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1.
Acta Trop ; 225: 106179, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34627758

RESUMO

Babesiosis is an emerging zoonotic disease that is typically caused by Babesia microti infection. Clinical treatment of B. microti infection is challenging; hence, it is crucial to find new effective drugs. The current laboratory screening methods for anti-B. microti drugs are not optimized. We conducted drug-suppressive and drug-therapeutic tests to investigate whether use of an immunosuppressant and the target gene-based qPCR are helpful to reduce the number of animals affected and to improve parasite detection in an immunocompetent mouse model. These results were verified by subpassage test. In the drug-suppressive test, no B. microti were observed after immunosuppressant administration or in subpassage mice in the 100 mg/kg robenidine hydrochloride (ROBH) group. The opposite results were observed in the control, 50 mg/kg ROBH, atovaquone (ATO) + azithromycin (AZM), and proguanil hydrochloride (PGH) groups. Significant differences were observed in the EIR and target gene relative values (both P < 0.001) between the control group and any ROBH groups. In the drug-therapeutic test, recrudescence occurred in the 50 mg/kg ROBH, ATO+AZM, and control groups. This was not observed in the 100 mg/kg ROBH group after immunosuppressant administration. Similar findings were observed in the subpassage test. This suggests that a 4-day anti-B. microti drug-suppressive test can be used in preliminary drug screening. Potentially effective drugs can be verified by immunosuppressant test in subsequent drug-therapeutic tests. Thus, a laboratory evaluation method of anti-B. microti drug efficacy was optimized, which is highly accurate and requires a short drug screening time.


Assuntos
Babesia microti , Babesiose , Preparações Farmacêuticas , Animais , Babesiose/tratamento farmacológico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Camundongos
2.
Neural Regen Res ; 17(6): 1278-1285, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34782572

RESUMO

There is no effective treatment for hemiplegia after hypertensive intracerebral hemorrhage. Considering that the branches of L4 nerve roots in the lumbar plexus root control the movement of the lower extremity anterior and posterior muscles, we investigated a potential method of nerve repair using the L4 nerve roots. Rat models of hindlimb hemiplegia after a hypertensive intracerebral hemorrhage were established by injecting autogenous blood into the posterior limb of internal capsule. The L4 nerve root on the healthy side of model rats was transferred and then anastomosed with the L4 nerve root on the affected side to drive the extensor and flexor muscles of the hindlimbs. We investigated whether this method can restore the flexible movement of the hindlimbs of paralyzed rats after hypertensive intracerebral hemorrhage. In a beam-walking test and ladder rung walking task, model rats exhibited an initial high number of slips, but improved in accuracy on the paretic side over time. At 17 weeks after surgery, rats gained approximately 58.2% accuracy from baseline performance and performed ankle motions on the paretic side. At 9 weeks after surgery, a retrograde tracing test showed a large number of fluoro-gold-labeled motoneurons in the left anterior horn of the spinal cord that supports the L4-to-L4 nerve roots. In addition, histological and ultramicrostructural findings showed axon regeneration of motoneurons in the anterior horn of the spinal cord. Electromyography and paw print analysis showed that denervated hindlimb muscles regained reliable innervation and walking coordination improved. These findings suggest that the L4-to-L4 nerve root transfer method for the treatment of hindlimb hemiplegia after hypertensive intracerebral hemorrhage can improve the locomotion of hindlimb major joints, particularly of the distal ankle. Findings from study support that the L4-to-L4 nerve root transfer method can effectively repair the hindlimb hemiplegia after hypertensive intracerebral hemorrhage. All animal experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (No. IACUC-1906009) in June 2019.

