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1.
J Pharm Anal ; 14(4): 100905, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38665224

RESUMO

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

2.
BMC Musculoskelet Disord ; 25(1): 288, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38614984

RESUMO

BACKGROUND: Teriparatide, a recombinant parathyroid hormone, is pivotal in osteoporosis treatment, particularly in post-surgical recovery for hip fractures. This study investigates its efficacy in functional recovery post-hip fracture surgery in elderly patients, a demographic particularly susceptible to osteoporotic fractures. METHODS: In this retrospective cohort study, 150 elderly patients with proximal femoral fractures undergoing open reduction and internal fixation were enrolled. They were categorized into two groups: receiving 20 µg of daily teriparatide injections for 18 months and receiving standard antiresorptive medications during a 24-month follow-up. Detailed records of patient demographics, Fracture Risk Assessment Tool scores, and comorbidities were kept. Key outcomes, including bone mineral density (BMD) and functional scores (Barthel Index and Visual Analog Scale for hip pain), were evaluated at 3 and 24 months post-surgery. RESULTS: Out of the original cohort, 126 patients (20 men and 106 women with an average age of 85.5 ± 9.3 years) completed the study. The teriparatide group exhibited significant enhancements in both functional scores and BMD when compared to the control group. Notably, functional improvements were less pronounced in male patients compared to female patients. Additionally, the incidence of new fractures was markedly lower in the teriparatide group. CONCLUSION: Administering teriparatide daily for 18 months post-surgery for proximal femoral fractures significantly benefits very elderly patients by improving functionality and bone density, with observed differences in recovery between genders. These results reinforce the efficacy of teriparatide as a potent option for treating osteoporosis-related fractures in the elderly and highlight the importance of considering gender-specific treatment and rehabilitation strategies.


Assuntos
Fraturas do Quadril , Osteoporose , Fraturas Proximais do Fêmur , Idoso , Feminino , Humanos , Masculino , Idoso de 80 Anos ou mais , Teriparatida/uso terapêutico , Densidade Óssea , Estudos Retrospectivos , Fraturas do Quadril/cirurgia , Osteoporose/complicações , Osteoporose/tratamento farmacológico
3.
Chemistry ; : e202401063, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654592

RESUMO

14,14'-Bidibenzo[a,j]anthracenes (BDBAs) were prepared by iridium-catalyzed annulation of 5,5'-biterphenylene with alkynes. Overcrowded BDBAs with highly distorted molecular halves and a small interplanar angle between two anthryl moieties (down to approximately 31º, currently the lowest reported value) were verified by X-ray crystallography. The strong intramolecular interactions and electronic couplingsbetween two molecular halves resulted in upfield 1H NMR signals, redshifted absorption and emission bands, and a reduced HOMO-LUMO gap. Photodynamic investigations on BDBAs indicated that the formation of the conventional symmetry-breaking charge transfer (SBCT) state was suspended by restricted rocking around the central C-C bond. Such a mechanism associated with this highly constrained conformation was examined for the first time.

4.
Colloids Surf B Biointerfaces ; 237: 113868, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522282

RESUMO

Silver nanoparticles (AgNPs) is an excellent antibacterial agent, which is widely used in medical, food, environmental and other fields, but AgNPs are easy to accumulate in aqueous solution, so their application in various fields is limited. Therefore, it is particularly important to propose a new application method or to prepare a new composite material. In this study, OA/PVA was obtained by cross-linking oxalic acid (OA) with polyvinyl alcohol (PVA). Then Ag/NCC was obtained by in situ reduction of AgNPs on nanocellulose crystals (NCC). Finally, Ag/NCC/OA/PVA composite antimicrobial films with good waterproofing effect were prepared by mixing Ag/NCC with OA/PVA. Subsequently, the films were characterized using SEM, UV-vis, FTIR and XRD, as well as physicochemical properties such as mechanical strength and hydrophilic properties were determined. The results indicated that the Ag/NCC/OA/PVA films possess good light transmittance, mechanical properties, water resistance, antibacterial activity, and biodegradability. The results of the mechanism study showed that Ag/NCC/OA/PVA films can destroy cell integrity, inhibit succinate dehydrogenase (SDH) activity, thereby reducing intracellular ATP levels. And induce a large number of reactive oxygen species (ROS) production, eventually leading to the death of C. sakazakii. In summary, Ag/NCC/OA/PVA film has good physical and chemical properties, antibacterial activity and biocompatibility, and has promising applications in food and medical antibacterial fields.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Prata/farmacologia , Prata/química , Álcool de Polivinil/química , Nanopartículas Metálicas/química , Ácido Oxálico/farmacologia , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia , Biofilmes
5.
Materials (Basel) ; 17(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38541564

