Publications by authors named "Xiaolei Zhang"

559 Publications

X-ray triggered pea-shaped LuAG:Mn/Ca nano-scintillators and their applications for photodynamic therapy.

J Mater Chem B 2022 Aug 15. Epub 2022 Aug 15.

School of Material Science and Engineering, University of Jinan, Jinan, China.

Photodynamic therapy (PDT) is a new minimally invasive technology for disease diagnosis and treatment. However, the biological tissue attenuation of visible light renders the depth of its penetration in tissues quite modest, which significantly restricts its therapeutic applicability. Therefore, it is an essential but yet a difficult task to enhance the X-ray sensitization impact while concurrently limiting the tissue scattering by the rational design of novel biological vectors. Herein, a novel LuAlO:Mn/[email protected] nanoparticle system (LAMCCS) based on a pea-shaped LuAG:Mn/Ca nano-scintillator (LAMC) activating photosensitizer agent (Ce6) was designed. Due to the high radiosensitization of LAMC nano-scintillators and efficient energy conversion efficiency between LAMC and Ce6, more singlet oxygen (O) could be generated to efficiently damage DNA fragments and reveal a good effect of inhibiting the long-term proliferation of tumor cells . Significantly, synergistic therapy with PDT/radiotherapy (RT) and from LAMCCS nanocomposites may still maintain a high tumor growth inhibition rate of 72% than single RT of 10% . Owing to their excellent ability for X-ray sensitization and energy conversion, LAMCCS nanocomposites may have significant tumor growth suppression rates under lower X-ray dose irradiation due to their outstanding X-ray sensitization and energy conversion capabilities, which may open up a new avenue for the advancement of cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2tb01080aDOI Listing
August 2022

Discovery of small molecule Gq/11 protein inhibitors against uveal melanoma.

Acta Pharm Sin B 2022 Aug 4;12(8):3326-3340. Epub 2022 May 4.

National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Guangdong Province Engineering Laboratory for Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Constitutively activated G proteins caused by specific mutations mediate the development of multiple malignancies. The mutated Gq/11 are perceived as oncogenic drivers in the vast majority of uveal melanoma (UM) cases, making directly targeting Gq/11 to be a promising strategy for combating UM. Herein, we report the optimization of imidazopiperazine derivatives as Gq/11 inhibitors, and identified GQ262 with improved Gq/11 inhibitory activity and drug-like properties. GQ262 efficiently blocked UM cell proliferation and migration . Analysis of the apoptosis-related proteins, extracellular signal-regulated kinase (ERK), and yes-associated protein (YAP) demonstrated that GQ262 distinctly induced UM cells apoptosis and disrupted the downstream effectors by targeting Gq/11 directly. Significantly, GQ262 showed outstanding antitumor efficacy with good safety at the testing dose. Collectively, our findings along with the favorable pharmacokinetics of GQ262 revealed that directly targeting Gq/11 may be an efficient strategy against uveal melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apsb.2022.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366314PMC
August 2022

Corynoline Alleviates Osteoarthritis Development via the Nrf2/NF-B Pathway.

Oxid Med Cell Longev 2022 28;2022:2188145. Epub 2022 Jul 28.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Purpose: OA is a multifactorial joint disease in which inflammation plays a substantial role in the destruction of joints. Corynoline (COR), a component of , has anti-inflammatory effects.

Materials And Methods: We evaluated the significance and potential mechanisms of COR in OA development. The viabilities of chondrocytic cells upon COR exposure were assessed by CCK-8 assays. Western blot, qPCR, and ELISA were used to assess extracellular matrix (ECM) degeneration and inflammation. The NF-B pathway was evaluated by western blot and immunofluorescence (IF). Prediction of the interacting proteins of COR was done by molecular docking, while Nrf2 knockdown by siRNAs was performed to ascertain its significance. Micro-CT, H&E, Safranin O-Fast Green (S-O), toluidine blue staining, and immunohistochemical examination were conducted to assess the therapeutic effects of COR on OA in destabilization of medial meniscus (DMM) models.

Results: COR inhibited ECM degeneration and proinflammatory factor levels and modulated the NF-B pathway in IL-1-treated chondrocytes. Mechanistically, COR bound Nrf2 to downregulate the NF-B pathway. Moreover, COR ameliorated the OA process in DMM models.

Conclusion: We suggest that COR ameliorates OA progress through the Nrf2/NF-B axis, indicating COR may have a therapeutic potential for OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/2188145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356246PMC
August 2022

Therapeutic effect and mechanism of danshensu on coronary heart disease using liquid chromatography combined with mass spectrometry metabolomics.

J Chromatogr B Analyt Technol Biomed Life Sci 2022 Jul 28;1208:123400. Epub 2022 Jul 28.

Department of Blood Transfusion, Jiamusi Central Hospital, 256 Zhongshan Street, Xiangyang District, Jiamusi City, Heilongjiang Province, China. Electronic address:

Metabolomics can discover the biomarkers and metabolic pathways, provides the possibility for insights into the pharmacological action and mechanism of natural products. The therapeutic effect and mechanism of danshensu (DSS) on total metabolic pathways has not been well investigated. The aim of this study was to explore the disturbed endogenous biomarkers and metabolic pathways reflecting the pharmacological activity of DSS, and mechanism of action of DSS using comprehensive metabolome analysis based on high-throughput metabolomics technology combined with ultra-high performance liquid chromatography (UPLC) coupled with quadrupole tandem time-of-flight mass spectrometry (Q-TOF-MS) and pattern recognition method. Through the changes of the overall metabolic profile and the related biomarkers, the intervention effect of natural product danshensu (DSS) treatment on CHD model rats was revealed. The results showed that after the model replication was established, the metabolic profile was clearly separated, and a total of 26 potential biomarkers were screened out, and involving 8 metabolic pathways. After different doses of DSS solution were given, a total of 20 biomarkers could be significantly regulated, mainly involving primary bile acid biosynthesis, glycerophospholipid metabolism, and lipid metabolism. It showed UPLC-MS-based metabolomics can be used for discovering potential biomarkers and metabolic pathways of CHD, and to further understand and dissecting pharmacological effects and mechanisms of natural products via metabolomics techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2022.123400DOI Listing
July 2022

GIGYF1 disruption associates with autism and impaired IGF-1R signaling.

