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Ferroptosis is a form of programmed cell death with important biological functions in the progression of various diseases, and targeting ferroptosis is a new tumor treatment strategy. Studies have shown that sodium butyrate plays a tumor-suppressing role in the progression of various tumors, however, the mechanism of NaBu in endometrial cancer is unclear. Cell viability, clone formation, proliferation, migration, invasion abilities and cell cycle distribution were assessed by CCK8 assay, Clone formation ability assay, EdU incorporation, Transwell chambers and flow cytometry. The level of ferroptosis was assayed by the levels of ROS and lipid peroxidation, the ratio of GSH/GSSG and the morphology of mitochondria. Molecular mechanisms were explored by metabolome, transcriptome, RNA-pulldown and mass spectrometry. The in-vivo mechanism was validated using subcutaneous xenograft model. In this study, NaBu was identified to inhibit the progression of endometrial cancer in vitro and in vivo. Mechanistically, RBM3 has a binding relationship with SLC7A11 mRNA. NaBu indirectly downregulates the expression of SLC7A11 by promoting the expression of RBM3, thereby promoting ferroptosis in endometrial cancer cells. In conclusion, Sodium butyrate can promote the expression of RBM3 and indirectly downregulate the expression of SLC7A11 to stimulate ferroptosis, which may be a promising cancer treatment strategy.
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In this work, we constructed theoretical models by embedding Fe-TCPP and Fe-(mIM)n (n = 2,3,4) active sites into hole-graphene, and the structural stability was evaluated using molecular dynamics simulations. Based on the theoretical models, we systematically studied the oxygen reduction reaction (ORR) mechanism and the effect of spatial confinement and ligands with DFT calculations. The analysis of the ORR reaction pathway shows that Fe-TCPP and Fe-(mIM)4 have good catalytic activity. Subsequently, the confinement effect (5-14 Å) was introduced to investigate its influence on the catalytic activity. The Fe-TCPP and Fe-(mIM)4 active sites have the lowest overpotential at an axial space of 8 Å and 9 Å, respectively. We select four ligands (bpy, pya, CH3, and bIm) to explore their effect on the catalytic activity of the Fe-TCPP active site. With the modification of bpy, pya, and bIm_N (Fe-N4 sites become Fe-N5 active sites), the overpotential decreases by 26-31%. In the present work, the best catalytic system is Fe-TCPP_pya, which is on the top of the volcano plot.
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Printers can release numerous particles to contaminate indoor environments and pose health risks. Clarifying the exposure level and physicochemical properties of printer-emitted particles (PEPs) will help to evaluate the health risks of printer operator. In our study, the particles concentration in the printing shop was monitored in real time for a long time (12 h/day, total 6 days), and the PEPs were collected to characterize their physicochemical properties including shape, size and compositions. The result showed that the concentration of PEPs is closely related to the printing workload and the highest particle mass concentration of PM10 and PM2.5 was 212.73 µg m-3 and 91.48 µg m-3, respectively. The concentration of PM1 in the printing shop was in the range of 11.88-80.59 µg m-3 for mass value, and 174.83-1348.84 P cm-3 for count value which changed with the printing volume. The particle sizes of PEPs were less than 900 nm, 47.99% of PEPs was less than 200 nm, and 14.21% of the particles were at the nanoscale. PEPs contained 68.92% organic carbon (OC), 5.31% elemental carbon (EC), 3.17% metal elements, and 22.60% other inorganic additives, which contained more OC and metal elements than toners. Total polycyclic aromatic hydrocarbons (PAHs) levels were 18.95 ng/mg in toner and 120.70 ng/mg in PEPs. The carcinogenic risk of PAHs in PEPs was 1.40 × 10-7. These findings suggested future studies should pay more attention to the health effects of printing workers exposed to nanoparticles.
