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1.
Bioact Mater ; 9: 183-197, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34820565

RESUMO

Inflammatory response plays a critical role in myocardial infarction (MI) repair. The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration, while the therapeutic strategy that simulates and enhances this natural process has not been established. Here, we constructed engineered neutrophil apoptotic bodies (eNABs) to simulate natural neutrophil apoptosis, which regulated inflammation response and enhanced MI repair. The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties, and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride (HAL). The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release, thereby further enhancing the anti-inflammation effects. In in vivo studies, the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function. This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.

2.
Front Microbiol ; 12: 770656, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777324

RESUMO

In the past two decades, coronavirus (CoV) has emerged frequently in the population. Three CoVs (SARS-CoV, MERS-CoV, SARS-CoV-2) have been identified as highly pathogenic human coronaviruses (HP-hCoVs). Particularly, the ongoing COVID-19 pandemic caused by SARS-CoV-2 warns that HP-hCoVs present a high risk to human health. Like other viruses, HP-hCoVs interact with their host cells in sophisticated manners for infection and pathogenesis. Here, we reviewed the current knowledge about the interference of HP-hCoVs in multiple cellular processes and their impacts on viral infection. HP-hCoVs employed various strategies to suppress and evade from immune response, including shielding viral RNA from recognition by pattern recognition receptors (PRRs), impairing IFN-I production, blocking the downstream pathways of IFN-I, and other evasion strategies. This summary provides a comprehensive view of the interplay between HP-hCoVs and the host cells, which is helpful to understand the mechanism of viral pathogenesis and develop antiviral therapies.

3.
ACS Appl Mater Interfaces ; 13(45): 53787-53797, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34726366

RESUMO

As most of the known systems are flashtype, long-lasting chemiluminescence (CL) emissions are extremely needed for the application of cold light sources, accurate CL quantitative analysis, and biological mapping. In this work, the flashtype system of luminol was altered to a long lasting CL system just because of the paper substrate. The Cu(II)-based organic complex was loaded on the paper surface, which can trigger luminol-H2O2 to produce a long lasting CL emission for over 30 min. By using 1,10-phenanthroline-2,9-dicarboxylic acid (PDA) as the ligand, a hexacoordinated Cu(II)-based organic complex was synthesized by the simple freeze-drying method. It is interesting that the complex morphology can be controlled by adding different amounts of water in the synthesizing procedure. The complex with a certain size can be definitely trapped in the pores of the cellulose. Then, slow diffusion, which can be attributed to the long lasting CL emission, was produced. With the high catalytic activity of the complex, reactive oxygen species from H2O2 was generated and was responsible for the high CL intensity. By using the paper substrate, the flash-type luminol system can be easily transferred to the long-duration CL system without any extra reagent. This long-lasting emission system was used for hydrogen sulfide detection by the CL imaging method. This paper-based sensor has great potential for CL imaging in the clinical field in the future.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34770050

RESUMO

The reinfection rate of schistosomiasis after mass drug administration (MDA) has not been documented in Sudan. We aimed to explore the transmission dynamics of urogenital schistosomiasis after MDA, targeting school-aged children in the White Nile State of Sudan, assessing the prevalence, reinfection rate, and incidence. A single dose of praziquantel (40 mg/kg) was administered to 1951 students in five primary schools from January to February 2018 immediately after a baseline survey, and follow-up surveys were performed at 2 weeks and 6 months after treatment. We examined Schistosoma haematobium eggs by centrifugation methods. The overall reinfection rate at 6 months after treatment was 9.8% (95% confidence interval: 0.5-17.4%). By school, the reinfection rate was highest in the Al Hidaib school, whose prevalence was highest at baseline. The reinfection rate was significantly higher in high-infection areas than low-infection areas (p = 0.02). Of the prevalence at 6 months in high-infection areas, 41% of cases were due to reinfection. MDA interventions are decided upon and undertaken at the district level. A more targeted treatment strategy should be developed with a particular focus on tracking high-risk groups, even within a school or a community.