RESUMO

The large-scale ingot of the 7xxx-series aluminum alloys fabricated by direct chill (DC) casting often suffers from foundry defects such as cracks and cold shut due to the formidable challenges in the precise controlling of casting parameters. In this manuscript, by using the integrated computational method combining numerical simulations with machine learning, we systematically estimated the evolution of multi-physical fields and grain structures during the solidification processes. The numerical simulation results quantified the influences of key casting parameters including pouring temperature, casting speed, primary cooling intensity, and secondary cooling water flow rate on the shape of the mushy zone, heat transport, residual stress, and grain structure of DC casting ingots. Then, based on the data of numerical simulations, we established a novel model for the relationship between casting parameters and solidification characteristics through machine learning. By comparing it with experimental measurements, the model showed reasonable accuracy in predicting the sump profile, microstructure evolution, and solidification kinetics under the complicated influences of casting parameters. The integrated computational method and predicting model could be used to efficiently and accurately determine the DC casting parameters to decrease the casting defects.

6.
Mar Biotechnol (NY) ; 26(2): 230-242, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38502428

RESUMO

Antibiotics are widely used in aquaculture to treat the bacterial diseases. However, the improper use of antibiotics could lead to environmental pollution and development of resistance. As a safe and eco-friendly alternative, antimicrobial peptides (AMPs) are commonly explored as therapeutic agents. In this study, a mutant strain of Tetraselmis subcordiformis containing AMP NZ2114 was developed and used as an oral drug delivery system to reduce the use of antibiotics in turbot (Scophthalmus maximus) aquaculture. The gut, kidney, and liver immune-related genes and their effects on gut digestion and bacterial communities in turbot fed with NZ2114 were evaluated in an 11-day feeding experiment. The results showed that compared with the group fed with wild-type T. subcordiformis, the group fed with T. subcordiformis transformants containing NZ2114 was revealed with decreased levels of both pro-inflammatory factors (TNF-α and IL-1ß), inhibitory effect on Staphylococcus aureus, Vibrio parahaemolyticus, and Vibrio splendidus demonstrated by the in vitro simulation experiments, and increased richness and diversity of the gut microbiota of turbot. In conclusion, our study provided a novel, beneficial, and low-cost method for controlling bacteria in turbot culture through the oral drug delivery systems.


Assuntos
Linguados , Microalgas , Animais , Linguados/imunologia , Linguados/genética , Linguados/microbiologia , Administração Oral , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Aquicultura , Clorófitas , Vibrio/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Fígado/metabolismo , Fígado/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
7.
Artigo em Inglês | MEDLINE | ID: mdl-38502628

RESUMO

The hybrid deep models of Vision Transformer (ViT) and Convolution Neural Network (CNN) have emerged as a powerful class of backbones for vision tasks. Scaling up the input resolution of such hybrid backbones naturally strengthes model capacity, but inevitably suffers from heavy computational cost that scales quadratically. Instead, we present a new hybrid backbone with HIgh-Resolution Inputs (namely HIRI-ViT), that upgrades prevalent four-stage ViT to five-stage ViT tailored for high-resolution inputs. HIRI-ViT is built upon the seminal idea of decomposing the typical CNN operations into two parallel CNN branches in a cost-efficient manner. One high-resolution branch directly takes primary high-resolution features as inputs, but uses less convolution operations. The other low-resolution branch first performs down-sampling and then utilizes more convolution operations over such low-resolution features. Experiments on both recognition task (ImageNet-1K dataset) and dense prediction tasks (COCO and ADE20K datasets) demonstrate the superiority of HIRI-ViT. More remarkably, under comparable computational cost (  âˆ¼ 5.0 GFLOPs), HIRI-ViT achieves to-date the best published Top-1 accuracy of 84.3% on ImageNet with 448×448 inputs, which absolutely improves 83.4% of iFormer-S by 0.9% with 224×224 inputs.

8.
Mar Drugs ; 22(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38535479

RESUMO

Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L-1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L-1), phycoerythrin (102.95 mg L-1), and polysaccharide (1.42 g L-1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum.


Assuntos
Gluconatos , Porphyridium , Ficoeritrina , Gluconato de Cálcio , Polissacarídeos
9.
Kaohsiung J Med Sci ; 40(4): 360-373, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38340032

RESUMO

Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage-associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti-inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 µg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis-associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescent staining, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS-induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5-lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro-inflammatory factors, that is, interleukin-6 and tumor necrosis factor-α (IL-6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5-mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD.