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Opioids remain the most powerful analgesics for moderate to severe pain but their clinical use, misuse and abuse has been an alarming medical problem, especially for those users at child-bearing age. Mu-opioid receptor (MOR) biased agonists have been suggested as superior alternatives with better therapeutic ratios. We recently discovered and characterized a novel MOR biased agonist, LPM3480392, which demonstrates robust analgesic effect, favorable pharmacokinetic performance, and mild respiratory suppression in vivo. To understand the safety profile of LPM3480392 on the reproductive system and embryonic development, this study evaluated the effects of LPM3480392 on the fertility and early embryonic development, embryo-fetal development, and pre- and postnatal development in rats. Results showed that LPM3480392 had mild effects on parental male and female animals, accompanied by subtle early embryonic loss and delayed ossification of fetal development during organogenesis period. In addition, although minor effects were found on normal developmental milestones and behaviors in the pups, there was no evidence of malformed effect. In conclusion, these results suggest that LPM3480392 has a favorable safety profile with only minor effects on the reproductive and developmental outcomes in animals, which support the development of LPM3480392 as a novel analgesic.
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The expression of linear DNA sequence is precisely regulated by the three-dimensional (3D) architecture of chromatin. Morphine-induced aberrant gene networks of neurons have been extensively investigated; however, how morphine impacts the 3D genomic architecture of neurons is still unknown. Here, we applied digestion-ligation-only high-throughput chromosome conformation capture (DLO Hi-C) technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons. After receiving continuous morphine administration for 90 days on rhesus monkeys, we discovered that morphine re-arranged chromosome territories, with a total of 391 segmented compartments being switched. Morphine altered over half of the detected topologically associated domains (TADs), most of which exhibited a variety of shifts, followed by separating and fusing types. Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops. Moreover, all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops, and were further validated to be significantly changed. Collectively, an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine effects. Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.
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Introduction: Schizophrenia is a serious mental illness that requires effective treatment with minimal adverse effects. As preclinical and clinical research progresses, trace amine-associated receptor 1 (TAAR1) is becoming a potential new target for the treatment of schizophrenia. Methods: We used molecular docking and molecular dynamics (MD) simulations to discover TAAR1 agonists. The agonistic or inhibitory effects of compounds on TAAR1, 5-HT1A, 5-HT2A, and dopamine D2-like receptors were determined. We used an MK801-induced schizophrenia-like behavior model to assess the potential antipsychotic effects of compounds. We also performed a catalepsy assay to detect the adverse effects. To evaluate the druggability of the compounds, we conducted evaluations of permeability and transporter substrates, liver microsomal stability in vitro, human ether-à-go-go-related gene (hERG), pharmacokinetics, and tissue distribution. Results: We discovered two TAAR1 agonists: compounds 50A and 50B. The latter had high TAAR1 agonistic activity but no agonistic effect on dopamine D2-like receptors and demonstrated superior inhibition of MK801-induced schizophrenia-like behavior in mice. Interestingly, 50B had favorable druggability and the ability to penetrate the blood-brain barrier (BBB) without causing extrapyramidal symptoms (EPS), such as catalepsy in mice. Conclusion: These results demonstrate the potential beneficial role of TAAR1 agonists in the treatment of schizophrenia. The discovery of a structurally novel TAAR1 agonist (50B) may provide valuable assistance in the development of new treatments for schizophrenia.
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The anomalous metallic state (AMS) emerging from a quantum superconductor-to-metal transition is a subject of great current interest since this exotic quantum state exhibits unconventional transport properties that challenge the core physics principles of Fermi liquid theory. As the AMS concept is historically derived from disordered two-dimensional (2D) systems, related studies have predominately concentrated on 2D materials. The AMS behaviors in three-dimensional (3D) systems have been rarely reported to date, which raises intriguing questions on the fundamental nature of pertinent physics. Here, we report experimental evidence for a 3D AMS in highly compressed titanium metal that exhibits superconductivity with a critical temperature (Tc) reaching near-record 25.1 K among elemental superconductors, offering a favorable material template for exploring 3D AMS. At sufficiently strong magnetic fields, unusual transport behaviors set in over a wide pressure range, showcasing AMS hallmarks of a low-temperature saturation resistance below the Drude value and giant positive magnetoresistance. These findings reveal a 3D AMS in simple elemental systems and, more importantly, provide a fresh platform for probing the decades-long enigmatic underlying physics.
