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The placenta plays a pivotal role in the maintenance of normal pregnancy, but how it forms, matures, and performs its function remains poorly understood. Here, we describe a novel mouse line (Prl3d1-iCre) that expresses iCre recombinase under the control of the endogenous prl3d1 promoter. Prl3d1 has been proposed as a marker for distinguishing trophoblast giant cells (TGCs) from other trophoblast cells in the placenta. The in vivo efficiency and specificity of the Cre line were analyzed by interbreeding Prl3d1-iCre mice with B6-G/R reporter mice. Through anatomical studies of the placenta and other tissues of Prl3d1-iCre/+; B6-G/R mouse mice, we found that the tdTomato signal was expressed in parietal trophoblast giant cells (P-TGCs). Thus, we report a mouse line with ectopic Cre expression in P-TGCs, which provides a valuable tool for studying human pathological pregnancies caused by implantation failure or abnormal trophoblast secretion due to aberrant gene regulation.
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Placenta , Proteína Fluorescente Roja , Trofoblastos , Animales , Femenino , Ratones , Embarazo , Células Gigantes/metabolismo , Integrasas/genética , Integrasas/metabolismo , Ratones Transgénicos , Placenta/metabolismoRESUMEN
Background: Cerebral ischemia-reperfusion injury is a common complication of ischemic stroke that affects the prognosis of patients with ischemic stroke. The lipid-soluble diterpene Tanshinone IIA, which was isolated from Salvia miltiorrhiza, has been indicated to reduce cerebral ischemic injury. In this study, we investigated the molecular mechanism of Tanshinone IIA in alleviating reperfusion-induced brain injury. Methods: Middle cerebral artery occlusion animal models were established, and neurological scores, tetrazolium chloride staining, brain volume quantification, wet and dry brain water content measurement, Nissl staining, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were performed. The viability of cells was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays, while cell damage was measured by lactate dehydrogenase release in the in vitro oxygen glucose deprivation model. In addition, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were used to evaluate the therapeutic effect of Tanshinone IIA on ischemia/reperfusion (I/R) induced brain injury, as well as its effects on the inflammatory response and neuronal apoptosis, in vivo and in vitro. Furthermore, this study validated the targeting relationship between miR-124-5p and FoxO1 using a dual luciferase assay. Finally, we examined the role of Tanshinone IIA in brain injury from a molecular perspective by inhibiting miR-124-5p or increasing FoxO1 levels. Results: After treatment with Tanshinone IIA in middle cerebral artery occlusion-reperfusion (MCAO/R) rats, the volume of cerebral infarction was reduced, the water content of the brain was decreased, the nerve function of the rats was significantly improved, and the cell damage was significantly reduced. In addition, Tanshinone IIA effectively inhibited the I/R-induced inflammatory response and neuronal apoptosis, that is, it inhibited the expression of inflammatory cytokines IL-1ß, IL-6, TNF-α, decreased the expression of apoptotic protein Bax and Cleaved-caspase-3, and promoted the expression of antiapoptotic protein Bcl-2. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, Tanshinone IIA also inhibited the expression of inflammatory factors in neuronal cells and inhibited the occurrence of neuronal apoptosis. In addition, Tanshinone IIA promoted the expression of miR-124-5p. Transfection of miR-124-5p mimic has the same therapeutic effect as Tanshinone IIA and positive therapeutic effect on OGD cells, while transfection of miR-124-5p inhibitor has the opposite effect. The targeting of miR-124-5p negatively regulates FoxO1 expression. Inhibition of miR-124-5p or overexpression of FoxO1 can weaken the inhibitory effect of Tanshinone IIA on brain injury induced by I/R, while inhibition of miR-124-5p and overexpression of FoxO1 can further weaken the effect of Tanshinone IIA. Conclusion: Tanshinone IIA alleviates ischemic-reperfusion brain injury by inhibiting neuroinflammation through the miR-124-5p/FoxO1 axis. This finding provides a theoretical basis for mechanistic research on cerebral ischemia-reperfusion injury.
