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1.
Zool Res ; 45(3): 520-534, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38682434

ABSTRACT

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate; however, the molecular mechanisms underpinning its pathogenesis are not well elucidated. Here, a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus (SGIV), focusing on the roles of key metabolites. Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver. Furthermore, SGIV significantly reduced the contents of lipid droplets, triglycerides, cholesterol, and lipoproteins. Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways, with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid (ALA), consistent with disturbed lipid homeostasis in the liver. Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide, carbohydrate, amino acid, and lipid metabolism, supporting the conclusion that SGIV infection induced liver metabolic reprogramming. Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid (LA) metabolites, and the accumulation of L-glutamic acid (GA), accompanied by alterations in immune, inflammation, and cell death-related genes. Further experimental data showed that ALA, but not GA, suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host. Collectively, these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.


Subject(s)
Fish Diseases , Iridovirus , Liver , alpha-Linolenic Acid , Animals , alpha-Linolenic Acid/metabolism , Fish Diseases/virology , Fish Diseases/metabolism , Liver/metabolism , Liver/virology , Iridovirus/physiology , DNA Virus Infections/veterinary , DNA Virus Infections/virology , Metabolomics , Antiviral Agents/pharmacology , Transcriptome , Metabolic Reprogramming , Multiomics
2.
Front Cell Infect Microbiol ; 13: 1240303, 2023.
Article in English | MEDLINE | ID: mdl-37731822

ABSTRACT

Background: The COVID-19 pandemic has brought about significant changes in the medical field, yet the use of botulinum toxin type A has remained uninterrupted. Plastic surgeons must carefully consider the timing of administering botulinum toxin type A to patients who have recovered from COVID-19. Methods: A questionnaire survey was conducted among patients who had contracted and recovered from SARS-CoV-2 within a month. The survey aimed to investigate various indicators in patients who had received botulinum toxin A injections at the same site before and after their infection, including pain scores and allergic reactions and the occurrence of complications. Results: The pain scores of patients who contracted SARS-CoV-2 infection between 14-21 days post-infection exhibited significant variation from previous injections. However, patients who contracted the infection between 22-28 days post-infection did not exhibit significant variation from previous injections. Furthermore, the incidence of allergic reactions and complications following botulinum toxin injection within one month after contracting the infection did not significantly differ from that observed prior to infection. Conclusion: Administering botulinum toxin type A three weeks after COVID-19 recovery is a justifiable and comparatively secure approach.


Subject(s)
Botulinum Toxins, Type A , COVID-19 , Hypersensitivity , Humans , Botulinum Toxins, Type A/adverse effects , SARS-CoV-2 , Pandemics , Pain/drug therapy , Pain/etiology , Injections, Intraocular
3.
Nat Prod Res ; : 1-7, 2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37695019

ABSTRACT

There is growing evidence that bioactive substances produced by microbial endophytes have applicability in medicine, agriculture and industry. To enrich the bioactive substances, in our search for new bioactive metabolites from fungi Aspergillus, the phytochemical reinvestigation on the Aspergillus sp. 0338 was carried out, and this led to the isolation of three new (1-3) and five known alkaloids (4-8). Their structures were elucidated by spectroscopic analysis, including extensive 1D and 2D NMR techniques, as well as comparison with literature values. Additionally, compounds 1-3 were evaluated for their anti-MRSA activities. The results revealed that compounds 1-3 exhibited good inhibitions with IZD of 15.2 ± 1.8, 14.6 ± 2.0, and 13.4 ± 2.2 mm, respectively.

4.
World J Psychiatry ; 13(9): 607-619, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37771645

ABSTRACT

Deep transcranial magnetic stimulation (DTMS) is a new non-invasive neuromodulation technique based on repetitive transcranial magnetic stimulation tech-nology. The new H-coil has significant advantages in the treatment and mechanism research of psychiatric and neurological disorders. This is due to its deep stimulation site and wide range of action. This paper reviews the clinical progress of DTMS in psychiatric and neurological disorders such as Parkinson's disease, Alzheimer's disease, post-stroke motor dysfunction, aphasia, and other neurological disorders, as well as anxiety, depression, and schizophrenia.

