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1.
Bioact Mater ; 20: 574-597, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35846846

RESUMO

The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies to diseases such as osteoarthritis. Tissue engineering has been proposed as a promising strategy to meet the demand of simultaneous regeneration of both cartilage and subchondral bone by constructing integrated gradient tissue-engineered osteochondral scaffold (IGTEOS). This review brought forward the main challenges of establishing a satisfactory IGTEOS from the perspectives of the complexity of physiology and microenvironment of osteochondral tissue, and the limitations of obtaining the desired and required scaffold. Then, we comprehensively discussed and summarized the current tissue-engineered efforts to resolve the above challenges, including architecture strategies, fabrication techniques and in vitro/in vivo evaluation methods of the IGTEOS. Especially, we highlighted the advantages and limitations of various fabrication techniques of IGTEOS, and common cases of IGTEOS application. Finally, based on the above challenges and current research progress, we analyzed in details the future perspectives of tissue-engineered osteochondral construct, so as to achieve the perfect reconstruction of the cartilaginous and osseous layers of osteochondral tissue simultaneously. This comprehensive and instructive review could provide deep insights into our current understanding of IGTEOS.

2.
Biomed Res Int ; 2022: 6871269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35915804

RESUMO

Macrophages play an essential role in the pathogenesis of most inflammatory diseases. Recent studies have shown that mechanical load can influence macrophage function, leading to excessive and uncontrolled inflammation and even systemic damage, including cardiovascular disease and knee osteoarthritis. However, the molecular mechanism remains unclear. In this study, murine RAW264.7 cells were treated with mechanical stretch (MS) using the Flexcell-5000T Tension System. The expression of inflammatory factors and cytokine release were measured by RT-qPCR, ELISA, and Western blotting. The protein expression of NF-κB p65, Iκb-α, p-Iκb-α, RhoA, ROCK1, and ROCK2 was also detected by Western blotting. Then, Flow cytometry was used to detect the proportion of macrophage subsets. Meanwhile, Y-27632 dihydrochloride, a ROCK inhibitor, was added to knockdown ROCK signal transduction in cells. Our results demonstrated that MS upregulated mRNA expression and increased the secretion levels of proinflammatory factors iNOS, IL-1ß, TNF-α, and IL-6. Additionally, MS significantly increased the proportion of CD11b+CD86+ and CD11b+CD206+ subsets in RAW264.7 macrophages. Furthermore, the protein expression of RhoA, ROCK1, ROCK2, NF-κB p65, and IκB-α increased in MS-treated RAW264.7 cells, as well as the IL-6 and iNOS. In contrast, ROCK inhibitor significantly blocked the activation of RhoA-ROCK and NF-κB pathway, decreased the protein expression of IL-6 and iNOS, reduced the proportion of CD11b+CD86+ cells subpopulation, and increased the proportion of CD11b+CD206+ cell subpopulation after MS. These data indicate that mechanical stretch can regulate the RAW264.7 macrophage polarization and enhance inflammatory responses in vitro, which may contribute to activation the RhoA-ROCK/NF-κB pathway.


Assuntos
NF-kappa B , Quinases Associadas a rho , Animais , Inflamação/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
3.
Water Res ; 222: 118896, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35914502

