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Energy storage devices operating at low temperatures are plagued by sluggish kinetics, reduced capacity, and notorious dendritic growth. Herein, novel potassium dual-ion batteries (PDIBs) capable of superior performance at -60 °C, and fabricated by combining MXenes and polytriphenylamine (PTPAn) as the anode and cathode, respectively, are presented. Additionally, the reason for the anomalous kinetics of K+ (faster at low temperature than at room temperature) on the Ti3C2 anode is investigated. Theoretical calculations, crossover experiments, and in situ XRD at room and low temperatures revealed that K+ tends to bind with solvent molecules rather than anions at subzero temperatures, which not only inhibits the participation of PF6 - in the formation of the solid electrolyte interphase (SEI), but also guarantees co-intercalation behavior and suppresses undesirable K+ storage. The advantageous properties at low temperatures endow the Ti3C2 anode with fast K+ kinetics to unlock the outstanding performance of PDIB at ultralow temperatures. The PDIBs exhibit superior rate capability and high capacity retention at -40 °C and -60 °C. Impressively, after charging-discharging for 20,000â cycles at -60 °C, the PDIB retained 86.7 % of its initial capacity. This study reveals the influence of temperatures on MXenes and offers a unique design for dual-ion batteries operating at ultralow temperatures.
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This study examined low bone mineral density (BMD) prevalence and associated factors among Chinese people living with HIV (PLWH), uncovering a persistent high BMD risk in older individuals, even after adjusting for age and body mass index (BMI). Notably, lopinavir/ritonavir (LPV/r) therapy was linked to reduced BMD, highlighting the imperative need for regular BMD monitoring and interventions in older PLWH. PURPOSE: HIV infection and antiretroviral therapy (ART) have been shown to contribute to lower BMD, resulting in an increased susceptibility to osteopenia and osteoporosis. However, there is limited knowledge about the prevalence of reduced BMD and its associated factors among Chinese PLWH. In this cross-sectional study, we aimed to investigate the prevalence and factors associated with low BMD among PLWH in China. METHODS: We retrospectively enrolled PLWH and non-HIV volunteers who underwent dual-energy X-ray absorptiometry (DXA) scans to measure bone density. Demographic information, laboratory test results, ART regimens, and treatment duration were collected. Univariate and multiple regression analyses were performed to identify factors influencing abnormal bone mass in PLWH. RESULTS: A total of 829 individuals were included in this study, comprising the HIV group (n = 706) and the non-HIV group (n = 123). The prevalence of low BMD among all PLWH was found to be 13.88% (98 out of 706). However, among PLWH aged 50 years and above, the prevalence increased to 65.32% (81 out of 124). In contrast, control subjects in the same age group had a prevalence of 38.21% (47 out of 123). After adjusting for age and BMI, older PLWH still demonstrated a higher prevalence of low BMD compared to the non-HIV group (68.24% vs 34.94%, P < 0.001). Multivariate analysis revealed that older age was strongly associated with a higher risk of low BMD among PLWH, with an odds ratio (OR) of 6.28 for every 10-year increase in age in the ART-naïve population (95% confidence intervals [CIs], 3.12-12.65; P < 0.001) and OR of 4.83 in the ART-experienced population (3.20-7.29, P < 0.001). Within the ART-experienced group, current LPV/r treatment was associated with an increased risk of low BMD (OR = 3.55, 1.24-10.14, P < 0.05), along with lower BMI (OR = 0.84, 0.75-0.95, P < 0.05), and elevated alkaline phosphatase (OR = 1.02, 1.01-1.03, P < 0.01). CONCLUSION: The prevalence of low BMD is higher among PLWH aged 50 years and above compared to non-HIV individuals. The use of LPV/r for ART is associated with reduced BMD. These findings emphasize the importance of regular monitoring of BMD in older PLWH and the need for appropriate interventions to mitigate the risks of osteopenia and osteoporosis in this population.