5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(4): 843-847, 2023 Jul.
Article in Chinese | MEDLINE | ID: mdl-37545084

ABSTRACT

Objective: To summarize the clinical efficacy and nursing experience of intrauterine blood transfusion (IUT) treatment for fetal anemia cases. Methods: The clinical data of 4 fetal anemia cases receiving IUT in Beijing Obstetrics and Gynecology Hospital, Capital Medical University between 2020 and 2022 were collected. Four pregnant women aged 24-38 years were included in the study. They carried fetuses with anemia of unknown causes. The four pregnant women developed anxiety after they were informed of the diagnosis of fetal anemia. One-on-one psychological counseling before the IUT procedure and one-on-one companionship over the course of the surgery were provided for the pregnant women. In addition, they were closely monitored for blood transfusion reactions. Postprocedural observation of the puncture site and 24-hour monitoring of the newborns were also conducted. Results: The four pregnant women underwent 1-3 times of IUT in the second and third trimesters, with the minimum gestational age at the time of IUT being 25 + weeks and the blood transfusion volume being 20-107 mL/time. Two pregnant women experienced irregular uterine contractions during IUT in the third trimester. Other than that, all other IUT treatments were successful. After IUT, there was a significant improvement in fetal hemoglobin, peak systolic velocity of the middle cerebral artery (MCA-PSV), and cardiothoracic area ratio. One case did not give birth in our hospital and the outcome of the fetus was not known. The other three fetuses achieved good outcomes. Conclusion: Positive preprocedural psychological counseling for pregnant women, close intraoprocedural and postprocedural pregnancy monitoring, and the prevention of maternal and fetal complications are the key to improving the clinical efficacy of IUT and achieving a good fetal outcome.


Subject(s)
Anemia , Fetal Diseases , Nursing Care , Female , Humans , Pregnancy , Anemia/diagnosis , Anemia/therapy , Blood Flow Velocity , Blood Transfusion, Intrauterine/methods , Fetal Blood , Fetal Diseases/diagnosis , Fetal Diseases/therapy , Fetus , Retrospective Studies , Treatment Outcome , Young Adult , Adult
6.
J Colloid Interface Sci ; 650(Pt A): 526-540, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37423180

ABSTRACT

Tumor microenvironment (TME) stimuli-responsive nanoassemblies are emerging as promising drug delivery systems (DDSs), which acquire controlled release by structural transformation under exogenous stimulation. However, the design of smart stimuli-responsive nanoplatforms integrated with nanomaterials to achieve complete tumor ablation remains challenging. Therefore, it is of utmost importance to develop TME-based stimuli-responsive DDSs to enhance drug-targeted delivery and release at tumor sites. Herein, we proposed an appealing strategy to construct fluorescence-mediated TME stimulus-responsive nanoplatforms for synergistic cancer therapy by assembling photosensitizers (PSs) carbon dots (CDs), chemotherapeutic agent ursolic acid (UA), and copper ions (Cu2+). First, UA nanoparticles (UA NPs) were prepared by self-assembly of UA, then UA NPs were assembled with CDs via hydrogen bonding force to obtain UC NPs. After combining with Cu2+, the resulting particles (named UCCu2+ NPs) exhibited quenched fluorescence and photosensitization due to the aggregation of UC NPs. Upon entering the tumor tissue, the photodynamic therapy (PDT) and the fluorescence function of UCCu2+ were recovered in response to TME stimulation. The introduction of Cu2+ triggered the charge reversal of UCCu2+ NPs, thereby promoting lysosomal escape. Furthermore, Cu2+ resulted in additional chemodynamic therapy (CDT) capacity by reacting with hydrogen peroxide (H2O2) as well as by consuming glutathione (GSH) in cancer cells through a redox reaction, hence magnifying intracellular oxidative stress and enhancing the therapeutic efficacy due to reactive oxygen species (ROS) therapy. In summary, UCCu2+ NPs provided an unprecedented novel approach for improving the therapeutic efficacy through the three-pronged (chemotherapy, phototherapy, and heat-reinforced CDT) attacks to achieve synergistic therapy.