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Abietanos , Lesiones Traumáticas del Encéfalo , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , MicroARNs , Daño por Reperfusión , Humanos , Ratas , Animales , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , MicroARNs/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/complicaciones , Oxígeno/metabolismo , Reperfusión/efectos adversos , Glucosa/metabolismo , Agua , ApoptosisRESUMEN
The aim of this study was to investigate the molecular mechanism by which miR-497-5p regulates neuronal injury after ischemic stroke through the BDNF/TrkB/Akt signaling pathway. PC12 cells were used to construct a stroke injury model by oxygen-glucose deprivation/reoxygenation (OGD/R). The expression level of miR-497-5p was measured by RT-qPCR. CCK-8 kit was used to detect cell viability. Cell apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. MDA and SOD detection kits were used to detect MDA content and SOD activity. A double luciferase reporter system was used to verify the targeting relationship between miR-497-5p and BDNF. The expression of BDNF, TrkB, p-TrkB, Akt and p-Akt was detected by Western blot. We have found that miR-497-5p expression was inhibited after treatment with OGD/R. Simultaneously, cell apoptosis, MDA content and ROS were upregulated, while cell viability and SOD were significantly decreased in PC12 cells. The effects of OGD/R on PC12 cells were reversed with the downregulation of miR-497-5p. A double luciferase reporter assay demonstrated that miR-497-5p negatively targets BDNF. BDNF inhibited cell apoptosis and oxidative stress injury in PC12 cells. These findings suggest that miR-497-5p aggravates neuronal injury in experimental model of ischemic stroke by inhibiting the BDNF/TrkB/PI3K/Akt signaling pathway.
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Accidente Cerebrovascular Isquémico , MicroARNs , Ratas , Animales , Especies Reactivas de Oxígeno/metabolismo , MicroARNs/metabolismo , Factor Neurotrófico Derivado del Encéfalo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Oxígeno/metabolismo , Luciferasas/farmacología , Superóxido Dismutasa , Glucosa/metabolismo , ApoptosisRESUMEN
Mouse germinal vesicle (GV) oocytes are divided into surrounded nucleolus (SN) and nonsurrounded nucleolus (NSN) oocytes based on chromatin morphology. NSN oocytes spontaneously transform into SN oocytes after accumulating enough maternal transcripts. SN oocytes show transcriptional silencing. When oocyte maturation is abnormal or takes place in vitro, NSN oocytes do not go through SN stage before proceeding to MII. Nontransitive oocytes show developmental retardation, a low fertilization rate, and arrest at the two-cell embryo stage in mice. Here, chromatin-binding ribonucleic acid polymerase II (RNAP II) activity, newly synthesized RNA, and chromatin accessibility in GV oocytes were examined. In SN oocytes, RNAP II did not bind to DNA, neo-RNA was not generated in nuclei, and the phosphorylation state of RNAP II did not affect the chromatin-binding activity. The number of accessible genes in SN oocytes was remarkably lower than that in NSN oocytes. The accessibility of different functional genes was also different between the two types of oocytes. Thus, low chromatin accessibility leads to transcriptional silencing in SN oocytes.
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Secuenciación de Inmunoprecipitación de Cromatina , Cromatina , Animales , Ratones , Cromatina/metabolismo , Oocitos/metabolismo , Oogénesis/genética , Nucléolo Celular/metabolismoRESUMEN
OBJECTIVES: To describe the prevalence of self-reported musculoskeletal disorders among workers in the electronics manufacturing industry and to investigate the relations between work-related musculoskeletal disorders (WMSDs) and work-related variables. METHODS: An interview-based questionnaire survey was carried out in thirty electronics manufacturing factories in China in 2018. The prevalence of WMSDs was estimated using the modified Nordic Musculoskeletal Questionnaire (NMQ). A multivariate logistic regression model was applied to evaluate the effects of risk factors on WMSDs on multiple body parts. RESULTS: The 12-month prevalence of WMSDs among participants was 40.6%, and the common body sites affected were the neck (26.8%), shoulder (22.8%), upper back (14.9%), and lower back (14.8%). The results of logistic regression showed that female adults, > 5 job tenure and work-related factors (including awkward posture, lifting or carrying weights, excessive repetition, prolonged sitting, monotonous work and working under conditions of cold or temperature variations) led to a higher risk of WMSDs on most body parts. Upper back, wrist/hand and elbow pain levels were significantly higher for workers with vibration. However, more frequently, physical exercise was a protective factor against WMSDs on most body parts except the upper back, leg and knee. CONCLUSIONS: The study indicates a high prevalence of musculoskeletal pain among the electronics manufacturing industry in China. Different personal and work factors are related to the occurrence of WMSD on different body parts. Preventive measures should be implemented based on the characteristics of WMSD in the electronic manufacturing industry. Furthermore, the training and intervention guidance of ergonomic hazards in the workplace need to be strengthened by understanding the impact of bad posture, avoiding long-term sitting posture and increasing physical activities.