RESUMO

Currently, various strategies have been applied to activate persulfate (PS) for contaminant removal from water. However, the background phosphate ions in water affect PS activation and organic degradation, and the mechanism of their influence on the processes is still controversial. In this review, the possible effects of different phosphate forms (HPO42-, H2PO4-, and PO43-) on PS activation and contaminant degradation were systematically evaluated and summarized. Specifically, HPO42- promotes contaminant degradation in direct peroxymonosulfate (PMS) oxidation and thermal/PMS systems, while it exhibits inhibition to thermal/peroxodisulfate (PDS) and ultraviolet (UV)/PDS systems. Meanwhile, H2PO4- inhibits most oxidation processes based on PMS and PDS, except for non-metal dominated and metal assisted PMS systems. Coexisting HPO42- and H2PO4- could present beneficial effects in thermal, Co2+ and non-metal activated and metal assisted PMS systems. Nevertheless, their inhibitory effects were found in direct PMS oxidation, UV/PMS (or PDS) and metal dominated PMS systems. Generally, phosphate ions inhibit PMS/PDS activation through competing adsorption with PMS or PDS on the solid surface, forming a complex with metal ions, as well as occupying active sites on solid catalysts. In addition, phosphate ions can quench radicals for reduced degradation of contaminants. However, phosphate ions could weaken the bond dissociation energy via combining with PMS and contaminants or form a complex with Co2+, thus displaying a facilitative effect. This review further discusses major challenges and opportunities of PS activation with co-existing phosphates and will provide guidance for better PS utilization in real water treatment practice.

4.
Surg Oncol ; 44: 101818, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35930900

RESUMO

BACKGROUND: Breast cancer (BC) is a common malignant tumor. Apatinib in combination with other treatments has been used for BC; however, its safety and efficacy are not well-known. Therefore, this meta-analysis was performed to assess the efficacy and safety of apatinib in the treatment of BC. METHODS: Studies comparing the effects of apatinib-based therapy versus control among BC patients were included. On January 21, 2022, a systematic search was performed in 9 databases. The risk ratio (RR) with 95% confidence interval (CI) was used to estimate efficacy and safety. The I square value (I2) was used to assess heterogeneity. A leave-one-out sensitivity analysis was also conducted. Publication bias was assessed by funnel plots and Egger's and Begg's tests. RESULTS: A total of 31 studies including 2,258 BC patients were included. The results showed that apatinib group had a significant improvement in disease control rate (DCR, RR = 1.43, 95% CI = 1.35-1.52, I2 = 43.8%) and objective response rate (ORR, RR = 1.79, 95% CI = 1.51-2.13, I2 = 61.8%) compared to the control group. Except for hemorrhage, hypertension, and hand-foot syndrome, the adverse events were similar between apatinib group and control group. Subgroup analyses found statistically significant differences in DCR in all subgroups except for apatinib combined with radiation therapy and with paclitaxel liposome plus S1. For ORR, there were statistically significant differences in all subgroups except for the radiation therapy, and apatinib monotherapy subgroups. CONCLUSIONS: Our study shown apatinib showed good efficacy and acceptable safety in the treatment of BC patients. More high-quality randomized controlled trials from different regions and countries are needed to confirm our findings.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 282: 121659, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35930945

RESUMO

To understand the binding mechanism of a mixture of chiral phenothrin with human serum albumin (HSA), we used multi-spectroscopy, including steady-state fluorescence spectroscopic titration, three-dimensional fluorescence spectroscopy, circular dichroism, and FTIR spectra to explore the precise interactions between the complex. Based on the modified Stern-Volmer equation, the binding constant (Ka) was calculated under three temperatures, which revealed that phenothrin interacts with HSA through a static quenching mechanism. The thermodynamic parameters including enthalpy change (ΔH) and entropy change (ΔS) were determined by fitting the experimental data with van't Hoff equation, which indicates that electrostatic force and hydrogen bonds dominate the interplay in the phenothrin-HSA complex. Circular dichroism and FTIR showed the addition of phenothrin changed the secondary structure of proteins, in which the α-helicity decreased from 52.37% in free HSA to 50.02%. The esterase-like activity was reduced with the increase of phenothrin concentration, which may be attributed to the perturbated senior structure of HSA. Competitive displacement experiments confirmed that phenothrin inserted into the subdomain IIA (site I) of HSA. Several computational approaches such as molecular docking, frontier molecular orbital analysis, and electrostatic potential analysis were utilized to probe into the binding mode of the phenothrin-HSA complex. The binding behaviors of the chiral phenothrin mixture differed during the complexation. In conclusion, both the experimental and theoretical investigations provide useful information for better understanding and reducing the potential deleterious effects of the chiral phenothrin mixture on human long-term physio-pathological status.