Assuntos
Colite , Ferroptose , Doenças Inflamatórias Intestinais , Lignanas , Camundongos , Animais , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/efeitos adversos , Colite/induzido quimicamente , Colite/genética , Doenças Inflamatórias Intestinais/terapia , Inflamação , Interleucina-6 , Fator de Necrose Tumoral alfa/genética , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
10.
Angew Chem Int Ed Engl ; 63(15): e202400439, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38345401

RESUMO

Electroreduction of CO2 to C2+ products provides a promising strategy for reaching the goal of carbon neutrality. However, achieving high selectivity of C2+ products at high current density remains a challenge. In this work, we designed and prepared a multi-sites catalyst, in which Pd was atomically dispersed in Cu (Pd-Cu). It was found that the Pd-Cu catalyst had excellent performance for producing C2+ products from CO2 electroreduction. The Faradaic efficiency (FE) of C2+ products could be maintained at approximately 80.8 %, even at a high current density of 0.8 A cm-2 for at least 20 hours. In addition, the FE of C2+ products was above 70 % at 1.4 A cm-2. Experiments and density functional theory (DFT) calculations revealed that the catalyst had three distinct catalytic sites. These three active sites allowed for efficient conversion of CO2, water dissociation, and CO conversion, ultimately leading to high yields of C2+ products.

11.
Cell Metab ; 36(2): 438-453.e6, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38325338

RESUMO

The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.


Assuntos
Diabetes Mellitus , Núcleo Hipotalâmico Paraventricular , Animais , Núcleo Hipotalâmico Paraventricular/metabolismo , Transcriptoma/genética , Hipotálamo/metabolismo , Obesidade/metabolismo , Diabetes Mellitus/metabolismo , Perfilação da Expressão Gênica
12.
Curr Rheumatol Rep ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372871

RESUMO

PURPOSE OF REVIEW: The purpose of this literature review was to determine if medications used to treat osteoporosis are also effective for treating osteoarthritis (OA). RECENT FINDINGS: A total of 40 relevant articles were identified. Studies were categorized into those (1) discussing estrogen and selective estrogen receptor modulators (SERMs), (2) bisphosphonates, (3) parathyroid hormone (PTH) analogs, and (4) denosumab, and (5) prior review articles. A large amount of evidence suggests that estrogen and SERMs are effective at reducing OA symptoms and disease progression. Evidence suggests that bisphosphonates, the most common medications used to treat osteoporosis, can reduce OA symptoms and disease progression. In vivo studies suggest that PTH analogs may improve the cartilage destruction associated with OA; however, few human trials have examined its use for OA. Denosumab is approved to treat osteoporosis, bone metastases, and certain types of breast cancer, but little study has been done with respect to its effect on OA. The current evidence indicates that medications used to treat osteoporosis are also effective for treating OA. Estrogen, SERMs, and bisphosphonates have the most potential as OA therapies. Less is known regarding the effectiveness of PTH analogs and denosumab in OA, and more research is needed.

13.
Curr Neurovasc Res ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38409728

RESUMO

Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated. METHODS: All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment. RESULTS: EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation. CONCLUSION: The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.

14.
Gut Microbes ; 16(1): 2316932, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356294

RESUMO

Mitochondrial dynamics are critical in cellular energy production, metabolism, apoptosis, and immune responses. Pathogenic bacteria have evolved sophisticated mechanisms to manipulate host cells' mitochondrial functions, facilitating their proliferation and dissemination. Salmonella enterica serovar Typhimurium (S. Tm), an intracellular foodborne pathogen, causes diarrhea and exploits host macrophages for survival and replication. However, S. Tm-associated mitochondrial dynamics during macrophage infection remain poorly understood. In this study, we showed that within macrophages, S. Tm remodeled mitochondrial fragmentation to facilitate intracellular proliferation mediated by Salmonella invasion protein A (SipA), a type III secretion system effector encoded by Salmonella pathogenicity island 1. SipA directly targeted mitochondria via its N-terminal mitochondrial targeting sequence, preventing excessive fragmentation and the associated increase in mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and release of mitochondrial DNA and cytochrome c into the cytosol. Macrophage replication assays and animal experiments showed that mitochondria and SipA interact to facilitate intracellular replication and pathogenicity of S. Tm. Furthermore, we showed that SipA delayed mitochondrial fragmentation by indirectly inhibiting the recruitment of cytosolic dynamin-related protein 1, which mediates mitochondrial fragmentation. This study revealed a novel mechanism through which S. Tm manipulates host mitochondrial dynamics, providing insights into the molecular interplay that facilitates S. Tm adaptation within host macrophages.