3.
Gene ; 809: 146023, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34673205

RESUMO

Steroidogenic factor 1 (sf1) (officially designated as nuclear receptor subfamily 5 group A member 1 [NR5A1]) is an important regulator of gonad development. Previous studies on sf1 in fish have been limited to cloning and in vitro expression experiments. In this study, we used antisense RNA to down-regulate sf1 transcription and sf1 protein expression. Down-regulation of sf1 resulted in an increase in body weight and inhibition of gonadal development in both males and females with the consequent lower gonadosomatic index compared to fish in the control group. Hematoxylin-eosin staining of the gonads of fish with down-regulated sf1 revealed fewer seminiferous tubules and sperm in the testis of males. In addition, the oocytes were mainly stage II and many of them were atretic follicle. We conducted comparative transcriptome and proteome analyses between the sf1-down-regulated group and the control group. These analyses revealed multiple gene-protein pairs and pathways involved in regulating the observed changes, including 44 and 74 differently expressed genes and proteins in males and females, respectively. The results indicated that dysfunctional retinal metabolism and fatty acid metabolism could be causes of the observed weight gain and gonad abnormalities in sf1-down-regulated fish. These findings demonstrate the feasibility of using antisense RNA for gene editing in fish. This methodology allows the study gene function in species less amenable to gene editing as for example aquaculture species with long life cycles.


Assuntos
Peso Corporal/genética , Ciclídeos/genética , Ovário/crescimento & desenvolvimento , Fator Esteroidogênico 1/genética , Testículo/crescimento & desenvolvimento , Animais , Aquicultura , Ciclídeos/crescimento & desenvolvimento , Regulação para Baixo , Feminino , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Masculino , RNA Antissenso , Fator Esteroidogênico 1/metabolismo , Transfecção
4.
Int J Med Inform ; 157: 104638, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34775213

RESUMO

BACKGROUND: The cytological analysis of bronchoalveolar lavage fluid (BALF) plays an essential role in the differential diagnosis of respiratory diseases. In recent years, deep learning has demonstrated excellent performance in image processing and object recognition. OBJECTIVES: We aim to apply deep learning to the automated interpretation and analysis of BALF. METHOD: Visual images were acquired using an automated biological microscopy platform. We propose a three-step algorithm to automatically interpret BALF cytology based on a convolutional neural network (CNN). The clinical value was evaluated at the patient level. RESULTS: Our model successfully detected most cells in BALF specimens and achieved a sensitivity, precision, and F1 score of over 0.9 for most cell types. In two tests in the clinical context, the algorithm outperformed experienced practitioners. CONCLUSION: The program can automatically provide the cytological background of BALF and augment clinical decision-making for clinicians.


Assuntos
Algoritmos , Redes Neurais de Computação , Líquido da Lavagem Broncoalveolar , Diagnóstico Diferencial , Humanos , Processamento de Imagem Assistida por Computador
5.
Sci Rep ; 11(1): 23593, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34880339

RESUMO

A principle of choice in animal decision-making named probability matching (PM) has long been detected in animals, and can arise from different decision-making strategies. Little is known about how environmental stochasticity may influence the switching time of these different decision-making strategies. Here we address this problem using a combination of behavioral and theoretical approaches, and show, that although a simple Win-Stay-Loss-Shift (WSLS) strategy can generate PM in binary-choice tasks theoretically, budgerigars (Melopsittacus undulates) actually apply a range of sub-tactics more often when they are expected to make more accurate decisions. Surprisingly, budgerigars did not get more rewards than would be predicted when adopting a WSLS strategy, and their decisions also exhibited PM. Instead, budgerigars followed a learning strategy based on reward history, which potentially benefits individuals indirectly from paying lower switching costs. Furthermore, our data suggest that more stochastic environments may promote reward learning through significantly less switching. We suggest that switching costs driven by the stochasticity of an environmental niche can potentially represent an important selection pressure associated with decision-making that may play a key role in driving the evolution of complex cognition in animals.

6.
Pharmaceutics ; 13(12)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34959285

RESUMO

Triple-negative breast cancer (TNBC) is characterized by extensive tumor heterogeneity at both the pathologic and molecular levels, particularly accelerated aggressiveness, and terrible metastasis. It is responsible for the increased mortality of breast cancer patients. Due to the negative expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2, the progress of targeted therapy has been hindered. Higher immune response in TNBCs than for other breast cancer types makes immunotherapy suitable for TNBC therapy. At present, promising treatments in immunotherapy of TNBC include immune checkpoints (ICs) blockade therapy, adoptive T-cell immunotherapy, and tumor vaccine immunotherapy. In addition, nanomedicines exhibit great potential in cancer therapy through the enhanced permeability and retention (EPR) effect. Immunotherapy-involved combination therapy may exert synergistic effects by combining with other treatments, such as traditional chemotherapy and new treatments, including photodynamic therapy (PTT), photodynamic therapy (PDT), and sonodynamic therapy (SDT). This review focuses on introducing the principles and latest development as well as progress in using nanocarriers as drug-delivery systems for the immunotherapy of TNBC.

