inhibitor CC-115 hinders non-small cell lung cancer cell growth.

Cell Death Discov 2022 Jun 18;8(1):293. Epub 2022 Jun 18.

Department of Pulmonary and Critical Care Medicine, Shantou Central Hospital, Shantou, Guangdong, China.

Molecularly-targeted agents are still urgently needed for better non-small cell lung cancer (NSCLC) therapy. CC-115 is a potent DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR) dual blocker. We evaluated its activity in different human NSCLC cells. In various primary human NSCLC cells and A549 cells, CC-115 potently inhibited viability, cell proliferation, cell cycle progression, and hindered cell migration/invasion. Apoptosis was provoked in CC-115-stimulated NSCLC cells. The dual inhibitor, however, was unable to induce significant cytotoxic and pro-apoptotic activity in the lung epithelial cells. In primary NSCLC cells, CC-115 blocked activation of mTORC1/2 and DNA-PK. Yet, CC-115-induced primary NSCLC cell death was more potent than combined inhibition of DNA-PK plus mTOR. Further studies found that CC-115 provoked robust oxidative injury in primary NSCLC cells, which appeared independent of mTOR-DNA-PK dual blockage. In vivo studies showed that CC-115 oral administration in nude mice remarkably suppressed primary NSCLC cell xenograft growth. In CC-115-treated NSCLC xenograft tissues, mTOR-DNA-PK dual inhibition and oxidative injury were detected. Together, CC-115 potently inhibits NSCLC cell growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41420-022-01082-6DOI Listing
June 2022

Changes in Higher-Order Chromosomal Structure of Under Simulated Microgravity.

Front Microbiol 2022 30;13:879321. Epub 2022 May 30.

Beijing Institute of Biotechnology, Beijing, China.

Our previous work have shown that certain subpopulations of exhibit significant phenotypic changes under simulated microgravity (SMG), including enhanced biofilm formation and cellulose synthesis, which may be evoked by changes in gene expression patterns. It is well known that prokaryotic cells genomic DNA can be hierarchically organized into different higher-order three-dimensional structures, which can highly influence gene expression. It is remain elusive whether phenotypic changes induced by SMG in the subpopulations of are driven by genome higher-order structural changes. Here, we investigated the above-mentioned issue using the wild-type (WT) (WT was used as a control strain and continuously cultivated for 2 weeks under standard culture conditions of normal gravity) and two previous identified subpopulations (M1 and M2) obtained after 2 weeks of continuous incubation in a SMG device. By the combination of genome-wide chromosome conformation capture (Hi-C), RNA-seq and whole-genome methylation (WGS) analyses, we found that the along with the global chromosome interactions change, the compacting extent of M1, M2 subpopulations were much looser under SMG and even with an increase in active, open chromosome regions. In addition, transcriptome data showed that most differentially expressed genes (DEGs) were upregulated, whereas a few DEGs were downregulated in M1 and M2. The functions of both types DEGs were mainly associated with membrane fractions. Additionally, WGS analysis revealed that methylation levels were lower in M1 and M2. Using combined analysis of multi-omics data, we discovered that most upregulated DEGs were significantly enriched in the boundary regions of the variable chromosomal interaction domains (CIDs), in which genes regulating biofilm formation were mainly located. These results suggest that may regulate gene expression patterns through DNA methylation and changes in genome structure, thus resulting in new phenotypes in response to altered gravity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2022.879321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197264PMC
May 2022

Exopolysaccharide from Lactobacillus rhamnosus ZFM231 alleviates DSS-induced colitis in mice by regulating gut microbiota.

J Sci Food Agric 2022 Jun 16. Epub 2022 Jun 16.

School of Food Science and Biotechnology, Zhejiang Gongshang University, Xiasha, Hangzhou, Zhejiang, 310018, P. R. China.

Background: The exopolysaccharides (EPS) produced by Lactobacillus and other probiotics are associated with many benefits, such as immune regulation, antioxidant properties, antitumor effect, and regulation of intestinal microbe homeostasis. In the present work, the modulatory effect of EPS produced by Lactobacillus rhamnosus ZFM231 on the intestinal flora of mice with inflammatory bowel disease (IBD) induced by dextran sulfate solution (DSS) was investigated.