6.
Pharm Biol ; 60(1): 1478-1490, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35938504

RESUMO

CONTEXT: Yi-Qi Cong-Ming (YQCM) decoction has been widely used to prevent age-related hearing loss (ARHL), the most prevalent neurodegenerative disease in the elderly. OBJECTIVE: To explore the mechanism of YQCM decoction in the treatment of ARHL. MATERIALS AND METHODS: The chemical constituents of YQCM were screened from the Traditional Chinese Medicine Systems Pharmacology Database. Potential targets of YQCM against ARHL were predicted by DrugBank, GeneCards, and OMIM database. Protein-protein network and enrichment analysis were used for exploring possible molecular mechanisms. Molecular docking and an in vitro model of ARHL by exposing auditory cells with 100 µM H2O2 for 3 h were applied. Cell viability and mitochondrial membrane potential (ΔΨM) were detected by CCK-8 and high-content analysis. γH2AX and cleaved caspase-3 were detected by Western blot. RESULTS: The main compounds have good affinities with hub targets, especially AKT1, PTGS2, and CASP3. GO and KEGG analysis showed that the main biological process and key targets were related to negative regulation of the apoptotic process. H2O2 treatment could reduce the cell viability by 68% and impaired ΔΨM, while 90 µg/mL YQCM pre-treatment could restore the cell viability by 97.45% and increase ΔΨM (2-fold higher). YQCM pre-treatment also reduced γH2AX and cleaved caspase-3 protein levels. CONCLUSIONS: Our study suggested that YQCM prevents ARHL by modulating the apoptosis process in auditory hair cells. Moreover, this study proved that bioinformatics analysis combined with molecular docking and cell model is a promising method to explore other possible pharmacological interventions of ARHL.


Assuntos
Medicamentos de Ervas Chinesas , Perda Auditiva , Doenças Neurodegenerativas , Idoso , Caspase 3 , Medicamentos de Ervas Chinesas/uso terapêutico , Perda Auditiva/tratamento farmacológico , Humanos , Peróxido de Hidrogênio/toxicidade , Medicina Tradicional Chinesa/métodos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Doenças Neurodegenerativas/tratamento farmacológico
7.
Cancer Sci ; 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35950597

RESUMO

Adoptive transfer of T cell receptor (TCR) engineered T cells targeting viral epitopes represents a promising approach for treating virus-related cancers. However, efficient identification of epitopes for T cells and corresponding TCR remains challenging. Here, we report a workflow permitting rapid generation of human papillomavirus (HPV)-specific TCR-T cells. Six epitopes of viral proteins belonged to HPV16 or HPV18 were predicted of high affinity to A11:01 according to bioinformatic analysis. Subsequently, cytotoxic T cells (CTLs) induction were performed with these six antigen peptides separately, and antigen-specific T cells were sorted by FACS. TCR clonotypes of these virus-specific T cells were determined by next-generation sequencing. To improve the efficiency of TCRαß pairs validation, a lentiviral vector library containing 116 TCR constructs was generated, which was consisted of predominant TCRs according to TCR repoertire analysis. Later, TCR library transduced T cells were simulated with peptide pool-pulsed antigen presenting cells, then CD137-positive cells were sorted and subjected to TCR repoertire analysis. The top-hit TCRs and corresponding antigen peptides were deduced and validated. Through this workflow, a TCR targeting the E692-101 of HPV16 was identified. This HPV16-specific TCR-T cells showed high activities to HPV16-positive human cervical cancer cells in vitro and efficiently repressed tumor growth in murine model. This study provides a HPV16-specific TCR fitted to HLA-A11:01 population, and exemplifies an efficient approach which can be applied in large-scale screen of virus-specific TCRs, further encouraging researchers to exploit the therapeutic potential of TCR-T cell technique in treating virus-related cancers.