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Enfermedades Musculoesqueléticas , Dolor Musculoesquelético , Enfermedades Profesionales , Adulto , Humanos , Femenino , Prevalencia , Estudios Transversales , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/prevención & control , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Musculoesqueléticas/prevención & control , Factores de Riesgo , Encuestas y Cuestionarios , Dolor Musculoesquelético/epidemiología , Ergonomía , China/epidemiología , ElectrónicaRESUMEN
Engineering Pt-free catalysts for hydrogen evolution reaction (HER) with high activity and stability is of great significance in electrochemical hydrogen production. Herein, in situ chemical H intercalation into ultrafine Pd to activate this otherwise HER-inferior material to form the ultrafine IrPdH hydride as an efficient and stable HER electrocatalyst is proposed. The formation of PdIrH depends on a new hydrogenation strategy via using ethanol as the hydrogen resource. It is demonstrated that H atoms in IrPdH originate from the OH and CH2  of ethanol, which fills the gap of ethanol as the hydrogen source for the preparation of Pd hydride. Thanks to the incorporation of H/Ir atoms and ultrafine structure, the IrPdH exhibits superior HER activity and stability in the whole pH range. The IrPdH delivers very low overpotentials of 14, 25 and 60 mV at a current density of 10 mA cm-2 respectively in 0.5 m H2 SO4 , 1 m KOH, and 1 m PBS electrolytes, which are much better than those of commercial Pt/C and most reported noble metal electrocatalysts. Theoretical calculations confirm that interstitial hydrogen availably refines the electronic density of Pd and Ir sites, which optimizes the adsorption of *H and leads to the significant enhancement of HER performance.
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In this paper, we propose an interesting thermally tunable broadband metamaterial absorber based on ionic liquids at the microwave band, which has distinct modulation characteristics in different frequency bands. Numerical simulation results show that the absorption decreases with the increase of temperature in the low-frequency band from 2-10GHz, which decreases to 60% at 100 °C. Meanwhile, the absorption increases with the increase in temperature in the high-frequency band from 25GHz to 48GHz. In addition, the absorber still has good broadband absorption without the metal substrate, and the absorption reaches more than 80% in the frequency band of 13.96-34.10GHz. As an all-dielectric metamaterial absorber, its absorption increases with the increase in temperature, which reaches more than 90% in the range of 20.44-50GHz at 100 °C. At last, the designed metamaterial absorbers have been fabricated based on ionic liquids, and experimental results are presented to demonstrate the validity of the proposed structure. Furthermore, the simple design and wide frequency tuning range of the absorbers can promise a great potential application in sensors, detection, and frequency-selective thermal emitters.
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It is well known that hyperglycemia leads to the progression and expansion of various micro and macrovascular disease such as diabetic nephropathy (DN). Lycoperoside H (LH) alkaloidal saponin exhibited the antidiabetic effect, but its DN effect is unclear. In this experimental study, we scrutinized the renal protective effect of LH against the streptozotocin (STZ)-induced DN in rats and explore the underlying mechanism. Sprague-Dawley rats were used in this experimental study and an intraperitoneal injection of STZ (45 mg/kg) was used for the induction of diabetes, rats received the oral administration of LH (20 mg/kg). The blood glucose level, body weight, organ weight (renal and pancreas), and biochemical parameters were estimated. We also scrutinized the effect of LH to enhance intestinal barrier function and suppress inflammation and intestinal permeability. LH significantly (p < 0.001) decreased the glucose level and enhanced the body weight with a reduction of renal weight and boost the pancreas weight. LH significantly (p < 0.001) enhanced the creatinine level and decreased the albumin level, urine volume, urinary albumin excretion rate, and urinary albumin creatinine ratio in the urine. It also suppressed the renal parameters, such as creatinine, blood urea nitrogen, and urea. LH significantly (p < 0.001) altered the level of lipid and antioxidant parameters. LH treatment significantly (p < 0.001) suppressed the cytokines and inflammatory parameters. LH considerably enhanced the Ruminococcaceae, Blautia, and suppressed the abundance of Bifidobacterium, Clostridium, and Turicibacter. It reduced the F/B ratio along with alteration of community abundance of Firmicutes, Actinobacteria, Proteobacteria, Tenericutes, other bacteria, and Bacteroidetes. The current result suggests that LH suppressed the diabetic nephropathological condition via alteration of gut microbiota and inflammation.