Results: Results indicated that weight loss, colonic length, the disease activity index (DAI) score and colonic tissue damage in mice were significantly improved by EPS treatment. Compared with the model group, in the EPS-treated group, the diversity of and composition of gut microbiota at both phylum and genus levels were found to recover to the levels of normal group, indicating the effective modulation on gut microbiota by EPS; short-chain fatty acids (SCFAs), including acetic acid, propionic acid and butyric acid produced by intestinal microbial metabolism, increased significantly; the level of anti-inflammatory factor TGF-β significantly increased and the level of pro-inflammatory factor TNF-α significantly decreased in the colonic cells of EPS-treated mice.

Conclusion: It is clear that EPS produced by L. rhamnosus ZFM231 could find application in functional foods with the property of anti-ulcerative colitis. The experimental results provide new insights into the probiotic effect of EPS. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jsfa.12070DOI Listing
June 2022

Prognostic Nutritional Index Predicts Outcome of PD-L1 Negative and MSS Advanced Cancer Treated with PD-1 Inhibitors.

Biomed Res Int 2022 6;2022:6743126. Epub 2022 Jun 6.

Department of Oncology & Radiotherapy, Affiliated Kunshan Hospital of Jiangsu University, Jiangsu, China.

Purpose: Tumor mutational burden (TMB), microsatellite instability-high (MSI-H), and expression of programmed death ligand-1 (PD-L1) have emerged as predictive biomarkers for responsiveness to immune checkpoint inhibitors (ICIs) in several cancer types. However, for patients with negative PD-L1 expression, or microsatellite stability (MSS), some cases may experience favorable response to immunotherapy, and there is currently a lack of good relevant predictors. We tried to introduce several peripheral blood markers for predicting treatment outcome and immune-related adverse events (irAEs) in PD-L1 negative and MSS patients.

Methods: A retrospective study of 142 PD-L1 negative and MSS patients was carried out. The association of peripheral blood markers including lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin-to-globulin ratio (AGR), prognostic nutrition index (PNI), and other factors with clinicopathological characters and prognosis were assessed by Cox regression and Kaplan-Meier methods.

Results: Lower level of PNI and poor performance status (ECOG score of 2) was correlated with significantly shorter overall survival (OS) and worse outcome of ICIs. The multivariate analysis revealed that PNI (for OS HR = 0.465, 95% CI: 0.236-0.916, = 0.027; for PFS HR = 0.493, 95% CI: 0.251-0.936, = 0.031) and ECOG score (for OS HR = 4.601, 95% CI: 2.676-7.910, < 0.001; for PFS HR = 2.830, 95% CI: 1.707-4.691, < 0.001) were independent prognostic factors for OS and PFS. NLR was related to the onset of irAEs.

Conclusions: Pretreatment level of PNI and NLR, beyond PD-L1 expression and MSS, can improve the predictive accuracy for immunotherapy outcomes and has the potential to expand the candidate pool of patients for treatment with ICIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/6743126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192216PMC
June 2022

Robotic spleen-preserving total gastrectomy shows better short-term advantages: a comparative study with laparoscopic surgery.

Surg Endosc 2022 Jun 13. Epub 2022 Jun 13.

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

Background: Robotic surgery may be advantageous for complex surgery. We aimed to compare the intraoperative and postoperative short-term outcomes of spleen-preserving splenic hilar lymphadenectomy (SPSHL) during robotic and laparoscopic total gastrectomy.

Methods: From July 2016 to December 2020, the clinicopathological data of 115 patients who underwent robotic total gastrectomy combined with robotic SPSHL (RSPSHL) and 697 patients who underwent laparoscopic total gastrectomy combined with laparoscopic SPSHL (LSPSHL) were retrospectively analyzed. A 1:2 ratio propensity score matching (PSM) was used to balance the differences between the two groups to compare their outcomes. The Generic Error Rating Tool was used to evaluate the technical performance.

