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1.
Acta Pharmacol Sin ; 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705687

RESUMO

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.

2.
Comput Math Methods Med ; 2022: 4000733, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35761835

RESUMO

Growing evidence has demonstrated that high heterogeneity contributes to poor prognosis and malignancies. The existence of melanoma cancer stem-like cells (CSCs), which are a small subpopulation of melanoma cells, is responsible for tumour resistance to therapies. Recently, plant secondary metabolites have attracted attention because they are considered promising compounds that are isolated from herbs that could help to target different subpopulations of tumours. In the present study, we aimed to identify the antitumourigenic activities of the medicinal compound chelerythrine chloride (CHE) on melanoma CSCs. CHE (30-40 µmol/L) induced apoptosis in A375 and A2058 CSCs. A relatively low dose of CHE (1-5 µmol/L) inhibited the stemness of melanoma CSCs without inducing apoptosis. Coculture of CHE with A375 and A2058 cells also inhibited sphere formation and decreased stemness factors, including Nanog, Oct4, and Sox2. In functional characterizations, we observed that CHE treatment increased both cellular reactive oxygen species (ROS) and mitochondrial ROS, which resulted in a decrease in mitochondrial energy production and sphere formation. Abolishing CHE-induced ROS by N-acetyl-L-cysteine (NAC), a ROS scavenger, reversed the inhibitory effects of CHE on sphere formation, suggesting that CHE-induced ROS are the potential cause of the inhibition of sphere formation. In conclusion, CHE may exert its antitumour effect as an antistem cell natural compound, suggesting that selection of the antistem cell effects of natural compounds might be a promising strategy to overcome the poor prognosis of melanoma due to the presence of CSCs.


Assuntos
Melanoma , Células-Tronco Neoplásicas , Apoptose , Benzofenantridinas , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Melanoma/tratamento farmacológico , Mitocôndrias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Espécies Reativas de Oxigênio/uso terapêutico
3.
Front Microbiol ; 13: 892021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620101

RESUMO

Pseudomonas aeruginosa is an important opportunistic pathogen in cystic fibrosis patients and immunocompromised individuals, and the toxin-antitoxin (TA) system is involved in bacterial virulence and phage resistance. However, the roles of TA systems in P. aeruginosa are relatively less studied and no phage Cro-like regulators were identified as TA components. Here, we identified and characterized a chromosome-encoded prophage Cro-like antitoxin (CrlA) in the clinical isolate P. aeruginosa WK172. CrlA neutralized the toxicity of the toxin CrlA (CrlT) which cleaves mRNA, and they formed a type II TA system. Specifically, crlA and crlT are co-transcribed and their protein products interact with each other directly. The autorepression of CrlA is abolished by CrlT through the formation of the CrlTA complex. Furthermore, crlTA is induced in the stationary phase, and crlA is expressed at higher levels than crlT. The excess CrlA inhibits the infection of lytic Pseudomonas phages. CrlA is widely distributed among Pseudomonas and in other bacterial strains and may provide antiphage activities.

4.
Invest New Drugs ; 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35608716

RESUMO

ALK (anaplastic lymphoma kinase) gene rearrangements have been reported in 3-5% of NSCLC patients. Different ALK fusion forms can mediate different downstream signaling pathways and may exhibit different sensitivities to ALK tyrosine kinase inhibitors (TKIs). To identify more fusion partners that are sensitive to ALK-TKIs, we present a case of 46-year-old woman with stage IV lung adenocarcinoma. NGS panel analysis suggested that a novel SSFA2-ALK fusion was identified in this patient. Moreover, this fusion was validated through IHC (VENTANA ALK (D5F3) antibody) and FISH (ZytoLight ALK Break Apart FISH Probe). Importantly, to the best of our knowledge, there is no report about SSFA2-ALK fusion in solid cancers. Moreover, the patient achieved an admirable response to alectinib, with a clinical evaluation of complete response (CR). In summary, our findings expand the spectrum of ALK fusion patterns and provide robust evidence for the precise administration of alectinib in the future.