Assuntos
Schistosoma haematobium , Esquistossomose Urinária , Animais , Criança , Estudos de Coortes , Humanos , Incidência , Administração Massiva de Medicamentos , Prevalência , Reinfecção , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose Urinária/epidemiologia , Instituições Acadêmicas , Sudão/epidemiologia
5.
BMC Nephrol ; 22(1): 382, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781890

RESUMO

BACKGROUND: It has been noticed for years that ultrafiltration (UF) is important for survival in peritoneal dialysis. On the other hand, precise and convenient UF measurement suitable for patient daily practice is not as straight forward as it is to measure UF in the lab. Both overfill and flush before fill used to be source of measurement error for clinical practice. However, controversy finding around UF in peritoneal dialysis still exists in some situation. The current study was to understand the difference between clinical measured UF and real UF. The effect of evaporation and specific gravity in clinical UF measurement were tested in the study. METHODS: Four different brands of dialysate were purchased from the market. The freshest dialysate available in the market were intentionally picked. The bags were all 2 L, 2.5% dextrose and traditional lactate buffered PD solution. They were stored in four different conditions with controlled temperature and humidity. The bags were weighted at baseline, 6 months and 12 months of storage. Specific gravity was measured in mixed 24 h drainage dialysate from 261 CAPD patients when they come for their routine solute clearance test. RESULTS: There was significant difference in dialysate bag weight at baseline between brands. The weight declined significantly after 12 month's storage. The weight loss was greater in higher temperature and lower humidity. The dialysate in non-PVC package lose less weight than PVC package. The specific gravity of dialysate drainage was significantly higher than pure water and it was related to dialysate protein concentration. CONCLUSION: Storage condition and duration, as well as the type of dialysate package have significant impact in dialysate bag weight before use. Evaporation is likely to be the reason behind. The fact that specific gravity of dialysate drainage is higher than 1 g/ml overestimates UF in manual exchanges, which contributes to systemic measurement error of ultrafiltration in CAPD. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03864120 (March 8, 2019) (Understand the Difference Between Clinical Measured Ultrafiltration and Real Ultrafiltration).

6.
Food Funct ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34788772

RESUMO

Lung cancer is a common cancer with high mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for the majority. The clinical treatment effect of NSCLC is not ideal. The aim of this study was to investigate the inhibitory effect of sea cucumber peptide (SCP) on NSCLC and its mechanism. The results showed that SCP could effectively inhibit the proliferation, migration and invasion of A549 cells. In addition, SCP can also inhibit the formation of pleural effusion and tumor growth in lung cancer mice, reduce liver and kidney injury, increase the levels of IL-2 and IL-12, decrease the levels of IL-6 and TNF-α, and prolong the survival time of mice. The microRNA sequencing and immunohistochemistry of mouse tumors showed that the tumor suppressor gene TUSC2 targeted by miR-378a-5p was involved in the inhibition of tumor growth by SCP. This study provides an experimental basis for the further development of SCP as an anti-tumor nutritional supplement, and provides a new idea for exploring the molecular mechanism of food derived active peptides in anti-tumor applications.

7.
Interdiscip Sci ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817803

RESUMO

In 2002, our research group observed a gene clustering pattern based on the base frequency of A versus T at the second codon position in the genome of Vibrio cholera and found that the functional category distribution of genes in the two clusters was different. With the availability of a large number of sequenced genomes, we performed a systematic investigation of A2-T2 distribution and found that 2694 out of 2764 prokaryotic genomes have an optimal clustering number of two, indicating a consistent pattern. Analysis of the functional categories of the coding genes in each cluster in 1483 prokaryotic genomes indicated, that 99.33% of the genomes exhibited a significant difference (p < 0.01) in function distribution between the two clusters. Specifically, functional category P was overrepresented in the small cluster of 98.65% of genomes, whereas categories J, K, and L were overrepresented in the larger cluster of over 98.52% of genomes. Lineage analysis uncovered that these preferences appear consistently across all phyla. Overall, our work revealed an almost universal clustering pattern based on the relative frequency of A2 versus T2 and its role in functional category preference. These findings will promote the understanding of the rationality of theoretical prediction of functional classes of genes from their nucleotide sequences and how protein function is determined by DNA sequence.

