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1.
Medicine (Baltimore) ; 100(24): e26276, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128860

RESUMO

ABSTRACT: The aim of the case study is to examine the association between hypertension and the level of bone metabolism markers in newly diagnosed osteoporotic patients.A cross-sectional study of 518 subjects was done to see the association between hypertension and the level of osteocalcin (OC), bone-specific alkaline phosphatase (B-ALP), Tartrate-resistant acid phosphatase (TRAP.5B), and 25-hydroxy vitamin D (25-OHD). There were 243 (46.9%) osteoporosis patients with hypertension. Both univariate and multivariate analysis have suggested that lower OC and 25-OHD levels were associated with hypertension. The potential confounders-adjusted OC level was significantly lower in hypertensive female group than that in the female without hypertension group [ß = -0.20, 95% confidence interval (95% CI) = -0.37 to -0.03, P = .02 in final adjust model]. The potential confounders-adjusted 25-OHD level was significantly lower in hypertensive male group than that in male without hypertension group (ß = -0.34, 95% CI = -0.58 to -0.10, P = .01 in final adjust model). The B-ALP and TRACP.5B levels were positively associated with hypertension in all patients or subgroup analysis. However, all the correlations had no statistical significance for the B-ALP and TRACP.5B.In conclusion, the hypertension was associated with low level of OC and 25-OHD. Hypertension probably led to low bone turnover, which may be one of the mechanisms of hypertension-related osteoporosis.

2.
Clin Transl Med ; 11(4): e390, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33931967

RESUMO

BACKGROUND: Ferroptosis is essential to regulate tumor growth and serves as a promising therapeutic target to lung cancer. Ubiquitin-specific protease 35 (USP35) belongs to the deubiquitinases family that is associated with cell proliferation and mitosis. In this research, we aim to elucidate the potential role and molecular basis of USP35 in lung cancer. METHODS: Lung cancer cells were infected with lentiviral vectors to silence or overexpress USP35. Cell viability, colony formation, lipid reactive oxygen species production, intracellular iron metabolism, and other ferroptotic markers were detected. The role of USP35 on ferroptosis and tumor progression were also tested in mouse tumor xenograft models in vivo. RESULTS: USP35 was abundant in human lung cancer tissues and cell lines. USP35 knockdown promoted ferroptosis, and inhibited cell growth, colony formation, and tumor progression in lung cancer cells. USP35 overexpression did not affect tumorigenesis and ferroptosis under basal conditions, but reduced erastin/RSL3-triggered iron disturbance and ferroptosis, thereby facilitating lung cancer cell growth and tumor progression. Further studies determined that USP35 directly interacted with ferroportin (FPN) and functioned as a deubiquitinase to maintain its protein stability. More importantly, we observed that USP35 knockdown sensitized lung cancer cells to cisplatin and paclitaxel chemotherapy. CONCLUSION: USP35 modulates ferroptosis in lung cancer via targeting FPN, and it is a promising therapeutic target to lung cancer.

3.
BMC Vet Res ; 17(1): 200, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34049549

RESUMO

BACKGROUND: Highly pathogenic avian influenza viruses (HPAIVs) of H5 subtype pose a great threat to the poultry industry and human health. In recent years, H5N6 subtype has rapidly replaced H5N1 as the most predominate HPAIV subtype circulating in domestic poultry in China. In this study, we describe the genetic and phylogenetic characteristics of a prevalent H5N6 strain in Guangdong, China. RESULTS: Nucleotide sequencing identified a H5N6 subtype HPAIV, designated as A/chicken/Dongguan/1101/2019 (DG/19), with a multibasic cleavage site in the hemagglutinin (HA). Phylogenetic analysis revealed DG/19 was a reassortant of H5N1, H5N2, H5N8, and H6N6 subtypes of avian influenza viruses. A number of mammalian adaptive markers such as D36N in the HA were identified. CONCLUSIONS: Our results showed that HPAIV H5N6 strains still emerge in well-managed groups of chicken farms. Considering the increasing prevalence of H5N6 HPAIV, and the fact that H5N6 HPAIVs are well adapted to migratory birds, an enhanced surveillance for the East Asian-Australasian flyway should be undertaken to prevent potential threats to the poultry industry and human health.