J Clin Invest 2022 Aug 2. Epub 2022 Aug 2.

Center for Medical Genetics, Central South University, Changsha, China.

Autism spectrum disorder (ASD) represents a group of neurodevelopmental phenotypes with a strong genetic component. Excess of likely gene-disruptive (LGD) mutations of GIGYF1 was implicated in ASD. Here, we reported that GIGYF1 was the second most mutated gene among known ASD high-confidence risk genes. We investigated the inheritance of 46 GIGYF1 LGD variants, including the highly recurrent mutation, c.333del:p.L111Rfs*234. Inherited GIGYF1 heterozygous LGD variants were 1.8 times more common than de novo mutations. Unlike most high-confidence genes, ASD individuals with GIGYF1 LGD variants were less likely to have cognitive impairments. Using a Gigyf1 conditional knockout mouse model, we showed that haploinsufficiency in the developing brain led to social impairments without significant cognitive impairments. In contrast, homozygous mice showed more severe social disability as well as cognitive impairments. Gigyf1 deficiency in mice led to a reduction of upper layer cortical neurons accompanied by decreased proliferation and increased differentiation of neural progenitor cells. We showed that GIGYF1 regulated the recycling of IGF-1R to cell surface. Knockout of GIGYF1 led to a decreased level of IGF-1R on the cell surface disrupting the IGF-1R/ERK signaling pathway. In summary, our findings showed that GIGYF1 was a regulator of IGF-1R recycling. Haploinsufficiency of GIGYF1 was associated with autistic behaviors likely through interference with IGR-1R/ERK signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI159806DOI Listing
August 2022

Exosomes derived from bone marrow mesenchymal stem cells attenuate neurological damage in traumatic brain injury by alleviating glutamate-mediated excitotoxicity.

Exp Neurol 2022 Jul 25;357:114182. Epub 2022 Jul 25.

Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address:

Background: Traumatic brain injury (TBI) is one of the major contributors to disability and death worldwide. Glutamate-mediated excitotoxicity, one of the secondary injuries occurring after TBI, leads to extreme neuronal apoptosis, and can be a potential target for intervention. Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos) have demonstrated neuroprotective effects on TBI. However, their precise role and the underlying mechanism by which they regulate glutamate-mediated excitotoxicity have not yet been determined. Therefore, this study aimed to determine whether BMSCs-Exos alleviate glutamate excitotoxicity post-TBI and their associated mechanism.

Methods: BMSCs-Exos were extracted from the BMSCs incubation medium and identified by transmission electron microscopy, nanoparticle trafficking analysis, and western blotting. The neuroprotective effects of BMSCs-Exos on glutamate excitotoxicity were investigated in the glutamate-mediated excitotoxicity neuronal cell model and the TBI rat model (TBI induced by controlled cortical impact) using western blotting and TUNEL assay. Cortical lesion samples were collected post-TBI on day-1 and day-14 to study histology. In addition, cortical lesion volume on days 1, 3 and 7 following TBI was determined using T2-weighted magnetic resonance imaging (MRI), and cognitive function was assessed at 4 weeks following TBI using the Morris water maze (MWM) test.

Results: BMSCs-Exos were observed to be spherical with a mean diameter of 109.9 nm, and expressed exosomal markers CD9, CD81 and TSG101. BMSCs-Exos were efficiently endocytosed by astrocytes after co-incubation for 24 h. In vitro studies revealed that 125 μM of glutamate significantly induced neuronal apoptosis, which was attenuated by BMSCs-Exos in astrocyte-neuron co-cultures. This attenuation was mediated by the upregulation of glutamate transporter-1 (GLT-1) level and the downregulation of p-p38 MAPK level in astrocytes. Similar results were obtained in vivo, wherein we verified that PKH67-labeled BMSCs-Exos administered intravenously could reach the perilesional cortex crossing the blood-brain barrier and significantly reduce glutamate levels in the perilesional cortex of the TBI rat, accompanied by increased GLT-1 level and downregulation in p-p38 MAPK level. Additionally, western blotting and TUNEL staining also revealed that BMSCs-Exos significantly downregulated the expression of pro-apoptosis markers, including cleaved caspase-3 and cleaved caspase-9, and attenuated neuronal apoptosis following TBI. Immunohistochemical analysis and Nissl staining showed that BMSCs-Exos significantly increased GLT-1-positive cells, and the number of apoptotic neurons decreased in the perilesional cortex. Moreover, MRI and MWM results revealed that BMSCs-Exos significantly minimized cortical lesion volume and ameliorated cognitive function after TBI. The underlying neuroprotective mechanism of BMSCs-Exos may be due to an increase in GLT-1 level in astrocytes by blocking the p38 MAPK signaling pathway.

Conclusion: Taken together, our findings demonstrate that the implementation of BMSCs-Exos may be an effective prospective therapy for attenuating post-TBI neurological damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.expneurol.2022.114182DOI Listing
July 2022

Prevalence and burden of chronic cough in China: a national cross-sectional study.

ERJ Open Res 2022 Jul 25;8(3). Epub 2022 Jul 25.

National Center of Gerontology, Beijing Hospital, Beijing, China.

Background: Chronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD).

Methods: A representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded.