7.
Pharmaceutics ; 13(12)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34959445

RESUMO

Osteoarthritis (OA) is the most prevalent degenerative joint disease affecting millions of people worldwide. Currently, clinical nonsurgical treatments of OA are only limited to pain relief, anti-inflammation, and viscosupplementation. Developing disease-modifying OA drugs (DMOADs) is highly demanded for the efficient treatment of OA. As OA is a local disease, intra-articular (IA) injection directly delivers drugs to synovial joints, resulting in high-concentration drugs in the joint and reduced side effects, accompanied with traditional oral or topical administrations. However, the injected drugs are rapidly cleaved. By properly designing the drug delivery systems, prolonged retention time and targeting could be obtained. In this review, we summarize the drugs investigated for OA treatment and recent advances in the IA drug delivery systems, including micro- and nano-particles, liposomes, and hydrogels, hoping to provide some information for designing the IA injected formulations.

8.
Br J Ophthalmol ; 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34933895

RESUMO

PURPOSE: To describe the prevalence and risk factors of primary angle-closure glaucoma (PACG) and to explore nationality difference in Chinese. METHODS: The Yunnan Minority Eye Study was conducted in a rural multiethnic area in Yunnan province and included 6546 participants aged over 50 years. PACG was diagnosed based on International Society of Geographical and Epidemiologic Ophthalmology criteria by experienced ophthalmologists. Multivariate regression modelling was conducted to examine risk factors for PACG. Principal component analyis (PCA) was performed to evaluate the effects of ethnicity on PACG. RESULTS: The overall prevalence of PACG was 0.7% (95% CIs: 0.5% to 0.9%). PCA indicated that ethnicity is significantly related to the presence of PACG (p<0.001) after controlling for other risk factors. In addition, higher PACG prevalence was also correlated with older age (60-69 years group (OR: 3.47; 95% CI: 1.11 to 10.84; p<0.05) and 70-79 years group (OR: 4.71; 95% CI: 1.40 to 15.86; p<0.05) as compared with 50-59 years group), higher intraocular pressures (OR: 1.26; 95% CI: 1.17 to 1.36; p<0.001), shorter axial lengths (OR: 0.42; 95% CI: 0.32 to 0.56; p<0.001) and thinner central corneal thicknesses (OR: 0.89; 95% CI: 0.81 to 0.99; p<0.05). CONCLUSIONS: This multiethnic study on Chinese adults living in the same geographical location indicated that ethnicity is a significant risk factor for PACG. However, there were still some of the effects of ethnic differences on the prevalence of PACG that could not be explained and further studies should take culture and lifestyle factors into account.

9.
Front Pharmacol ; 12: 786613, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925042

RESUMO

Objective: The aim of the study was to investigate the different extent of inhibition of endogenous insulin secretion by the reduction of C-peptide levels in an euglycemic clamp study and its effects on the evaluation of pharmacokinetics, pharmacodynamics of insulin preparations, and quality of clamp study to determine the best reduction range of C-peptide levels. Methods: Healthy Chinese male volunteers were enrolled and underwent a single-dose euglycemic clamp test. Participants were subcutaneously injected with long-acting insulin glargine (0.4 IU/kg). Blood samples were collected pretest and up to 24 h post-test to assess pharmacokinetics (PK), pharmacodynamics (PD), and C-peptide levels. Results: We divided the 39 volunteers enrolled in the study into three groups according to the reduction of C-peptide levels: group A (ratio of C-peptide reduction <30%, n = 13), group B (ratio of C-peptide reduction between ≥ 30% and <50%, n = 15), and group C (ratio of C-peptide reduction ≥50%, n = 11); there were significant differences in the three groups (p = 0.000). The upper and lower limits of blood glucose oscillation in group C was statistically lower than the other groups, the range of oscillating glucose levels in group C was -17.0 ± 6.6% to -1.1 ± 6.7%. The AUC0-24 h in groups A, B, and C were 9.7 ± 2.2, 11.0 ± 2.9, and 11.9 ± 2.1 ng/ml × min, respectively, which indicated an increasing trend in the three groups (P trend = 0.041). For quality assessment, the average glucose (p = 0.000) and MEFTG (p = 0.001) levels in three groups were significantly different. Conclusion: The different extent of inhibition of endogenous insulin will influence the PK/PD of insulin preparations and the quality of the euglycemic clamp. Furthermore, the ratio of C-peptide reduction should be above 50% to free from the interference of endogenous insulin, and the range of blood glucose levels should be consistently maintained at -10% to 0 in the euglycemic clamp.