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Absorciometría de Fotón , Densidad Ósea , Infecciones por VIH , Osteoporosis , Humanos , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Prevalencia , Adulto , China/epidemiología , Estudios Retrospectivos , Osteoporosis/epidemiología , Factores de Riesgo , Anciano , Enfermedades Óseas Metabólicas/epidemiologíaRESUMEN
Understanding the doseâresponse relationship between patient engagement in cognitive behavioral therapy (CBT) and health outcomes is critical for developing and implementing effective CBT programs. In studies of CBT interventions, patient engagement is measured only at a single time point, and outcomes are typically assessed before and after the intervention. Examination of the doseâresponse relationship between patient engagement in CBT and outcomes is limited. It is unclear whether a doseâresponse relationship exists between patient engagement in on-site CBT intervention and anxiety and depression in people living with HIV (PLWH). If present, does this doseâresponse relationship occur early or later in the intervention? This study aimed to address this gap by examining the doseâresponse relationships between patient engagement and anxiety and depression in CBT interventions among PLWH. Utilizing data from a pilot randomized trial (10 participants) and a clinical controlled trial (70 participants), our secondary analysis spans baseline, 3-month, and 6-month assessments. Both trials implemented the nurse-led CBT intervention. Cluster analysis identified two groups based on on-site attendance and WeChat activity. Patients with good adherence (6-10 times) of on-site attendance exhibited significantly lower anxiety and depression scores at 3 months (ß = 1.220, P = 0.047; ß = 1.270, P = 0.019), with no significant differences observed at 6 months. WeChat activity did not significantly influence anxiety or depression scores. The findings highlight a significant short-term doseâresponse relationship, endorsing nurse-led CBT interventions for mental health in PLWH. Organizational strategies should focus on incentivizing and facilitating patient engagement, particularly through enhancing WeChat features.
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Ansiedad , Terapia Cognitivo-Conductual , Depresión , Infecciones por VIH , Participación del Paciente , Humanos , Terapia Cognitivo-Conductual/métodos , Masculino , Femenino , Proyectos Piloto , Depresión/terapia , Participación del Paciente/psicología , Persona de Mediana Edad , Adulto , Infecciones por VIH/psicología , Infecciones por VIH/complicaciones , Infecciones por VIH/terapia , Ansiedad/terapia , Resultado del TratamientoRESUMEN
Sodium layered-oxides (NaxTMO2) sustain severe interfacial stability issues when subjected to battery applications. Particularly at high potential, the oxidation limits including transition metal dissolution and solid electrolyte interphase reformation are intertwined upon the cathode, resulting in poor cycle ability. Herein, by rearranging the complex and structure of the Helmholtz absorption plane adjacent to NaxTMO2 cathodes, the mechanism of constructing stable cathode/electrolyte interphase (CEI) to push up oxidation limits is clarified. The strong absorbent fluorinated anions replace the solvents into the inner Helmholtz plane, thereby reorganizing the Helmholtz absorption structure and spontaneously inducing anion-dominated interphase to envelop more active sites for layered oxides. More importantly, such multi-component CEI proves effective for the long-term durability of a series of manganese-based oxide cathodes, which achieves a 1500-cycles lifetime against high oxidation voltage limit beyond 4.3 V. This work unravels the key role of breaking high-oxidation limits in attaining higher energy density of layered-oxide systems.
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Lysophosphatidic acid (LPA) is a bioactive phospholipid that plays a crucial role in cardiovascular diseases. Here, we question whether LPA contributes to myocardial ischemia/reperfusion (I/R) injury by acting on transient receptor potential vanilloid 1 (TRPV1) in spinal cord. By ligating the left coronary artery to establish an in vivo I/R mouse model, we observed a 1.57-fold increase in LPA level in the cerebrospinal fluid (CSF). The I/R-elevated CSF LPA levels were reduced by HA130, an LPA synthesis inhibitor, compared to vehicle treatment (4.74 ± 0.34 vs. 6.46 ± 0.94 µg/mL, p = 0.0014). Myocardial infarct size was reduced by HA130 treatment compared to the vehicle group (26 ± 8% vs. 46 ± 8%, p = 0.0001). To block the interaction of LPA with TRPV1 at the K710 site, we generated a K710N knock-in mouse model. The TRPV1K710N mice were resistant to LPA-induced myocardial injury, showing a smaller infarct size relative to TRPV1WT mice (28 ± 4% vs. 60 ± 7%, p < 0.0001). Additionally, a sequence-specific TRPV1 peptide targeting the K710 region produced similar protective effects against LPA-induced myocardial injury. Blocking the K710 region through K710N mutation or TRPV1 peptide resulted in reduced neuropeptides release and decreased activity of cardiac sensory neurons, leading to a decrease in cardiac norepinephrine concentration and the restoration of intramyocardial pro-survival signaling, namely protein kinase B/extracellular regulated kinase/glycogen synthase kinase-3ß pathway. These findings suggest that the elevation of CSF LPA is strongly associated with myocardial I/R injury. Moreover, inhibiting the interaction of LPA with TRPV1 by blocking the K710 region uncovers a novel strategy for preventing myocardial ischemic injury.