4.
J Biotechnol ; 334: 26-34, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34019962

RESUMO

Production of bio-based chemicals from renewable bioresource is a key driver for moving towards sustainable industry. Furfurylamine is known as an important furfural-upgrading product in organic synthesis, as well as monolithic synthetic pharmaceuticals, fibers, additives and polymers. In one-pot manner, biomass was tandemly catalyzed to furfurylamine with sulfonated Sn-PL catalyst and recombinant ω-transaminase biocatalyst. Sn-PL (2.4 wt%) catalyzed bamboo shoot shell, corncob and rice straw (75.0 g/L) to 76.5-113.0 mM furfural at 44.7-58.5 % yield in γ-valerolactone-water (2:8, v:v) at 170 ℃. The obtained biomass slurries containing furfural were biotransformed to furfurylamine at high yield (0.39-0.42 g furfurylamine/g xylan in biomass) with ω-transaminase biocatalyst using isopropylamine (3.0 mol isopropylamine/mol furfural) as amine donor at 35 ℃. Such a chemoenzymatic one-pot process combined the advantages of both solid acids and whole-cells catalysts, which provided an efficient and sustainable approach for preparing an important bio-based furan chemical furfurylamine.

5.
J Colloid Interface Sci ; 601: 70-77, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34058553

RESUMO

In this work, we introduced a fullerene acceptor (PC71BM) into the binary photo-active layer based on a polymer donor (PM6) and a non-fullerene small molecular acceptor (BTP-BO-4Cl), and as a consequence, the ternary organic solar cells realized a high-power conversion efficiency of 17.39% compared to 16.65% in binary solar cells. The performance enhancement was found to be due to the optimized morphology and hence balanced hole and electron mobilities, which is responsible for the suppressed charge recombination and hence high photocurrent in solar cells. In addition, PC71BM shows the complementary absorption with PM6 and BTP-BO-4Cl, which can broaden the absorption range of the photo-active layer and hence more photons from the sunlight can be utilized. Besides, PC71BM shows the cascade energy level alignment between PM6 and BTP-BO-4Cl, which is helpful for charge transfer from donor to acceptor. All these merits explain the high performance in ternary solar cells, and also demonstrate that ternary photovoltaics adopting non-fullerene acceptor with the fullerene acceptor as small amount of additive is an efficient strategy to gain high performing organic solar cells.

6.
Microbiome ; 9(1): 117, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016169

RESUMO

BACKGROUND: There is general consensus that consumption of dietary fermentable fiber improves cardiometabolic health, in part by promoting mutualistic microbes and by increasing production of beneficial metabolites in the distal gut. However, human studies have reported variations in the observed benefits among individuals consuming the same fiber. Several factors likely contribute to this variation, including host genetic and gut microbial differences. We hypothesized that gut microbial metabolism of dietary fiber represents an important and differential factor that modulates how dietary fiber impacts the host. RESULTS: We examined genetically identical gnotobiotic mice harboring two distinct complex gut microbial communities and exposed to four isocaloric diets, each containing different fibers: (i) cellulose, (ii) inulin, (iii) pectin, (iv) a mix of 5 fermentable fibers (assorted fiber). Gut microbiome analysis showed that each transplanted community preserved a core of common taxa across diets that differentiated it from the other community, but there were variations in richness and bacterial taxa abundance within each community among the different diet treatments. Host epigenetic, transcriptional, and metabolomic analyses revealed diet-directed differences between animals colonized with the two communities, including variation in amino acids and lipid pathways that were associated with divergent health outcomes. CONCLUSION: This study demonstrates that interindividual variation in the gut microbiome is causally linked to differential effects of dietary fiber on host metabolic phenotypes and suggests that a one-fits-all fiber supplementation approach to promote health is unlikely to elicit consistent effects across individuals. Overall, the presented results underscore the importance of microbe-diet interactions on host metabolism and suggest that gut microbes modulate dietary fiber efficacy. Video abstract.