Subject(s)
Biological Products , Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Neoplasms , Humans , Copper/chemistry , Carcinoma, Hepatocellular/drug therapy , Hydrogen Peroxide , Liver Neoplasms/drug therapy , Nanoparticles/chemistry , Cell Line, Tumor , Neoplasms/drug therapy , Glutathione , Tumor Microenvironment
7.
Appl Microbiol Biotechnol ; 107(16): 5257-5267, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37405431

ABSTRACT

The engineered probiotic Escherichia coli Nissle 1917 (EcN) is expected to be employed in the diagnosis and treatment of various diseases. However, the introduced plasmids typically require antibiotics to maintain genetic stability, and the cryptic plasmids in EcN are usually eliminated to avoid plasmid incompatibility which may change the inherent probiotic characteristics. Here, we provided a simple design to minimize the genetic change of probiotics by eliminating native plasmids and reintroducing the recombinants carrying functional genes. Specific insertion sites in the vectors showed significant differences in the expression of fluorescence proteins. Selected integration sites were applied in the de novo synthesis of salicylic acid, leading to a titer of 142.0 ± 6.0 mg/L in a shake flask with good production stability. Additionally, the design successfully realized the biosynthesis of ergothioneine (45 mg/L) by one-step construction. This work expands the application scope of native cryptic plasmids to the easy construction of functional pathways. KEY POINTS: • Cryptic plasmids of EcN were designed to express exogenous genes • Insertion sites with different expression intensities in cryptic plasmids were provided • Target products were stably produced by engineering cryptic plasmids.


Subject(s)
Anti-Bacterial Agents , Probiotics , Anti-Bacterial Agents/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Plasmids/genetics
8.
Pest Manag Sci ; 79(10): 3721-3730, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37253683

ABSTRACT

BACKGROUND: Natural products are important sources of biopesticides to control plant virus, and flavonoids are identified as promising anti-tobacco mosaic virus (TMV) agents. Since Desmodium caudatum is a rich source of flavonoids, this study focuses on the discovery of the new anti-TMV active flavonoids from D. caudatum and their possible mode of action. RESULTS: Three new (compounds 1-3) and nine known (compounds 4-12) C-alkylated flavonoids were isolated from D. caudatum. To the best of our knowledge, the framework of 1-3 was reported in natural products for the first time. In addition, 1-3, 5, and 6 showed notable anti-TMV activity with inhibition rates in the range of 35.8-64.3% at a concentration of 50 µg/mL, and these rates are higher than that of positive control (with inhibition rates of 34.6% ± 2.8). In addition, the structure-activity relationship study revealed that the (pyrrol-2-yl)methyl moiety on flavone can significantly increases the activity. This result is helpful to find new anti-TMV inhibitors. CONCLUSION: C-Alkylated flavonoids showed potent activities against TMV with multiple modes of actions. The increase of defense-related enzyme activities, up-regulate the expression of defense related genes, down-regulate the expression of Hsp70 protein by inhibiting the related Hsp genes that are involved in tobacco resistance to TMV. By the actions mentioned earlier, the infection of TMV was influenced, thereby achieving the effects of control of TMV. The successful isolation of the earlier-mentioned flavonoids provide the new source of biopesticides to TMV proliferation, and also contribute to the utilization of D. caudatum. © 2023 Society of Chemical Industry.


Subject(s)
Flavonoids , Tobacco Mosaic Virus , Flavonoids/pharmacology , Biological Control Agents/pharmacology , Structure-Activity Relationship , Nicotiana , Antiviral Agents/pharmacology
9.
Aquat Toxicol ; 257: 106431, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36827831

ABSTRACT

Thyroid disrupting chemicals (TDCs) have received much attention due to their potential adverse effects on animal and human health, which calls for rapid screen assays to identify them. The triiodothyronine (T3)-induced Xenopus metamorphosis assay (TiXMA) we developed previously has been successfully applied to the detection of the TDCs disrupting thyroid hormone (TH) signaling. Here, we attempted to expand the application of the TiXMA to the screening of the TDCs interfering with the hypothalamic-pituitary-thyroid (HPT) axis. Two well-known TH synthesis inhibitors methimazole (MMI) and sodium perchlorate (SP) were employed to test the sensitivity of the TiXMA to the TDCs interfering with the HPT axis. As expected, we observed that the two chemicals concentration-dependently antagonized T3-induced morphological changes and body weight reduction of X. laevis tadpoles following 96 h-exposure, in parallel with blocked thyroid development and down-regulated tshß expression in the brain. All the data show that both MMI and SP exert inhibitory effects on T3-induced metamorphosis, indicating that the TiXMA is capable of screening the TDCs interfering with the HPT axis. In comparison with Amphibian Metamorphosis Assay (AMA), a 21-day assay for screening the TDCs interfering with the HPT axis, the TiXMA has a remarkable advantage of shorter exposure duration (96 h).