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Lisofosfolípidos , Daño por Reperfusión Miocárdica , Ratones , Animales , Daño por Reperfusión Miocárdica/prevención & control , Canales Catiónicos TRPV/genética , Péptidos/metabolismo , Médula Espinal/metabolismoRESUMEN
BACKGROUND: Heart failure is associated with a high rate of mortality and morbidity, and ventricular remodeling invariably precedes heart failure. Ventricular remodeling is fundamentally driven by mechanotransduction that is regulated by both the nervous system and the immune system. However, it remains unknown which key molecular factors govern the neuro/immune/cardio axis that underlies mechanotransduction during ventricular remodeling. Here, we investigated whether the mechanosensitive Piezo cation channel-mediated neurogenic inflammatory cascade underlies ventricular remodeling-related mechanotransduction. METHODS: By ligating the left coronary artery of rats to establish an in vivo model of chronic myocardial infarction (MI), lentivirus-mediated thoracic dorsal root ganglion (TDRG)-specific Piezo1 knockdown rats and adeno-associated virus-PHP.S-mediated TDRG neuron-specific Piezo1 knockout mice were used to investigate whether Piezo1 in the TDRG plays a functional role during ventricular remodeling. Subsequently, neutralizing antibody-mediated TDRG IL-6 (interleukin-6) inhibition rats and adeno-associated virus-PHP.S-mediated TDRG neuron-specific IL-6 knockdown mice were used to determine the mechanism underlying neurogenic inflammation. Primary TDRG neurons were used to evaluate Piezo1 function in vitro. RESULTS: Expression of Piezo1 and IL-6 was increased, and these factors were functionally activated in TDRG neurons at 4 weeks after MI. Both knockdown of TDRG-specific Piezo1 and deletion of TDRG neuron-specific Piezo1 lessened the severity of ventricular remodeling at 4 weeks after MI and decreased the level of IL-6 in the TDRG or heart. Furthermore, inhibition of TDRG IL-6 or knockdown of TDRG neuron-specific IL-6 also ameliorated ventricular remodeling and suppressed the IL-6 cascade in the heart, whereas the Piezo1 level in the TDRG was not affected. In addition, enhanced Piezo1 function, as reflected by abundant calcium influx induced by Yoda1 (a selective agonist of Piezo1), led to increased release of IL-6 from TDRG neurons in mice 4 weeks after MI. CONCLUSIONS: Our findings point to a critical role for Piezo1 in ventricular remodeling at 4 weeks after MI and reveal a neurogenic inflammatory cascade as a previously unknown facet of the neuronal immune signaling axis underlying mechanotransduction.
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Inflamación , Canales Iónicos , Infarto del Miocardio , Remodelación Ventricular , Animales , Masculino , Ratones , Ratas , Modelos Animales de Enfermedad , Ganglios Espinales/metabolismo , Inflamación/metabolismo , Inflamación/patología , Interleucina-6/metabolismo , Interleucina-6/genética , Canales Iónicos/metabolismo , Canales Iónicos/genética , Mecanotransducción Celular , Ratones Noqueados , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Neuronas/metabolismo , Neuronas/patología , Ratas Sprague-Dawley , Remodelación Ventricular/genética , Remodelación Ventricular/fisiologíaRESUMEN
Ischemic stroke is a serious disease posing significant threats to human health and life, with the highest absolute and relative risks of a poor prognosis following the first occurrence, and more than 90% of strokes are attributable to modifiable risk factors. Currently, machine learning (ML) is widely used for the prediction of ischemic stroke outcomes. By identifying risk factors, predicting the risk of poor prognosis and thus developing personalized treatment plans, it effectively reduces the probability of poor prognosis, leading to more effective secondary prevention. This review includes 41 studies since 2018 that used ML algorithms to build prognostic prediction models for ischemic stroke, transient ischemic attack (TIA), and acute ischemic stroke (AIS). We analyzed in detail the risk factors used in these studies, the sources and processing methods of the required data, the model building and validation, and their application in different prediction time windows. The results indicate that among the included studies, the top five risk factors in terms of frequency were cardiovascular diseases, age, sex, national institutes of health stroke scale (NIHSS) score, and diabetes. Furthermore, 64% of the studies used single-center data, 65% of studies using imbalanced data did not perform data balancing, 88% of the studies did not utilize external validation datasets for model validation, and 72% of the studies did not provide explanations for their models. Addressing these issues is crucial for enhancing the credibility and effectiveness of the research, consequently improving the development and implementation of secondary prevention measures.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Estados Unidos , Humanos , Prevención Secundaria , Accidente Cerebrovascular/prevención & control , Factores de Riesgo , Aprendizaje AutomáticoRESUMEN