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Synopsis for table of contents: An exceptional number of synchronous MTC/PTC in the same thyroid gland is presented. This may be the most numerous case series reported in the literature. Synchronous PTC/MTC in the same thyroid gland were classified into 4 subtypes and the clinical and pathological aspects as well as the results are presented. Background and objectives: The synchronous occurrence of multiple neoplastic processes in the thyroid gland is unusual. We investigated the clinicopathological features of 30 medullary thyroid carcinomas (MTC) in association with papillary (PTC). Method: Retrospective analysis of operated patients for thyroid tumors. Synchronous PTC/MTC in the same thyroid gland were classified into 4 subtypes: (type I) True mixed MTC/PTC, MTC and PTC closely intermingled. (Type II) Collision MTC/PTC, i.e. tumors that meet at the same site, invade each other and appear as a single mass in the thyroid gland, i.e. MTC and PTC merge. (Type III) Synchronous anatomically separate tumors in the same thyroid lobe, i.e. separated from each other by non-tumorous thyroid parenchyma. (Type IV) Synchronous tumors occurring in separate anatomical lobes or in the isthmus. Clinical and pathological data were reviewed. Location: Department of thyroid surgery, China-Japan Union Hospital, Jilin University. Time frame: 14 years (June 2008-November 2022). Results: Thirty patients were identified with an overall prevalence of 28621 (0.1%). 17 (56.7%) were male, 13 (43.3%) female, mean age 51.3 ± 11.0 years, mean BMI 23.6 ± 3.6kg/m2. Mean duration of symptoms was 11.2 ± 18.4 months. Mean calcitonin level was 133.7 ± 196.4 pg/ml. Fine needle aspiration (FNA) was offered in 21 cases: 9 (42.9%) were suspected carcinoma, 9 (42.9%) PTC, 1 (4.8%) MTC, 2 (9.4%) MTC/PTC. Pathology revealed type I 4 (13.3%), type II 2 (6.7%), type III 14 (46.7%), type IV 10 (33.3%). The mean diameter of MTC was 1.6 ± 2.0cm, 18 (60%) were micro-MTC. The mean diameter of PTC was 0.9 ± 1.9 cm, 26 (86.7%) were micro-PTC. In 16 (53.3%) micro-PTC/-MTC occurred in synchronous sequence. Four patients had a recurrence: 2 had to be re-operated due to MTC recurrence, 2 died due to distant metastases (bone, liver). Conclusion: We report an exceptional number of MTC/PTC in the same thyroid gland. This may be the most numerous case series reported in the literature. The clinical and pathological aspects as well as the results are presented.
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Carcinoma Neuroendócrino , Carcinoma Papilar , Neoplasias Primárias Múltiplas , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide , Estudos Retrospectivos , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Carcinoma Neuroendócrino/cirurgiaRESUMO
LPM6690061 is a novel compound with 5-HT2A receptor antagonist and inverse agonist activities. To support the clinical trial and marketing application of LPM6690061, a series of pharmacology and toxicology studies have been conducted. In vitro and in vivo pharmacology studies showed that LPM6690061 had high inverse agonism and antagonism activities against human 5-HT2A receptors, and demonstrated significant antipsychotic-like effects in two rat models: the DOI-induced head-twitch model and the MK-801-induced hyperactivity model, which was more effective than the control drug pimavanserin. LPM6690061 did not have detectable side effects on the neurobehavioral activities and respiratory function in rats, or on the ECG or blood pressure in dogs at the doses of 2 and 6 mg/kg. The half maximal inhibitory concentration (IC50) of LPM6690061 for inhibiting hERG current was 1.02 µM. Three in vivo toxicology studies were conducted. In the single dose toxicity study in rats and dogs, the maximum tolerated dose of LPM6690061 was 100 mg/kg. In the 4-week repeat dose toxicity study in rats, the main detectable toxic reactions of LPM6690061 included moderate artery wall hypertrophy, minimal to mild mixed cell inflammation and increased macrophages in the lung, which generally recovered after a 4-week drug withdrawal period. In the 4-week repeat dose toxicity study in dogs, no detectable toxicity was observed. The doses of no-observed-adverse-effect-level (NOAEL) in rats and dogs were 10 mg/kg and 20 mg/kg, respectively. In conclusion, both in vitro and in vivo pharmacological and toxicological studies showed that LPM6690061 was a safe and efficacious 5-HT2A receptor antagonist/inverse agonist which supports the clinical development as a novel antipsychotic drug.
