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We aimed to investigate the species composition of a small mammal community and the prevalence of Echinococcus spp. in a typical endemic area of the Tibetan Plateau. One pika and five rodent species were identified based on the morphological characteristics of 1278 small mammal specimens collected during 2014-2019. Detection of Echinococcus DNA in tissue samples from small mammal specimens revealed that Ochotona curzoniae (pika, total prevalence: 6.02%, 26/432), Neodon fuscus (5.91%, 38/643), N. leucurus (2.50%, 3/120), and Alexandromys limnophilus (21.74%, 10/46) were infected by both E. multilocularis and E. shiquicus; Cricetulus longicaudatus (16.67%, 1/6) was infected by E. shiquicus; and no infection was detected in N. irene (0/15). Neodon fuscus and O. curzoniae were the two most abundant small mammal species. There was no significant difference in the prevalence of pika and the overall rodent species assemblage (6.26%, 53/846); however, the larger rodent populations suggested that more attention should be paid to their role in the transmission of echinococcosis in the wildlife reservoir, which has long been underestimated. Moreover, although DNA barcoding provides a more efficient method than traditional morphological methods for identifying large numbers of small mammal samples, commonly used barcodes failed to distinguish the three Neodon species in this study. The close genetic relationships between these species suggest the need to develop more powerful molecular taxonomic tools.
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Ulcerative colitis (UC) is a subtype of inflammatory bowel disease. Previous studies have suggested a link between senescence process and the body's inflammatory reaction, indicating that senescence may exacerbate UC, yet the relation between UC and senescence remains unclear. Tedizolid Phosphate (TED), a novel oxazolidinone antimicrobial, is indicated in acute bacterial skin infections, its impact on senescence is not known. Our research revealed that the UC inducer dextran sulfate sodium (DSS) triggers senescence in both colon epithelial NCM460 cells and colon tissues, and TED that screened from a compound library demonstrated a strong anti-senescence effect on DSS treated NCM460 cells. As an anti-senescence medication identified in this research, TED efficiently alleviated UC and colonic senescence in mice caused by DSS. By proteomic analysis and experimental validation, we found that DSS significantly inhibits the AMPK signaling pathway, while TED counteracts senescence by restoring AMPK activity. This research verified that the development of UC is accompanied with colon tissue senescence, and TED, an anti-senescence medication, can effectively treat UC caused by DSS and alleviate colon senescence. Our work suggests anti-senescence strategy is an effective approach for UC treatment.
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Proteínas Quinasas Activadas por AMP , Senescencia Celular , Colitis Ulcerosa , Colon , Sulfato de Dextran , Transducción de Señal , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Transducción de Señal/efectos de los fármacos , Colon/efectos de los fármacos , Colon/patología , Senescencia Celular/efectos de los fármacos , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones , Ratones Endogámicos C57BL , Línea Celular , Masculino , Oxazolidinonas/farmacología , Oxazolidinonas/uso terapéutico , Organofosfatos/farmacología , Organofosfatos/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2⯵g/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.
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Toxinas Marinas , Microcistinas , Sirtuinas , Espermatogonias , Animales , Masculino , Ratones , Apoptosis , Proliferación Celular , Roturas del ADN de Doble Cadena/efectos de los fármacos , Reparación del ADN , Toxinas Marinas/metabolismo , Toxinas Marinas/toxicidad , Ratones Endogámicos ICR , Microcistinas/metabolismo , Microcistinas/toxicidad , Semen , Sirtuinas/efectos de los fármacos , Sirtuinas/metabolismo , Espermatogonias/efectos de los fármacos , Espermatogonias/metabolismoRESUMEN
Intrauterine growth retardation (IUGR) is a major cause of perinatal morbidity and mortality. Previous studies showed that 1-nitropyrene (1-NP), an atmospheric pollutant, induces placental dysfunction and IUGR, but the exact mechanisms remain uncertain. In this research, we aimed to explore the role of mitophagy on 1-NP-evoked placental progesterone (P4) synthesis inhibition and IUGR in a mouse model. As expected, P4 levels were decreased in 1-NP-exposed mouse placentas and maternal sera. Progesterone synthases, CYP11A1 and 3ßHSD1, were correspondingly declined in 1-NP-exposed mouse placentas and JEG-3 cells. Mitophagy, as determined by LC3B-II elevation and TOM20 reduction, was evoked in 1-NP-exposed JEG-3 cells. Mdivi-1, a specific mitophagy inhibitor, relieved 1-NP-evoked downregulation of progesterone synthases in JEG-3 cells. Additional experiments showed that ULK1/FUNDC1 signaling was activated in 1-NP-exposed JEG-3 cells. ULK1 inhibitor or FUNDC1-targeted siRNA blocked 1-NP-induced mitophagy and progesterone synthase downregulation in JEG-3 cells. Further analysis found that mitochondrial reactive oxygen species (ROS) were increased and GCN2 was activated in 1-NP-exposed JEG-3 cells. GCN2iB, a selective GCN2 inhibitor, and MitoQ, a mitochondria-targeted antioxidant, attenuated GCN2 activation, FUNDC1-mediated mitophagy, and downregulation of progesterone synthases in JEG-3 cells. In vivo, gestational MitoQ supplement alleviated 1-NP-evoked reduction of placental P4 synthesis and IUGR. These results suggest that FUNDC1-mediated mitophagy triggered by mitochondrial ROS may contribute partially to 1-NP-induced placental P4 synthesis inhibition and IUGR.