Skin wounds are repaired by a complex series of events and overlapping phases in which bacterial infection and insufficient angiogenesis at the wound site delay the healing process. Thus, functional wound dressings with enhanced antibacterial activity and angiogenic capacity have attracted attention. Herein, bacterial cellulose (BC)-based dressings were successfully fabricated by functionalization with a polydopamine (PDA) coating and copper sulfide nanoparticles (CuS NPs). Under 808 nm laser illumination, the BC/PDA/CuS composite membranes exhibited outstanding adjustable photothermal and photodynamic activities as well as controlled Cu2+ release, endowing the composite membranes with synergetic antibacterial activity. Specially, a bactericidal efficiency of 99.7 % and 88.0 % for Staphylococcus aureus and Escherichia coli was achieved after treatment with BC/PDA/CuS5 sample under NIR irradiation (0.8 W/cm2, 10 min), respectively. Moreover, the BC/PDA/CuS5 composite membrane could enhance the angiogenesis due to the released Cu2+. In vivo experiments revealed that the BC/PDA/CuS5 composite membrane dressing could accelerate the wound closure process of the full-thickness skin defects with S. aureus by synergistically reducing inflammation, enhancing collagen deposition, and promoting vascularization under NIR irradiation. Additionally, the BC/PDA/CuS5 composite membrane exhibited high biocompatibility and biosafety. This work offers a new strategy to prepare multifunctional BC-based dressing for clinical wound healing.
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Celulosa , Staphylococcus aureus , Celulosa/farmacología , Cobre/farmacología , Antibacterianos/farmacología , Vendajes , HidrogelesRESUMEN
As a recently discovered waste removal system in the brain, cerebral lymphatic system is thought to play an important role in regulating the homeostasis of the central nervous system. Currently, more and more attention is being focused on the cerebral lymphatic system. Further understanding of the structural and functional characteristics of cerebral lymphatic system is essential to better understand the pathogenesis of diseases and to explore therapeutic approaches. In this review, we summarize the structural components and functional characteristics of cerebral lymphatic system. More importantly, it is closely associated with peripheral system diseases in the gastrointestinal tract, liver, and kidney. However, there is still a gap in the study of the cerebral lymphatic system. However, we believe that it is a critical mediator of the interactions between the central nervous system and the peripheral system.
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Sistema Nervioso Central , Sistema Linfático , Encéfalo/fisiología , HomeostasisRESUMEN
Dichloroacetate (DCA) is an investigational drug used to treat lactic acidosis and malignant tumours. It works by inhibiting pyruvate dehydrogenase kinase and increasing the rate of glucose oxidation. Some studies have documented the neuroprotective benefits of DCA. By reviewing these studies, this paper shows that DCA has multiple pharmacological activities, including regulating metabolism, ameliorating oxidative stress, attenuating neuroinflammation, inhibiting apoptosis, decreasing autophagy, protecting the bloodâbrain barrier, improving the function of endothelial progenitor cells, improving mitochondrial dynamics, and decreasing amyloid ß-protein. In addition, DCA inhibits the enzyme that metabolizes it, which leads to peripheral neurotoxicity due to drug accumulation that may be solved by individualized drug delivery and nanovesicle delivery. In summary, in this review, we analyse the mechanisms of neuroprotection by DCA in different diseases and discuss the causes of and solutions to its adverse effects.