Assuntos
Microbioma Gastrointestinal , Animais , Dieta , Fibras na Dieta , Vida Livre de Germes , Inulina , Camundongos
7.
Biomater Sci ; 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34019044

RESUMO

To overcome drug resistance in hypoxic tumors and the limitations of radiation impedance and radiation dose, we developed a nano-radiosensitizer to improve the efficacy of cancer radiotherapy. We used multifunctional mesoporous silica nanoparticles (MSNs) as the carriers for a novel anticancer selenadiazole derivative (SeD) and modified its surface with folic acid (FA) to enhance its cervical cancer-targeting effects, forming the nanosystem named SeD@MSNs-FA. Upon radiation, SeD@MSNs-FA inhibits the growth of cervical cancer cells by inducing apoptosis through the death receptor-mediated apoptosis pathway and S phase arrest, significantly improving the sensitivity of cervical cancer cells to X-ray radiation. The combined activity of SeD@MSN-FA and radiation can promote excessive production of intracellular reactive oxygen species (ROS) and induce cell apoptosis by affecting p53, protein kinase B (AKT), and mitogen-activated protein kinase (MAPK) pathways. Furthermore, SeD@MSNs-FA can effectively inhibit tumor growth of xenografted HeLa tumors in nude mice. The toxicity analysis of SeD@MSNs-FA nanoparticles in vivo and the histological analysis performed in the mouse model showed that under the current experimental conditions, the nanoparticles induced no significant damage to the heart, liver, spleen, lungs, kidneys, or other major organs. Taken together, this study provides a translational nanomedicine-based strategy for the simultaneous chemo- and radiotherapy of cervical cancer and sheds light on potential mechanisms that can be used to overcome radiotherapeutic resistance.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34006102

RESUMO

Achieving a high-energy charge-transfer state (ECT) and concurrently reduced energy loss is of vital importance in boosting the open-circuit voltage (Voc) of organic solar cells (OSCs), but it is difficult to realize. We report herein a novel design tactic to achieve this goal by incorporating a three-dimensional (3D) shape-persistent norbornenyl group into the terminals of acceptor-donor-acceptor-type nonfullerene acceptors (NFAs). Compared with ITIC-based OSCs, norbornenyl-fused 1,1-dicyanomethylene-3-indanone (CBIC) terminals endow IDTT-CBIC-based OSCs with simultaneously higher ECT and lower radiative and non-radiative voltage loss, hence enhancing Voc by 90 mV. CBIC also improves the miscibility and modulates the molecular packing structures for efficient charge carrier transport and a better short-circuit current density in IDTT-CBIC-based OSCs. Consequently, the power conversion efficiency is improved by 22%, compared to that of the OSC based on ITIC. Furthermore, the effectiveness of the use of CBIC as the terminals is observed using different electron-donating cores. The utilization of the 3D shape-persistent building blocks represents a breakthrough in the design strategies for terminal groups toward efficient NFA-based OSCs with high Voc.

9.
Preprint | bioRxiv | ID: ppbiorxiv-443228

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.