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Diabetes Mellitus Experimental , Nefropatías Diabéticas , Microbioma Gastrointestinal , Ratas , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Creatinina , Diabetes Mellitus Experimental/metabolismo , Estrés Oxidativo , Glucemia/metabolismo , Ratas Sprague-Dawley , Estreptozocina/efectos adversos , Riñón , Inflamación/metabolismo , Albúminas/efectos adversos , Albúminas/metabolismoRESUMEN
BACKGROUND: With the acceleration of industrialization and population aging, low back pain (LBP) has become the leading cause of life loss years caused by disability. Thus, it places a huge economic burden on society and is a global public health problem that needs urgent solution. This study aimed to conduct an epidemiological investigation and research on a large sample of workers in key industries in different regions of China, determine the incidence and distribution characteristics of LBP, explore the epidemic law, and provide a reference basis for alleviating global public health problems caused by LBP. METHODS: We adopted a modified epidemiological cross-sectional survey method and a stratified cluster sampling method. All on-duty workers who fulfill the inclusion criteria are taken as the research participants from the representative enterprises in key industries across seven regions: north, east, central, south, southwest, northwest, and northeast China. The Chinese version of the musculoskeletal disease questionnaire, modified by a standardized Nordic questionnaire, was used to collect information, and 57,501 valid questionnaires were received. Descriptive statistics were used, and multivariate logistic regression analysis (p < 0.05) was performed to explore the association between musculoskeletal disorders and potential risk factors. RESULTS: LBP annual incidence among workers in China's key industries is 16.4%. There was a significant difference in LBP incidence among occupational groups across different industries (p < 0.05). The multivariate regression model showed the following as risk factors for LBP: frequent repetitive movements with the trunk, working in the same positions at a high pace, trunk position, frequently turning around with your trunk, often working overtime, lifting heavy loads (i.e., more than 20 kg), education level, staff shortage, working age (years), cigarette smoking, use of vibration tools at work, body mass index, lifting heavy loads (i.e., more than 5 kg), and age (years). Physical exercise, often standing at work, and absolute resting time were protective factors. CONCLUSION: LBP incidence among key industries and workers in China is high. Thus, it is urgent to take relevant measures according to the individual, occupational, and psychosocial factors of LBP to reduce the adverse impact of LBP on workers' health.
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Dolor de la Región Lumbar , Enfermedades Profesionales , China/epidemiología , Estudios Transversales , Humanos , Dolor de la Región Lumbar/epidemiología , Dolor de la Región Lumbar/etiología , Enfermedades Profesionales/etiología , Prevalencia , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Changes in modern industrial production practices can easily lead to shoulder work-related musculoskeletal disorders (WMSD). The current reports on shoulder WMSD are limited to some industries are less well studied, and the sample size is usually small. This study aimed to describe the prevalence and severity of shoulder WMSD in a large sample of Chinese workers from 15 industries, analyze the possible correlations with sociodemographic and work-related variables, and compare the differences between industries. METHODS: A cross-sectional study was conducted among a sample of 55,749 participants from 252 enterprises in 15 industries throughout China. A Chinese version of the musculoskeletal disease questionnaire was used to collect the demographic factors, shoulder symptoms in past 12 months, and work-related factors including posture-related factors, repetition, vibration, work organization, job control, and environmental factors as independent variables. Descriptive statistics were used, and the binary logistic regression analysis was performed to explore the association between shoulder WMSD and potential demographic and work-related factors. RESULTS: Nearly 35.5% of participants reported shoulder pain and discomfort in the previous 12 months. Biopharmaceutical manufacturing (56.2%), medical services (54.4%), and aviation services (50.1%) were the three industries with the highest prevalence of shoulder WMSD. The pain score of aviation services workers was the highest. The related factors for shoulder WMSD varied among the different industries. CONCLUSION: Our study found a relatively high prevalence of shoulder WMSD in China. There were large differences in the prevalence of shoulder WMSD among industries, and the related factors were particular to each industry. Such information is useful to help occupational health practitioners and policymakers conduct preventive programs to reduce shoulder disorders in these working populations.