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Enfermedades Metabólicas , Neoplasias , Enfermedades del Sistema Nervioso , Fármacos Neuroprotectores , Humanos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Péptidos beta-Amiloides , Neoplasias/tratamiento farmacológicoRESUMEN
Objective: Diabetes mellitus (DM) implicates oxidative stress, apoptosis, and inflammation, all of which may contribute liver injury. Aerobic exercise is assured to positively regulate metabolism in the liver. This project was designed to investigate whether and how aerobic exercise improves DM-induced liver injury. Methods: Seven-week-old male db/db mice and age-matched m/m mice were randomly divided into a rest control group or a group that received 12 weeks of aerobic exercise by treadmill training (10 m/min). Haematoxylin and eosin (HE) staining, electron microscopy, Oil Red O staining and TUNEL assays were used to evaluate the histopathological changes in mouse liver. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TRIG), cholesterol (CHOL) were analyzed by serum biochemical analysis. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed via ELISA. Nuclear factor E2-associated factor-2 (Nrf2), nuclear factor κB (NF-κB) and JAK2/STAT3 pathway-related proteins were measured by immunofluorescence, Western blotting and q-PCR. F4/80 expression in liver tissues was assessed by immunohistochemistry. Results: In diabetic mice, exercise training significantly decreased the levels of serum TRIG, CHOL, IL-6, TNF-α, ALT and AST; prevented weight gain, hyperglycaemia, and impaired glucose and insulin tolerance. Morphologically, exercise mitigated the diabetes-induced increase in liver tissue microvesicles, inflammatory cells, F4/80 (macrophage marker) levels, and TUNEL-positive cells. In addition, exercise reduced the apoptosis index, which is consistent with the results for caspase-3 and Bax. Additionally, exercise significantly increased SOD activity, decreased MDA levels, activated Nrf2 and decreased the expression of NF-kB, phosphorylated JAK2 and STAT3 proteins in the livers of diabetic mice. Conclusion: This study demonstrated that aerobic exercise reversed liver dysfunction in db/db mice with T2DM by reducing oxidative stress, apoptosis and inflammation, possibly by enhancing Nrf2 expression and inhibiting the JAK2/STAT3 cascade response.
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An asymmetric wound dressing acts as a skin-like structure serves as a protective barrier between a wound and its surroundings. It allows for the absorption of tissue fluids and the release of active substances at the wound site, thus speeding up the healing process. However, the production of such wound dressings requires the acquisition of specialized tools, expensive polymers, and solvents that contain harmful byproducts. In this study, an asymmetric bacterial cellulose (ABC) wound dressing using starch as a porogen has been developed. By incorporating silver-metal organic frameworks (Ag-MOF) and curcumin into the ABC membrane, the wound dressing gains antioxidant, reactive oxygen species (ROS) scavenging, and anti-bacterial activities. Compared to BC-based wound dressings, this dressing promotes efficient dissolution and controlled release of curcumin and silver ions. In a full-thickness skin defect model, wound dressing not only inhibits the growth of bacteria on infected wounds but also regulates the release of curcumin to reduce inflammation and promote the production of epithelium, blood vessels, and collagen. Consequently, this dressing provides superior wound treatment compared to BC-based dressing.
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Curcumina , Plata , Plata/química , Curcumina/farmacología , Curcumina/química , Antibacterianos/farmacología , Antibacterianos/química , Cicatrización de Heridas , Celulosa/química , Antiinflamatorios/farmacologíaRESUMEN
STUDY DESIGN: This was a primary research study. OBJECTIVE: A risk nomogram was established and externally validated by exploring the related risk factors for delayed incision healing in patients undergoing open posterior lumbar surgery. SUMMARY OF BACKGROUND DATA: The use of a nomogram model to predict prognosis in patients with delayed incision healing is an evolving field given the complex presentation of patients with this condition. PATIENTS AND METHODS: This study reviewed 954 patients with data collected from January 2017 to December 2021 who were randomized into a training set and a validation set (7:3). We built a prediction model based on a training set of 616 patients. The "least absolute shrinkage and selection operator" regression model was applied to screen out the optimal prediction features, and binary logistic regression was used to develop a prediction model. The discrimination, calibration, and clinical applicability of the prediction model were assessed by using the area under the curve, C -index, calibration curve, and decision curve analysis. RESULTS: Postoperative delayed incision healing occurred in 214 (24.4%) patients. The least absolute shrinkage and selection operator regression model showed that smoking, white blood cell count, infection, diabetes, and obesity were involved in delayed incision healing ( P ≠ 0). A binary logistic regression model confirmed that smoking [odds ratio (OR) = 3.854, 95% CI: 1.578~9.674, P = 0.003], infection (OR = 119.524, 95% CI: 59.430~263.921, P < 0.001), diabetes (OR = 3.935, 95% CI: 1.628~9.703, P = 0.003), and obesity (OR = 9.906, 95% CI: 4.435~23.266, P < 0.001) were predictors of delayed incision healing, and a nomogram model was established. The area under the curve was 0.917 (95% CI: 0.876-0.959). The calibration curve showed good consistency. Decision curve analysis showed that when the risk threshold of delayed incision healing was >5%, the use of this nomogram was more clinically valuable. CONCLUSIONS: Smoking, infection, diabetes, and obesity are risk factors for delayed incision healing. The nomogram model could be used to predict the risk of delayed incision healing and could provide a reference for early clinical intervention.