8.
Front Plant Sci ; 12: 718981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721452

RESUMO

Light is highly heterogeneous in natural conditions, and plants need to evolve a series of strategies to acclimate the dynamic light since it is immobile. The present study aimed to elucidate the response of light reaction of photosynthesis to dynamic sunflecks in a shade-tolerant species Panax notoginseng and to examine the regulatory mechanisms involved in an adaptation to the simulated sunflecks. When P. notoginseng was exposed to the simulated sunflecks, non-photochemical quenching (NPQ) increased rapidly to the maximum value. Moreover, in response to the simulated sunflecks, there was a rapid increase in light-dependent heat dissipation quantum efficiency of photosystem II (PSII) (ΦNPQ), while the maximum quantum yield of PSII under light (F v'/F m') declined. The relatively high fluorescence and constitutive heat dissipation quantum efficiency of PSII (Φf,d) in the plants exposed to transient high light (400, 800, and 1,600 µmol m-2 s-1) was accompanied by the low effective photochemical quantum yield of PSII (ΦPSII) after the dark recovery for 15 min, whereas the plants exposed to transient low light (50 µmol m-2 s-1) has been shown to lead to significant elevation in ΦPSII after darkness recovery. Furthermore, PSII fluorescence and constitutive heat dissipation electron transfer rate (J f,d) was increased with the intensity of the simulated sunflecks, the residual absorbed energy used for the non-net carboxylative processes (J NC) was decreased when the response of electron transfer rate of NPQ pathway of PSII (J NPQ) to transient low light is restricted. In addition, the acceptor-side limitation of PSI [Y(NA)] was increased, while the donor-side limitation of photosystems I (PSI) [Y(ND)] was decreased at transient high light conditions accompanied with active cyclic electron flow (CEF). Meanwhile, when the leaves were exposed to transient high light, the xanthophyll cycle (V cycle) was activated and subsequently, the J NPQ began to increase. The de-epoxidation state [(Z + A)/(V + A + Z)] was strongly correlated with NPQ in response to the sunflecks. In the present study, a rapid engagement of lutein epoxide (Lx) after the low intensity of sunfleck together with the lower NPQ contributed to an elevation in the maximum photochemical quantum efficiency of PSII under the light. The analysis based on the correlation between the CEF and electron flow devoted to Ribulose-1, 5-bisphosphate (RuBP) oxygenation (J O) indicated that at a high light intensity of sunflecks, the electron flow largely devoted to RuBP oxygenation would contribute to the operation of the CEF. Overall, photorespiration plays an important role in regulating the CEF of the shade-tolerant species, such as P. notoginseng in response to transient high light, whereas active Lx cycle together with the decelerated NPQ may be an effective mechanism of elevating the maximum photochemical quantum efficiency of PSII under light exposure to transient low light.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34721642

RESUMO

Objective: This study aimed to explore the clinical efficacy and relevant mechanism of Tripterygium glycosides combined with low molecular weight heparin calcium (LMWH) in the treatment of Henoch-Schönlein purpura nephritis (HSPN) in children. Methods: 64 cases of children patients with HSPN treated at Qilu Hospital (Qingdao) from January 2015 to May 2020 were selected and randomly divided into the control group and the observation group and 32 cases in each group. Conventional medical treatment was applied in the two groups, besides which the control group was given LMWH while the observation group was given Tripterygium glycosides based on the control group. The clinical efficacy and the indexes of clinical symptoms of the two groups were compared. Immune globulin level, fibrinogen content (FIB), prothrombin time (PT), platelet level (PLT), and activated partial thromboplastin time (APTT) level of the two groups were compared before and after the treatment. Results: The total effective rate in the observation group was significantly higher than that of the control group, and the recurrence rate in the observation group was lower than that in the control group. After treatment, urine red blood cell count and 24 h urine protein were obviously better than those of the control group. There was no statistically significant difference in PT between the two groups of children before and after treatment. The levels of PLT and FIB in the two groups of patients after treatment were significantly lower than before treatment, and the PLT levels in the observation group were lower than those in the control group. Conclusion: The combination of Tripterygium glycosides and LMWH had good clinical effects in the treatment of children with HSPN, and it could improve the clinical symptoms, the mechanism of which might be related to the increase of PT, a decrease of PLT, and the improvement of coagulation function.