10.
Zhongguo Gu Shang ; 34(10): 965-70, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34726027

RESUMO

OBJECTIVE: To summarize the complications of core drilling intramedullary nail in the treatment of femoral shaft closed fracture and explore the treatment strategy. METHODS: From August 2014 to June 2018, a total of 215 patients with closed femoral shaft fractures were treated with closed reduction core drill intramedullary nail, including 129 males and 86 females, aged from 18 to 62 years, with an average of (44.2±10.6) years old. The time from injury to operation was 3 to 21 days. There were 102 cases of AO type A fracture, 82 cases of AO type B fracture and 31 cases of AO type C fracture. The time of operation, the amount of blood loss during operation, the duration of hospitalization, the time of fracture healing and the HSS score of knee joint function at the last follow-up were recorded. The observation of complications included:iatrogenic fracture, core drill broken, core drill twist, postoperative infection, and fracture nonunion. RESULTS: The average operation time was (63.2± 15.6) min and intraoperative blood loss was (150.0±34.5) ml. All the incisions reached grade A healing. Patients were follow up for a mean of (18.5±3.2) months, the average hospital stay was (4.3±1.2) days, and the average fracture healing time was (5.6±2.3) months. At the final follow-up, the average HSS score of knee joint was 90.3±4.7. Related complications occurred in 37 cases (17.2%). The core drill related complications occurred in 13 cases (6.0%), including core drill broken in 5 cases (2.3%), core removal in 1 case and slotting in 4 cases;core drill twist in 8 cases (3.7%). After the core was cut, the core was removed. Similar complicationsof conventional intramedullary nail:iatrogenic fracture was performed in 12 cases (5.6%), including 10 cases of fracture end split and 2 cases of distal perimedullary fracture of intramedullary nail. The patients with cleavage at the fracture end were not treated after judging their stability, and the patients with fracture around the distal end of the intramedullary nail were fixed with auxiliary steel plate during operation;1 case(0.4%) with delayed infection after operation, debridement and external fixation was replaced and healed after bone transfer; fracture nonunion occurred in 11 cases (5.1%), of which 7 cases (3.3%) were hypertrophic nonunion and healed with additional plate. Atrophic nonunion occurred in 4 cases (1.9%), which healed after additional steel plate and bone graft. CONCLUSION: Core drilling intramedullary nail is an effective method for the treatment of closed femoral shaft fracture, and the complications include core drill related complications and conventional intramedullary nail similar complications. Accurate preoperative evaluation, careful operation during operation and early postoperative symptomatic treatment can effectively reduce the occurrence of related complications.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas Fechadas , Adulto , Pinos Ortopédicos , Feminino , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas/efeitos adversos , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Phys Chem Chem Phys ; 23(39): 22760-22767, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34608903

RESUMO

Optimizing the efficiency of heat dissipation across an interface is a great challenge with the continuously increasing integration of microelectronic devices. In this work, an effective method in tuning the heat conduction across the Al/graphene/SiO2 interface is reported. It was found that the interfacial thermal conductance of Al/irradiated graphene/SiO2 can be increased by a factor of 3, as compared with that of Al/pristine graphene/SiO2. The X-ray photoelectron spectroscopy (XPS) analysis indicates that ion irradiation may promote the formation of CO bonds on the irradiated graphene surface, which is beneficial to the enhancement of interfacial thermal conductance. The density functional theory (DFT) calculations reveal that in addition to the formed bonds between O atoms and Al atoms, the adsorption strength between Al and irradiated graphene is intensified, which plays a dominant role in enhancing the interfacial thermal conductance of Al/graphene/SiO2.