8.
World J Gastrointest Oncol ; 14(6): 1124-1140, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35949216

RESUMO

BACKGROUND: The functions of infiltrating CD8+ T cells are often impaired due to tumor cells causing nutrient deprivation in the tumor microenvironment. Thus, the mechanisms of CD8+ T cell dysfunction have become a hot research topic, and there is increased interest on how changes in metabolomics correlate with CD8+ T cell dysfunction. AIM: To investigate whether and how glutamine metabolism affects the function of infiltrating CD8+ T cells in hepatocellular carcinoma. METHODS: Immunohistochemical staining and immunofluorescence were performed on surgically resected liver tissues from patients. Differentially expressed genes in infiltrating CD8+ T cells in hepatocellular carcinoma were detected using RNA sequencing. Activated CD8+ T cells were co-cultured with Huh-7 cells for 3 d. The function and mitochondrial status of CD8+ T cells were analyzed by flow cytometry, quantitative real-time polymerase chain reaction, and transmission electron microscopy. Next, CD8+ T cells were treated with the mitochondrial protective and damaging agents. Functional alterations in CD8+ T cells were detected by flow cytometry. Then, complete medium without glutamine was used to culture cells and their functional changes and mitochondrial status were detected. RESULTS: There were a large number of infiltrating PD-1+CD8+ T cells in liver cancer tissues. Next, we co-cultured CD8+ T cells and Huh-7 cells to explore the regulatory effect of hepatoma cells on CD8+ T cells. Flow cytometry results revealed increased PD-1 expression and decreased secretion of perforin (PRF1) and granzyme B (GZMB) by CD8+ T cells in the co-culture group. Meanwhile, JC-1 staining was decreased and the levels of reactive oxygen species and apoptosis were increased in CD8+ T cells of the co-culture group; additionally, the mitochondria of these cells were swollen. When CD8+ T cells were treated with the mitochondrial protective and damaging agents, their function was restored and inhibited, respectively, through the mitochondrial damage and apoptotic pathways. Subsequently, complete medium without glutamine was used to culture cells. As expected, CD8+ T cells showed functional downregulation, mitochondrial damage, and apoptosis. CONCLUSION: Glutamine deprivation impairs the function of infiltrating CD8+ T cells in hepatocellular carcinoma through the mitochondrial damage and apoptotic pathways.

9.
Sci Total Environ ; : 157970, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35963406

RESUMO

A directional leaching in drip irrigation along with intercropping was developed for enhanced phytoremediation of soils contaminated with arsenic (As). Spatiotemporal variations of As levels in soil and effects of irrigation eluents on As migration were analyzed in drip irrigation. Moreover, accumulated levels of As in Zea mays L. and Brassica rapa L. ssp. chinensis (the intercropping species) under drip irrigation and flood irrigation were compared to evaluate the enhancement on phytoremediation by drip irrigation. Results showed that As exhibited a directional migration in soil under drip irrigation, in which the solution of potassium dihydrogen phosphate (PDP) as the eluent significantly promoted As directional migration in soil. Compared to the flood-irrigated intercropping treatments, the As levels in crops (Brassica rapa L. ssp. chinensis) decreased significantly and that of remediating plants (Zea mays L. seedlings) increased significantly under the drip-irrigated intercropping condition. Drip irrigation coupled with intercropping dramatically reduced the risk of As contamination in crops and improved the phytoremediation of As-contaminated soil. PDP further enhanced the disparate effect of drip irrigation on As accumulation by crops and remediation plants.