Results: Chronic cough was found in 3.6% (95% CI 3.1-4.1) of Chinese adults, 2.4% (95% CI 1.9-3.1) of those aged 20-49 years and 6.0% (95% CI 5.3-6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p<0.0001) and more emergency visits (p=0.0042) and hospital admissions (p=0.0002). Furthermore, the impact of chronic cough on PCS score was more significant in those aged 50 years or older, or with COPD (p0.0018 or 0.0002, respectively), with the impact on hospital admission being more significant in those with COPD or with SAD (p=0.0026 or 0.0065, respectively).

Conclusions: Chronic cough is prevalent in China and is associated with a poorer health status, especially in individuals aged 50 years or older and those with the diagnosis of COPD or SAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00075-2022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309344PMC
July 2022

Exercise-induced FNDC5/irisin protects nucleus pulposus cells against senescence and apoptosis by activating autophagy.

Exp Mol Med 2022 Jul 26;54(7):1038-1048. Epub 2022 Jul 26.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang Province, China.

Intervertebral disc degeneration (IVDD) is a major cause of low back pain (LBP), and excessive senescence and apoptosis of nucleus pulposus (NP) cells are major pathological changes in IVDD. Physical exercise could effectively delay the process of intervertebral disc degeneration; however, its mechanism is still largely unknown. Irisin is an exercise-induced myokine released upon cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), and its levels increase after physical exercise. Here, we show that after physical exercise, FNDC5/irisin levels increase in the circulation and NP, senescence and apoptosis are reduced, autophagy is activated in NP tissue, and the progression of IVDD is delayed. Conversely, after knocking out FNDC5, the benefits of physical exercise are compromised. Moreover, the overexpression of FNDC5 in NP tissue effectively alleviated the degeneration of the intervertebral disc (IVD) in rats. By showing that FNDC5/irisin is an important mediator of the beneficial effects of physical exercise in the IVDD model, the study proposes FNDC5/irisin as a novel agent capable of activating autophagy and protecting NP from senescence and apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s12276-022-00811-2DOI Listing
July 2022

Proteomic analysis reveals key differences between squamous cell carcinomas and adenocarcinomas across multiple tissues.

Nat Commun 2022 Jul 18;13(1):4167. Epub 2022 Jul 18.

Department of Pathology, Zhongshan Hospital, State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Fudan University, Shanghai, China.

Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are two main histological subtypes of solid cancer; however, SCCs are derived from different organs with similar morphologies, and it is challenging to distinguish the origin of metastatic SCCs. Here we report a deep proteomic analysis of 333 SCCs of 17 organs and 69 ACs of 7 organs. Proteomic comparison between SCCs and ACs identifies distinguishable pivotal pathways and molecules in those pathways play consistent adverse or opposite prognostic roles in ACs and SCCs. A comparison between common and rare SCCs highlights lipid metabolism may reinforce the malignancy of rare SCCs. Proteomic clusters reveal anatomical features, and kinase-transcription factor networks indicate differential SCC characteristics, while immune subtyping reveals diverse tumor microenvironments across and within diagnoses and identified potential druggable targets. Furthermore, tumor-specific proteins provide candidates with differentially diagnostic values. This proteomics architecture represents a public resource for researchers seeking a better understanding of SCCs and ACs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-022-31719-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293992PMC
July 2022

MiR-1306-5p promotes cell proliferation and inhibits cell apoptosis in acute myeloid leukemia by downregulating PHF6 expression.

Leuk Res 2022 Jun 23;120:106906. Epub 2022 Jun 23.

Department of Medical Basic, Jiangsu College of Nursing, No. 9, Science and Technology Avenue, Huai'an 223005, Jiangsu, China. Electronic address:

Background: Deregulated expression of miRNAs contributes to the development of numerous malignancies, including acute myeloid leukemia (AML). The present work focused on investigating the role of miR-1306-5p in AML pathogenesis and the possible mechanisms.

Methods: The expression levels of miR-1306-5p and PHF6 were assessed in 30 healthy controls and 48 newly diagnosed AML patients. CCK-8 assay, EdU staining, quantitative real-time PCR, TUNEL assay, western blots, and flow cytometry were used to characterize the changes induced by miR-1306-5p or PHF6 overexpression or inhibition. In addition, Starbase and miRWalk databases were adopted to predict the miR-1306-5p target genes.

Results: Here we reported that upregulation of miR-1306-5p was a frequent event in both primary leukemic cells from AML patients and AML cell lines. Functional assays indicated that downregulation of miR-1306-5p leads to AML cell growth arrest, less proliferation, and elevated rates of apoptosis. Mechanistically, miR-1306-5p targets PHF6, a protein that plays a key role in gene transcription regulation. Our data further showed that PHF6 was downregulated in AML patients and cell lines, and depletion of PHF6 expression using RNA interference further enhanced the proliferation while reducing the apoptosis of those leukemic cells.

Conclusion: Our findings show that miR-1306-5p promotes proliferation and prevents apoptosis in AML by directly modulating PHF6 expression and consequently contributes to AML development and progression. miR-1306-5p may function as an oncogene in AML, providing a promising therapeutic target for AML patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2022.106906DOI Listing
June 2022

DeepRF: A deep learning method for predicting metabolic pathways in organisms based on annotated genomes.

Comput Biol Med 2022 Aug 20;147:105756. Epub 2022 Jun 20.