12.
Theor Popul Biol ; 142: 91-99, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34627803

RESUMO

The evolution of cooperation in Prisoner's Dilemmas with additive random cost and benefit for cooperation cannot be accounted for by Hamilton's rule based on mean effects transferred from recipients to donors weighted by coefficients of relatedness, which defines inclusive fitness in a constant environment. Extensions that involve higher moments of stochastic effects are possible, however, and these are connected to a concept of random inclusive fitness that is frequency-dependent. This is shown in the setting of pairwise interactions in a haploid population with the same coefficient of relatedness between interacting players. In an infinite population, fixation of cooperation is stochastically stable if a mean geometric inclusive fitness of defection when rare is negative, while fixation of defection is stochastically unstable if a mean geometric inclusive fitness of cooperation when rare is positive, and these conditions are generally not equivalent. In a finite population, the probability for cooperation to ultimately fix when represented once exceeds the probability under neutrality or the corresponding probability for defection if the mean inclusive fitness of cooperation when its frequency is 1/3 or 1/2, respectively, exceeds 1. All these results rely on the simplifying assumption of a linear fitness function. It is argued that meaningful applications of random inclusive fitness in complex settings (multi-player game, diploidy, population structure) would generally require conditions of weak selection and additive gene action.

13.
Clin Rheumatol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709497

RESUMO

OBJECTIVE: The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires. METHODS: We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors. RESULTS: HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks. CONCLUSION: This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction. TRIAL REGISTRATION: http://www.chictr.org.cn/enindex.aspx , ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab.

14.
Fish Shellfish Immunol ; 119: 409-419, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34687881

RESUMO

Fish gills are the primary organ that respond to sudden changes in the dissolved oxygen (DO) level in the aquatic environment. Hypoxic stress impairs the normal function of gill tissues. However, little is known about the mechanisms of the response of yellow catfish gills to hypoxic stress. In this study, we compared transcriptomic and physiological changes in gill tissues of hybrid yellow catfish (Tachysurus fulvidraco ♀ × Pseudobagrus vachellii ♂) between a hypoxia-treated group (DO: 1.5 mg/L) and a control group (DO: 6.5 mg/L). In fish in the hypoxia-treated group, gill filaments underwent adaptive changes, and the number of vacuoles in gill tissues increased. Exposure to hypoxic conditions for 96 h resulted in increased anaerobic metabolism and decreased antioxidant and immune capacity in gill tissues. Transcriptome analyses revealed 1556 differentially expressed genes, including 316 up-regulated and 1240 down-regulated genes, between fish in the hypoxia-treated and control groups. Functional analyses indicated that the main pathway enriched with differentially expressed genes was immune response, followed by energy metabolism and signal transduction. Under hypoxic stress, the transcript levels of genes involved in the NOD-like receptor signaling pathway initially increased rapidly but then decreased over time, suggesting that the NOD-like receptor-mediated immune response plays an essential role in hypoxia tolerance and resistance in hybrid yellow catfish. Our results provide novel insights into which immune-related genes and pathways are activated under hypoxic stress, and reveal details of early adaptation of the immune response and defense mechanisms under hypoxic stress.

15.
FEBS J ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34698446

RESUMO

Mediator is a large modular protein assembly whose function as a coactivator of transcription is conserved in all eukaryotes. The Mediator complex can integrate and relay signals from gene-specific activators bound at enhancers to activate the general transcription machinery located at promoters. It has thus been described as a bridge between these elements during initiation of transcription. Here, we review recent studies on Mediator relating to its structure, gene specificity and general requirement, roles in chromatin architecture as well as novel concepts involving phase separation and transcriptional bursting. We revisit the mechanism of action of Mediator and ultimately put forward models for its mode of action in gene activation.