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Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Humanos , Estudios Transversales , Hombro , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/epidemiología , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/epidemiología , Prevalencia , Encuestas y Cuestionarios , China/epidemiología , Factores de RiesgoRESUMEN
Increased palmitic acid (PA) levels have been found in females with reduced fertility due to metabolic disorders. However, effective antioxidant astaxanthin (AXE) might positively affect animal reproduction. Therefore, the present study was designed to evaluate the impact of a high concentration of PA on oocyte maturation and the possible protective effect of AXE against high PA concentration in pigs. Firstly, different concentrations (0.2, 0.5, 0.8 mM) of PA were conducted on in vitro maturation (IVM) of pig oocytes (PA0.2, PA0.5, and PA0.8), while no addition of PA was performed as the control group (Ctrl). Results showed that the cumulus cell expansion index (CCEI) was lower in PA0.5 and PA0.8 groups compared to Ctrl group (p < .05). In PA0.5 group, not only did the percentage of matured oocytes with the first polar body (PB1) reduced, that with more oocytes arrested at germinal vesicle (GV) stage (53.44% ± 7.16% vs. 20.93% ± 5.16%, p < .05), but also a higher number of transzonal projections (TZPs) was observed in PA0.5 than Ctrl group. Besides, supplement of PA resulted in a dose-dependent decrease in mitochondrial activity. Although no difference of lipid content was observed between PA0.5 and Ctrl groups, the lipid content was at a higher level in PA0.2 group than in the other three groups. Hence, concentration of 0.5 mM of PA was performed in the following experiments, and 2.5 µM AXE carried out to investigate the possible relief effects of PA (PA0.5 + AXE). Results showed that the percentage of matured oocytes with PB1 was higher in PA0.5 + AXE than in PA0.5 group (63.43% ± 1.50% vs. 55.33% ± 0.81%, p < .01), and ROS levels both in oocytes and their cumulus cells (CCs) reduced in PA0.5 + AXE when compared to PA0.5 group. In addition, the rate of CCs with apoptosis decreased in PA0.5 + AXE, and the expression level of caspase 3 and BAX was lower than PA0.5 group. In conclusion, the maturation of pig oocytes was inhibited by the high concentration of PA; however, this negative effect of PA-induced might be relieved by the supplement of AXE.
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Técnicas de Maduración In Vitro de los Oocitos , Ácido Palmítico , Femenino , Animales , Porcinos , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Técnicas de Maduración In Vitro de los Oocitos/métodos , Ácido Palmítico/farmacología , Ácido Palmítico/metabolismo , Células del Cúmulo , OocitosRESUMEN
OBJECTIVE: To study the effect of pranlukast (Pran) on neonatal rats with periventricular leukomalacia (PVL). METHODS: The rats, aged 3 days, were randomly divided into a sham-operation group, a PVL group, and a Pran group. A rat model of PVL was prepared by right common carotid artery ligation and postoperative hypoxia. The rats in the sham-operation group were given isolation of the right common carotid artery without ligation or hypoxic treatment. The rats in the Pran group were given intraperitoneal injection of Pran (0.1 mg/kg) once every 12 hours, for 3 consecutive days, and those in the sham-operation group and the PVL group were given intraperitoneal injection of an equal volume of normal saline. On day 14 after modeling, hematoxylin-eosin (HE) staining was used to observe the pathological changes of brain tissue; immunofluorescent staining was used to measure the expression of myelin basic protein (MBP) in brain tissue (n=8); Western blot was used to measure the expression of cyclic nucleotide phosphodiesterase (CNPase), MBP, and G protein-coupled receptor 17 (GPR17) (n=8). On day 21 after modeling, Morris water maze test was used to evaluate the learning and memory abilities of rats in each group (n=8). RESULTS: The results of HE staining showed that the PVL group had greater pathological changes of white matter than the sham-operation group, and compared with the PVL group, the Pran group had a significant improvement in such pathological changes. The results of immunofluorescence assay showed that the PVL group had a lower mean fluorescence intensity of MBP than the sham-operation group (P<0.05), and the Pran group had a higher mean fluorescence intensity of MBP than the PVL group (P<0.05). Western blot showed that compared with the sham-operation group, the PVL group had significantly lower relative expression of MBP and CNPase (P<0.05) and significantly higher relative expression of GPR17 (P<0.05), and compared with the PVL group, the Pran group had significantly higher relative expression of MBP and CNPase (P<0.05) and significantly lower relative expression of GPR17 (P<0.05). Morris water maze test showed that compared with the sham-operation group, the PVL group had a significant increase in escape latency and a significant reduction in the number of platform crossings, and compared with the PVL group, the Pran group had a significant reduction in escape latency and a significant increase in the number of platform crossings (P<0.05). CONCLUSIONS: Pran can alleviate brain damage, promote myelination, and improve long-term learning and memory abilities in neonatal rats with PVL, possibly by reducing the expression of GPR17.
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Leucomalacia Periventricular , Animales , Animales Recién Nacidos , Cromonas , Ratas , Receptores Acoplados a Proteínas GRESUMEN
Serine protease inhibitors (serpins) are a large protein family that is involved in various physiological processes and is known to regulate innate immunity pathways. However, research for the functional study of serpins in lamprey is limited. In the present study, a serpin gene was cloned and characterized from Lampetra japonica at molecular, protein and cellular levels, named L-serpin which belongs to family F serine protease inhibitors (serpin family). The L-serpin includes a serpin domain in the N-terminus. The mRNA transcript of L-serpin was extensively expressed in kidney, supraneural body, intestine, liver, heart, gill and the highest expression in leukocytes. The mRNA expression level of L-serpin increased significantly after Vibrio anguillarum, Staphylocccus aureus and Poly I:C stimulation and dramatically peak at 8â¯h. It is demonstrated that the L-serpin protected cells from lethal Gram-negative endotoxemia through associating with inhibition of lipopolysaccharide (LPS)-triggered cell death and inflammatory factors expression. Surface plasmon resonance (SPR) and the microbe binding assay were used to determine that L-serpin interacts directly with LPS (KDâ¯=â¯6.14â¯×â¯10-7â¯M). Furthermore, we confirmed L-serpin is a major inhibitor of complement activation by inactivating lamprey-C1q protein (KDâ¯=â¯2.06â¯×â¯10-6â¯M). Taken together, these findings suggest that L-serpin is a endogenous anti-inflammatory factor to defend against Gram-negative bacterial challenge and involved in lamprey innate immunity.