5.
J Affect Disord ; 310: 223-227, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35550826

RESUMO

OBJECTIVE: To examine whether early symptom improvement can predict eventual remission following electroconvulsive therapy (ECT) with ketamine plus propofol (ketofol) anesthesia in patients with treatment-resistant depression (TRD). METHODS: Thirty Han Chinese subjects suffering from TRD were administered ketofol anesthesia during ECT. Remission was defined as a score of ≤7 on the 17-item Hamilton Depression Rating Scale (HAMD-17). Receiver operating characteristic (ROC) curves were applied to identify the number of ECT sessions (i.e., 1, 2, 3, or 4 ECT sessions) that had the best discriminative capacity for eventual remission. The best definition of early improvement to predict final remission was determined by using the Youden index. RESULTS: Of the 30 patients with TRD, 16 (53.3%) and 30 (100%) were classified as remitters and responders, respectively. A 45% reduction in the HAMD-17 score after 3 ECT sessions was the optimum definition of early improvement in the prediction of eventual remission, with relatively good sensitivity (88%) and specificity (93%). Patients with than without early improvement had a greater possibility of achieving favorable ECT outcomes. CONCLUSION: Final remission of TRD following ECT with ketofol anesthesia appeared to be predicted by early improvement, as indicated by a 45% reduction in HAMD-17 score after 3 ECT sessions.


Assuntos
Anestesia , Transtorno Depressivo Resistente a Tratamento , Eletroconvulsoterapia , Depressão , Transtorno Depressivo Resistente a Tratamento/terapia , Humanos , Resultado do Tratamento
6.
Artigo em Inglês | MEDLINE | ID: mdl-35622399

RESUMO

Two strains designated as c1T and c7T, were isolated from the landfill leachate of a domestic waste treatment plant in Huizhou City, Guangdong Province, PR China. The cells of both strains were aerobic, rod-shaped, non-motile and formed yellow colonies on Reasoner's 2A agar plates. Strain c1T grew at 10-42 °C (optimum, 30 °C), pH 4.5-10.5 (optimum, pH 7.0) and 0-2.0 % (w/v) NaCl (optimum, 0-0.5 %). Strain c7T grew at 10-42 °C (optimum, 30 °C), pH 4.5-10.5 (optimum, pH 6.0) and 0-2.0 % (w/v) NaCl (optimum, 0-0.5 %). Phylogenetic analyses revealed that strains c1T and c7T belong to the genus Novosphingobium. The 16S rRNA gene sequence similarities of strains c1T and c7T to the type strains of Novosphingobium species were 94.5-98.2 % and 94.3-99.1 %, respectively. The calculated pairwise average nucleotide identity values among strains c1T, c7T and the reference strains were in the range of 75.2-85.9 % and the calculated pairwise average amino acid identity values among strains c1T, c7T and reference strains were in the range of 72.0-88.3 %. Their major respiratory quinone was Q-10, and the major cellular fatty acids were C18 : 1 ω7c, C18 : 0, C16 : 1 ω7c, C16 : 0 and C14 : 0 2OH. The major polar lipids of strains c1T and c7T were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, sphingoglycolipid, unidentified lipids and unidentified phospholipid. Based on phenotypic, chemotaxonomic, phylogenetic and genomic results from this study, strains c1T and c7T should represent two independent novel species of Novosphingobium, for which the names Novosphingobium percolationis sp. nov. (type strain c1T=GDMCC 1.2555T=KCTC 82826T) and Novosphingobium huizhouense sp. nov. (type strain c7T=GDMCC 1.2556T=KCTC 82827T) are proposed. The gene function annotation results of strains c1T and c7T suggest that they could play an important role in the degradation of organic pollutants.


Assuntos
Filogenia , Sphingomonadaceae , Poluentes Químicos da Água , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Sphingomonadaceae/classificação , Sphingomonadaceae/isolamento & purificação , Ubiquinona/análogos & derivados , Ubiquinona/química
7.
Arch Gynecol Obstet ; 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35635620

RESUMO

PURPOSE: Hysterosalpingo-contrast sonography (HyCoSy) is the preferred method for evaluating fallopian tubal patency, and it is associated with improved rates of natural pregnancy among infertile patients. However, the mechanism underlying the improvement in pregnancy rates following HyCoSy remains unclear. This study aimed to investigate the effect of HyCoSy examination on endometrial receptivity as well as pregnancy rates among infertile women. METHODS: This prospective study included 120 women with unexplained infertility who visited our department between June 2018 and February 2021. These patients were classified into the study group (n = 60) and the control group (n = 60) depending on their willingness to undergo three-dimensional HyCoSy in the present cycle (study group) or 6 months later (control group). Endometrial characteristics, including endometrial thickness and pattern as well as the endometrial blood flow distribution pattern, were measured twice by transvaginal Doppler ultrasonography in the preovulatory phase before and after HyCoSy examination. Participants were followed for 6 months to observe the outcome of spontaneous conception. RESULTS: Compared with the control group, the study group had a significantly higher cumulative pregnancy rate at 6 months after HyCoSy (21.6% [13/60] vs 5.0% [3/60], P = 0.007). More patients in the study group showed improved endometrial blood flow distribution (P = 0.021, χ2 = 7.699), but no differences in endometrial thickness and pattern were observed between the groups (P > 0.05). CONCLUSION: HyCoSy examination may improve endometrial perfusion and has a therapeutic effect on improving spontaneous pregnancy among women with unexplained infertility.