Institute of Artificial Intelligence, School of Computer Science, Wuhan University, China. Electronic address:

The rapid increase of metabolomics has led to an increasing focus on metabolic pathway modeling and reconstruction. In particular, reconstructing an organism's metabolic network based on its genome sequence is a key challenge in systems biology. The method used to address this problem predicts the presence or absence of metabolic pathways from known pathways in a reference database. However, this method is based on manual metabolic pathway construction and cannot be used for large genome sequencing data. To address such problems, we apply a supervised machine learning approach consisting of deep neural networks to learn feature representations of metabolic pathways and feed these representations into random forests to predict metabolic pathways. The supervised learning model, DeepRF, predicts all known and unknown metabolic pathways in an organism. Evaluation of DeepRF on over 318,016 instances shows that the model can predict metabolic pathways with high-performance metrics accuracy (>97%), recall (>95%), and precision (>99%). Comparing DeepRF with other methods in the literature shows that DeepRF produces more reliable results than other methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiomed.2022.105756DOI Listing
August 2022

Aberrant nucleosome organization in mouse SCNT embryos revealed by ULI-MNase-seq.

Stem Cell Reports 2022 07 23;17(7):1730-1742. Epub 2022 Jun 23.

Clinical and Translation Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address:

Somatic cell nuclear transfer (SCNT) can reprogram terminally differentiated somatic cells into totipotent embryos, but with multiple defects. The nucleosome positioning, as an important epigenetic regulator for gene expression, is largely unexplored during SCNT embryonic development. Here, we mapped genome-wide nucleosome profiles in mouse SCNT embryos using ultra-low-input MNase-seq (ULI-MNase-seq). We found that the nucleosome-depleted regions (NDRs) around promoters underwent dramatic reestablishment, which is consistent with the cell cycle. Dynamics of nucleosome position in SCNT embryos were delayed compared to fertilized embryos. Subsequently, we found that the aberrant gene expression levels in inner cell mass (ICM) were positively correlated with promoter NDRs in donor cells, which indicated that the memory of nucleosome occupancy in donor cells was a potential barrier for SCNT-mediated reprogramming. We further confirmed that the histone acetylation level of donor cells was associated with the memory of promoter NDRs. Our study provides insight into nucleosome reconfiguration during SCNT preimplantation embryonic development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.stemcr.2022.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287678PMC
July 2022

Accelerate sulfamethoxazole degradation and detoxification by persulfate mediated with Fe&dithionite: Experiments and DFT calculation.

J Hazard Mater 2022 08 1;436:129254. Epub 2022 Jun 1.

School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen 518055, China.

Advanced oxidation process (AOPs) is one of the most effective technologies for organic pollutants removal. In this study, diverse reactive species generation and enhanced sulfamethoxazole (SMX) degradation were investigated based on persulfate (PDS) activated by Fe&dithionite (DTN). When involving Fe&dithionite in PDS, SMX degradation efficiency reached 84 % within 30 min following a pseudo-first-order kinetic, which was higher than those in Fe/PDS (50.4 %) and Fe/O/DTN (41.3 %). SO and OH were identified as dominant reactive species with a crucial role of FeSO based on quenching experiment and electron spin resonance (ESR). The contributions of SO, OH, and other species to SMX degradation were 60.1 %, 33.9 %, and 6 %, respectively. In Fe/DTN/PDS system, SMX was effectively degraded under nearly neutral pH (5.0-9.0), with activation energy of 96.04 kJ·mol. The experiments and density functional theory (DFT) calculation demonstrated that three functional groups (benzenesulfonamido, benzene ring, and oxazole ring) were attacked for SMX degradation. Moreover, acute toxicity to Vibrio fischeri has enhanced in the earlier degradation process due to the intermediates and weaken with the continuous reaction. This work not only provides a high-activity SO-AOP for refractory pollutant treatment with possible dual radical generation resources, but elucidated diverse reactive species formation with Fe&dithionite.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2022.129254DOI Listing
August 2022

Metformin inactivates the cGAS-STING pathway through autophagy and suppresses senescence in nucleus pulposus cells.

J Cell Sci 2022 Aug 2;135(15). Epub 2022 Aug 2.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325088 Zhejiang Province, China.

Intervertebral disc degeneration (IVDD) is a complex process involving many factors, among which excessive senescence of nucleus pulposus cells is considered to be the main factor. Our previous study found that metformin can inhibit senescence in nucleus pulposus cells; however, the mechanism of such an action was still largely unknown. In the current study, we found that metformin inactivates the cGAS-STING pathway during oxidative stress. Furthermore, knockdown of STING (also known as STING1) suppresses senescence, indicating that metformin might exert its effect through the cGAS-STING pathway. Damaged DNA is a major inducer of the activation of the cGAS-STING pathway. Mechanistically, our study showed that DNA damage was reduced during metformin treatment; however, suppression of autophagy by 3-methyladenine (3-MA) treatment compromised the effect of metformin on DNA damage. In vivo studies also showed that 3-MA might diminish the therapeutic effect of metformin on IVDD. Taken together, our results reveal that metformin may suppress senescence via inactivating the cGAS-STING pathway through autophagy, implying a new application for metformin in cGAS-STING pathway-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/jcs.259738DOI Listing
August 2022

Discovery of Novel Benzo[4,5]imidazo[1,2-]pyrazin-1-amine-3-amide-one Derivatives as Anticancer Human A Adenosine Receptor Antagonists.

J Med Chem 2022 07 17;65(13):8933-8947. Epub 2022 Jun 17.

Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. China.

The blockade of A adenosine receptor (AAR) activates immunostimulatory response through regulating signaling in tumor microenvironment. Thus, AAR has been proposed as a promising target for cancer immunotherapy. In this work, we designed a new series of benzo[4,5]imidazo[1,2-]pyrazin-1-amine derivatives bearing an amide substitution at 3-position to obtain potent antitumor antagonist . The structure-activity relationship studies were performed by molecular modeling and radioactive assay. The anticancer activities were evaluated by 3',5'-cyclic adenosine monophosphate (cAMP) functional and T cell activation assay. The most potent compound showed much higher affinity toward AAR ( = 0.08 nM) and exhibited more significant immunostimulatory anticancer activity than clinical antagonist AZD4635. More importantly, significantly inhibited the growth of triple-negative breast cancer by reversing immunosuppressive tumor microenvironment in the xenograft mouse model without severe toxicity at the testing dose. These results make a promising immunotherapy anticancer drug candidate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.2c00101DOI Listing
July 2022

Impact of schizophrenia GWAS loci converge onto distinct pathways in cortical interneurons vs glutamatergic neurons during development.