10.
Front Oncol ; 12: 889284, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957867

RESUMO

Objectives: Anaplastic thyroid cancer (ATC) cells cannot retain the radionuclide iodine 131 (131I) for treatment due to the inability to uptake iodine. This study investigated the feasibility of combining radionuclides with photothermal agents in the diagnosis and treatment of ATC. Methods: 131I was labeled on human serum albumin (HSA) by the standard chloramine T method. 131I-HSA and indocyanine green (ICG) were non-covalently bound by a simple stirring to obtain 131I-HSA-ICG nanoparticles. Characterizations were performed in vitro. The cytotoxicity and imaging ability were investigated by cell/in vivo experiments. The radio-photothermal therapy efficacy of the nanoparticles was evaluated at the cellular and in vivo levels. Results: The synthesized nanoparticles had a suitable size (25-45 nm) and objective biosafety. Under the irradiation of near-IR light, the photothermal conversion efficiency of the nanoparticles could reach 24.25%. In vivo fluorescence imaging and single-photon emission CT (SPECT)/CT imaging in small animals confirmed that I-HSA-ICG/131I-HSA-ICG nanoparticles could stay in tumor tissues for 4-6 days. Compared with other control groups, 131I-HSA-ICG nanoparticles had the most significant ablation effect on tumor cells under the irradiation of an 808-nm laser. Conclusions: In summary, 131I-HSA-ICG nanoparticles could successfully perform dual-modality imaging and treatment of ATC, which provides a new direction for the future treatment of iodine-refractory thyroid cancer.

11.
Nutrients ; 14(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35956280

RESUMO

Many researchers have found that Pb exposure can cause oxidative stress damage to the body's tissue. Black soybean peptide (BSP) has a variety of physiological functions, especially in terms of oxidative stress. Nevertheless, the mitigation function of BSPs on Pb-induced oxidative stress damage in PC12 cells has not been clearly defined. In this study, cell viability was detected by CCK8. Oxidative stress indicators, such as ROS, GSH/GSSG, MDA, SOD, CAT, GPx, and GR, were tested with biochemical kit. Protein expression of Keap1, Nrf2, and TXNIP was measured by Western blot. Compared with the control group, Pb reduced the cell viability of PC12 cells. However, BSP treatment significantly increased the viability of PC12 cells induced by lead exposure (p < 0.05). Lead can enrich the contents of MDA and ROS, but decrease the amount of CAT, SOD, GR, GPx, and GSH/GSSG in PC12 cells, while BSP can alleviate it (p < 0.05). Lead can enhance the expression of Keap1 and TXNIP proteins, but reduce Nrf2 expression. In contrast, BSPs reversed this phenomenon (p < 0.05). BSPs can alleviate oxidative stress injury induced by lead in PC12 cells through the Keap1/Nrf2/TXNIP signaling pathway.


Assuntos
Fator 2 Relacionado a NF-E2 , Soja , Animais , Proteínas de Ciclo Celular/metabolismo , Dissulfeto de Glutationa/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Chumbo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Soja/metabolismo , Superóxido Dismutase/metabolismo
12.
J Inflamm Res ; 15: 4537-4545, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966002

RESUMO

Introduction: Silica nanoparticles (SiNPs) are one of the most widely used inorganic nanomaterials, and exposure to SiNP has been demonstrated to induce pulmonary inflammation, primarily promoted by the NLRP3-mediated macrophage pyroptosis. However, mechanisms underlying the activation of NLRP3 signaling are complex, and whether cathepsin B (CTSB), an enzyme released by the ruptured lysosome, could trigger NLRP3 assembly is controversial. Methods: To further characterize the role of CTSB in silica-induced pyroptosis, we conducted this study by establishing SiNP exposure models in vitro. The morphological features of SiNPs were exhibited by the SEM and TEM, and the effects of SiNPs' internalization on macrophages were examined by the TEM and immunofluorescent staining. Moreover, Western blot was performed to detect the expression of proteins related to pyroptosis and CTSB after blocking the expression of NLRP3 and CTSB. Results: We found that SiNPs internalization caused the rupture of macrophage membrane and promoted the aging of cells with increased intracellular vacuoles. Also, the expression of NLRP3, ASC, Caspase-1, GSDMD, Pro-IL-1ß, IL-1ß, and CTSB increased under the stimulation of SiNP, which could be suppressed by additional treatment with MCC950, an NLRP3-specific inhibitor. Besides, we found SiNP joint treatment with leupeptin, a CTSB inhibitor, could inhibit the expression of CTSB, but it had no effect on the expression of NLRP3, ASC, and Caspase-1, and the process of macrophage pyroptosis was also not affected. Conclusion: SiNP exposure induces rupture of macrophages and the release of lysosomal CTSB, but CTSB fails to specifically act on the NLRP3 inflammasome to induce pyroptosis which is causally linked to lung inflammation and fibrosis.