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Enfermedades de los Peces/inmunología , Regulación de la Expresión Génica/inmunología , Inmunidad Innata/genética , Lampreas/genética , Lampreas/inmunología , Serpinas/genética , Serpinas/inmunología , Secuencia de Aminoácidos , Animales , Femenino , Proteínas de Peces/química , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Perfilación de la Expresión Génica/veterinaria , Lipopolisacáridos/farmacología , Masculino , Filogenia , Poli I-C/farmacología , Alineación de Secuencia/veterinaria , Serpinas/química , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/veterinaria , Staphylococcus aureus/fisiología , Vibrio/fisiología , Vibriosis/inmunología , Vibriosis/veterinariaRESUMEN
PURPOSE: Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of renal cell carcinomas. Various microRNAs (miRs) have been reported to affect the tumorigenesis of ccRCC. However, the role of miR-384 in ccRCC is still unknown. Thus, the purpose of this study was to investigate the function of miR-384 in ccRCC. METHODS: qRT-PCR or Western blot were employed to examine the expressions of miR-384 and CDK6 in ccRCC tissues or cell lines. MTT and transwell assays were applied to measure cell proliferation and motility. The survival rate was analyzed by Kaplan-Meier method accompanied with log-rank test. Dual luciferase assay was used to verify the relationship among miR-384 and CDK6 in ccRCC cells. RESULTS: MiR-384 was downregulated in ccRCC tissues and cell lines, and its overexpression inhibited cell proliferation and motility in ccRCC. In addition, miR-384 was found to be a marker for good prognosis in ccRCC. Furthermore, CDK6 was confirmed to be directly targeted by miR-384, and upregulation of CDK6 restored the inhibitory effects of miR- 384 in ccRCC. CONCLUSION: MiR-384 repressed tumorigenesis by regulating CDK6 in ccRCC and predicted good prognosis for ccRCC.
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Carcinogénesis/genética , Quinasa 6 Dependiente de la Ciclina/genética , Neoplasias Renales/genética , MicroARNs/genética , Carcinogénesis/patología , Línea Celular , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo/genética , Femenino , Células HEK293 , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Regulación hacia Arriba/genéticaRESUMEN
Human Waardenburg syndrome 2A (WS2A) is a dominant hearing loss (HL) syndrome caused by mutations in the microphthalmia-associated transcription factor (MITF) gene. In mouse models with MITF mutations, WS2A is transmitted in a recessive pattern, which limits the study of hearing loss (HL) pathology. In the current study, we performed ENU (ethylnitrosourea) mutagenesis that resulted in substituting a conserved lysine with a serine (p. L247S) in the DNA-binding domain of the MITF gene to generate a novel miniature pig model of WS2A. The heterozygous mutant pig (MITF +/L247S) exhibits a dominant form of profound HL and hypopigmentation in skin, hair, and iris, accompanied by degeneration of stria vascularis (SV), fused hair cells, and the absence of endocochlear potential, which indicate the pathology of human WS2A. Besides hypopigmentation and bilateral HL, the homozygous mutant pig (MITF L247S/L247S) and CRISPR/Cas9-mediated MITF bi-allelic knockout pigs both exhibited anophthalmia. Three WS2 patients carrying MITF mutations adjacent to the corresponding region were also identified. The pig models resemble the clinical symptom and molecular pathology of human WS2A patients perfectly, which will provide new clues for better understanding the etiology and development of novel treatment strategies for human HL.