Subject(s)
Methimazole , Water Pollutants, Chemical , Animals , Humans , Xenopus laevis , Methimazole/toxicity , Methimazole/metabolism , Water Pollutants, Chemical/toxicity , Thyroid Gland , Metamorphosis, Biological , Larva
10.
Nat Prod Res ; : 1-8, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36787178

ABSTRACT

Chamaecrista rotundifolia (C. rotundifolia) is a perennial herb of leguminosae, which increasingly being grown as a forage in China. In our search for original bioactive metabolites from Cassia plants, the phytochemical reinvestigation of the C. rotundifolia was carried out, which led to the isolation of three new (1-3) and six known (4-9) chromones. Their structures were confirmed by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-9 were evaluated for their anti-rotavirus activities, and the results revealed that compounds 1-9 exhibited potential anti-rotavirus activities with therapeutic index (TI) valves in the range of 12.0 ∼ 20.2, respectively.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-993178

ABSTRACT

Objective:To explore the method of constructing automatic delineation model for clinical target volume (CTV) and partially organs at risk (OAR) of postoperative radiotherapy for prostate cancer based on convolutional neural network, aiming to improve the clinical work efficiency and the unity of target area delineation.Methods:Postoperative CT data of 117 prostate cancer patients manually delineated by one experienced clinician were retrospectively analyzed. A multi-class auto-delineation model was designed based on 3D UNet. Dice similarity coefficient (DSC), 95% Hausdorf distance (95%HD), and average surface distance (ASD) were used to evaluate the segmentation ability of the model. In addition, the segmentation results in the test set were evaluated by two senior physicians. And the CT data of 78 patients treated by other physicians were also collected for external validation of the model. The automatic segmentation of these 78 patients by CTV-UNet model was also evaluated by two physicians.Results:The mean DSC for tumor bed area (CTV1), pelvic lymph node drainage area (CTV2), bladder and rectum of CVT-UNet auto-segmentation model in the test set were 0.74, 0.82, 0.94 and 0.79, respectively. Both physicians' scoring results of the test set and the external validation showed more consensus on the delineation of CTV2 and OAR. However, the consensus of CTV1 delineation was less.Conclusions:The automatic delineation model based on convolutional neural network is feasible for CTV and related OAR of postoperative radiotherapy for prostate cancer. The automatic segmentation ability of tumor bed area still needs to be improved.

12.
Front Mol Neurosci ; 15: 822088, 2022.
Article in English | MEDLINE | ID: mdl-35600074

ABSTRACT

Cell pyroptosis is one of the main forms of neuronal injury after cerebral ischemia-reperfusion. It is accompanied by an inflammatory reaction and regulated by the caspase gene family. Electroacupuncture (EA) can reduce neuronal injury caused by cerebral ischemia-reperfusion, and we speculated that EA can prevent neuronal pyroptosis after cerebral ischemia-reperfusion by regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1 pathway. The cerebral ischemia-reperfusion injury model of C57 and caspase-1 gene knockout (Cas-1 ko) mice was established by Longa's method. EA was conducted at acupoints Chize (LU5), Hegu (LI4), Sanyinjiao (SP6), and Zusanli (ST36) for 1.5 h after cerebral ischemia-reperfusion injury for 20 min, and observation was carried out after 24 h. Neurological deficit scores evaluated the neurological function, cerebral infarction volume was observed by triphenyl tetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, TUNEL and caspase-1 double-labeled fluorescence staining, and NLRP3 and caspase-1 double-labeled immunofluorescence staining that were used to observe the morphology of neurons in hippocampus, and the protein expression of NLRP3, pro-caspase-1, cleaved caspase-1 p20, pro-interleukin-1ß (IL-1ß), cleaved IL-1ß, and GSDMD was detected by Western blot assay. Results showed that EA could reduce the score of neurological deficit, reduce the volume of cerebral infarction and improve the degree of nerve cell injury, and inhibit NLRP3, pro-caspase-1, cleaved caspase-1 p20, pro-IL-1ß, cleaved IL-1ß, and GSDMD protein expression. In summary, EA plays a neuroprotective role by reducing the pyroptotic neurons that were caspase 1-mediated and inflammatory response after cerebral ischemia-reperfusion.