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Antipsicóticos , Serotonina , Ratos , Humanos , Animais , Cães , Agonismo Inverso de Drogas , Receptor 5-HT2A de Serotonina , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêuticoRESUMO
AIMS: 20(R)-Panaxadiol (20(R)-PD) can inhibit tumor proliferation. Three series of novel 20(R)-PD derivatives were synthesized by modifying the A-ring. BACKGROUND: 20(R)-PD, a tetracyclic triterpenoid, is a non-natural saponin present in the form of protopanaxadiol. Because of its essential biological activities, especially anti-tumor activity, structural modification of 20(R)-PD and the development of innovative and novel 20(R)-PD derivatives with better anti-tumor activity are increasingly relevant. OBJECTIVE: The objective of this work was to synthesize and evaluate the in vitro anti-proliferative activities of 20(R)-PD derivatives in LNCaP, LS180, and MKN45 cancer cells. Structural modifications were performed at the C-3 position and A-ring. METHOD: The in vitro anti-proliferative activities of novel derivatives in LNCaP, LS180, and MKN45 cells were evaluated by the MTT assay. The effects of compounds 5 and C9 on apoptosis were determined by flow cytometry. RESULT: Compounds 5, B2, C2, C4, C7, C8, C9, C10, and C11 exhibited good anti-proliferative activities in LNCaP, LS180, and MKN45 cells in vitro. The best anti-proliferative activity was observed for the C-series derivatives with the introduction of amino acids at the C-3 position. C9 exhibited good potent activity with an IC50 of 2.89 µM. CONCLUSION: Compound C9 is a potential candidate with potent anti-proliferative activity.
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Chamomile essential oil (CEO) is extracted from chamomile and mainly used in aromatherapy. The chemical constituents and its antitumor activity on Triple-negative breast cancer (TNBC) was explored in the present study. Gas chromatography-mass spectrometry (GC/MS) was employed to analyze the chemical constituents of CEO. The cell viability, migration and invasion of TNBC cell MDA-MB-231 were measured using MTT, wound scratch and Transwell assay, respectively. The protein expression of PI3K/Akt/mTOR signaling pathway was determined by Western blot. CEO is rich in terpenoids (63.51 %), among which the identified terpenoids and their derivatives are mainly Caryophyllene (29.57 %), d-Cadinene (12.81 %), Caryophyllene oxide (14.51 %), etc. Three concentration of CEO (1, 1.5, 2â µg/mL) significantly inhibited the proliferation, migration and invasion of MDA-MB-231â cells with a dose dependent manner. Moreover, the phosphorylation of PI3K, Akt and mTOR was inhibited by CEO. The results revealed that there was abundant terpenoids in the CEO which account for 63.51 %. CEO significantly inhibited the proliferation, migration and invasion of MDA-MB-231â cells, exhibiting antitumor effect on TNBC. The antitumor effect of CEO might attribute to its inhibition on PI3K/Akt/mTOR signaling pathway. However, further study should be conducted in more TNBC cell lines and animal models to provide further evidence for TNBC treatment by CEO.