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Modelos Animales de Enfermedad , Etilnitrosourea/toxicidad , Pérdida Auditiva/genética , Factor de Transcripción Asociado a Microftalmía/genética , Mutación , Síndrome de Waardenburg/genética , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Femenino , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/patología , Humanos , Masculino , Factor de Transcripción Asociado a Microftalmía/antagonistas & inhibidores , Mutagénesis , Mutágenos/toxicidad , Homología de Secuencia , Porcinos , Porcinos Enanos , Síndrome de Waardenburg/inducido químicamente , Síndrome de Waardenburg/patologíaRESUMEN
The aim of present research work is study the effect of levofloxacononone chalcone derivatives on apoptosis and autophagy of HCC SMMC-7721 cells in patients with hepatocellular carcinoma (HCC). The HCC SMMC-7721 cells in the logarithmic phase growth were inoculated, and the proliferation of SMMC -7721 cells was detected by MTT assay. The effect of levofloxacononone chalcone derivatives on SMMC-7721 cell cycle and apoptosis rate was detected by flow cytometry. Cells were treated by autophagy inhibitor chloroquine to validate the effect of levofloxacononone chalcone derivatives on cell proliferation and apoptosis. Levofloxacononone chalcone derivatives could significantly inhibit the proliferation of SMMC-7721 cells. Compared with the control group, the apoptosis rate of cells treated with levofloxacononone chalcone derivatives was increased significantly in 24h, showing significant difference between groups. Chloroquine could increase the inhibitory effect of low-dose levofloxacononone chalcone derivatives on SMMC-7721 cell proliferation, and decrease the inhibitory effect of high-dose levofloxacononone chalcone derivatives on SMMC-7721 cell proliferation. Levofloxacononone chalcone derivatives can obviously induce the apoptosis and autophagy of SMMC-7721 cells, at a low dose, its autophagy can protect cells; and at a high dose, the autophagy can decrease the cell proliferation rate, to promote cell apoptosis.
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Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Chalcona/análogos & derivados , Chalcona/farmacología , Chalconas/farmacología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Chalcona/administración & dosificación , Cloroquina/farmacología , Relación Dosis-Respuesta a Droga , HumanosRESUMEN
Extensive research has been conducted on the role of CXCR3 in immune responses and inflammation. However, the role of CXCR3 in the reproductive system, particularly in oocyte development, remains unknown. In this study, we present findings on the involvement of CXCR3 in the meiotic division process of mouse oocytes. We found CXCR3 was expressed consistently throughout the entire maturation process of mouse oocyte. Inhibition of CXCR3 impaired the asymmetric division of oocyte, while the injection of Cxcr3 mRNA was capable of restoring these defects. Further study showed that inhibition of CXCR3 perturbed spindle migration by affecting LIMK/cofilin pathway-mediated actin remodeling. Knockout of CXCR3 led to an upregulation of actin-binding protein and an increased ATP level in GV-stage oocytes, while maintaining normal actin dynamics during the process of meiosis. Additionally, we noticed the expression level of DYNLT1 is markedly elevated in CXCR3-null oocytes. DYNLT1 bound with the Arp2/3 complex, and knockdown of DYNLT1 in CXCR3-null oocytes impaired the organization of cytoplasmic actin, suggesting the regulatory role of DYNLT1 in actin organization, and the compensatory expression of DYNLT1 may contribute to maintain normal actin dynamics in CXCR3-knockout oocytes. In summary, our findings provide insights into the intricate network of actin dynamics associated with CXCR3 during oocyte meiosis.
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Actinas , Oocitos , Receptores CXCR3 , Animales , Oocitos/metabolismo , Oocitos/fisiología , Ratones , Actinas/metabolismo , Actinas/genética , Receptores CXCR3/metabolismo , Receptores CXCR3/genética , Femenino , Meiosis/fisiología , Ratones NoqueadosRESUMEN
Acute kidney injury (AKI) is a common, multicause clinical condition that, if ignored, often progresses to chronic kidney disease (CKD) and end-stage kidney disease, with a mortality rate of 40-50%. However, there is a lack of universal treatment for AKI. Inflammation is the basic pathological change of early kidney injury, and inflammation can exacerbate AKI. Macrophages are the primary immune cells involved in the inflammatory microenvironment of kidney disease. Therefore, regulating the function of macrophages is a crucial breakthrough for the AKI intervention. Our team chemically modified pyxinol, an ocotillol-type ginsenoside, to prepare PJ16 with higher solubility and bioavailability. In vitro, using a model of macrophages stimulated by LPS, it was found that PJ16 could regulate macrophage function, including inhibiting the secretion of inflammatory factors, promoting phagocytosis, inhibiting M1 macrophages, and promoting M1 transition to the M2c macrophage. Further investigation revealed that PJ16 may shield renal tubular epithelial cells (HK-2) damaged by LPS in vitro. Based on this, PJ16 was validated in the animal model of unilateral ureteral obstruction, which showed that it improves renal function and inhibits renal tissue fibrosis by decreasing inflammatory responses, reducing macrophage inflammatory infiltration, and preferentially upregulating M2c macrophages. In conclusion, our study is the first to show that PJ16 resists AKI and fibrosis by mechanistically regulating macrophage function by modulating the phenotypic transition from M1 to M2 macrophages, mainly M2c macrophages.