Mol Psychiatry 2022 Jun 14. Epub 2022 Jun 14.

Department of Cell biology and Anatomy, New York Medical College, Valhalla, NY, 10595, USA.

Remarkable advances have been made in schizophrenia (SCZ) GWAS, but gleaning biological insight from these loci is challenging. Genetic influences on gene expression (e.g., eQTLs) are cell type-specific, but most studies that attempt to clarify GWAS loci's influence on gene expression have employed tissues with mixed cell compositions that can obscure cell-specific effects. Furthermore, enriched SCZ heritability in the fetal brain underscores the need to study the impact of SCZ risk loci in specific developing neurons. MGE-derived cortical interneurons (cINs) are consistently affected in SCZ brains and show enriched SCZ heritability in human fetal brains. We identified SCZ GWAS risk genes that are dysregulated in iPSC-derived homogeneous populations of developing SCZ cINs. These SCZ GWAS loci differential expression (DE) genes converge on the PKC pathway. Their disruption results in PKC hyperactivity in developing cINs, leading to arborization deficits. We show that the fine-mapped GWAS locus in the ATP2A2 gene of the PKC pathway harbors enhancer marks by ATACseq and ChIPseq, and regulates ATP2A2 expression. We also generated developing glutamatergic neurons (GNs), another population with enriched SCZ heritability, and confirmed their functionality after transplantation into the mouse brain. Then, we identified SCZ GWAS risk genes that are dysregulated in developing SCZ GNs. GN-specific SCZ GWAS loci DE genes converge on the ion transporter pathway, distinct from those for cINs. Disruption of the pathway gene CACNA1D resulted in deficits of Ca currents in developing GNs, suggesting compromised neuronal function by GWAS loci pathway deficits during development. This study allows us to identify cell type-specific and developmental stage-specific mechanisms of SCZ risk gene function, and may aid in identifying mechanism-based novel therapeutic targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-022-01654-zDOI Listing
June 2022

Long-term follow-up of motor cortex stimulation on central poststroke pain in thalamic and extrathalamic stroke.

Pain Pract 2022 Jun 10. Epub 2022 Jun 10.

Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: To investigate the long-term effects of motor cortex stimulation (MCS) on central poststroke pain (CPSP) in patients with thalamic and extrathalamic stroke.

Materials And Methods: We retrospectively analyzed 21 cases of CPSP patients who were treated with MCS. Pain intensity was evaluated using the visual analog scale (VAS) and Neuropathic Pain Symptom Inventory (NPSI) before the operation and at follow-up assessments. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI).

Results: The average follow-up time was 65.43 ± 26.12 months. In the thalamus stroke group (n = 11), the mean preoperative VAS score was 8.18 ± 0.75 and the final mean follow-up VAS score was 4.0 ± 2.14. The mean total NPSI score at the last follow-up (20.45 ± 12.7) was significantly reduced relative to the pre-MCS score (30.27 ± 8.97, p < 0.001). Similarly, the mean PSQI value at the last follow-up (12.63 ± 1.91) was significantly reduced compared with the pre-MCS value (16.55 ± 1.97, p < 0.001). In the extrathalamic stroke group (n = 11), the mean preoperative VAS score was 8.2 ± 0.79 and the final mean follow-up VAS score was 6.6 ± 2.12. The mean total NPSI score before MCS was not statistically different from that at the last follow-up. There were no statistical differences in sleep quality before versus after surgery.

Conclusion: Motor cortex stimulation has higher long-term efficacy in CPSP patients with stroke confined to the thalamus than in CPSP patients with stroke involving extrathalamic structures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/papr.13137DOI Listing
June 2022

The formation and distinct characteristics of aerobic granular sludge with filamentous bacteria in low strength wastewater.

Bioresour Technol 2022 Sep 3;360:127409. Epub 2022 Jun 3.

School of Civil and Environmental Engineering, Shenzhen Key Laboratory of Water Resource Application and Environmental Pollution Control, Harbin Institute of Technology, Shenzhen, Shenzhen, Guangdong 518055, PR China; Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055, PR China; State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, PR China. Electronic address:

In low strength wastewater, aerobic granular sludge (AGS) with filamentous bacteria is often found and regarded as unstable AGS. However, in this study, a new view is proposed that AGS with filamentous bacteria (FAGS) may be the result of low strength wastewater selection. FAGS was found when AGS was cultivated for 30 days. By increasing the settling time, FAGS could keep the mixed liquid suspension (MLSS) at 0.89 g/L. FAGS showed excellent ammonia nitrogen removal performance. The ammonia nitrogen oxidation rate and denitrification rate of FAGS were 1.72 and 1.20 times higher than that of AGS, respectively. FAGS have large specific surface area (15.99 m/g), high extracellular polymeric substances (EPS) content (>200 mg/gVSS), and strong stability (integrity coefficient: 2 ∼ 8%). Furthermore, FAGS showed higher potential than AGS in many aspects such as carbon metabolism, nitrogen metabolism, and toxicant degradation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2022.127409DOI Listing
September 2022

CBR3-AS1 Accelerates the Malignant Proliferation of Gestational Choriocarcinoma Cells by Stabilizing SETD4.

Dis Markers 2022 24;2022:7155525. Epub 2022 May 24.

Department of Reproductive Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Background: Gestational choriocarcinoma (GC) is a rare malignant gestational trophoblastic tumor. Long noncoding RNA (lncRNA) CBR3 antisense RNA 1 (CBR3-AS1) has been reported to serve as a critical oncogene and facilitate tumor progression. Besides, we found that CBR3-AS1 is implicated in GC progression.