13.
Int J Womens Health ; 14: 1037-1045, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966402

RESUMO

Background: Human papillomavirus (HPV) is a major cause of cervical cancer (CC) occurrence. This study aimed to explore whether abnormal microRNA (miR)-3653 is associated with HPV infection and to investigate the clinical value of miR-3653 in the diagnosis and prognosis of CC. Methods: Tumor tissues and adjacent non-cancerous tissues were collected from 136 patients with CC. Cervical tissues from 101 patients with uterine fibroids were collected as controls. The expression of miR-3653 was measured by quantitative real-time PCR. The ability of miR-3653 to discriminate between HPV positive (HPV+) and HPV negative (HPV-) CC patients, and to discriminate patients from controls was assessed by receiver operating characteristic analysis. Kaplan-Meier curves and Log rank tests were used to evaluate the relationship of miR-3653 with survival of CC patient. Whether miR-3653 could function as a prognostic indicator was evaluated by univariate and multivariate Cox analyses. Results: miR-3653, highly expressed in CC tissues, was associated with HPV infection, tumor diameter, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis in CC patients. Additionally, miR-3653 was increased in HPV+ controls, CC patients and CC cells. Moreover, miR-3653 could screen HPV+ controls, screen HPV+ patients and screen CC patients. Furthermore, miR-3653 was associated with the survival of CC patients (log-rank P < 0.001) and could serve as an independent prognostic indicator for CC patients. Conclusion: miR-3653, increased in CC, is related to HPV infection and may serve as a diagnostic and prognostic biomarker for CC patients.

14.
ChemSusChem ; 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916074

RESUMO

Photocatalysis is a promising technology for conversion of the glycerol into formic acid, but photocatalytic oxidation of C-C bonds in glycerol exhibits poor selectivity towards formic acid because the photogenerated radicals (e.g., hydroxyl radicals) further oxidize formic acid to CO 2 . In this work, we revealed a synergy of photogenerated holes and superoxide radicals that achieved the selective oxidation of glycerol into formic acid over the TiO 2 catalyst. The charge separation of pristine TiO 2 was improved with the aid of oxygen, which resulted in efficient hole oxidation of the C-C bonds in glycerol to formic acid. Surface active species was controlled to prevent being converted to hydroxyl radicals on TiO 2 via controlling the oxygen and water contents , which solved the problem of formic acid peroxidation without sophisticated catalyst modifications. Mechanism studies suggested that glyceraldehyde and glycolaldehyde were the intermediates to generate formic acid. This work provides a green and efficient approach to produce formic acid as a liquid hydrogen carrier from bio-based alcohols.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35916839

RESUMO

Enzyme immobilization is essential to the commercial viability of various critical large-scale biocatalytic processes. However, vast challenges remain for the immobilization systems, such as difficulties in loading large enzymes, enzyme leaching, and limitations for large-scale fabrication. Herein, we describe a green and scalable strategy to prepare high-performance biocatalysts through in situ assembly of enzymes with covalent organic frameworks (COFs) under ambient conditions (aqueous solution and room temperature). The obtained biocatalysts possess exceptional reusability and stability and serve as efficient biocatalysts for important industrial reactions that cannot be efficiently catalyzed by free enzymes or traditional enzyme immobilization systems. Notably, this versatile enzyme immobilization platform is applicable to various COFs and enzymes. The reactions in an aqueous solution occurred within a short timeframe (ca. 10-30 min) and could be scaled up readily (ca. 2.3 g per reaction).