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Óleos Voláteis , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células MDA-MB-231 , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Camomila/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Terpenos/farmacologia , Proliferação de CélulasRESUMO
Extracellular matrix protein 2 (ECM2), which regulates cell proliferation and differentiation, has recently been reported as a prognostic indicator for multiple cancers, but its value in lower grade glioma (LGG) remains unknown. In this study, LGG transcriptomic data of 503 cases in The Cancer Genome Atlas (TCGA) database and 403 cases in The Chinese Glioma Genome Atlas (CGGA) database were collected to analyze ECM2 expression patterns and the relationship with clinical characteristics, prognosis, enriched signaling pathways, and immune-related markers. In addition, a total of 12 laboratory samples were used for experimental validation. Wilcoxon or Kruskal-Wallis tests demonstrated highly expressed ECM2 in LGG was positively associated with malignant histological features and molecular features such as recurrent LGG and isocitrate dehydrogenase (IDH) wild-type. Also, Kaplan-Meier (KM) curves proved high ECM2 expression could predict shorter overall survival in LGG patients, as multivariate analysis and meta-analysis claimed ECM2 was a deleterious factor for LGG prognosis. In addition, the enrichment of immune-related pathways for ECM2, for instance JAK-STAT pathway, was obtained by Gene Set Enrichment Analysis (GSEA) analysis. Furthermore, positive relationships between ECM2 expression with immune cells infiltration and cancer-associated fibroblasts (CAFs), iconic markers (CD163), and immune checkpoints (CD274, encoding PD-L1) were proved by Pearson correlation analysis. Finally, laboratory experiments of RT-qPCR and immunohistochemistry showed high expression of ECM2, as well as CD163 and PD-L1 in LGG samples. This study identifies ECM2, for the first time, as a subtype marker and prognostic indicator for LGG. ECM2 could also provide a reliable guarantee for further personalized therapy, synergizing with tumor immunity, to break through the current limitations and thus reinvigorating immunotherapy for LGG. AVAILABILITY OF DATA AND MATERIALS: Raw data from all public databases involved in this study are stored in the online repository (chengMD2022/ECM2 (github.com)).
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Neoplasias Encefálicas , Glioma , Humanos , Antígeno B7-H1 , Janus Quinases , Prognóstico , Fatores de Transcrição STAT , Transdução de Sinais , Glioma/genética , Glioma/terapia , Imunoterapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapiaRESUMO
Using data from the China Migrants Dynamic Survey (CMDS) in 2017, this study assessed adverse selection and the impact of mobility factors on adverse selection by analyzing two samples of young migrant workers. The results of the sample analysis showed that young migrant workers with higher health risks were more inclined to enroll in health insurance, indicating the presence of adverse selection. Mobility distance and settle intention have a heterogeneous effect on adverse selection, with young workers who migrate inter-provincially and intend to settle down being more susceptible. The analysis of the insured samples showed that the phenomenon of adverse selection was also evident in the choice of health insurance, with individuals with higher risks preferring Urban Employee Basic Medical Insurance (UEBMI), which has better financial coverage and benefits compared to Rural Residents' Basic Medical Insurance (URRBMI). The heterogeneity test confirmed that mobility distance plays a role in determining the likelihood of adverse selection, with inter-city and inter-province young migrant workers being more likely to show adverse selection.
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Migrantes , Humanos , Seguro Saúde , Cidades , Inquéritos e Questionários , ChinaRESUMO
Purpose: To figure out the difference of integrity of Gerota's fascia and perirenal fat between Retroperitoneal Laparoscopic Radical Nephrectomy (RLRN) and Transperitoneal Laparoscopic Radical Nephrectomy (TLRN). Methods: This is a prospective comparative study of patients with Renal Cell Carcinoma (RCC) from a designated tertiary center in Lanzhou, China. We have developed and propose a scoring tool to quantify the integrity of nephrectomy specimens from both approaches. The integrity score is based on 6 common conditions of nephrectomy specimens. Specimens are scored on a 1 to 6-point scale according to the integrity of Gerota's fascia and perirenal fat. We applied the integrity score to 142 consecutive patients. Integrity scores were compared between RLRN and TLRN groups. Factors associated with low integrity score were assessed by logistic regression. Results: Among 142 patients, 79 (55.6%) patients and 63 (44.4%) patients, respectively, underwent RLRN and TLRN. There was a significant difference in the distribution of integrity score between the two groups (P < 0.001). RLRN (odds ratio 10.65, 95%CI 4.29-26.45, P < 0.001), tumor size (odds ratio 1.22, 95%CI 1.04-1.42, P = 0.015) and Body Mass Index (BMI) (odds ratio 0.83, 95%CI 0.72-0.96, P = 0.010) were significantly associated with low integrity score. The logistic regression equation showed good power to predict low integrity score. Conclusion: RLRN has poor integrity of Gerota's fascia and the perirenal fat. The integrity score can be used to evaluate the extent of resection and specimen completeness in LRN. Postoperative evaluation of the integrity score is of great value for urologists to evaluate the risk of tumor residue.