Materials And Methods: Gene and protein expression was detected via quantitative reverse transcription PCR (RT-qPCR) and western blot analyses, respectively. CCK-8 assay and colony formation assay were performed to assess cell proliferative abilities while flow cytometry analysis was applied for cell cycle and apoptosis. To analyze the specific mechanism among CBR3-AS1, SET domain containing 4 (SETD4), and polypyrimidine tract binding protein 1 (PTBP1), RNA binding protein immunoprecipitation (RIP), RNA pulldown, and mRNA stability assays were conducted.

Results: CBR3-AS1 was markedly upregulated in GC cells, and its downregulation suppressed cell proliferation, induced cell cycle arrest, but promoted cell apoptosis in GC. SETD4 was determined as the downstream mRNA of CBR3-AS1 and positively regulated by CBR3-AS1 in GC cells. Furthermore, CBR3-AS1 could interact with its RNA binding protein (RBP) PTBP1, thereby stabilizing SETD4 mRNA. Rescue assays verified that CBR3-AS1 facilitates GC cell malignant proliferation via SETD4.

Conclusion: CBR3-AS1 accelerates the malignant proliferation of GC cells via stabilizing SETD4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/7155525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9155919PMC
June 2022

Chronic Obstructive Pulmonary Disease With Asthma-Like Features in the General Population in China.

Front Med (Lausanne) 2022 6;9:876240. Epub 2022 May 6.

State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.

Background: Patients with features of both asthma and chronic obstructive pulmonary disease (COPD) are seen commonly in the clinic but less is known in the general population. We investigated the prevalence and the heterogeneity of COPD with concomitant features of asthma in Chinese adult population.

Methods: COPD was defined as post-bronchodilator ratio of forced expiratory volume in 1s (FEV) to forced vital capacity of less than the lower limits of normal. COPD with concomitant features of asthma was defined as either COPD with asthma diagnosed by self-reported physician-diagnosis or by presence of current wheeze, or as COPD with high bronchodilator response (HBR) defined as an increase in FEV >15% and >400 ml after bronchodilator.

Results: COPD with concomitant features of asthma was found in 1.62% (95% CI 1.31-2.00) of adults (≥20 years) or in 15.2% (95% CI 13.0-17.7) of COPD patients. Compared with COPD with HBR, COPD with asthma diagnosis or wheeze were older (61.8 ± 1.1 years vs. 47.4 ± 2.8 years, < 0.001), and with a lower post-bronchodilator FEV%pred (68.2 ± 2.3 vs. 96.6 ± 3.4, < 0.001). Age, smoking status, biomass use and allergic rhinitis were associated with increasing prevalence of COPD with asthma diagnosis or wheeze, and had greater impaired health status, more comorbidities and more acute exacerbations in the preceding 12 months.

Conclusions: COPD with concomitant features of asthma is common in people with COPD and those with COPD with asthma diagnosis or wheeze experience worse clinical severity than COPD with HBR. These findings will help toward the definition of the asthma-COPD overlap condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2022.876240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120624PMC
May 2022

The application of pediatric early warning score (PEWS) in emergency observation room.

J Pediatr Nurs 2022 May 18;66:1-5. Epub 2022 May 18.

Department of Pediatric Emergency Medicine and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai 201102, PR China. Electronic address:

Objective: To explore the value of pediatric early warning scoring system (PEWS) in an emergency observation room in China.

Methods: The children who had been admitted consecutively to the emergency observation room from Jan, 2019 to Aug, 2020 were selected. Three most important time-points including the first value (admission value), the highest value during the observation (highest value), and final value (discharge value) of Brighton Pediatric Early Warning Score (PEWS) was evaluated in all patients.

Results: 4717 patients were included. They were categorized into 3 groups, namely, discharged group (G1, n = 2320), specialized ward group (G2, n = 2128), and ICU group (G3, n = 269). The different PEWS values of admission value, highest value, and discharge value were significantly different among the 3 groups (P<0.001). Highest value of G1 and G2 were significantly lower than that of G3 (P<0.001). AUROC curves of different PEWS values were used to predict the possibility of PICU admission and PICU mortality within 24 h of admission, and the values were 0.698, 0.878, 0.974 and 0.709, 0.883, 0.951, respectively. The cutoff values for PICU admission of 3 different PEWS values were 2.5 (sensitivity 0.635, specificity 0.699), 3.5 (sensitivity 0.817, specificity 0.9), 3.5 (sensitivity 0.837, specificity 0.985). The cutoff values for PICU mortality of 3 different PEWS values were 4 (sensitivity 0.625, specificity 0.799), 4.5 (sensitivity 0.722, specificity 0.79), 4.5 (sensitivity 0.883, specificity 0.987). The discharge value had the strongest prediction ability.

Conclusions: PEWS can be used for early identification and warning of critically ill children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pedn.2022.05.011DOI Listing
May 2022

[Retracted] MicroRNA‑133a acts as a tumour suppressor in breast cancer through targeting LASP1.

Oncol Rep 2022 Jul 18;48(1). Epub 2022 May 18.

Department of Oncology, Dongying People's Hospital, Dongying, Shandong 257091, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting assay data shown in Figs. 5B, 5E, 6C and 7A were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 39: 473‑482, 2018; DOI: 10.3892/or.2017.6114].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2022.8330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164267PMC
July 2022

The Double-Edged Sword of SIRT3 in Cancer and Its Therapeutic Applications.

Front Pharmacol 2022 27;13:871560. Epub 2022 Apr 27.

National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.