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Mitofagia , Placenta , Humanos , Ratones , Femenino , Embarazo , Animales , Progesterona , Especies Reactivas de Oxígeno , Línea Celular Tumoral , Retardo del Crecimiento Fetal , Mitocondrias/fisiología , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genéticaRESUMEN
BACKGROUND: A significant relationship between gastric cancer (GC) and depression has been found in the last 20 years. However, there is no comprehensive information that helps researchers find popular and potential research directions on GC and depression. AIM: To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between GC and depression. METHODS: We used the Web of Science Core Collection to search and collate the literature on GC and depression from 2000 to 2022 on 31 May, 2023. Then, visualization analysis was performed using VOSviewer software (version 1.6.19) and the Bibliometrix package in R software. RESULTS: We retrieved 153 pertinent publications from 2000 to 2022. The annual publication count showed an overall upward trend. China had the most prominent publications and significant contributions to this field (n = 64, 41.83%). Before 2020, most studies focused on "the effect of GC on the development and progression of depression in patients." The latest research trends indicate that "the effect of depression on the occurrence and development of GC and its mechanism" will receive more attention in the future. CONCLUSION: The study of "the effect of depression on the occurrence and development of GC and its mechanism" has emerged as a novel research theme over the past two years, which may become a research hotspot in this field. This study provides new insights into the hotpots and frontiers of the relationship between GC and depression, potentially guiding researchers toward hot research topics in the future.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/epidemiología , Depresión/epidemiología , Bibliometría , China/epidemiología , Programas InformáticosRESUMEN
Patients with Rett syndrome suffer from a loss-of-function mutation of the Mecp2 gene, which results in various symptoms including autistic traits and motor deficits. Deletion of Mecp2 in the brain mimics part of these symptoms, but the specific function of methyl-CpG-binding protein 2 (MeCP2) in the cerebellum remains to be elucidated. Here, we demonstrate that Mecp2 deletion in Purkinje cells (PCs) reduces their intrinsic excitability through a signaling pathway comprising the small-conductance calcium-activated potassium channel PTP1B and TrkB, the receptor of brain-derived neurotrophic factor. Aberration of this cascade, in turn, leads to autistic-like behaviors as well as reduced vestibulocerebellar motor learning. Interestingly, increasing activity of TrkB in PCs is sufficient to rescue PC dysfunction and abnormal motor and non-motor behaviors caused by Mecp2 deficiency. Our findings highlight how PC dysfunction may contribute to Rett syndrome, providing insight into the underlying mechanism and paving the way for rational therapeutic designs.