13.
Zhen Ci Yan Jiu ; 47(5): 422-7, 2022 May 25.
Article in Chinese | MEDLINE | ID: mdl-35616416

ABSTRACT

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression level of Caspase-3, so as to explore its mechanism in inhibiting apoptosis after cerebral ischemia reperfusion. METHODS: SD male rats were randomly divided into sham-operation, model, EA and Caspase-3 inhibitor groups (n=20 rats in each group). The focal cerebral ischemia/reperfusion injury rat model was established by occlusion of the middle cerebral artery. Rats of the EA group received EA at "Hegu" (LI4), "Chize" (LU5), "Zusanli" (ST36) and "Sanyinjiao" (SP6) on the affected side for 20 min. Rats of the inhibitor group were given intracerebroventricular injection of inhibitor Z-DEVD-FMK 5 µg before modeling. The neurological deficit scores (NDS) were assessed by using Longa's method, the infarct size of the brain assessed after staining with 2% triphenyltetrazolium chloride. The apoptosis index of nerve cells were observed by TUNEL staining, PCR and Western blot were used to detect the mRNA and protein expressions of Caspase-3 in the hippocampus, separately. RESULTS: After modeling, the NDS, infarct volume, the apoptosis index of hippocampus CA1 area, and Caspase-3 mRNA and protein expression levels were significantly increased in the model group compared with the sham-operation group (P<0.01). After intervention, the NDS, infarct volume, the apoptosis index, Caspase-3 mRNA and protein expression levels were all significantly decreased in the EA and Caspase-3 inhibitor groups re-levant to the model group (P<0.05). CONCLUSION: EA can improve the neurological function in cerebral ischemia/reperfusion rats, which may be related to its effect in inhibiting of Caspase-3 expression.


Subject(s)
Brain Ischemia , Electroacupuncture , Reperfusion Injury , Animals , Brain Ischemia/genetics , Brain Ischemia/therapy , Caspase 3/genetics , Caspases , Cerebral Infarction , Hippocampus , Male , RNA, Messenger , Rats , Rats, Sprague-Dawley , Reperfusion Injury/genetics , Reperfusion Injury/therapy
14.
Nat Prod Res ; 36(1): 223-228, 2022 Jan.
Article in English | MEDLINE | ID: mdl-32524860

ABSTRACT

Two new benzoic acid derivatives, named methyl(S)-3-hydroxy-4-(2- hydroxy -6-methylheptan-2-yl)benzoate (1) and 2-hydroxy-3-(6- hydroxy-6-methylhept-1-en-2-yl)benzoic acid (2), were isolated from the ethanol extract of an endophytic fungus Aspergillus versicolor derived from the medicinal plant Euphorbia royleana. The structures of compounds (1-2) were elucidated using NMR and MS methods.


Subject(s)
Benzoic Acid , Euphorbia , Aspergillus , Molecular Structure
15.
Synth Syst Biotechnol ; 7(1): 453-459, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34938904

ABSTRACT

Biotransformation of soybean phytosterols into 9α-hydroxy-4-androstene-3,17-dione (9-OHAD) by mycobacteria is the core step in the synthesis of adrenocortical hormone. However, the low permeability of the dense cell envelope largely inhibits the overall conversion efficiency of phytosterols. The antigen 85 (Ag85) complex encoded by fbpA, fbpB, and fbpC was proposed as the key factor in the combined catalysis of mycoloyl for producing mycolyl-arabinogalactan (m-AG) and trehalose dimycolate (TDM) in mycobacterial cell envelope. Herein, we confirmed that fbpC3 was essential for the biotransformation of trehalose monomycolate (TMM) to TDM in Mycolicibacterium neoaurum. The deficiency of this gene raised the cell permeability, thereby enhancing the steroid uptake and utilization. The 9-OHAD yield in the fbpC3-deficient 9-OHAD-producing strain was increased by 21.3%. Moreover, the combined deletion of fbpC3 and embC further increased the 9-OHAD yield compared to the single deletion of fbpC3. Finally, after 96 h of bioconversion in industrial resting cells, the 9-OHAD yield of 11.2 g/L was achieved from 20 g/L phytosterols and the productivity reached 0.116 g/L/h. In summary, this study suggested the critical role of the fbpC3 gene in the synthesis of TDM in M. neoaurum and verified the feasibility of improving the bioconversion efficiency of phytosterols through the cell envelope engineering strategy.