Results: After PSM, the baseline preoperative characteristics of the 115 patients in the RSPSHL and 230 patients in the LSPSHL groups were balanced. The dissection time of the region of the splenic artery trunk (5.4 ± 1.9 min vs. 7.8 ± 3.6 min, P < 0.001), the estimated blood loss during SPSHL (9.6 ± 4.8 ml vs. 14.9 ± 7.8 ml, P < 0.001), and the average number of intraoperative technical errors during SPSHL (15.1 ± 3.4 times/case vs. 20.7 ± 4.3 times/case, P < 0.001) were significantly lower in the RSPSHL group than in the LSPSHL group. The RSPSHL group showed higher dissection rates of No. 10 (78.3% vs. 70.0%, P = 0.104) and No. 11d (54.8% vs. 40.4%, P = 0.012) lymph nodes and significantly improved postoperative recovery results in terms of times to ambulation, first flatus, and first intake (P < 0.05). The splenectomy rates of the two groups were similar (1.7% vs. 0.4%, P = 0.539), and there was no significant difference in morbidity and mortality within postoperative 30 days (13.0% vs. 15.2%, P = 0.589).

Conclusion: Compared to LSPSHL, RSPSHL has more advantages in terms of surgical qualities and postoperative recovery process with similar morbidity and mortality. For complex SPSHL, robotic surgery may be a better choice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-022-09352-1DOI Listing
June 2022

An immunosuppressive scoring system to predict recurrence and assist in decision regarding postoperative adjuvant treatment in gastric cancer.

Am J Cancer Res 2022 15;12(5):2050-2067. Epub 2022 May 15.

Department of Gastric Surgery, Fujian Medical University Union Hospital Fuzhou, Fujian, China.

Inhibition of the immune microenvironment is the main cause of tumor recurrence after surgery in patients with gastric cancer (GC). In this study, immunohistochemistry and multiple immunofluorescence staining were used to evaluate immunosuppressive indicators and immune biomarkers in 825 patients with gastric cancer from three centers. We constructed an immunosuppressive recurrence score (IRS) using LASSO Cox regression based on the expression of six immunosuppressive indicators and found that the IRS and IRS-based nomogram were significantly accurate and reliable in predicting recurrence. Moreover, an elevated IRS was associated with locoregional recurrence and postoperative adjuvant chemotherapy failure. Furthermore, an increase in IRS indicated inhibition of the antitumor effect of CD8 tumor-infiltrating lymphocytes in the invasive margin. Thus, we propose that the IRS can predict the recurrence outcome of patients with GC by distinguishing the immunosuppressive status, which is helpful in the selection of individualized adjuvant treatment plans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185630PMC
May 2022

Study on sand liquefaction induced by Songyuan earthquake with a magnitude of M5.7 in China.

Sci Rep 2022 Jun 10;12(1):9588. Epub 2022 Jun 10.

Institute of Disaster Prevention, Sanhe, 065201, Hebei Province, China.

A large-scale sand liquefaction producing typical and novel surface phenomena was found at the epicenter of Songyuan M5.7 earthquake occurring on May 28, 2018. Field survey and experimental test encompassing boring sampling, standard penetration test (SPT), cone penetration test (CPT), scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray fluorescence (XRF) were performed to ascertain the liquefaction damage and site characteristic. Cone penetration test is an excellent assay for the identification of liquefied sand layer and acquisition of physio-mechanical parameter. Moreover, the assay is applicable for in-situ post-earthquake investigation. Factors promoting the formation and controlling the distribution of the sand liquefaction were analyzed. The liquefaction impacted an 80 km2 area, and was primarily embodied as sand boil and water sprout on rice field, despite producing no significant structural damage. Due to the simple profile of local soil layer, ground motion, geomorphic condition, and groundwater level were the main factors governing the distribution of the liquefaction. Majority of the liquefied sand layer was discovered at the depth less than 10 m. However, deep layer liquefaction at the depth greater than 18 m was also discovered, which was demonstrated by the upward movement of liquefied sand towards the upper silty clay layer at the depth of 17 m. Most importantly, we have identified loess liquefaction, a phenomenon which had not been reported previously in Northeast China. Lastly, it is important to highlight the risk of significant liquefaction damage at Songyuan. Hence, investigating the liquefaction risk is potentially beneficial for augmenting planning on earthquake mitigation, engineering reconnaissance, and design project.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-13549-8DOI Listing
June 2022

Market access for Chinese herbal medicinal products in Europe-A ten-year review of relevant products, policies, and challenges.