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Trastorno Autístico , Síndrome de Rett , Humanos , Animales , Proteína 2 de Unión a Metil-CpG/genética , Proteína 2 de Unión a Metil-CpG/metabolismo , Síndrome de Rett/genética , Síndrome de Rett/metabolismo , Células de Purkinje/metabolismo , Trastorno Autístico/genética , Transducción de Señal , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Diclofenac sodium has a short half-life (about 1.5 hours), requiring repeated administration, and as a result, serious complications, such as GI bleeding, peptic ulcer, and kidney and liver dysfunction, are generated. Hence, a sustained/controlled drug delivery system is needed to overcome the complications caused by the administration of diclofenac sodium. AIMS: This study aimed to fabricate and evaluate carbopol/polyvinyl alcohol-based pH-sensitive hydrogels for controlled drug delivery. OBJECTIVE: pH-sensitive carbopol/polyvinyl alcohol graft-poly(acrylic acid) hydrogels (Cp/PVA-g-PAa hydrogels) were developed for the controlled delivery of diclofenac sodium. METHODS: The combination of carbopol/polyvinyl alcohol, acrylic acid, and ethylene glycol dimethacrylate was used as polymer, monomer, and cross-linker, respectively. The effects of the formulation's composition on porosity, swelling index, and release pattern of diclofenac sodium from the developed hydrogels were investigated. RESULTS: An increase in porosity and swelling was observed with the increasing amounts of carbopol and acrylic acid, whereas polyvinyl alcohol showed the opposite effect. Due to the formation of a highly viscous system, the drug release decreased with the increasing concentrations of carbopol and polyvinyl alcohol while increased with increasing acrylic acid concentration. The pH-responsive properties of the fabricated hydrogels were demonstrated by dynamic swelling and drug release studies at three different pH values. Higher dynamic swelling and diclofenac sodium (model drug) release were found at high pH values compared to low pH values, i.e., pH 7.4 > 4.6 > 1.2, respectively. Cytotoxicity studies reported no toxic effect of the prepared hydrogels, thus indicating that the prepared hydrogels are safe to be used on clinical basis. CONCLUSION: The prepared carbopol/polyvinyl alcohol crosslinked hydrogel can be used as a promising carrier for the controlled release of drugs.
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Diclofenaco , Alcohol Polivinílico , Humanos , Alcohol Polivinílico/química , Alcohol Polivinílico/farmacología , Reactivos de Enlaces Cruzados/química , Reactivos de Enlaces Cruzados/farmacología , Sistemas de Liberación de Medicamentos , Hidrogeles/química , Concentración de Iones de Hidrógeno , Liberación de FármacosRESUMEN
Our previous study showed 1-Nitropyrene (1-NP) exposure disrupted testicular testosterone synthesis in mouse, but the exact mechanism needs further investigation. The present research found 4-phenylbutyric acid (4-PBA), an endoplasmic reticulum (ER) stress inhibitor, recovered 1-NP-induced ER stress and testosterone synthases reduction in TM3 cells. GSK2606414, a protein kinase-like ER kinase (PERK) kinase inhibitor, attenuated 1-NP-induced PERK-eukaryotic translation initiation factor 2α (eIF2α) signaling activation and downregulation of steroidogenic proteins in TM3 cells. Both 4-PBA and GSK2606414 attenuated 1-NP-induced steroidogenesis disruption in TM3 cells. Further studies used N-Acetyl-L-cysteine (NAC) as a classical antioxidant to explore whether oxidative stress-activated ER stress mediated 1-NP-induced testosterone synthases reduction and steroidogenesis disruption in TM3 cells and mouse testes. The results showed NAC pretreatment mitigated oxidative stress, and subsequently attenuated ER stress, particularly PERK-eIF2α signaling activation, and downregulation of testosterone synthases in 1-NP-treated TM3 cells. More importantly, NAC extenuated 1-NP-induced testosterone synthesis in vitro and in vivo. The current work indicated that oxidative stress-caused ER stress, particularly PERK-eIF2α pathway activation, mediates 1-NP-downregulated steroidogenic proteins and steroidogenesis disruption in TM3 cells and mouse testes. Significantly, the current study provides a theoretical basis and demonstrates the experimental evidence for the potential application of antioxidant, such as NAC, in public health prevention, particularly in 1-NP-induced endocrine disorder.
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Antioxidantes , Testículo , Masculino , Ratones , Animales , Testículo/metabolismo , Antioxidantes/metabolismo , Factor 2 Eucariótico de Iniciación/metabolismo , Estrés del Retículo Endoplásmico/fisiología , Testosterona/metabolismo , Estrés Oxidativo , Acetilcisteína/farmacología , Acetilcisteína/metabolismoRESUMEN
The functions of Kir4.1 in oligodendrocyte development have been in controversial. We recently reported that inhibiting Kir4.1 impeded oligodendrocyte precursor cell (OPC) differentiation and oligodendrocyte (OL) maturation, due to Kir4.1 altering intracellular pH of OPCs through Na+/H+ exchangers. However, our conclusion was limited by in vitro observation, thereby it becomes necessary to seek in vivo evidence to determine the roles of Kir4.1 on OPC development and CNS myelination. Here, we used Olig1-Cre to knockout Kir4.1 in OPCs from the early developmental stage. We found that the cell-specific deletion of Kir4.1 significantly impeded OPC differentiation and reduced the number of mature OLs in the cerebral cortex and the corpus callosum. Hence, our in vivo evidence supports that Kir4.1 can regulate OPC differentiation and is essential to CNS myelination.