16.
Opt Express ; 29(24): 39838-39846, 2021 Nov 22.
Article in English | MEDLINE | ID: mdl-34809339

ABSTRACT

We present an aluminum (Al) laminated nanostructure stacked on a glass substrate to produce highly transmitted narrowband ultraviolet (UV) filters. The laminated nanostructure was mainly composed of an Al nanohole array, and each Al nanohole had a coaxial Al nanoring at the bottom. This UV filter showed a single dominant peak with a high transmission over 50% and a narrow bandwidth less than 80 nm in the 200-400 nm waveband that was achieved based on the synergy of surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR). The electric field profiles of the laminated nanostructure indicate that SPR selects the transmission wavelength and LSPR contributes to single peak. This narrowband UV filter can be utilized in UV detectors.

17.
Gynecol Obstet Invest ; 86(6): 533-541, 2021.
Article in English | MEDLINE | ID: mdl-34818258

ABSTRACT

BACKGROUND: Ovarian cancer, one of the most malignant diseases in female, is associated with poor diagnosis and low 5-year survival rate. Taxol is a widely used chemotherapeutic drug for the treatment of ovarian cancer by targeting the microtubules of the mitotic spindle to induce cancer cell death. However, with the widespread clinical applications of Taxol, a large fraction of ovarian cancer patients developed drug resistance. RESULTS: Here, we report miR-138-5p is significantly downregulated in epithelial ovarian cancer tissues compared with their matched normal ovarian tissues. Overexpression of miR-138-5p effectively sensitized ovarian cancer cells to Taxol. By establishing Taxol-resistant cell line from the epithelial ovarian cancer cell line, HO-8910, we found miR-138-5p was significantly downregulated in Taxol-resistant cells. Furthermore, overexpression of miR-138-5p dramatically overcame the chemoresistance of Taxol-resistant cells. Intriguingly, bioinformatic analysis indicated miR-138-5p had putative binding sites for cyclin-dependent kinase 6 (CDK6). This negative regulation was further verified from epithelial ovarian cancer tissues. Luciferase assay demonstrated miR-138-5p could directly bind to 3'UTR of CDK6. Importantly, silencing CDK6 expression by siRNA successfully increased the sensitivity of both parental and Taxol-resistant ovarian cancer cells. Finally, rescue experiments clearly elucidated restoration of CDK6 in miR-138-5p-overexpressing ovarian cancer cells successfully recovered the Taxol resistance. CONCLUSION: In summary, these findings suggest important molecular mechanisms for the miR-138-5p-mediated Taxol sensitivity of ovarian cancer via directly targeting CDK6, suggesting miR-138-5p is an effective therapeutic target for the noncoding RNA-based anti-chemoresistance treatment.


Subject(s)
MicroRNAs , Ovarian Neoplasms , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Cell Proliferation , Cyclin-Dependent Kinase 6 , Female , Humans , MicroRNAs/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Paclitaxel/pharmacology
18.
Cardiovasc Toxicol ; 21(12): 1045-1057, 2021 12.
Article in English | MEDLINE | ID: mdl-34537923

ABSTRACT

Astaxanthin (AST) has a variety of biochemical effects, including anti-inflammatory, antioxidative, and antihypertensive functions. The aim of the present study was to determine whether AST ameliorates blood pressure in salt-induced prehypertensive rats by ROS/MAPK/NF-κB pathways in hypothalamic paraventricular nucleus.To explore the central effects of AST on the development of blood pressure, prehypertensive rats were induced by a high-salt diet (HS, 8% NaCl) and its control groups were treated with normal-salt diet (NS, 0.3% NaCl). The Dahl salt-sensitive (S) rats with HS diet for 6 weeks received AST or vehicle by gastric perfusion for 6 weeks. Compared to those with NS diet, rats with HS diet exhibited increased mean arterial pressure (MAP) and heart rate (HR). These increases were associated with higher plasma level of norepinephrine (NE), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6); elevated PVN level of reactive oxygen species (ROS), NOX2, and NOX4, that of IL-1ß, IL-6, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), phosphorylation extracellular-signal-regulated kinase (p-ERK1/2), phosphorylation Jun N-terminal kinases (p-JNK), nuclear factor-kappa B (NF-κB) activity; and lower levels of IL-10, superoxide dismutase (SOD), and catalase (CAT) in the PVN. In addition, our data demonstrated that chronic AST treatment ameliorated these changes in the HS but not NS diet rats. These data suggested that AST could alleviate prehypertensive response in HS-induced prehypertension through ROS/MAPK/NF-κB pathways in the PVN.