Assuntos
Microbioma Gastrointestinal , Salmonella typhimurium , Animais , Salmonella typhimurium/metabolismo , Proteína Estafilocócica A/genética , Proteína Estafilocócica A/metabolismo , Sorogrupo , Dinâmica Mitocondrial , Proteínas de Bactérias/metabolismo , Macrófagos/metabolismo , Proliferação de Células
15.
J Nanobiotechnology ; 22(1): 66, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368393

RESUMO

BACKGROUND: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. RESULTS: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. CONCLUSION: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.


Assuntos
Transtorno do Espectro Autista , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Humanos , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Exossomos/metabolismo , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/terapia , Transtorno do Espectro Autista/metabolismo , Hibridização in Situ Fluorescente , Fosfatidilinositol 3-Quinases/metabolismo , Estudos Prospectivos , Distribuição Tecidual , Neurogênese , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Interferon gama/metabolismo
16.
Reprod Toxicol ; 124: 108552, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38296003

RESUMO

A widely used type II pyrethroid pesticide cypermethrin (CYP) is one of endocrine disrupting chemicals (EDCs) with anti-androgenic activity to induce male reproductive toxicology. However, the mechanisms have not been fully elucidated. This study was to explore the effects of CYP on apoptosis of mouse Sertoli cells (TM4) and the roles of endoplasmic reticulum (ER)-mitochondria coupling involving 1,4,5-trisphosphate receptor type1-glucose-regulated protein 75-voltage-dependent anion channel 1 (IP3R1-GRP75-VDAC1). TM4 were cultured with different concentrations of CYP. Flow cytometry, calcium (Ca2+) fluorescent probe, transmission electron microscopy and confocal microscopy, and western blot were to examine apoptosis of TM4, mitochondrial Ca2+, ER-mitochondria coupling, and expressions of related proteins. CYP was found to increase apoptotic rates of TM4 significantly. CYP was shown to significantly increase expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP). Concentration of mitochondrial Ca2+ was increased by CYP treatment significantly. CYP significantly enhanced ER-mitochondria coupling. CYP was shown to increase expressions of IP3R, Grp75 and VDAC1 significantly. We suggest that CYP induces apoptosis in TM4 cells by facilitating mitochondrial Ca2+ overload regulated by ER-mitochondria coupling involving IP3R1-GRP75-VDAC1. This study identifies a novel mechanism of CYP-induced apoptosis in Sertoli cells.


Assuntos
Proteínas de Choque Térmico HSP70 , Proteínas de Membrana , Piretrinas , Células de Sertoli , Camundongos , Animais , Masculino , Células de Sertoli/metabolismo , Mitocôndrias , Retículo Endoplasmático/metabolismo , Piretrinas/toxicidade , Apoptose , Cálcio/metabolismo
17.
BMC Musculoskelet Disord ; 25(1): 62, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218794

RESUMO

BACKGROUND: Femoral neck fractures in older adult patients are a major concern and often necessitate surgical intervention. This study compared the clinical outcomes of 2 surgical techniques: the femoral neck system (FNS) and cannulated compression screws (CCSs). METHODS: A total of 40 female patients (mean age 73.50 ± 11.55 years) with femoral neck fractures of Pauwels classification type II and receiving surgical fixation between 2020 and 2022 were enrolled. The patients were categorized into an FNS group (n = 12) or a CCS group (n = 28), and surgical duration, intraoperative blood loss, length of hospital stay, and incidence of postoperative adverse events were analyzed. RESULTS: No significant intergroup differences in demographic characteristics were discovered. The mean surgical duration for all patients was 52.88 ± 22.19 min, with no significant difference between the groups. However, the FNS group experienced significantly higher intraoperative blood loss (P = 0.002) and longer hospital stay (P = 0.023) than did the CCS group. The incidence of osteonecrosis was higher in the CCS group, whereas the incidence of nonunion or malunion was higher in the FNS group. The surgical method did not appear to be a significant risk factor. The main risk factor for revision surgery was longer duration until the first adverse event (P = 0.015). CONCLUSION: The FNS does not appear to provide superior surgical outcomes compared with CCSs in older adult women with Pauwels classification type II femoral neck fractures. A longer duration between surgical fixation and the first adverse event before stabilization of the fracture site may be a risk factor for revision surgery.