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[This corrects the article DOI: 10.3389/fbioe.2022.984424.].
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Background: Osteoarthritis (OA) is a common joint degenerative disease that can affect multiple joints. Genetic events may play an important regulatory role in the early stages of the disease, but the specific mechanisms have not yet been fully elucidated. The main purpose of this study was to screen for disease-causing hub genes and effective small molecule drugs to reveal the pathogenesis of OA and to develop novel drugs for treatment. Methods: Two gene expression profile datasets, GSE55235 and GSE55457, were integrated and further analyzed. The consistently differentially expressed genes (DEGs) were identified, and functional annotation and pathway analysis of these genes were performed with GO and KEGG. A protein-protein interaction network (PPI) of the DEGs was generated using STRING, and potential small molecule drug screening was performed on the connectivity map (CMap). Results: A total of 158 consistently differentially expressed genes were identified from the two profile datasets. The functions of these DEGs are mainly related to the TNF signaling pathway, osteoclast differentiation, MAPK signaling pathway and so on. The PPI network contains 127 nodes and 1802 edges, and the ten hub genes were interleukin 6 (IL6), vascular endothelial growth factor A (VEGFA)and so on. 7 small molecule drugs were identified as potential interactors with these hubs. Conclusions: This study explains the disorder of expression in the pathological process of OA at transcriptome, which will help to understand the pathogenesis of OA.
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Objective: This study aimed to investigate the effect of a two-week machine massage on the physical properties of the erector spinae and serum biochemical indexes of adolescent athletes after training. Methods: Sixteen male adolescent wrestlers were recruited (age: 15 ± 1 year; height: 166 ± 7 cm; weight: 56 ± 7 kg) and randomly assigned to machine massage (MA, 8) and control (CO, 8) groups. Participants in the MA group received machine massage for 20 min after each wrestling training from Monday to Saturday (except on Thursday) for two weeks, while the participants in the CO group recovered naturally. Over the course of two weeks, all the participants underwent similar wrestling training program under the guidance of a professional coach. Before and after the intervention, serum urea and creatine kinase (CK) levels were measured in a fasting state. A Myoton Pro digital muscle evaluation system was used to measure the physical properties of the erector spinae, including the oscillation frequency, logarithmic decrement of a muscle's natural oscillation, and dynamic stiffness. Results: After two weeks of machine massage treatment, the dynamic stiffness of the erector spinae in the MA group decreased by 12.90% and that in the CO group increased by 2.34%, indicating a significant difference between the two groups (p = 0.04, Æ 2 = 0.286). The decrease in the logarithmic decrement of a muscle's natural oscillation value in the MA was significantly greater than that in the CO (p = 0.003, Æ 2 = 0.286). Moreover, the serum CK values decreased by 33.84% in the MA group and by 1.49% in the CO group, despite a trend of change between the groups (p = 0.062, Æ2 = 0.084). No significant difference was found in the improvement in serum urea levels between the two groups after two weeks of treatment. Conclusion: Results of the present study indicated that a two-week machine massage had a positive effect on the improvement of the physical properties of the erector spinae of wrestlers during training.