Subject(s)
Antihypertensive Agents/pharmacology , Arterial Pressure/radiation effects , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Oxidative Stress/drug effects , Paraventricular Hypothalamic Nucleus/drug effects , Prehypertension/prevention & control , Reactive Oxygen Species/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Disease Models, Animal , Male , Paraventricular Hypothalamic Nucleus/enzymology , Paraventricular Hypothalamic Nucleus/physiopathology , Phosphorylation , Prehypertension/enzymology , Prehypertension/etiology , Prehypertension/physiopathology , Rats, Inbred Dahl , Signal Transduction , Sodium Chloride, Dietary , Xanthophylls/pharmacology
19.
Eur J Pharm Biopharm ; 168: 131-138, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34438020

ABSTRACT

Currently licensed vaccines require a cold-chain to maintain efficacy. This cold-chain requirement reduces the availability of vaccines in resource-poor areas of the world. Commercially available human papillomavirus (HPV) vaccines protect against the most common HPV types related to cervical cancer; however, their impact is limited in many regions due to cold-chain requirements. The goal of this study was to test the thermostability of an adjuvanted, trivalent HPV L1 capsomere-based vaccine (containing HPV types 16, 18, and 31) that was formulated by using lyophilization to embed the antigens within a solid, glassy matrix. Thermal stabilities were determined by storing the vaccine formulations for 3 months at 50 °C, followed by immunization of BALB/c mice and measurement of antibody responses. Antibody responses to capsomere vaccines formulated with alum were unchanged after storage for 3 months at 50 °C. Neutralizing responses to these vaccines were unchanged by high-temperature storage, and were equivalent to those generated after administration of the commercially available liquid HPV vaccine Gardasil®9.


Subject(s)
Alphapapillomavirus/immunology , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/chemistry , Animals , Capsid Proteins/immunology , Drug Stability , Drug Storage , Female , Humans , Mice , Mice, Inbred BALB C , Papillomavirus Infections/immunology , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/immunology , Temperature , Time Factors
20.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(7): 918-922, 2021 Jul 15.
Article in Chinese | MEDLINE | ID: mdl-34308603

ABSTRACT

OBJECTIVE: To review the diagnosis and management of fat necrosis after autologous fat transplantation of breast. METHODS: Based on the latest related literature, the pathology, clinical and radiographic examinations, influence factors, as well as the management of fat necrosis after autologous fat transplantation for breast augmentation and reconstruction were summarized. RESULTS: Fat necrosis after breast autologous fat transplantation is histologically manifested as hyaline degeneration, fibrosis, and calcification. The diagnosis of fat necrosis includes clinical examination, imaging examination (ultrasound, mammography, and MRI), and biopsy. The occurrence of fat necrosis is closely related to patient's own reason and fat transplantation technology. Optimizing the process of fat acquisition, purification, and transplantation can reduce the occurrence of fat necrosis. Intervention or not after fat necrosis depends on the nature of the nodules. According to the nature of the the nodules, various methods such as simple aspiration, vibration amplification of sound energy at resonance liposuction, or direct excision can be selected. CONCLUSION: Fat necrosis after autologous fat transplantation of breast are difficult to control. How to process fat to minimize the injury and maximize the activity of grafted fat needs further researches.


Subject(s)
Fat Necrosis , Mammaplasty , Adipose Tissue , Breast/diagnostic imaging , Breast/surgery , Fat Necrosis/diagnosis , Fat Necrosis/etiology , Humans , Mammaplasty/adverse effects , Transplantation, Autologous
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