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Diabetes Mellitus , Nomogramas , Humanos , Estudios Retrospectivos , Fumar , ObesidadRESUMEN
Objectives: With the prolongation of life span and increasing incidence of comorbidities, polypharmacy has become a challenge for people living with HIV/AIDS (PLWH). This review aimed to identify barriers and facilitators to maintaining a high level of polypharmacy adherence in people living with HIV/AIDS. Methods: Nine electronic databases were searched for studies from 1996 to October 2021. Studies were included if they were conducted with adults living with HIV/AIDS and reported barriers and facilitators to maintaining a high level of polypharmacy adherence. This review presents a conceptual framework model to help understand the barriers and facilitators. Results: Twenty-nine studies were included. The majority of publications were observational studies. Eighty specific factors were identified and further divided into five categories, including individual factors, treatment-related factors, condition-related factors, healthcare provider-related factors, and socioeconomic factors, based on the multidimensional adherence model (MAM). Conclusion: Eighty factors associated with polypharmacy adherence among people living with HIV/AIDS were identified and grouped into five major categories. Healthcare providers can make decisions based on the five categories of relevant factors described in this paper when developing interventions to enhance polypharmacy adherence. It is recommended that medications be evaluated separately and that an overall medication evaluation be conducted at the same time to prevent inappropriate polypharmacy use.
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BACKGROUND: Neuromyelitis optica (NMO) is a severe neurological demyelinating autoimmune disease affecting the optic nerves and spinal cord. The binding of neuromyelitis optica immunoglobulin G (NMO- IgG) and aquaporin-4 (AQP4) on the surface of astrocytes in the serum and cerebrospinal fluid is the main pathogenesis of NMO. Currently, therapeutic strategies for NMO include a reduction of the secondary inflammation response and the number of NMO-IgG, which can only alleviate clinical symptoms rather than fundamentally preventing a series of pathological processes caused by NMO-IgG binding to AQP4. OBJECTIVE: The purpose of this study was to investigate the blocking effect of melanthioidine on the binding of NMO-IgG to AQP4 and its potential cytotoxicity. METHODS: The current study developed a cell-based high-throughput screening approach to identify a molecular blocker of NMO-IgG binding to AQP4 using the Chinese hamster lung fibroblast (V79) cells expressing M23- AQP4. By screening ~400 small molecules, we identified melanthioidine with blocking effects without affecting AQP4 expression or its water permeability. RESULTS: Melanthioidine effectively blocked the binding of NMO-IgG to AQP4 in immunofluorescence assays and reduced complement-dependent cytotoxicity against both NMO-IgG/complement-treated Fischer rat thyroid- AQP4 cells and primary astrocytes. The docking computations identified the putative sites of blocker binding at the extracellular surface of AQP4. CONCLUSION: This study serves as proof of a potential NMO therapy by using a small-molecule blocker to target NMO pathogenesis.