8.
Immunopharmacol Immunotoxicol ; : 1-9, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35438054

RESUMO

BACKGROUND: The abnormal expression of long non-coding RNA (lncRNA) is closely related to disease progression. However, the role and mechanism of lncRNA H19 (lncH19) in sepsis-induced lung injury remain to be elucidated. METHODS: Cercal ligation and puncture (CLP) mice models and lipopolysaccharide (LPS)-induced cell injury model was used to construct sepsis-induced lung injury in vivo and in vitro. The expression of lncH19, microRNA (miR)-301a-3p, and adenylate cyclase 1 (Adcy1) mRNA was assessed using quantitative real-time PCR. The concentrations of inflammatory factors were determined by ELISA assay. Cell proliferation and apoptosis were determined using cell counting kit 8 assay, EdU staining, and flow cytometry. The protein expression of apoptosis markers and Adcy1 was examined by western blot analysis. Oxidative stress was assessed by detecting the contents of oxidative stress markers. The interaction between miR-301a-3p and lncH19 or Adcy1 was confirmed using RNA pull-down assay, dual-luciferase reporter assay, and RIP assay. RESULTS: LncH19 was lowly expressed in CLP mice models and LPS-induced cell injury models. Overexpressed lncH19 could alleviate CLP-induced lung injury in mice, as well as LPS-induced cell apoptosis, inflammation, and oxidative stress. MiR-301a-3p could be sponged by lncH19, and its overexpression could reverse the inhibition of lncH19 on LPS-induced cell injury. Adcy1 was a target of miR-301a-3p, and its expression was upregulated by lncH19. Silencing of Adcy1 could abolish the suppressive effect of the miR-301a-3p inhibitor on LPS-induced cell injury. CONCLUSION: LncH19 might inhibit sepsis-induced lung injury by acting as a sponge of miR-301a-3p to upregulate Adcy1. HIGHLIGHTSLncH19 overexpression relieves CLP-induced lung injury and LPS-induced cell injury.LncH19 directly sponges miR-301a-3p.MiR-301a-3p targets Adcy1.

9.
Org Biomol Chem ; 20(17): 3486-3490, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35388864

RESUMO

The efficient construction of cyclopropyl spiroindoline skeletons and the exploration of related follow-up synthetic transformations have elicited considerable interest amongst members of the chemistry community. Here, we describe a formal (2 + 1) annulation and three-component (1 + 1 + 1) cascade cyclisation via sulphur ylide cyclopropanation under mild conditions. The spiro-cyclopropyl iminoindoline moiety can be readily transformed into another medicinally interesting pyrrolo[3,4-c]quinoline framework through a novel rearrangement process.


Assuntos
Enxofre , Ciclização
10.
ACS Omega ; 7(12): 10187-10195, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35382326

RESUMO

Under the hydrothermal condition, a new type of two-dimensional coordination polymer ([Cd(D-Cam)(3-bpdb)]n, Cd-CP) has been constructed. It is composed of D-(+)-Camphoric-Cd(II) (D-cam-Cd(II)) one-dimensional chain and bridging 1,4-bis(3-pyridyl)-2,3-diaza-1,3-butadiene (3-bpdb) ligands. Cd-CP has a good removal effect for Hg(II) and Pb(II), and the maximum adsorption capacity is 545 and 450 mg/g, respectively. Interestingly, thermodynamic studies have shown that the adsorption processes of Hg(II) and Pb(II) on Cd-CP use completely different thermodynamic mechanisms, in which the adsorption of Hg(II) is due to a strong electrostatic interaction with Cd-CP, while that of Pb(II) is through a weak coordination with Cd-CP. Moreover, Cd-CP has a higher affinity for Hg(II), and when Hg(II) and Pb(II) coexist, Cd-CP preferentially adsorbs Hg(II).