10.
J Clin Transl Hepatol ; 9(5): 661-671, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34722181

RESUMO

Background and Aims: Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways. Methods: Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC. Results: Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expression Omnibus database and our in-house RNA-Seq database. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50-0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiver operator characteristic curve of 0.79 (95% CI: 0.75-0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PPP2CA may be involved in HCC were determined using miRWalk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks. Conclusions: PPP2CA is up-regulated in HCC and higher expression correlates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.

11.
Front Cardiovasc Med ; 8: 763984, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722687

RESUMO

We evaluated the metabolic profile in pig hearts at postnatal day 1, 3, 7, and 28 (P1, P3, P7, and P28, respectively) using a targeted liquid chromatography tandem mass spectrometry assay. Our data showed that there is a clear separation of the detected metabolites in P1 vs. P28 hearts. Active anabolisms of nucleotide and proteins were observed in P1 hearts when cardiomyocytes retain high cell cycle activity. However, the active posttranslational protein modification, metabolic switch from glucose to fatty acids, and the reduced ratio of collagen to total protein were observed in P28 hearts when cardiomyocytes withdraw from cell cycle.

12.
J Virol ; : JVI0147621, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730396

RESUMO

Human cytomegalovirus (HCMV) establishes a persistent/latent infection after primary infection, and host factor(s) plays a key role in regulating HCMV infection status. The spread of reactivated HCMV via the hematogenous or neural route usually results in severe diseases in newborns and immunocompromised individuals. As the primary reservoirs in vivo, cells of myeloid lineage have been utilized extensively to study HCMV infection. However, the molecular mechanism of HCMV latency/reactivation in neural cells is still poorly understood. We previously showed that HCMV infected T98G cells maintain a large number of viral genomes and support HCMV reactivation from latency upon cAMP/IBMX treatment. Here we employed iTRAQ-based proteomics to characterize cellular protein changes during HCMV latency and reactivation in T98G cells. A total of 168 differentially expressed proteins (DEPs) were identified, including 89 proteins in latency and 85 proteins in reactivation. Bioinformatics analysis showed that a few biological pathways were associated with HCMV latency or reactivation. Moreover, we validated 16 DEPs by both mRNA and protein expression profiles and further evaluated the effects of ApoE and PI3K pathway on HCMV infection. ApoE knockdown reduced HCMV loads and virus release, whereas overexpressing ApoE hampered HCMV latent infection, indicating a role in HCMV latency establishment/maintenance. Blocking the PI3K pathway by LY294002, a PI3K inhibitor, induced HCMV reactivation from latency in T98G cells. Overall, this comparative proteomic analysis delineates the cellular protein changes during HCMV latency and reactivation and provides a road map to advance our understanding of the mechanism(s) in the context of neural cells. IMPORTANCE Human cytomegalovirus (HCMV) is a highly transmissible beta-herpesvirus that has a prevalence of 60%-90% worldwide. This opportunist pathogen poses a significant threat to newborns and immunosuppressed individuals. One major obstacle for developing effective therapeutics is a poor understanding of HCMV latency/reactivation mechanisms. This study presents, for the first time, a systemic analysis of host cell protein expression changes during HCMV latency establishment and reactivation processes in neural cells. We showed that ApoE was downregulated by HCMV to facilitate latent infection. Also, the proteomic analysis has associated a few PI3K pathway-related proteins with HCMV reactivation. Altogether, this study highlights multiple host proteins and signaling pathways that can be further investigated as potential druggable targets for HCMV-related diseases, especially brain disorders.