16.
Oxid Med Cell Longev ; 2021: 6621921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497682

RESUMO

Lung ischemia reperfusion (IR) is known to occur after lung transplantation or cardiac bypass. IR leads to tissue inflammation and damage and is also associated with increased morbidity and mortality. Various receptors are known to partake in activation of the innate immune system, but the downstream mechanism of tissue damage and inflammation is yet unknown. MicroRNAs (miRNAs) are in the forefront in regulating ischemia reperfusion injury and are involved in inflammatory response. Here, we have identified by high-throughput approach and evaluated a distinct set of miRNAs that may play a role in response to IR in rat lung tissue. The top three differentially expressed miRNAs were validated through quantitative PCRs in the IR rat lung model and an in vitro model of IR of hypoxia and reoxygenation exposed type II alveolar cells. Among the miRNAs, miR-18a-5p showed consistent downregulation in both the model systems on IR. Cellular and molecular analysis brought to light a crucial role of this miRNA in ischemia reperfusion. miR-18a-5p plays a role in IR-mediated apoptosis and ROS production and regulates the expression of neuropeptide Galanin. It also influences the nuclear localization of transcription factor: nuclear factor-erythroid 2-related factor (Nrf2) which in turn may regulate the expression of the miR-18a gene. Thus, we have not only established a rat model for lung IR and enumerated the important miRNAs involved in IR but have also extensively characterized the role of miR-18a-5p. This study will have important clinical and therapeutic implications for and during transplantation procedures.

17.
BMC Cardiovasc Disord ; 21(1): 455, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548012

RESUMO

OBJECTIVE: To investigate the relationship between ST-segment resolution (STR) and myocardial scar thickness after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Forty-two STEMI patients with single-branch coronary artery stenosis or occlusion were enrolled. ST-segment elevations were measured at emergency admission and at 24 h after PCI. Late gadolinium-enhanced cardiac magnetic resonance imaging (CMR-LGE) was performed 7 days after PCI to evaluate myocardial scars. Statistical analyses were performed to assess the utility of STR to predict the development of transmural (> 75%) or non-transmural (< 75%) myocardial scars, according to previous study. RESULTS: The sensitivity and specificity of STR for predicting transmural scars were 96% and 88%, respectively, at an STR cut-off value of 40.15%. The area under the curve was 0.925. Multivariate logistic proportional hazards regression analysis disclosed that patients with STR < 40.15% had a 170.90-fold higher probability of developing transmural scars compared with patients with STR ≥ 40.15%. Pearson correlation and linear regression analyses showed STR percentage was significantly associated with myocardial scar thickness and size. CONCLUSION: STR < 40.15% at 24 h after PCI may provide meaningful diagnostic information regarding the extent of myocardial scarification in STEMI patients.

18.
Phys Rev E ; 104(2-1): 024402, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34525609

RESUMO

The concept of a multiplex network can be used to characterize the dispersal paths and states of different species in a patch habitat system. The multiplex network is one of three types of multilayer networks. In this study, the effect of a multiplex network on the long-term stable coexistence of species is investigated using the concept of metapopulation. Based on the mean field approximation, the stability analysis of a two-species system shows that, compared to the single layer network, the multiplex network is more conducive to the stable coexistence of species when one species has a stronger colonization ability. That is, in such a patch habitat system, if the dispersal paths of the stronger species are different than those of the weaker species, then the larger the heterogeneity of the dispersal network of the stronger species is, the more likely the long-term stable coexistence of species. This result provides a different perspective for understanding the biodiversity in heterogeneous habitats.

19.
ACS Sens ; 6(9): 3146-3162, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34516080

RESUMO

Biosensors have been flourishing in the field of drug discovery with pronounced developments in the past few years. They facilitate the screening and discovery of innovative drugs. However, there is still a lack of critical reviews that compare the merits and shortcomings of these biosensors from a pharmaceutical point of view. This contribution presents a critical and up-to-date overview on the recent progress of tailored biosensors, including surface plasmon resonance, fluorescent, photoelectrochemical, and electrochemical systems with emphasis on their mechanisms and applications in drug screening, efficacy assessment, and toxicity evaluation. Multiple functional nanomaterials have also been incorporated into the biosensors. Representative examples of each type of biosensors are discussed in terms of design strategy, response mechanism, and potential applications. In the end, we also compare the results and summarize the major insights gained from the works, demonstrating the challenges and prospects of biosensors-assisted drug discovery.


Assuntos
Técnicas Biossensoriais , Avaliação Pré-Clínica de Medicamentos
20.
Adv Sci (Weinh) ; 8(21): e2101991, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34514733

RESUMO

Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter-organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet-induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose-regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK-ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.

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