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Neuromielitis Óptica , Ratas , Animales , Cricetinae , Neuromielitis Óptica/tratamiento farmacológico , Neuromielitis Óptica/patología , Inmunoglobulina G/farmacología , Acuaporina 4/metabolismo , Médula Espinal/metabolismo , Cricetulus , Astrocitos/metabolismo , AutoanticuerposRESUMEN
BACKGROUND: Anoctamin-1 (ANO1) was identified as an unfavorable prognostic marker in pancreatic cancer. However, the exact implication of ANO1 in pancreatic cancer is still poorly understood. Here we investigated the effect of ANO1 in pancreatic cancer progression under the context of oncogenic KRAS, aiming at finding a new therapeutic target. METHODS: Knockdown and overexpression of oncogenic KRAS as well as ANO1 in PDAC cell lines were performed by lentivirus infection. Cell proliferation and migration assay, RNA seq analysis were performed in PDAC cells bearing different status of ANO1 and KRAS. In vivo mice model was used to investigate the xenograft tumor growth with different status of KRAS and ANO1. RESULTS: Our results showed that ANO1 expression level is elevated in poorly differentiated cancer cells. Overexpression of ANO1 in PDAC cancer cells was found to promote cancer cell proliferation in vitro and in vivo, which synergized with the introduction of oncogenic KRAS. Consistently, knockdown of ANO1 expression was found to suppress cancer growth in vitro and in vivo. RNA seq analysis revealed that the observed synergistic cancer-promoting effect from ANO1 and oncogenic KRAS is likely due to concurrent activating key genes involved in lipid metabolism including HMGCS1. CONCLUSION: The outcome from our study suggests that ANO1 plays an important role in promoting pancreatic cancer development, especially at the presence of oncogenic KRAS. Considering the prevalence of KRAS mutation in pancreatic cancer patients, suppression ANO1 may represent a potential effective therapeutic measure in pancreatic cancer treatment.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animales , Ratones , Carcinoma Ductal Pancreático/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Anoctamina-1/genética , Neoplasias Pancreáticas/metabolismo , Proliferación Celular/genética , Línea Celular Tumoral , Proteínas de Neoplasias/metabolismo , Neoplasias PancreáticasRESUMEN
Objective: The aim of tissue engineering (TE) is to replace the damaged tissues or failed organs, or restore their missing functions. The important means to achieve this aim is to integrate biomaterials and life elements. Hydrogels are very attractive biomaterials in the field of TE. In particular, engineering extracellular matrices (ECMs) formed by photosensitive hydrogels have captivated much attention, because photopolymerization has many advantages over traditional polymerization approaches, such as rapidity of reaction, spatiotemporal controllability of polymerization process, and operability at physiological temperature, especially it can realize the fabrications of engineering ECMs in the presence of living cells. There have been many excellent reviews on the applications of photosensitive hydrogels in TE in recent years, however, it is inevitable that researchers may have left out many important facts due to exploring the literature from one or a few aspects. It is also a great challenge for researchers to explore the internal relationships among countries, institutions, authors, and references from a large number of literatures in related fields. Therefore, bibliometrics may be a powerful tool to solve the above problems. A bibliometric and visualized analysis of publications concerning the photosensitive hydrogels for TE applications was performed, and the knowledge domain, research hotspots and frontiers in this topic were identified according to the analysis results. Methods: We identified and retrieved the publications regarding the photosensitive hydrogels for TE applications between 1996 and 2022 from Web of Science Core Collection (WoSCC). Bibliometric and visualized analysis employing CiteSpace software and R-language package Bibliometrix were performed in this study. Results: 778 publications meeting the eligibility criteria were identified and retrieved from WoSCC. Among those, 2844 authors worldwide participated in the studies in this field, accompanied by an average annual article growth rate of 15.35%. The articles were co-authored by 800 institutions from 46 countries/regions, and the United States published the most, followed by China and South Korea. As the two countries that published the most papers, the United States and China could further strengthen cooperation in this field. Univ Colorado published the most articles (n = 150), accounting for 19.28% of the total. The articles were distributed in 112 journals, among which Biomaterials (n = 66) published the most articles, followed by Acta Biomaterialia (n = 54) and Journal of Biomedical Materials Research Part A (n = 42). The top 10 journals published 47.8% of the 778 articles. The most prolific author was Anseth K (n = 33), followed by Khademhosseini A (n = 29) and Bryant S (n = 22). A total of 1443 keywords were extracted from the 778 articles and the keyword with the highest centrality was "extracellular matrix" (centrality: 0.12). The keywords appeared recently with strong citation bursts were "gelatin", "3d printing" and "3d bioprinting", representing the current research hotspots in this field. "Gelma", "3d printing" and "thiol-ene" were the research frontiers in recent years. Conclusion: This bibliometric and visualized study offered a comprehensive understanding of publications regarding the photosensitive hydrogels for TE applications from 1996 to 2022, including the knowledge domain, research hotspots and frontiers in this filed. The outcome of this study would provide insights for scholars in the related research filed.