Reprogramming of cellular energy metabolism is considered an emerging feature of cancer. Mitochondrial metabolism plays a crucial role in cancer cell proliferation, survival, and metastasis. As a major mitochondrial NAD-dependent deacetylase, sirtuin3 (SIRT3) deacetylates and regulates the enzymes involved in regulating mitochondrial energy metabolism, including fatty acid oxidation, the Krebs cycle, and the respiratory chain to maintain metabolic homeostasis. In this article, we review the multiple roles of SIRT3 in various cancers, and systematically summarize the recent advances in the discovery of its activators and inhibitors. The roles of SIRT3 vary in different cancers and have cell- and tumor-type specificity. SIRT3 plays a unique function by mediating interactions between mitochondria and intracellular signaling. The critical functions of SIRT3 have renewed interest in the development of small molecule modulators that regulate its activity. Delineation of the underlying mechanism of SIRT3 as a critical regulator of cell metabolism and further characterization of the mitochondrial substrates of SIRT3 will deepen our understanding of the role of SIRT3 in tumorigenesis and progression and may provide novel therapeutic strategies for cancer targeting SIRT3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2022.871560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092499PMC
April 2022

Composition and Leaching Toxicity of Hydrochloric Acid Pickling Sludge Generated from the Hot-Dip Galvanized Steel Industry.

ACS Omega 2022 Apr 12;7(16):13826-13840. Epub 2022 Apr 12.

State Key Laboratory of Heavy Oil Processing, China University of Petroleum-Beijing at Karamay, Karamay 834000, China.

Steel hydrochloric acid pickling sludge (SHPS), containing the heavy metals Fe, Zn, and Ni and a high chloride salt content, is considered a type of hazardous solid waste because of its potential harm to human health and the environment. In addition, the SHPS yield is large, but the main treatment currently used is only safe for landfills. Although studying the composition and leaching toxicity of SHPS is of great importance, only a small amount of related literature is available. This paper can help compensate for this deficiency. SHPS is analyzed from the aspects of its formation mechanism, pH, moisture content, elemental concentration, phase composition, microstructure, and leaching toxicity. The results show that its pH ranges from 2.25 to 11.11, and the moisture content ranges from 45.47% to 83.34%. Additionally, the concentration of Fe is the highest, with values from 29.80% to 50.65%, while other alkali metal elements, namely, Ca, K, and Na, have values of 0.36% to 23.07%, 0.02% to 19.82%, and 0.38% to 3.31%, respectively. Heavy metal elements, namely, Zn, Ni, Mn, Cr, and Pb, have values of 0.02% to 14.88%, 0.001% to 0.05%, 0.03% to 0.38%, 0.01% to 0.09%, and 0.02% to 0.19%, respectively. Anions, namely, SO , Cl, F, and NO , have contents of 0.09% to 0.34%, 0.54% to 5.73%, 0.001% to 0.04%, and 0.01% to 0.15%, respectively. X-ray diffraction (XRD) analysis shows that Fe and Zn are mainly present in oxides, Ca is present as CaO and CaCO, and chlorine is present in NaCl. Moreover, scanning electron microscopy (SEM) analysis shows that the microscopic structure consists mainly of bright and fluffy irregular spheres; stripes; flakes; and dark, very small irregular particles. The leaching toxicity test based on HJ/T 299-2007 (China) was performed, where SHPS samples were treated with a mixed solution of sulfuric acid, nitric acid, and pure water (pH = 3.20 ± 0.05) at a liquid-to-solid ratio of 10:1 for a period of 18 h. The leachate was filtered and analyzed for Cr, Ni, Mn, Zn, etc. The leaching results indicate that Zn and Ni are the main elements that cause SHPS to be hazardous to the environment. These research results can provide a reference for later researchers studying the effective treatment of SHPS, such as more effective treatments for reducing toxicity and resource utilization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.2c00121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088911PMC
April 2022

Longitudinal Variations of CDC42 in Patients With Acute Ischemic Stroke During 3-Year Period: Correlation With CD4 T Cells, Disease Severity, and Prognosis.

Front Neurol 2022 25;13:848933. Epub 2022 Apr 25.

Department of Neurology, ShanXi Province People's Hospital of Shanxi Medical University, Taiyuan, China.

Objective: Cell division cycle 42 (CDC42) modulates CD4 T-cell differentiation, blood lipids, and neuronal apoptosis and is involved in the pathogenesis of acute ischemic stroke (AIS); however, the clinical role of CDC42 in AIS remains unanswered. This study aimed to evaluate the expression of CDC42 in a 3-year follow-up and its correlation with disease severity, T helper (Th)1/2/17 cells, and the prognosis in patients with AIS.

Methods: Blood CDC42 was detected in 143 patients with AIS at multiple time points during the 3-year follow-up period and in 70 controls at admission by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, blood Th1, Th2, and Th17 cells and their secreted cytokines (interferon-γ (IFN-γ), interleukin-4 (IL-4), and interleukin-17A (IL-17A)) in patients with AIS were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively.

Results: Compared with controls ( < 0.001), CDC42 was reduced in patients with AIS. CDC42 was negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score ( < 0.001), whereas, in patients with AIS (all < 0.050), it was positively associated with Th2 cells and IL-4 but negatively correlated with Th17 cells and IL-17A. CDC42 was decreased from admission to 3 days and gradually increased from 3 days to 3 years in patients with AIS (<0.001). In a 3-year follow-up, 24 patients with AIS recurred and 8 patients died. On the 3rd day, 7th day, 1st month, 3rd month, 6th month, 1st year, 2nd year, and 3rd year, CDC42 was decreased in recurrent patients than that in non-recurrent patients (all < 0.050). CDC42 at 7 days ( = 0.033) and 3 months ( = 0.023) was declined in reported deceased patients than in survived patients.

Conclusion: CDC42 is used as a biomarker to constantly monitor disease progression and recurrence risk of patients with AIS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2022.848933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081787PMC
April 2022

Polyester fabrics coated with cupric hydroxide and cellulose for the treatment of kitchen oily wastewater.