11.
Curr Biol ; 32(7): R307-R308, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35413253

RESUMO

Respiratory syncytial virus (RSV) is an enveloped non-segmented negative sense RNA virus that belongs to Orthopneumovirus genus of the Pneumoviridae family in the order Mononegavirales. The virus is the leading cause of severe respiratory disease in children under two years of age and is responsible for substantial disease burden in infants and elder people in both developed and developing countries1,2. RSV is only known to circulate among humans, though it was first isolated from chimpanzees3. The virus can experimentally infect mice, rats, cotton rats, ferrets, and hamsters, but does not naturally circulate in these animal populations4. We found that Malayan pangolins (Manis javanica) were naturally infected with RSVs that have 99.4-99.8% genomic identity with strains circulating in humans. Phylogenetic analyses revealed that five RSVs in pangolins were RSV-A ON1 and seven were RSV-B BA genotypes, both of which are currently prevalent in humans worldwide. These findings suggest that humans might transmit their viruses to endangered wildlife.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Idoso , Animais , Furões , Genótipo , Humanos , Lactente , Camundongos , Pangolins , Filogenia , Infecções por Vírus Respiratório Sincicial/veterinária , Vírus Sincicial Respiratório Humano/genética
12.
Acta Histochem ; 124(4): 151872, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35367814

RESUMO

OBJECTIVE: This study aimed to investigate the protective role of the signal transducer and activator of transcription 4 (STAT4) in diabetic cardiomyopathy. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats (6-8 weeks old) were purchased from the Experimental Animal Center of Zhengzhou University. The rats were randomly divided into the control and diabetic cardiomyopathy groups. Rat models of diabetic cardiomyopathy were established by a high-sugar and high-fat diet combined with a peritoneal injection of streptozocin. Pathological changes in the heart were visualized using Hematoxylin-eosin (HE) staining and Masson's staining. Moreover, cell apoptosis was detected using terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) staining and Annexin V apoptosis detection kit. Furthermore, H9C2 cells were transfected with lentivirus overexpressing STAT4 and treated with high glucose. The CCK-8 assay was performed to determine cell viability. Finally, Western blotting was used to determine the expression of STAT4, Bax, and Bcl-2. RESULTS: The myocardial tissue of the diabetic cardiomyopathy models showed hypertrophy, myocardial fibrosis and collagen deposition. Furthermore, TUNEL staining showed increased apoptosis and decreased expression of STAT4 in the myocardial cells. Moreover, the myocardial tissues of the DCM models showed increased expression of Bax/Bcl-2 and a high percentage of Annexin V positive cells. The H9C2 cells showed decreased expression of STAT4 following high glucose treatment. However, the H9C2 cells overexpressing STAT4 showed decreased expression of Bax/Bcl-2 and reduced percentage of Annexin V positive cells. CONCLUSION: The DCM group had decreased myocardial expression of STAT4. Furthermore, overexpression of STAT4 was shown to reduce high glucose-induced apoptosis.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Animais , Anexina A5/efeitos adversos , Apoptose , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/patologia , Glucose , Humanos , Masculino , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT4/metabolismo , Proteína X Associada a bcl-2
13.
Antioxidants (Basel) ; 11(3)2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35326251

RESUMO

Accumulation of amyloid beta (Aß) is a major pathological hallmark of Alzheimer's disease (AD). In this study, we evaluated the protective effect of membrane-free stem cell extract (MFSCE), which is a component of adipose-tissue-derived stem cells, on cognitive impairment in Aß25-35-injected AD mice. The ICR mice were i.c.v. injected with Aß25-35 and then treated with MFSCE for 14 days (i.p.). The Aß25-35-injected mice showed deficits in spatial and object perception abilities, whereas treatment with MFSCE inhibited Aß25-35-induced learning and memory impairment in the T-maze, novel object recognition, and Morris water maze tests. Moreover, Aß25-35-induced lipid peroxidation and nitric oxide overproduction were attenuated by treatment with MFSCE. These antioxidant effects of MFSCE were related to the inhibition of the apoptotic signaling pathway. In particular, the combination treatment of MFSCE and pyridoxal 5'-phosphate (PLP) showed greater suppression of Bax and cleaved caspase-3 protein expression compared to the MFSCE- or PLP-only treatment. Furthermore, the MFSCE and PLP combination significantly downregulated the amyloidogenic-pathway-related protein expressions, such as amyloid precursor protein, presenilin 1, and presenilin 2. Therefore, the MFSCE and PLP combination may synergistically prevent Aß25-35-induced neuronal apoptosis and amyloidogenesis, which contributes to cognitive improvement and has potential therapeutic implications for AD patients.