13.
BMC Neurol ; 21(1): 432, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740330

RESUMO

OBJECTIVE: To explore the sensitivity of median and ulnar nerve sensory latency differences in diagnosing carpal tunnel syndrome (CTS) at different severities. METHODS: CTS patients were divided into three groups based on disease severity (mild, moderate, and severe). Distal latency of sensory nerve action potential (SNAP) for the median and ulnar nerves was recorded. The sensitivity of SNAP distal latency to CTS and its correlation with CTS severity were analyzed. RESULTS: Significant differences were found in the median nerve sensory action potential distal latency (MSDL) and in the median and ulnar sensory latency difference to ring finger (MUD) but not in the ulnar nerve sensory action potential distal latency (USDL) between CTS and control. The sensitivity and specificity were 92.2 and 99.4% with an MSDL cutoff value of 2.40 ms, respectively, and were both 100% with a MUD cutoff value of 0.33 ms. There was no significant difference in USDL among the CTS and control groups. Significant differences were found in MSDL and MUD among the CTS severities and between mild and moderate CTS, but not between mild and severe CTS or between moderate and severe CTS. Correlations with CTS severity were observed for MSDL and MUD but not for USDL. CONCLUSION: The ulnar nerve of the CTS patients was not damaged. A smaller MSDL reflected median nerve damage, which can be used for the early diagnosis of CTS. MUD correlated with CTS severity with a higher sensitivity than MSDL, which can provide therapeutic insight without pain to patients.


Assuntos
Síndrome do Túnel Carpal , Síndrome do Túnel Carpal/diagnóstico , Síndrome do Túnel Carpal/terapia , Dedos , Humanos , Nervo Mediano , Condução Nervosa , Nervo Ulnar
14.
Ann Transl Med ; 9(18): 1417, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733969

RESUMO

Background: Twin to twin transfusion syndrome (TTTS) is a serious syndrome that can affect twin pregnancies involving a single placenta, impacts some of twin gestations with monochorionic diamniotic (MCDA) placentas. We validated the ultrasound characteristics of 11-13 weeks' gestation to predict TTTS and selective intrauterine growth restriction (sIUGR) in MCDA pregnancies. Methods: We retrospectively included all of the MCDA twin pregnancies with ultrasound characteristics, including the crown-rump length (CRL), ductus venosus pulsatility index for veins (DV PIV), and nuchal translucency (NT) thickness, at 11-13 weeks' gestation, followed by mean difference and discordance comparison. Receiver operating characteristic (ROC) curves were constructed for the comparison of values of these predictive markers for identification of MCDA pregnancies with high-risk of adverse outcomes. Results: A total of 98 MCDA pregnancies were included in this study. Among the 98, 34 (34.7%) developed sIUGR, whereas 10 (10.2%) expressed TTTS. Significant differences in NT discordance were found among the normal, sIUGR, and TTTS groups; moreover, a significant difference was found between pregnancies with normal outcomes and sIUGR (P<0.001), normal and TTTS (P<0.001), and sIUGR and TTTS (P<0.001). Difference in NT was determined to be the best predictive marker for sIUGR [area under the curve (AUC) =0.769; 95% confidence interval (CI): 0.591 to 0.992], and NT discordance was considered the best predictive marker for TTTS (AUC =0.802; 95% CI: 0.485 to 0.936). Conclusions: Significant differences in NT discordance were found between the normal, sIUGR, and TTTS groups, while NT difference and NT discordance were identified as predictive markers for sIUGR and TTTS, respectively.

15.
Biomaterials ; 279: 121223, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34736149

RESUMO

Harnessing developmental processes for tissue engineering represents a promising yet challenging approach to regenerative medicine. Tooth avulsion is among the most serious traumatic dental injuries, whereas functional tooth regeneration remains uncertain. Here, we established a strategy using decellularized tooth matrix (DTM) combined with human dental pulp stem cell (hDPSC) aggregates to simulate an odontogenesis-related developmental microenvironment. The bioengineered teeth reconstructed by this strategy regenerated three-dimensional pulp and periodontal tissues equipped with vasculature and innervation in a preclinical pig model after implantation into the alveolar bone. These results prompted us to enroll 15 patients with avulsed teeth after traumatic dental injuries in a pilot clinical trial. At 12 months after implantation, bioengineered teeth led to the regeneration of functional teeth, which supported continued root development, in humans. Mechanistically, exosomes derived from hDPSC aggregates mediated the tooth regeneration process by upregulating the odontogenic and angiogenic ability of hDPSCs. Our findings suggest that odontogenic microenvironment engineering by DTM and stem cell aggregates initiates functional tooth regeneration and serves as an effective treatment for tooth avulsion.