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Células Precursoras de Oligodendrocitos , Ratones , Animales , Ratones Noqueados , Oligodendroglía/fisiología , Diferenciación Celular/fisiología , Neurogénesis , Vaina de Mielina/fisiologíaRESUMEN
@#Abstract: Objective To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.
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The species of Saussurea sagittifolia Y. S. Chen & S. R. Yi belongs to the family Asteraceae (Cardueae). The complete chloroplast genome of S. sagittifolia was assembled and annotated for the first time in this study. The complete chloroplast genome of S. sagittifolia was 152,535 bp, including a large single-copy (LSC) region of 83,511 bp, a small single-copy (SSC) region of 18,632 bp, and a pair of inverted repeats (IRs) of 25,196 bp. The overall GC content of the chloroplast genome was 37.7%. The chloroplast genome encoded 131 genes, including 87 protein-coding genes, 36 tRNA genes, and eight rRNA genes. Phylogenetic analysis based on complete chloroplast sequences revealed that it related closely to Saussurea medusa.
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The aim of the current investigation was based on the development of pH-responsive hydrogels of chondroitin sulfate, carbopol, and polyvinyl alcohol polymerized with acrylic acid in the presence of ammonium persulfate and ethylene glycol dimethylacrylate for controlled drug delivery. A free radical polymerization technique was used for the preparation of these pH-responsive hydrogels. The gel fraction of the prepared hydrogels was increased with the increase in the chondroitin sulfate, carbopol, polyvinyl alcohol, and acrylic acid content, while the sol-fraction was decreased. Swelling and drug release studies were performed in various pH conditions. Greater swelling and drug release were observed at high pH values (pH 4.6 and 7.4) as compared to low pH value (pH 1.2), representing the pH-responsive nature of the synthesized hydrogels. Porosity and drug loading were increased with the incorporation of high concentrations of hydrogel contents except polyvinyl alcohol, which showed reverse effects. Similarly, biodegradation study reported a slow degradation rate of the prepared hydrogels with the increase in hydrogel constituents. Cytotoxicity study proved the safe use of developed hydrogels as no toxic effect was shown on T84 human colon cancer cells. Similarly, various characterizations, including Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy, were performed for prepared hydrogels. Hence, we could demonstrate that the prepared hydrogels can be used as a promising drug carrier for the controlled delivery of drugs.
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The aim of the current study was to prepare glutamic acid crosslinked poly(itaconic acid/methacrylic acid) microgels for pH-responsive delivery of ketorolac tromethamine, using aqueous free radical polymerization technique. The polymerization of polymer with monomers was carried out by a crosslinking agent N', N'-methylene bisacrylamide in the presence of initiator ammonium persulfate. The prepared microgels were characterized for structure, surface morphology, thermal stability, and crystallinity. Similarly, studies such as sol-gel analysis, drug loading, and polymer volume fraction were performed for the fabricated microgels. The pH-sensitivity of the developed microgels was investigated at three different pH values i.e., pH 1.2, 4.6, and 7.4 by swelling and in-vitro drug release studies. Maximum swelling and drug release were found at pH 7.4 as compared to pH 1.2 and 4.6, which indicated the pH-sensitive nature of the prepared microgels. The toxicity of the prepared microgels was evaluated by cell line and HET-CAM test, which demonstrated no toxic effect of the prepared microgels. In-vivo study was carried out on rabbits and high plasma concentration was reported for the drug loaded microgels as compared to drug solution and commercial product Keten. Hence, the prepared microgel system could be employed as an excellent carrier for the controlled drug delivery system.