Phytomedicine 2022 Aug 3;103:154237. Epub 2022 Jun 3.

Leiden University-European Center for Chinese Medicine and Natural Compounds, Institute of Biology Leiden, Leiden University, Leiden 2333BE, The Netherlands; SU Biomedicine B.V., Leiden 2333BE, The Netherlands; Northwest University, Xi'an 710069, China; Center for Drug Discovery & Technology Development of Yunnan Traditional Medicine, Kunming 650217, China. Electronic address:

Background: With increased consumer demand in Europe for natural and efficacious health products, the use of herbal products in the market is rising. Products of Chinese herbal medicine (CHM) could greatly expand European consumer options; however, only seven herbal medicinal products (HMPs) based on CHM formulae have been registered in the European Union (EU) since 2012.

Purpose: This study reviews the ten-year registration status of HMPs based on CHM formulae in Europe and identifies major challenges and possible solutions for pharmaceutical companies seeking market access for new HMPs.

Methods: An overview of relevant EU regulations identifies pathways to market access in EU countries for CHM products. A discussion of successful attempts to register HMPs based on CHM formulae since 2012 highlights specific challenges that applicants can expect to face.

Results: CHM products can enter the EU market as HMPs through the full or well-established use marketing authorization, or through the simplified registration procedure. Alternatively, some CHM products have entered the market as dietary supplements, nutritional foods, and agricultural products; however, under these categories, claims for medicinal use cannot be advertised. Since the registration of the first CHM product, Diao Xin Xue Kang (with the single component of Dioscorea nipponica rhizome), in 2012, only six other HMPs based on CHM formulae have been successfully registered. Among these, four are mono-component products. The remaining two products contain combinations of several herbal ingredients. It is more difficult to register combination products than mono-component products, due to their more complex composition and differences in registration requirements (esp. concerning establishing indications) in China and Europe.

Conclusions: To promote the successful registration of CHM products in Europe, pharmaceutical companies are advised to: demonstrate full control of, and the ability to test, their supply chain and manufacturing procedures following the guidance of European competent authorities; carefully adhere to all steps of the registration process and advices from European competent authorities; take the medication habits and pharmaceutical needs of European market into consideration; and establish collaboration with European local organizations, as appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2022.154237DOI Listing
August 2022

Psychosocial resources moderate the association between stress and insomnia among patients with digestive system cancers.

Psychol Health Med 2022 Jun 9:1-8. Epub 2022 Jun 9.

Department of Health Psychology, School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, P.R. China.

This study explored the profiles of psychosocial resources combined with resilience and family care, and analyzed their moderating effects on the relationship between stress and insomnia in patients with digestive system cancers. A total of 366 patients were recruited to participate in this study from two tertiary hospitals in China. They were assessed using the Perceived Stress Scale - 4 items, Insomnia Severity Index, Family Concern Index Questionnaire, and 10-item Connor-Davidson Resilience Scale. Latent profile analysis and the BCH (Bolck, Croon & Hagenaars) method were used to identify the subtypes and estimate the moderating role of psychosocial coping resources. About 62.3% of participants had insomnia symptoms. Insomnia was positively correlated to the stress ( = 0.25, < 0.001). The latent classes were the low resources class (32.8%), the medium resources class (46.1%), and high resources class (21.1%). Among these, in low (estimate value = 0.563, = 0.003) and medium (estimate value = 0.301, = 0.029) resources class, stress had an effect on insomnia. There was no association between stress and insomnia in high resources class (estimate value = 0.165, = 0.637). Stress might be associated with to insomnia problems, whereas patients with high psychosocial resources are more not vulnerable. Interventions to improve family function and resilience could contribute to easing the insomnia of patients with digestive system cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13548506.2022.2085877DOI Listing
June 2022

Citrus Peel Flavonoid Extracts: Health-Beneficial Bioactivities and Regulation of Intestinal Microecology .

Front Nutr 2022 24;9:888745. Epub 2022 May 24.

Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China.

Citrus peel and its extracts are rich in flavonoids, which are beneficial to human health. In this study, the extraction, component analysis, biological activity and intestinal microbiota regulation of citrus peel flavonoid extracts (CPFEs) were investigated. CPFEs from 14 Chinese cultivars were purified by ultrasound-assisted extraction and XAD-16 macroporous resin. The total flavonoid content of lemon was greatest at 103.48 ± 0.68 mg/g dry weight (DW) by NaNO-Al(NO)-NaOH spectrophotometry. Using high-performance liquid chromatography-diode array detection, the highest concentrations of naringin, hesperidin and eriocitrin were found in grapefruit (52.03 ± 0.51 mg/g DW), chachiensis (43.02 ± 0.37 mg/g DW) and lemon (27.72 ± 0.47 mg/g DW), respectively. Nobiletin was the most polymethoxylflavone in chachiensis at 16.91 ± 0.14 mg/g DW. CPFEs from chachiensis and grapefruit had better antioxidant activity, α-glucosidase inhibitory and sodium glycocholate binding ability. In addition, chachiensis and grapefruit CPFEs had positive effects on intestinal microecology, as evidenced by a significant increase in the relative abundance of spp., and production of short-chain fatty acids, especially acetic acid, by a simulated human intestinal model. Collectively, our results highlight the biological function of CPFEs as prebiotic agents, indicating their potential use in food and biomedical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2022.888745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171401PMC
May 2022

Influence of Surface Roughness on Biodegradability and Cytocompatibility of High-Purity Magnesium.

Materials (Basel) 2022 Jun 3;15(11). Epub 2022 Jun 3.

Department of Oral Implantology, Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.

High-purity magnesium (Mg) is a promising biodegradable metal for oral and maxillofacial implants. Appropriate surface roughness plays a critical role in the degradation behavior and the related cellular processes of biodegradable Mg-based metals. Nevertheless, the most optimized surface roughness has been questionable, especially for Mg-based oral and maxillofacial implants. Three representative scales of surface roughness were investigated in this study, including smooth (Sa < 0.5 µm), moderately rough (Sa between 1.0-2.0 µm), and rough (Sa > 2.0 µm). The results indicated that the degradation rate of the Mg specimen in the cell culture medium was significantly accelerated with increased surface roughness. Furthermore, an extract test revealed that Mg with different roughness did not induce an evident cytotoxic effect. Nonetheless, the smooth Mg surface had an adversely affected cell attachment. Therefore, the high-purity Mg with a moderately rough surface exhibited the most optimized balance between biodegradability and overall cytocompatibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma15113991DOI Listing
June 2022

A Multifunctional and Fast-Response Lysosome-Targetable Fluorescent Probe for Monitoring pH and Isoxaflutole.

Int J Mol Sci 2022 Jun 2;23(11). Epub 2022 Jun 2.

Department of Applied Chemistry, College of Arts and Sciences, Northeast Agricultural University, Harbin 150030, China.

A new chemosensor, namely -(2-morpholinoethyl)acetamide-4-morpholine-1,8-naphthimide (), was designed and synthesized through an amidation reaction. was fabricated as a multifunctional fluorescent probe for monitoring pH and isoxaflutole. exhibited excellent stability in MeCN/HO (/, 9/1), with an obvious "off-on" fluorescence response toward pH changes due to intramolecular charge transfer (ICT), where the linear response ranges of in the weakly acidic system were from 4.2 to 5.0 and from 5.0 to 6.0 with apparent p = 4.62 ± 0.02 and 5.43 ± 0.02. Based on morpholine as the lysosome targetable unit, could selectively locate lysosomes in live cells. also successfully detected the presence of H in test papers. Finally, could specifically recognize isoxaflutole at a detection limit of 0.88 μM. A possible sensing mechanism was identified based on density function theory calculations. These results indicate that could be a superior potential chemosensor for detecting pH and isoxaflutole selectively and sensitively and could be used in real sample detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms23116256DOI Listing
June 2022

Acrolein Promotes Aging and Oxidative Stress via the Stress Response Factor DAF-16/FOXO in .