10.
J Neuroinflammation ; 18(1): 85, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33810797

RESUMO

BACKGROUND: Prenatal synthetic glucocorticoid (sGC) exposure increases the susceptibility to cognitive and affective disorders in postnatal life. We previously demonstrated that prenatal sGC exposure results in an increase in corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) expression in the hippocampus of rats, and CRHR1 is involved in synapse formation via regulation of C-X-C chemokine ligand 5 (CXCL5) in hippocampus. We sought to investigate that the roles of CRHR1 and CXCL5 in learning and memory impairment caused by prenatal sGC exposure. METHODS: Pregnant rats were administered with saline or dexamethasone (DEX) from gestational day (GD) 14 to GD21. DEX offspring at 2-day old were treated with saline and CRHR1 antagonists (antalarmin and CP154526) for 7 days. Some DEX offspring received intra-hippocampal injection of AAV9 carrying CXCL5 gene. Spatial learning and memory was assessed by Morris water maze test. Immunofluorescence analysis was applied to show synapsin I and PSD95 signals in hippocampus. Synapsin I and PSD95 protein level and CXCL5 concentration were determined by western blotting and ELISA, respectively. Organotypic hippocampal slice cultures were used to investigate the effect of DEX on CXCL5 production in vitro. RESULTS: Both male and female DEX offspring displayed impairment of spatial learning and memory in adulthood. Synapsin I and PSD95 signals and CXCL5 levels were decreased in DEX offspring. DEX offspring with antalarmin and CP154526 treatment showed improved spatial learning and memory. Antalarmin and CP154526 treatment increased synapsin I and PSD95 signals and CXCL5 concentration in hippocampus. Bilaterally hippocampal injection of AAV9 carrying CXCL5 gene improved the spatial learning and memory and increased CXCL5 concentration and synapsin I and PSD95 levels in hippocampus. DEX dose-dependently suppressed CXCL5 production in cultured hippocammpal slices, which was prevented by antalarmin treatment. CONCLUSION: CRHR1 and CXCL5 signaling in the hippocampus are involved in spatial learning and memory deficits caused by prenatal DEX exposure. CRHR1 activation contributes to decreased CXCL5 production in hippocampus induced by prenatal DEX treatment. Our study provides a molecular basis of prenatal GC exposure programming spatial learning and memory.

11.
Exp Biol Med (Maywood) ; : 15353702211011052, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926259

RESUMO

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.

12.
Chem Commun (Camb) ; 57(35): 4243-4246, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33913972

RESUMO

Commercial sodium citrate is proposed as the self-sacrificial cathode additive for the first time to offset the initial sodium loss. The optimum additive can obviously increase the energy density of the as-constructed hard carbon//Na3V2(PO4)2F3/rGO full-cell by 28.9% without sacrificing its other electrochemical properties, showing promising application prospects in sodium ion batteries.

13.
Preprint | bioRxiv | ID: ppbiorxiv-440104

RESUMO

In the search for treatment schemes of COVID-19, we start by examining the general weakness of coronaviruses and then identify approved drugs attacking that weakness. The approach, if successful, should identify drugs with a specific mechanism that is at least as effective as the best drugs proposed and are ready for clinical trials. All coronaviruses translate their non-structural proteins ([~]16) in concatenation, resulting in a very large super-protein. Homo-harringtonine (HHT), which has been approved for the treatment of leukemia, blocks protein elongation very effectively. Hence, HHT can repress the replication of many coronaviruses at the nano-molar concentration. In two mouse models, HHT clears SARS-CoV-2 in 3 days, especially by nasal dripping of 40 ug per day. We also use dogs to confirm the safety of HHT delivered by nebulization. The nebulization scheme could be ready for large-scale applications at the onset of the next epidemics. For the current COVID-19, a clinical trial has been approved by the Ditan hospital of Beijing but could not be implemented for want of patients. The protocol is available to qualified medical facilities.

14.
Preprint | bioRxiv | ID: ppbiorxiv-437647

RESUMO

Safe and effective vaccination is critical to combatting the COVID-19 pandemic. Here, we developed a trimeric SARS-CoV-2 receptor-binding domain (RBD) subunit vaccine candidate that simulates the natural structure of the spike (S) trimer glycoprotein. Immunization with RBD-trimer induced robust humoral and cellular immune responses and a high level of neutralizing antibodies that were maintained for at least 4 months. Moreover, the antibodies that were produced in response to the vaccine effectively neutralized the SARS-CoV-2 501Y.V2 variant. Of note, when the titers of the antibodies dropped to a sufficiently low level, only one boost quickly activated the anamnestic immune response, resulting in complete protection against the SARS-CoV-2 challenge in rhesus macaques without typical histopathological changes or viral replication in the lungs and other respiratory tissues. Our results indicated that immunization with SARS-CoV-2 RBD-trimer could raise long-term and broad immunity protection in nonhuman primates, thereby offering an optimal vaccination strategy against COVID-19.