Assuntos
Fraturas do Colo Femoral , Necrose da Cabeça do Fêmur , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Colo do Fêmur , Perda Sanguínea Cirúrgica , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Fraturas do Colo Femoral/cirurgia , Fraturas do Colo Femoral/etiologia , Necrose da Cabeça do Fêmur/etiologia , Estudos Retrospectivos , Resultado do Tratamento
18.
Sci Rep ; 14(1): 1447, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228655

RESUMO

Premature ovarian failure (POF) caused by chemotherapy is a growing concern for female reproductive health. The use of metformin (MET), which has anti-oxidative and anti-inflammatory effects, in the treatment of POF damaged by chemotherapy drugs remains unclear. In this study, we investigated the impact of MET on POF caused by cyclophosphamide (CTX) combined with busulfan (BUS) and M1 macrophages using POF model mice and primary granule cells (GCs). Our findings demonstrate that intragastric administration of MET ameliorates ovarian damage and alleviates hormonal disruption in chemotherapy-induced POF mice. This effect is achieved through the reduction of inflammatory and oxidative stress-related harm. Additionally, MET significantly relieves abnormal inflammatory response, ROS accumulation, and senescence in primary GCs co-cultured with M1 macrophages. We also observed that this protective role of MET is closely associated with the AMPK/PPAR-γ/SIRT1 pathway in cell models. In conclusion, our results suggest that MET can protect against chemotherapy-induced ovarian injury by inducing the expression of the AMPK pathway while reducing oxidative damage and inflammation.


Assuntos
Antineoplásicos , Metformina , Insuficiência Ovariana Primária , Humanos , Camundongos , Feminino , Animais , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/prevenção & controle , Insuficiência Ovariana Primária/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Metformina/uso terapêutico , Células da Granulosa/metabolismo , Antineoplásicos/farmacologia
19.
IEEE Trans Image Process ; 33: 625-638, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38198242

RESUMO

How to model the effect of reflection is crucial for single image reflection removal (SIRR) task. Modern SIRR methods usually simplify the reflection formulation with the assumption of linear combination of a transmission layer and a reflection layer. However, the large variations in image content and the real-world picture-taking conditions often result in far more complex reflection. In this paper, we introduce a new screen-blur combination based on two important factors, namely the intensity and the blurriness of reflection, to better characterize the reflection formulation in SIRR. Specifically, we present Screen-blur Reflection Networks (SRNet), which executes the screen-blur formulation in its network design and adapts to the complex reflection on real scenes. Technically, SRNet consists of three components: a blended image generator, a reflection estimator and a reflection removal module. The image generator exploits the screen-blur combination to synthesize the training blended images. The reflection estimator learns the reflection layer and a blur degree that measures the level of blurriness for reflection. The reflection removal module further uses the blended image, blur degree and reflection layer to filter out the transmission layer in a cascaded manner. Superior results on three different SIRR methods are reported when generating the training data on the principle of the screen-blur combination. Moreover, extensive experiments on six datasets quantitatively and qualitatively demonstrate the efficacy of SRNet over the state-of-the-art methods.

20.
Chemosphere ; 350: 141088, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38163470

RESUMO

Recently, using microalgae to remediate heavy metal polluted water has been attained a huge attention. However, heavy metals are generally toxic to microalgae and consequently decrease biomass accumulation. To address this issue, the feasibility of adding exogenous glucose, employing algae-bacteria system and algae-bacteria-activated carbon consortium to enhance microalgae growth were evaluated. The result showed that Cd2+ removal efficiency was negatively correlated with microalgal specific growth rate. The exogenous glucose alleviated the heavy metal toxicity to algal cells and thus increased the microalgae growth rate. Among the different treatments, the algae-bacteria-activated carbon combination had the highest biomass concentration (1.15 g L-1) and lipid yield (334.97 mg L-1), which were respectively 3.03 times of biomass (0.38 g L-1) and 4.92 times of lipid yield (68.08 mg L-1) in the single microalgae treatment system. Additionally, this algae-bacteria-activated carbon consortium remained a high Cd2+ removal efficiency (91.61%). In all, the present study developed an approach that had a great potential in simultaneous heavy metal wastewater treatment and microalgal lipid production.


Assuntos
Metais Pesados , Microalgas , Cádmio/toxicidade , Carvão Vegetal , Biomassa , Metais Pesados/toxicidade , Lipídeos , Bactérias , Glucose
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