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Microgeles , Animales , Ácido Glutámico , Concentración de Iones de Hidrógeno , Ketorolaco Trometamina , Polímeros/química , ConejosRESUMEN
Previous study found 1-NP disrupted steroidogenesis in mouse testis, but the underlying mechanism remained elusive. The current work aims to explore the roles of ROS-promoted AKAP1 degradation and excessive mitochondrial fission in 1-NP-induced steroidogenesis disruption in MLTC-1 cells. Transmission electron microscope analysis found 1-NP promoted excessive mitochondrial fission. Further data showed 1-NP disrupted mitochondrial function. pDRP1 (Ser637), a negative regulator of mitochondrial fission, was reduced in 1-NP-treated MLTC-1 cells. Mechanistically, 1-NP caused degradation of AKAP1, an upstream regulator of pDRP1 (Ser637). MG132, a proteasome inhibitor, attenuated 1-NP-induced AKAP1 degradation and downstream pDRP1 (Ser637) reduction, thereby ameliorating 1-NP-downregulated steroidogenesis. Further analysis found that cellular ROS was elevated and NOX4, HO-1 and SOD2 were upregulated in 1-NP-exposed MLTC-1 cells. NAC, a well-known commercial antioxidant, alleviated 1-NP-induced excessive ROS and oxidative stress. 1-NP-induced AKAP1 degradation and subsequent downregulation of pDRP1 (Ser637) were prevented by NAC pretreatment. Moreover, NAC attenuated 1-NP-resulted T synthesis disturbance in MLTC-1 cells. The present study indicates that ROS mediated AKAP1 degradation and subsequent pDRP1 (Ser637) dependent mitochondrial fission is indispensable in 1-NP caused T synthesis disruption. This study provides a new insight into 1-NP-induced endocrine disruption, and offers theoretical basis in public health prevention.
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Células Intersticiales del Testículo , Dinámicas Mitocondriales , Proteínas de Anclaje a la Quinasa A/metabolismo , Animales , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Pirenos , Especies Reactivas de Oxígeno/metabolismo , Testosterona/metabolismoRESUMEN
Investigations on the fatigue crack growth of commercial pure titanium are carried out with cruciform specimens under different biaxial load ratios (λ = 0, 0.5, and 1) and crack inclination angles (ß = 90°, 60°, and 45°) in this paper. Based on the finite element results, the modified solution of stress intensity factors KI and KII for cruciform specimens containing mixed mode I-II crack is obtained by considering crack size, biaxial load ratio, and crack inclination angles. The experimental results show that the maximum tangential stress criterion is fit for the prediction of crack initiation angles for mixed model I-II crack under uniaxial or biaxial loading condition. When the biaxial load ratio increases, the crack propagation angle becomes smaller, and so does the fatigue crack growth rate of mode I crack or mixed mode I-II crack. Based on an equivalent stress intensity factor, a new valid stress intensity factor is proposed to better describe the biaxial fatigue crack growth behavior, which can demonstrate the contribution of mode I and mode II of stress intensity factor.
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Metabolism and aging are closely connected. The choline derivative glycerophosphocholine (GPC), an important precursor of the neurotransmitter acetylcholine, plays important roles in brain and nervous system function. Although it has been reported to alleviate cognitive decline in aged mice, whether GPC could promote longevity and other fitness factors remains unclear. Here, we find endogenous GPC level declines in the plasma of ageing humans. In Caenorhabditis elegans (C. elegans), GPC extends lifespan and improves exercise capacity during aging. Likewise, GPC inhibits lipofuscin accumulation. We further show that GPC treatment has no adverse effect on nematodes' reproductive abilities and body length. In addition to its benefits under normal conditions, GPC enhances the stress resistance of C. elegans. Mechanically, we find GPC significantly inhibits the reactive oxygen species (ROS) accumulation in worms. Our findings indicate the health benefits of GPC and its potential application in strategies to improve lifespan and healthspan.
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Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.