16.
Front Immunol ; 13: 896685, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924243

RESUMO

Cell therapy is a distinguished targeted immunotherapy with great potential to treat solid tumors in the new era of cancer treatment. Cell therapy products include genetically engineered cell products and non-genetically engineered cell products. Several recent cell therapies, especially chimeric antigen receptor (CAR)-T cell therapies, have been approved as novel treatment strategies for cancer. Many clinical trials on cell therapies, in the form of cell therapy alone or in combination with other treatments, in solid tumors, have been conducted or ongoing. However, there are still challenges since adverse events and the limited efficacy of cell therapies have also been observed. Here, we concisely summarize the clinical milestones of the conducted and ongoing clinical trials of cell therapy, introduce the evolution of CARs, discuss the challenges and limitations of these therapeutic modalities taking CAR-T as the main focus, and analyze the disparities in the regulatory policies in different countries.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Linfócitos T
17.
J Environ Manage ; 318: 115637, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35949089

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) have become a serious threat to human health and ecological security due to their persistence and high toxicity. Lake sediments are in a relatively closed environment, so PAHs and other pollutants can be preserved for a long time. Accurate analysis of the sources of PAHs in sediments is an important prerequisite for PAH pollution control. However, the existing PAHs source resolution receptor model (the absolute principal component analysis - multilinear regression (APCA-MLR) and positive matrix factorization (PMF)) has many defects, such as great uncertainty in the process of matrix rotation. In this study, we collected sediment samples from Taihu Lake and tested their PAH content, and the existing receptor model was improved. High PAH contents were distributed in Meiliang Bay, Zhushan Bay, Gonghu Bay and areas close to the shore. "High-High" areas were distributed in Meiliang Bay, Gonghu Bay and areas close to the shore. "Low-Low" areas appeared in the central and southern parts of Taihu Lake. The results show that the improved positive matrix factorization partition computing (PMF-PC) model is significantly better than the APCA-MLR and PMF models in terms of both numerical simulation accuracy and the spatial distribution consistency of PAHs. The correlations (R2) between the measured and simulated values of low-molecular-weight PAHs (L-PAHs), high-molecular-weight PAHs (H-PAHs) and PAHs were 0.992, 0.989 and 0.993, respectively. The contributions of biomass sources, coal combustion sources and petroleum sources to PAHs in Taihu Lake sediments reached 16.7%, 31.7% and 51.6%, respectively. Fossil fuel sources were mainly concentrated in areas near the shore, and the contribution was lower in areas far from the shore. Although the algorithm still needs to be improved, the PMF-PC model may become a useful tool for the source apportionment of PAHs in sediments.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , China , Monitoramento Ambiental/métodos , Sedimentos Geológicos/análise , Humanos , Lagos , Poluentes Químicos da Água/análise
18.
Front Oncol ; 12: 930846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936746

RESUMO

Objective: To systematically summarize the landscape and characteristics of all approved new anticancer drugs for the last 10 years in China and the United States (US) to further inform the trend, current state, and existing gap in the availability and affordability of cancer medicine between the two countries. Methods: Mainly based on the Pharmcube database, a list and detailed information of anticancer drugs approved in China and the United States were acquired. The annual number, time lag, and basic characteristics, including drug type, mechanism, enterprise type, indication population, drug target, and cancer type of approved drugs were compared. Results: Eighty-seven and 118 new anticancer drugs were approved in China and the US, respectively, showing a stable trend in the US, while a significant increase was observed after 2016 in China. Of the 42 cancer medicines launched in both countries, the US took precedence, and the median time lag markedly decreased, from 6.53 years in 2012 to 0.88 years in 2020. A total of 14.4% of drugs were applicable to children in the US, while only 2.3% were applicable in China, and there was no difference in drug type and enterprise. Thirty-one and 43 targets were explored, with respect to 27 and 36 cancer types in China and the US, respectively, during the period. In addition, the expenditure of drugs on PD-1 and PD-L1 in China was generally lower than that in America. Conclusion: The availability of new anticancer drugs has increased dramatically in the past decade, particularly in China. Compared with the US, the launch of new anticancer drugs in China lags behind, but the time lag has been shortened significantly, and better affordability is observed in immune drugs. More attention should be given to differentiated innovation, and unmet medical needs in special populations like childhood tumors, which are important directions of new drug R&D in China.