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BACKGROUND: Natural polymers are organic compounds produced by living organisms. In nature, they exist in three main forms, including proteins, polysaccharides and nucleic acids. In recent years, with the continuous research on drug and gene delivery systems, scholars have found that natural polymers have promising applications in drug and gene delivery systems due to their excellent properties such as biocompatibility, biodegradability, low immunogenicity and easy modification. However, since the structure, physicochemical properties, pharmacological properties and biological characteristics of biopolymer molecules have not yet been entirely understood, further studies are required before large-scale clinical application. METHODS: This review focuses on recent advances in the representative natural polymers such as proteins (albumin, collagen, elastin), polysaccharides (chitosan, alginate, cellulose) and nucleic acids. RESULTS: We introduce the characteristics of various types of natural polymers, and further outline the characterization methods and delivery forms of these natural polymers. CONCLUSION: Finally, we discuss possible challenges for natural polymers in subsequent experimental studies and clinical applications. It provides an important strategy for the clinical application of natural polymers in drug and gene delivery systems.
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Recent studies have shown that autophagy plays an important role in gynecological tumours, and ubiquitin modification of autophagy regulatory components is essential to regulate autophagic. In this study, we found that UBE2C affects endometrial cancer cell apoptosis and proliferation by inhibiting autophagy. Electron microscopy observation of cell ultrastructure and experimental biochemical analysis showed that EC cells with UBE2C expression knocked down display typical autophagic characteristics. Cells were cotreated with the autophagy pharmacological inhibitors chloroquine and/or bafilomycin A1, and mRFP-GFP-LC3 assays were performed to monitor autophagic flux and determine whether UBE2C suppresses the autophagy program. Investigation of the corresponding mechanism by which UBE2C inhibits autophagy revealed that UBE2C induces K48-linked SIRT1 ubiquitination and promotes ubiquitination-dependent degradation of SIRT1, subsequently reducing H4K16 deacetylation levels and epigenetically inhibiting the expression of autophagy-related genes. The results of CCK-8, Hoechst staining, and immunofluorescence assays further indicated that deletion of the autophagy-related gene BECN1 significantly attenuates UBE2C knockdown-induced cell apoptosis. Moreover, overexpression of UBE2C promoted tumor growth in the xenograft mice model. While, the introduction of rapamycin, an agonist of autophagy, successfully reversed tumor growth and apoptosis inhibition mediated by UBE2C overexpression in vitro and in vivo. Taken together, our results suggested that UBE2C-mediated ubiquitination and degradation of SIRT1 contribute to the malignant progression of endometrial cancer through epigenetic inhibition of autophagy. Implications: Our study highlights the tumorigenic role and regulatory mechanism of UBE2C in EC; UBE2C inhibits EC cell apoptosis through autophagy-related mechanisms and our findings provide new insights into the treatment of endometrial cancer.
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Although the removal ability of potassium ferrate (K2FeO4) on aqueous heavy metals has been confirmed by many researchers, little information focuses on the difference between the individual and simultaneous treatment of elements from the same family of the periodic table. In this project, two heavy metals, arsenic (As) and antimony (Sb) were chosen as the target pollutants to investigate the removal ability of K2FeO4 and the influence of humic acid (HA) in simulated water and spiked lake water samples. The results showed that the removal efficiencies of both pollutants gradually increased along the Fe/As or Sb mass ratios. The maximum removal rate of As(III) reached 99.5% at a pH of 5.6 and a Fe/As mass ratio of 4.6 when the initial As(III) concentration was 0.5 mg/L; while the maximum was 99.61% for Sb(III) at a pH of 4.5 and Fe/Sb of 22.6 when the initial Sb(III) concentration was 0.5 mg/L. It was found that HA inhibited the removal of individual As or Sb slightly and the removal efficiency of Sb was significantly higher than that of As with or without the addition of K2FeO4. For the co-existence system of As and Sb, the removal of As was improved sharply after the addition of K2FeO4, higher than Sb; while the latter was slightly better than that of As without K2FeO4, probably due to the stronger complexing ability of HA and Sb. X-ray energy dispersive spectroscopy (EDS), X-ray diffractometer (XRD), and X-ray photoelectron spectroscopy (XPS) were used to characterize the precipitated products to reveal the potential removal mechanisms based on the experimental results.