16.
Environ Technol ; : 1-12, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34739353

RESUMO

Chromium (Cr) pollution is the primary pollution problem of the soil in tannery. However, the effect of tanning chemicals on Cr migration in soil has not been clearly elucidated. Column leaching tests were designed in this study to reveal the transport and transformation of Cr from basic chromium sulfate (BCS) into soil and the effects of lime on Cr migration and transformation. The results showed that BCS was mainly leached out in the state of Cr(VI) after entering the soil, and the Cr concentration in leachate decreased with the increase of the bulking thickness of the BCS. Compared with the soil absent of lime, the concentration of total Cr in the leachate from soil with lime decreased by 8.80-88.1%. The proportions of Cr in the residual fraction were generally increased in the soil with lime, whereas other fractions were decreased. The presence of lime can reduce the migration and toxicity of BCS in soil to a certain extent. The analysis of soil bacterial community showed that the relative abundance of Proteobacteria increased significantly with the exposure to BCS and the Burkholderiaceae was the dominant bacteria family in the BCS contaminated soil. Understanding the mobility of BCS and lime and the bacterial community in BCS contaminated soil is conducive to the risk assessment of the tannery site.

17.
Adv Mater ; : e2106194, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726310

RESUMO

Nanoparticles have been explored in glioblastomas as they can traverse the blood-brain barrier and target glioblastoma selectively. However, direct observation of nanoparticle trafficking into glioblastoma cells and their underlying intracellular fate after systemic administration remains uncharacterized. Here, based on high-resolution transmission electron microscopy experiments of an intracranial glioblastoma model, it is shown that ligand-modified nanoparticles can traverse the blood-brain barrier, endocytose into the lysosomes of glioblastoma cells, and undergo endolysosomal escape upon photochemical ionization. Moreover, an optimal dose of metronomic chemotherapy using dual-drug-loaded nanocarriers can induce an augmented antitumor effect directly on tumors, which has not been recognized in previous studies. Metronomic chemotherapy enhances antitumor effects 3.5-fold compared with the standard chemotherapy regimen using the same accumulative dose in vivo. This study provides a conceptual framework that can be used to develop metronomic nanoparticle regimens as a safe and viable therapeutic strategy for treating glioblastomas and other advanced-stage solid tumors.

18.
Signal Transduct Target Ther ; 6(1): 405, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795208

RESUMO

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

19.
J Fish Biol ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34813107

RESUMO

Since 1850, each successive decade has been warmer than any preceding one. Warming could have major contribution to the growth of fish larvae. To evaluate the influence of water temperature on the growth of larvae who spawned in later spring and early summer, we selected Scomberomorus niphonius with important ecological and economic value as a sample fish species. We conducted high-resolution spatiotemporal surveys during the 2015 spawning season at an important spawning ground in China. We found that the temperature required for larval survival was stricter than that for spawning. Within the appropriate temperature range, a rapid rise in water temperature was favorable for larval hatching, but S. niphonius hatched at relatively low temperature exhibited a faster growth rate in the yolk-sac and pre-flexion stages. The accumulated temperature and hatching temperature significantly affected the growth rate of S. niphonius larvae. The model that considered developmental stages provided a better explanation of the data than the model that only considered the temperature effect. The model improvement in terms of variance explained was higher for the early developmental stages than for the later developmental stages, suggesting that stage-specific temperature influences were prominent in the earlier stages, like the yolk-sac stage, and then reduced. Our results implied that water temperature anomalies could hazard fish larvae, especially for fish spawning in late spring and early summer. Given that early-life stage fish are highly sensitive to water temperature, it is imperative to incorporate the potential effects of climate change into fisheries management. This article is protected by copyright. All rights reserved.

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