19.
Mater Today Bio ; 16: 100360, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35937574

RESUMO

Periodontitis is a bacterial-induced, chronic inflammatory disease characterized by progressive destruction of tooth-supporting structures. Pathogenic bacteria residing in deep periodontal pockets after traditional manual debridement can still lead to local inflammatory microenvironment, which remains a challenging problem and an urgent need for better therapeutic strategies. Here, we integrated the advantages of metal-organic frameworks (MOFs) and hydrogels to prepare an injectable nanocomposite hydrogel by incorporating dexamethasone-loaded zeolitic imidazolate frameworks-8 (DZIF) nanoparticles into the photocrosslinking matrix of methacrylic polyphosphoester (PPEMA) and methacrylic gelatin (GelMA). The injectable hydrogel could be easily injected into deep periodontal pockets, achieving high local concentrations without leading to antibiotic resistance. The nanocomposite hydrogel had high antibacterial activity and constructs with stable microenvironments maintain cell viability, proliferation, spreading, as well as osteogenesis, and down-regulated inflammatory genes expression in vitro. When evaluated on an experimental periodontitis rat model, micro-computed tomography and histological analyses showed that the nanocomposite hydrogel effectively reduced periodontal inflammation and attenuated inflammation-induced bone loss in a rat model of periodontitis. These findings suggest that the nanocomposite hydrogel might be a promising therapeutic candidate for treating periodontal disease.

20.
Int Urol Nephrol ; 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35943662

RESUMO

PURPOSE: In this paper, we aimed to prove that resveratrol can inhibit inflammation in the detrusor smooth muscle of diabetic rats, which may provide a new direction for diabetic cystopathy (DCP) treatment. METHODS: We induced a Sprague-Dawley (SD) rat model of type 1 diabetes by intraperitoneal injections of streptozotocin (STZ). Then, we separated the SD rats into four groups: (1) an excipient-treated control group; (2) a resveratrol-treated control group; (3) an excipient-treated streptozotocin (STZ)-injected group; and (4) a resveratrol-treated STZ-injected group. We administered the resveratrol or excipient by intragastric administration. After 12 weeks of diabetes induction, we measured the blood-sugar concentrations and bladder weights, and we took the bladder tissues of each group of rats for hematoxylin-eosin staining to observe the histological changes. We used real-time quantitative polymerase chain reaction (qPCR) and Western blotting to analyze the expression levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin (IL)-6, and IL-1ß. RESULTS: The bodyweights of the diabetic rats were appreciably reduced, while the bladder weights and blood-glucose concentrations were substantially increased. Oral resveratrol could not improve the changes in the bodyweights and blood-glucose concentrations, but it had a certain effect on the bladder weights. In a macroscopic evaluation, the bladder walls of the STZ-induced diabetes rats were thickened, and, from the H&E staining, we could see that the bladder tissues of the diabetic rats had inflammatory cell infiltration, edema, and the capillary congestion of the mucosa and lamina propria. After resveratrol treatment, the bladder-wall thickening was reduced, and the tissue damage and inflammation were significantly ameliorated. We could associate all these changes with markedly heightened expressions of TNF-α, IL-1ß, IL-6, and NF-κB in the detrusor smooth muscle (DSM) tissues of the diabetic rats. Oral treatment with resveratrol alleviated the expressivity of the inflammatory cytokines in the DSM tissues. CONCLUSIONS: Resveratrol treatment ameliorated the histological changes in the bladder and inhibited the expressions of DSM-tissue inflammatory factors in diabetes rats. Resveratrol may provide a new direction of research for the treatment of diabetic cystopathy.

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