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ADN Helicasas , Nucleotidiltransferasas , Proteínas de Unión a Poli-ADP-Ribosa , ARN Helicasas , Proteínas con Motivos de Reconocimiento de ARN , ADN/metabolismo , ADN Helicasas/genética , ADN Helicasas/metabolismo , Nucleotidiltransferasas/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , ARN Helicasas/genética , ARN Helicasas/metabolismo , Proteínas con Motivos de Reconocimiento de ARN/genética , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , Gránulos de EstrésRESUMEN
Glutamic acid-co-poly(acrylic acid) (GAcPAAc) hydrogels were prepared by the free radical polymerization technique using glutamic acid (GA) as a polymer, acrylic acid (AAc) as a monomer, ethylene glycol dimethylacrylate (EGDMA) as a cross-linker, and ammonium persulfate (APS) as an initiator. Increase in gel fraction was observed with the increasing concentration of glutamic acid, acrylic acid, and ethylene glycol dimethylacrylate. High percent porosity was indicated by developed hydrogels with the increase in the concentration of glutamic acid and acrylic acid, while a decrease was seen with the increasing concentration of EGDMA, respectively. Maximum swelling and drug release was exhibited at high pH 7.4 compared to low pH 1.2 by the newly synthesized hydrogels. Similarly, both swelling and drug release increased with the increasing concentration of glutamic acid and acrylic acid and decreased with the increase in ethylene glycol dimethylacrylate concentration. The drug release was considered as non-Fickian transport and partially controlled by viscoelastic relaxation of hydrogel. In-vivo study revealed that the AUC0-∞ of fabricated hydrogels significantly increased compared to the drug solution and commercial product Keten. Hence, the results indicated that the developed hydrogels could be used as a suitable carrier for controlled drug delivery.
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The current study was conducted to evaluate and analyze the effect of alginate, itaconic acid, and N,N'-methylene bisacrylamide in formulation of a novel alginate based microgels for sustained release of theophylline. The fabricated microgels were characterized by PXRD, SEM, FTIR, TGA and DSC respectively. FTIR revealed that alginate reacted with itaconic acid during polymerization reaction and confirmed the overlapping of itaconic acid on the backbone of alginate. TGA and DSC depicted high thermal stability of the fabricated microgels as compared to pure unreacted polymer and monomer. Likewise, dynamic swelling and percent drug release studies were carried out at different pH media i.e., pH 1.2, 4.6 and 7.4 respectively. Greater dynamic swelling and percent drug release was observed at higher pH 7.4 as compared to lower pH 4.6 and 1.2 due to the deprotonation of COOH groups of both alginate and itaconic acid respectively. The drug release mechanism from the fabricated microgels could be described by first order model. In-vivo pharmacokinetic study was performed on rabbits and exhibited sustained release in rabbits. Hence, the developed microgels indicated higher potential as the delivery system for the sustained delivery of theophylline.
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Alginatos/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Microgeles/química , Animales , Fenómenos Químicos , Cromatografía Líquida de Alta Presión , Preparaciones de Acción Retardada , Portadores de Fármacos/síntesis química , Composición de Medicamentos , Liberación de Fármacos , Cinética , Masculino , Estructura Molecular , Polímeros , Conejos , Análisis Espectral , TermogravimetríaRESUMEN
OBJECTIVE: To explore the efficacy of functional electrical stimulation (FES)-assisted rehabilitation cycling on the functional recovery of lower limbs in patients with hemiplegic stroke and the assessment value of surface electromyography (sEMG). METHODS: A total of 66 patients with stroke accompanied by hemiplegia of the lower limbs were enrolled in the present prospective study and randomly divided into the experimental group and control group, with 33 patients in each group. FES-assisted rehabilitation cycling was applied in the experimental group, while only rehabilitation cycling was performed without setting the stimulation parameters in the control group. sEMG and the Fugl-Meyer assessment (FMA) were carried out, and the modified Barthel index (MBI) of the lower limbs was assessed before treatment and after 4 weeks and 8 weeks of treatment. RESULTS: There were no significant differences in the evaluation results of sEMG, FMA, and MBI of the lower limbs between the two groups of patients before the treatment (p > 0.05). After 4 weeks of treatment, compared with the control group, there were significant differences in the results of sEMG, FMA, and MBI of the lower limbs in the experimental group (p < 0.05). In the experimental group, the difference in sEMG was statistically significant (p < 0.05). After 8 weeks of treatment, compared with the control group, there were significant differences in the results of sEMG, FMA, and MBI of the lower limbs in the experimental group (p < 0.05). In the experimental group, the differences in the results of sEMG, FMA, and MBI of the lower limbs were statistically significant (p < 0.05). The inter-group comparison of the results of sEMG, FMA and MBI of the lower limbs was statistically significant (p < 0.05) in the control group. CONCLUSION: FES-assisted rehabilitation cycling might promote the recovery of the motor function of the lower limbs in patients with stroke and improve the sEMG signal of the lower limbs.