14.
Zhongguo Zhen Jiu ; 42(3): 267-70, 2022 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-35272402

RESUMO

OBJECTIVE: To observe the effect of acupuncture on visual acuity, intraocular pressure, visual field, retinal and choroidal thickness on optic disc and macular area in patients with optic atrophy. METHODS: A total of 33 patients with optic atrophy were treated with acupuncture. Acupuncture was given at Chengqi (ST 1), Shangjingming (Extra), Qiuhou (EX-HN 7) and Fengchi (GB 20) etc., 30 min each time, once a day, for 14 days. The visual acuity, intraocular pressure, visual field indexes (mean deviation [MD], pattern standard deviation [PSD] and visual field index [VFI]), optic disc retinal nerve fiber layer thickness, macular retinal thickness and choroidal thickness of optic disc and sub-foveal were compared before and after treatment. RESULTS: Compared before treatment, the visual acuity was increased (P<0.05), the MD value was decreased (P<0.05), the thickness of nerve fiber layer on the upper temporal side of optic disc was thinner (P<0.05), and the choroidal thickness of average, nasal side and lower temporal side of optic disc was increased (P<0.05). There was significant correlation between visual field MD and retinal nerve fiber layer thickness in different quadrants before and after treatment (P<0.01). CONCLUSION: Acupuncture could improve visual acuity, increase choroidal thickness in part of optic disc area in patients with optic atrophy.


Assuntos
Terapia por Acupuntura , Atrofia Óptica , Disco Óptico , Humanos , Atrofia Óptica/terapia , Disco Óptico/diagnóstico por imagem , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica
15.
Front Pharmacol ; 13: 806837, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250558

RESUMO

Several approaches to expand human hematopoietic stem cells (hHSCs) clinically along with retainable capability of multipotential differentiation have been reported, but only a few have advanced to evaluation in clinical trials, which limits the application of HSC-based therapy. Here we show a phthalide derivative, Levistilide A (LA), can serve as a promising molecule to expand functional human umbilical cord blood (UCB) HSCs ex vivo. An in-house screen identified LA out of nine natural products as an outstanding candidate for hHSCs expansion. Additionally, our data indicated that LA treatment not only increased the numbers of phenotype-defined HSCs, but also enhanced their colony formation ability. Xenotransplantation assays showed that LA treatment could maintain unaffected engraftment of hHSCs with multilineage differentiation capacity. Further experiments revealed that LA enhanced the antioxidant activity of hHSCs by reducing intracellular and mitochondrial reactive oxygen species (ROS) levels. The identification of LA provides a new strategy in solving the clinical issue of limited numbers of UCB HSCs.

16.
J Extracell Vesicles ; 11(3): e12194, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35230743

RESUMO

Extracellular vesicle (EV)-based therapies and vaccines are emerging. However, employment at the scale for population-based dose development is always a huge bottleneck. In order to overcome such a roadblock, we introduce a simple and straightforward approach for promoting cellular production of dendritic cell derived EVs (DEVs) by leveraging phototherapy based light induction. Under the optimization of light wavelengths, intensities, and exposure times, we achieved more than 13-fold enhancement in DEV production rate, while maintaining good integral quality and immune function from produced EVs. The LED light at 365 nm is optimal to reliably trigger enhanced cellular production of EVs no matter cell line types. Our observation and other reported studies support longer near UV wavelength does not impair cell growth. We conducted a series of investigations in terms of size, zeta potential, morphology, immune surface markers and cytokines, biocompatibility, cellular uptake behaviour, and immune-modulation ability on eliciting cellular responses in vitro. We also validated the biodistribution, immunogenicity, and administration safety using light-promoted DEVs in mice models from both male and female genders. Overall data supports that light promoted DEVs are highly immune functional with great biocompatibility for serving as good therapeutic platforms. The in vivo animal study also demonstrated light-promoted DEVs are as well tolerated as native DEVs, with no safety concerns. Taken together, the data supports that light promoted DEVs are in excellent quality, high biocompatibility, in vivo tolerant, and viable for serving as an ideal therapeutic platform in scalable production.