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Astrocytes play a key role in the response to injury and noxious stimuli, but its role in myocardial ischemia-reperfusion (I/R) injury remains largely unknown. Here we determined whether manipulation of spinal astrocyte activity affected myocardial I/R injury and the underlying mechanisms. By ligating the left coronary artery to establish an in vivo I/R rat model, we observed a 1.7-fold rise in glial fibrillary acidic protein (GFAP) protein level in spinal cord following myocardial I/R injury. Inhibition of spinal astrocytes by intrathecal injection of fluoro-citrate, an astrocyte inhibitor, decreased GFAP immunostaining and reduced infarct size by 29% relative to the I/R group. Using a Designer Receptor Exclusively Activated by Designer Drugs (DREADD) chemogenetic approach, we bi-directionally manipulated astrocyte activity employing GFAP promoter-driven Gq- or Gi-coupled signaling. The Gq-DREADD-mediated activation of spinal astrocytes caused transient receptor potential vanilloid 1 (TRPV1) activation and neuropeptide release leading to a 1.3-fold increase in infarct size, 1.2-fold rise in serum norepinephrine level and higher arrhythmia score relative to I/R group. In contrast, Gi-DREADD-mediated inhibition of spinal astrocytes suppressed TRPV1-mediated nociceptive signaling, resulting in 35% reduction of infarct size and 51% reduction of arrhythmia score from I/R group, as well as lowering serum norepinephrine level from 3158 ± 108 to 2047 ± 95 pg/mL. Further, intrathecal administration of TRPV1 or neuropeptide antagonists reduced infarct size and serum norepinephrine level. These findings demonstrate a functional role of spinal astrocytes in myocardial I/R injury and provide a novel potential therapeutic approach targeting spinal cord astrocytes for the prevention of cardiac injury.
Asunto(s)
Daño por Reperfusión Miocárdica , Ratas , Animales , Daño por Reperfusión Miocárdica/metabolismo , Astrocitos/metabolismo , Médula Espinal/metabolismo , Arritmias Cardíacas , Infarto/metabolismo , NorepinefrinaRESUMEN
BACKGROUND: Opioid-reduced anesthesia may accelerate postoperative rehabilitation by reducing opioid-related side effects. The objective was to investigate the feasibility of opioid-reduced general anesthesia based on esketamine and to observe postoperative nausea and vomiting (PONV), postoperative pain, hemodynamics and other adverse reactions in gynecological day surgery compared with the traditional opioid-based anesthesia program. METHOD: This study was conducted as a prospective parallel-group randomized controlled trial. A total of 141 adult women undergoing gynecological day surgery were included. Patients were randomly assigned to receive traditional opioid-based anesthesia (Group C) with alfentanil, or opioid-reduced anesthesia (a moderate-opioid group (Group MO) and low-opioid group (Group LO) with esketamine and alfentanil). For anesthesia induction, the three groups received 20, 20, 10 µg/kg alfentanil respectively and Group LO received an additional 0.2 mg/kg esketamine. For maintenance of anesthesia, the patients in Group C received 40 µg/kg/h alfentanil, and those in Group MO and Group LO received 0.5 mg/kg/h esketamine. RESULTS: Patients in the three groups had comparable clinical and surgical data. A total of 33.3% of patients in Group C, 18.4% of patients in Group MO and 43.2% of patients in Group LO met the primary endpoint (p = 0.033), and the incidence of nausea within 24 hours after surgery in Group MO was lower than in Group LO (p < 0.05). The extubation time, median length of stay in the hospital after surgery and visual analog scale (VAS) of postoperative pain were equivalent in the three groups. The frequencies of adverse hemodynamic events in the MO 1(0, 2) and LO 0(0, 1) groups were significantly decreased (p < 0.05). Compared with Group C, the median length of stay in the postanesthesia care unit (PACU) in Group LO was increased, 60.0 (36.25, 88.75) vs. 42.5 (25, 73.75) minutes (p < 0.05). CONCLUSIONS: Opioid-reduced anesthesia based on esketamine is feasible and provides effective analgesia for patients. Esketamine provided a positive analgesic effect and the opioid-reduced groups showed more stable hemodynamics. However, less or no use of opioids did not result in a more comfortable prognosis. TRIAL REGISTRATION: This study was registered at Chictr.org.cn (NO. ChiCTR2100053153 ); November 13, 2021.