15.
Preprint | bioRxiv | ID: ppbiorxiv-434928

RESUMO

A safe, efficacious and deployable vaccine is urgently needed to control COVID-19 pandemic. We report here the preclinical development of a COVID-19 vaccine candidate, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and NHPs, and also elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 g or 50 g ZF2001 prevented infection with SARS-CoV-2 in lung, trachea and bronchi, with milder lung lesions. No evidence of disease enhancement is observed in both models. ZF2001 is being evaluated in the ongoing international multi-center Phase 3 trials (NCT04646590) and has been approved for emergency use in Uzbekistan.

16.
BMC Pediatr ; 21(1): 104, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648480

RESUMO

BACKGROUND: Chorioamnionitis is associated with various neonatal short- and long-term morbidities. The effect of chorioamnionitis on premature children's outcomes remains controversial. The aim of this study is to investigate the relationship between histological chorioamnionitis (HCA) and physiological development, wheezing, and atopic diseases in preterm children. METHODS: Singleton, preterm children (< 34 weeks), whose mother underwent pathological placental examinations, were retrospectively enrolled and the outcomes were assessed at 24-40 months during follow-up. Wheezing and atopic diseases including eczema, food allergies, and allergic rhinitis were screened by a questionnaire along with medical diagnosis. Anthropometric indexes and blood pressure were measured. Cognitive and behavioural developments were assessed by the Gesell Development and Diagnosis Scale. Blood IgE and routine examination were analyzed with venous blood and serum metabolomic profiling was assessed via liquid chromatography-mass spectrometry (LC-MS). A multivariate logistic regression model was used to estimate the association between HCA and the current outcomes. RESULTS: Among the 115 enrolled children, 47 were exposed to HCA. The incidence of wheezing was significantly higher in children exposed to HCA, as 38.30% of children who were exposed to HCA and 16.18% of children who were not had been diagnosed with wheezing. After adjusting for related confounders in the multivariate logistic regression model, there remained a 2.72-fold increased risk of wheezing in children with HCA (adjusted odds ratio, aOR, 2.72; 95% confidence interval, 1.02-7.23). Moreover, 163 differential metabolites, such as butanoic acid, annotemoyin 1 and charine, were identified in the HCA exposed children's serum. Enrichment analysis revealed that these compounds participated in diverse key metabolomic pathways relating to physical and neuro- developments, including glycerophospholipid, alpha-linolenic acid and choline metabolisms. There were no significant differences in atopic diseases, serum IgE, eosinophils' level, anthropometric indexes, blood pressure, or cognitive or behavioural developments between the two groups. CONCLUSION: HCA exposure is associated with an increased risk of wheezing in preterm children less than 34 gestational weeks.


Assuntos
Corioamnionite , Criança , Corioamnionite/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Placenta , Gravidez , Sons Respiratórios/etiologia , Estudos Retrospectivos
17.
Hippocampus ; 31(5): 512-521, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33580728

RESUMO

Sodium salicylate, one of the non-steroidal anti-inflammatory drugs, is widely prescribed in the clinic, but a high dose of usage can cause hyperactivity in the central nervous system, including the hippocampus. At present, the neural mechanism underlying the induced hyperactivity is not fully understood, in particular, in the hippocampus under an in vivo condition. In this study, we found that systemic administration of sodium salicylate increased the field excitatory postsynaptic potential slope and the population spike amplitude in a dose-dependent manner in the hippocampal dentate gyrus area of rats with in vivo field potential extracellular recordings, which indicates that sodium salicylate enhances basal synaptic transmission and neural excitation. In the presence of picrotoxin, a GABA-A receptor antagonist, sodium salicylate failed to increase the initial slope of the field excitatory postsynaptic potential and the amplitude of the population spike in vivo. To further explore how sodium salicylate enhances the neural excitation, we made whole-cell patch-clamp recordings from hippocampal slices. We found that perfusion of the slice with sodium salicylate decreased electrically evoked GABA receptor-mediated currents, increased paired-pulse ratio, and lowered frequency and amplitude of miniature inhibitory postsynaptic currents. Together, these results demonstrate that sodium salicylate enhances the neural excitation through suppressing GABAergic synaptic transmission in presynaptic and postsynaptic mechanisms in the hippocampal dentate gyrus area. Our findings may help understand the side effects caused by sodium salicylate in the central nervous system.