Assuntos
Vesículas Extracelulares , Animais , Linhagem Celular , Proliferação de Células , Citocinas , Feminino , Masculino , Camundongos , Distribuição Tecidual
17.
Adv Sci (Weinh) ; 9(16): e2200027, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35343112

RESUMO

The past decade has witnessed the explosive development of cancer immunotherapies. Nevertheless, low immunogenicity, limited specificity, poor delivery efficiency, and off-target side effects remain to be the major limitations for broad implementation of cancer immunotherapies to patient bedside. Encouragingly, advanced biomaterials offering cell-specific modulation of immunological cues bring new solutions for improving the therapeutic efficacy while relieving side effect risks. In this review, focus is given on how functional biomaterials can enable cell-specific modulation of cancer immunotherapy within the cancer-immune cycle, with particular emphasis on antigen-presenting cells (APCs), T cells, and tumor microenvironment (TME)-resident cells. By reviewing the current progress in biomaterial-based cancer immunotherapy, here the aim is to provide a better understanding of biomaterials' role in targeting modulation of antitumor immunity step-by-step and guidelines for rationally developing targeting biomaterials for more personalized cancer immunotherapy. Moreover, the current challenge and future perspective regarding the potential application and clinical translation will also be discussed.


Assuntos
Materiais Biocompatíveis , Neoplasias , Materiais Biocompatíveis/uso terapêutico , Humanos , Imunoterapia , Neoplasias/terapia , Linfócitos T , Microambiente Tumoral
18.
J Adv Res ; 36: 133-145, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35116173

RESUMO

Introduction: The COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. Objectives: We assumed that antibodies may serve as biomarkers for predicting the clinical outcome of hospitalized COVID-19 patients on admission. Methods: By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. Results: Nonsurvivors (n = 955) induced higher levels of IgG responses against most of non-structural proteins than survivors (n = 79) on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend < 0.05). Additionally, IgG responses to all of these 10 non-structural/accessory proteins were also associated with the severity of disease, and differential kinetics and serum positive rate of these IgG responses were confirmed in COVID-19 patients of varying severities within 20 days after symptoms onset. The area under curves (AUCs) for these IgG responses, determined by computational cross-validations, were between 0.62 and 0.71. Conclusions: Our findings might have important implications for improving clinical management of COVID-19 patients.


Assuntos
COVID-19 , Anticorpos Antivirais , Humanos , Imunoglobulina G , SARS-CoV-2 , Índice de Gravidade de Doença
19.
Zhongguo Zhong Yao Za Zhi ; 47(2): 484-491, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35178993

RESUMO

Amyloid ß-protein(Aß) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aß_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aß-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aß, and may reduce Aß-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.


Assuntos
Ginsenosídeos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Ginsenosídeos/farmacologia , Humanos , Mitofagia/fisiologia , Células PC12 , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Ratos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
20.
Environ Sci Pollut Res Int ; 29(18): 27560-27570, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34981382

RESUMO

Soil microbial stoichiometry reflects carbon (C) and nutrient (e.g., nitrogen (N) and phosphorus (P)) elemental balances under land-use change (LUC). However, how soil microbial community (SMC) structure and stoichiometry respond to long-term LUC in forests is still unclear. Here, we investigated three 36-year-old typical plantations, Cryptomeria fortunei, Metasequoia glyptostroboides, and Cunninghamia lanceolata, and the natural forest to assess their soil microbial stoichiometry and SMC structure. Three plots (30×30 m2) were randomly set in each forest site. In each plot of every forest site, soil samples of three depths (0-10, 10-30, and 30-60 cm) were collected. Dissolved organic C, N, and P (abbreviated as DOC, DON, and DOP, respectively) and environmental factors were measured. We also detected microbial biomass C, N, and P as well as SMC structure. The results showed that the soil microbial C:N:P stoichiometry had a strong or strict homeostasis regardless of soil depth and exhibited decoupling from the SMC structure at each depth. The SMC structure across forest types was mainly driven by mean annual soil temperature (MAST) and DOC at 0-10 cm depth, by soil water content and MAST at 10-30 cm depth, and by DOC to DOP ratio at 30-60 cm depth. Thus, SMC structure could be jointly regulated by available resources and environment. These results suggest that the C dynamics in forests tend to gain resilience or re-equilibrium over more than three decades after forest conversion. These findings highlight the importance of reforested plantations forest management for sustaining soil C over a long term.


Assuntos
Cunninghamia , Solo , Carbono/análise , China , Florestas , Nitrogênio/análise , Fósforo/análise , Solo/química , Microbiologia do Solo
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