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Lesión Renal Aguda , Lipopolisacáridos , Animales , Lipopolisacáridos/efectos adversos , Riñón/patología , Lesión Renal Aguda/tratamiento farmacológico , Macrófagos , Inflamación/patología , FibrosisRESUMEN
OBJECTIVES: Although studies have shown that work-related musculoskeletal disorders (WMSDs) are common and continue to be a major source of disability and work time loss, there are few reports about elbow WMSDs. The aim of this study was to explore the prevalence and associated factors of elbow WMSDs. METHODS: The valid questionnaires of 57501 workers from 15 different industries nationwide were collected and the c2 test and logistic regression analysis were applied to reveal the prevalence and risk factors of elbow WMSDs. RESULTS: The findings indicated that the overall prevalence of elbow WMSDs among workers was 7.3%. However, the prevalence of elbow WMSDs in toy manufacturing was 21.3%, which was significantly higher than that in other industries (P < .05). Logistic regression analysis showed that age 40 and above, married, very poor health, left-handedness, lifting weights (more than 20 kg each time), work requiring upper limb or hand force, work in an uncomfortable position, repetitive operations within 1 minute, using vibrating tools, work involving cold, cool draughts, or temperature changes, work being completed in the same workshop, work being done outdoors, frequent dealings with customers, 2 shifts, often working overtime, staff shortage, and often working for colleagues were risk factors for elbow WMSDs. A higer education level, monthly income, and enough rest time were protective factors for elbow WMSDs. CONCLUSIONS: Toy manufacturing is a high-risk industry for elbow WMSDs. Promotion of education about ergonomics should be strengthened, and workers' ergonomics awareness should be improved to reduce the impact of WMSDs.
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Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Humanos , Adulto , Estudios Transversales , China/epidemiología , Femenino , Masculino , Factores de Riesgo , Enfermedades Profesionales/epidemiología , Enfermedades Musculoesqueléticas/epidemiología , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios , Codo , Adulto Joven , Modelos LogísticosRESUMEN
Background: Atrial fibrillation (AF) is the most prevalent sustained arrhythmia. L1 cell adhesion molecule (L1CAM) served as a crucial regulator of signaling pathways. This research sought to examine the clinical value and functions of soluble L1CAM in the serum of AF patients. Methods: In total, 118 patients (valvular heart disease patients [VHD, total: n = 93; AF: n = 47; sinus rhythm (SR): n = 46] and healthy controls [n = 25]) were recruited in this retrospective study. Plasma levels of L1CAM were detected by enzyme-linked immunosorbent assays. The Pearson's correlation approach, as applicable, was used for analyzing the correlations. The L1CAM was shown to independently serve as a risk indicator of AF in VHD after being analyzed by the multivariable logistic regression. To examine the specificity and sensitivity of AF, receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used. A nomogram was developed for the visualisation of the model. We further evaluate the prediction model for AF using calibration plot and decision curve analysis. Results: The plasma level of L1CAM was substantially decreased in AF patients as opposed to healthy control and SR patients (healthy control = 46.79 ± 12.55 pg/ml, SR = 32.86 ± 6.11 pg/ml, AF = 22.48 ± 5.39 pg/ml; SR vs. AF, P < 0.001; control vs. AF, P < 0.001). L1CAM was significantly and negatively correlated with LA and NT-proBNP (LA: r = -0.344, P = 0.002; NT-proBNP: r = -0.380, P = 0.001). Analyses using logistic regression showed a substantial correlation between L1CAM and AF in patients with VHD (For L1CAM, Model 1: OR = 0.704, 95%CI = 0.607-0.814, P < 0.001; Model 2: OR = 0.650, 95% CI = 0.529-0.798, P < 0.001; Model 3: OR = 0.650, 95% CI = 0.529-0.798, P < 0.001). ROC analysis showed that inclusion of L1CAM in the model significantly improved the ability of other clinical indicators to predict AF. The predictive model including L1CAM, LA, NT-proBNP and LVDd had excellent discrimination and a nomogram was developed. The model had good the calibration and clinical utility. Conclusion: L1CAM was shown to independently serve as a risk indicator for AF in VHD. In AF patients with VHD, the prognostic and predictive effectiveness of models incorporating L1CAM was satisfactory. Collectively, L1CAM may be a protective molecule for atrial fibrillation in patients with valvular heart disease.