Chemosphere 2022 Sep 3;302:134840. Epub 2022 May 3.

College of Sericulture, Textile and Biomass Sciences, Southwest University, 400716, Chongqing, PR China; Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile, 400716, Chongqing, PR China; State Key Laboratory of Silkworm Genome Biology, Southwest University, 400716, Chongqing, PR China. Electronic address:

In recent years, kitchen oily wastewater has received much attention because of its harmful effects on the ecological environment. Therefore, separation of oil from kitchen oily wastewater has become an urgent issue. In this study, this problem could be solved using polyester fabrics covered with cupric hydroxide and cellulose. The functional fabric was obtained by the dipping-rolling-drying process which is an easy and practical way to prepare the fabric and could improve the hydrophilicity of polyester. The functional polyester fabric could separate oil/water mixtures completely under the force of gravity with a high water flux of 2079 L m h-3620 L m h and high separation efficiency of 99.6%. Because kitchen oily wastewater contains floating oil and emulsified oil, we also tested the separation of oil-in-water emulsions. The functional polyester fabric could successfully separate the emulsions with the water flux of 1210 L m h-2018 L m h and a separation efficiency of 99.0%. Moreover, the water flux and separation efficiency of functional polyester fabric remained unchanged after the immersion in salt, alkali, and acid solutions, indicating that the functional polyester fabric exhibited commendable environmental stability. The oil in Chongqing Street Noodles soup with a high oil content was separated to simulate real-life oil/water separation, confirming that the functional polyester fabric could be applied to the treatment of kitchen oily wastewater.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2022.134840DOI Listing
September 2022

Copper-Catalyzed Borylation of Acyl Chlorides with an Alkoxy Diboron Reagent: A Facile Route to Acylboron Compounds.

Chemistry 2022 Jul 13;28(42):e202201329. Epub 2022 Jun 13.

Institut für Anorganische Chemie and Institute for Sustainable Chemistry & Catalysis with Boron, Julius-Maximilians-Universität Würzburg, Am Hubland, 97074, Würzburg, Germany.

Herein, the copper-catalyzed borylation of readily available acyl chlorides with bis(pinacolato)diboron, (B pin ) or bis(neopentane glycolato)diboron (B neop ) is reported, which provides stable potassium acyltrifluoroborates (KATs) in good yields from the acylboronate esters. A variety of functional groups are tolerated under the mild reaction conditions (room temperature) and substrates containing different carbon-skeletons, such as aryl, heteroaryl and primary, secondary, tertiary alkyl are applicable. Acyl N-methyliminodiacetic acid (MIDA) boronates can also been accessed by modification of the workup procedures. This process is scalable and also amenable to the late-stage conversion of carboxylic acid-containing drugs into their acylboron analogues, which have been challenging to prepare previously. A catalytic mechanism is proposed based on in situ monitoring of the reaction between p-toluoyl chloride and an NHC-copper(I) boryl complex as well as the isolation of an unusual lithium acylBpinOBpin compound as a key intermediate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202201329DOI Listing
July 2022

Opsonized nanoparticles target and regulate macrophage polarization for osteoarthritis therapy: A trapping strategy.

J Control Release 2022 07 12;347:237-255. Epub 2022 May 12.

Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.

Osteoarthritis (OA) is a chronic disease caused by joint inflammation. Its occurrence and development depend on a continuous inflammation environment. The activated M1 macrophages play a critical role in the inflammatory response of OA. Regulating the pro-inflammatory M1 to anti-inflammatory M2 macrophages in the OA articular cavity could be a rational strategy for OA treatment. It has been acknowledged that activated macrophages could proactively capture opsonized nanoparticles in the bloodstream and then accumulate into the reticuloendothelial system (RES) organs. Based on this fact, a trapping strategy is proposed, which transforms a normal nanoparticle into an opsonized attractant to target and regulate macrophage polarization. In this study, the opsonized nanoparticle (IgG/[email protected]) had several key features, including an immunoglobulin IgG (the opsonized layer), an anti-inflammatory agent berberine (Bb), and an oxidative stress-responsive bilirubin grafted polylysine biomaterial (BR-PLL) for drug loading (the inner nanocore). In vitro studies confirmed that IgG/[email protected] prefer to be phagocytosed by M1 macrophage, not M0. And the internalized IgG/[email protected] effectively promoted macrophage polarization toward the M2 phenotype and protected nearby chondrocytes. In vivo studies suggested that IgG/[email protected] significantly enhanced therapeutic outcomes by suppressing inflammation and promoting cartilage repair while not prolonging the retention period compared to non-opsonized counterparts. This proof-of-concept study provided a novel opsonization trapping strategy for OA drug delivery and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2022.04.037DOI Listing
July 2022

Ultrasonication effects on physicochemical properties of starch-lipid complex.

Food Chem 2022 Sep 25;388:133054. Epub 2022 Apr 25.

State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong 250353, China; School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong 250353, China. Electronic address:

The starch-lipid complex between the pea starch (PSt) and glycerol monolaurate (GM) was prepared using ultrasound with different amplitudes, durations and application sequences. Fourier-transform infrared and nuclear magnetic resonance spectra showed the formation of amylose-lipid complex between PSt and GM in the ultrasonic field. Stronger diffraction intensities were observed in samples treated by ultrasonication, whereas the thermogravimetric analysis indicated that the thermal stability of starch was improved by the formation of the V-type inclusion complexes. An ultrasound pre-treatment prior to the addition of a guest molecule (UC) was more favorable to induce the formation of an amylose-lipid complexes than ultrasound treatment after PSt was incorporated with GM (CU). The UC-treated samples showed stronger diffraction intensities, higher melting enthalpy values and enzyme-resistant than that of CU-treated PSt-GM complexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2022.133054DOI Listing
September 2022
-->