18.
Nanoscale ; 13(9): 4705-4727, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33625411

RESUMO

Tumor microenvironment is a complex ecosystem composed of tumor extracellular matrix, fibroblasts, blood vessels, and immune cells, promoting tumor development by secreting various growth factors, hydrolase, and inflammatory factors. Tumor-associated macrophages (TAMs) constitute the largest number of immune cells in the TME, and they have a "double-edged sword" effect on tumor growth, invasion, metastasis, angiogenesis, and immunosuppression. Under the regulation of different cytokines in the TME, the bidirectional TAMs can switch their phenotypes between tumoricidal M1-like and pro-tumorigenic M2-like macrophages. TAM polarization suggests that scientists can use this property to design drugs targeting this regulation as a promising immunotherapy strategy to enhance tumor therapy efficiency. In this review, we summarize a brief introduction of TAMs and their implications for tumorigenesis. Next, we review recent advances in designing various functionalized nanomedicines and their applications in nanomedicine-based cancer therapies that target TAMs by killing them, inhibiting macrophage recruitment, and repolarizing them from pro-tumorigenic M2-like to tumoricidal M1-like macrophages. Simultaneously, the regulation of nanomedicines on the signaling pathways accounting for these effects is also summarized. This review will not only provide background scientific information for the understanding of TAMs and their roles in cancer treatment but also help scientists design nanomedicines based on tumor TAMs, which can help achieve better clinical treatment outcomes for tumors.


Assuntos
Nanomedicina , Neoplasias , Ecossistema , Humanos , Imunoterapia , Neoplasias/terapia , Microambiente Tumoral
19.
Dalton Trans ; 50(4): 1384-1389, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33432945

RESUMO

Two isostructural 3D Hofmann-type frameworks, [FeII(dbdpe)MII(CN)4]·4H2O (M = Pt for 1 and Pd for 2), were synthesized based on a bis-monodentate ligand dbdpe (1,2-dibromo-1,2-di(pyridin-4-yl)ethane). Both compounds underwent similar one-step incomplete spin crossover (SCO) processes in the presence of lattice water molecules, i.e., T1/2↓ = 185 K for 1 and 187 K for 2 without any hysteresis loop, while their dehydrated products exhibited paramagnetic behaviours. The application of pressure on 1 broadened the hysteresis loop to 13-25 K and shifted the transition temperature from 185 to 298 K, whereas the SCO completeness was not well improved. Variable temperature X-ray crystallographic studies clearly confirmed the incomplete SCO behaviors, and the intermolecular hydrogen bonds might promote the cooperativity in the SCO processes.

20.
Brain Res Bull ; 169: 18-24, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33400956

RESUMO

Resveratrol, a naturally occurring stilbene found in red wine, is known to modulate the activity of several types of ion channels and membrane receptors, including Ca2+, K+, and Na+ ion channels. However, little is known about the effects of resveratrol on some important receptors, such as glycine receptors and GABAA receptors, in the central nervous system (CNS). In the present study, the effects of resveratrol on glycine receptor or GABAA receptor-mediated currents in cultured rat inferior colliculus (IC) and auditory cortex (AC) neurons were studied using whole-cell voltage-clamp recordings. Resveratrol itself did not evoke any currents in IC neurons but it reversibly decreased the amplitude of glycine-induced current (IGly) in a concentration-dependent manner. Resveratrol did not change the reversal potential of IGly but it shifted the concentration-response relationship to the right without changing the Hill coefficient and with decreasing the maximum response of IGly. Interestingly, resveratrol inhibited the amplitude of IGly but not that of GABA-induced current (IGABA) in AC neurons. More importantly, resveratrol inhibited GlyR-mediated but not GABAAR-mediated inhibitory postsynaptic currents in IC neurons using brain slice recordings. Together, these results demonstrate that resveratrol noncompetitively inhibits IGly in auditory neurons by decreasing the affinity of glycine to its receptor. These findings suggest that the native glycine receptors but not GABAA receptors in central neurons are targets of resveratrol during clinical administrations.

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