Foods 2022 May 28;11(11). Epub 2022 May 28.

State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang 330047, China.

For this investigation, () served, for the first time, as a model organism to evaluate the toxic effect and possible underlying mechanisms under acrolein (ACR) exposure. The results showed that ACR exposure (12.5-100 μM) shortened the lifespan of . The reproductive capacity, body length, body width, and locomotive behavior (head thrash) of were diminished by ACR, especially the doses of 50 and 100 μM. Furthermore, ACR significantly enhanced the endogenous ROS levels of , inhibited the antioxidant-related enzyme activities, and affected the expression of antioxidant related genes. The increasing oxidative stress level promoted the migration of DAF-16 into the nucleus that was related to the DAF-16/FOXO pathway. It was also confirmed by the significant decrease of the lifespan-shortening trend in the knockout mutant. In conclusion, ACR exposure induced aging and oxidative stress in , resulting in aging-related decline and defense-related DAF-16/FOXO pathways' activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods11111590DOI Listing
May 2022

ZmSPO11-2 is critical for meiotic recombination in maize.

Chromosome Res 2022 Jun 8. Epub 2022 Jun 8.

MOE Key Laboratory of Crop Heterosis and Utilization, National Maize Improvement Center of China, China Agricultural University, Beijing, 100094, China.

Most plant species have three or more SPO11/TOPOVIA homologs and two TOPOVIB homologs, which associate to trigger meiotic double-strand break (DSB) formation and subsequent meiotic recombination. In Zea mays L. (maize), ZmSPO11-1 and ZmMTOPVIB have been reported to be indispensable for the initiation of meiotic recombination, yet the function of ZmSPO11-2 remains unclear. In this study, we characterized meiotic functions of ZmSPO11-2 during male meiosis in maize. Two independent Zmspo11-1 knock-out mutants exhibited normal vegetative growth but both male and female sterility. The formation of meiotic DSBs of DNA molecules was fully abolished in the Zmspo11-2 plants, leading to the defective homologous chromosome paring, synapsis, recombination, and segregation. However, the bipolar spindle assembly was not noticeably affected in Zmspo11-2 meiocytes. Overall, our results demonstrate that as its partner ZmSPO11-1 and ZmMTOPVIB, ZmSPO11-2 plays essential roles in DSB formation and homologous recombination in maize meiosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10577-022-09694-5DOI Listing
June 2022

IFN-τ mediated miR-26a targeting PTEN to activate PI3K/AKT signalling to alleviate the inflammatory damage of bEECs.

Sci Rep 2022 Jun 7;12(1):9410. Epub 2022 Jun 7.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Endometritis is the failure of embryo implantation and an important cause of infertility in dairy cows. IFN-τ is a type I interferon unique to ruminants. In regulating the process of inflammatory response, IFN-τ can be expressed through MicroRNAs (miRNAs) to regulate the process of inflammation. However, IFN-τ regulates lipopolysaccharide (LPS)-induced inflammatory injury of bEECs through the highly conserved miR-26a in mammals, and the mechanism remains unclear. Bovine endometrial epithelial cells (bEECs)were isolated and cultured to establish an inflammatory injury model. RT-qPCR and ELISA were used to detect the secretion of inflammatory factors. Dual-luciferase assays and target gene silencing assays determine the regulatory role of miRNAs. The target protein was detected by immunofluorescence and western blotting. This study showed that the expression of miR-26a was significantly down-regulated in mouse endometrium inflammatory injury tissue and LPS stimulated bEECs; and IFN-τ reversed the expression of miR-26a. The study also showed that the overexpression of miR-26a significantly inhibited the secretion of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. In addition, studies have shown that miR-26a inhibits its translation by targeting PTEN 3'-UTR, which in turn activates the Phosphatidylinositide 3-kinases/protein kinase B (PI3K/AKT) pathway, so that nuclear factor kappa-B (NF-κB) signaling is inhibited. In summary, the results of this study further confirm that IFN-τ as an anti-inflammatory agent can up-regulate the expression of miR-26a and target the PTEN gene to inhibit the inflammatory damage of bEECs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-12681-9DOI Listing
June 2022
-->