Publications by authors named "Bo Liu"

4,266 Publications

  • Page 1 of 1

Long-term outcome of combined catheter ablation and left atrial appendage closure in atrial fibrillation patients.

Int J Cardiol 2022 Aug 8. Epub 2022 Aug 8.

Department of Cardiology, School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address:

Background: The combined procedure of catheter ablation and left atrial appendage closure (LAAC) aims to simultaneously control the heart rhythm and reduce the risk of strokes in patients with atrial fibrillation (AF). The study aims to evaluate the procedural safety and long-term outcome of the combined procedure in a large patient cohort.

Methods: Clinical data of AF patients who underwent the combined procedure was retrospectively analyzed. Procedural and imaging follow-up parameters were compared between the transesophageal echocardiography-guided standard process and fluoroscopy-guided modified process, and between the single-seal WATCHMAN and dual-seal LACBES devices. Long-term outcomes included all-cause mortality, thromboembolic events, major bleeding, and recurrence of atrial tachyarrhythmias.

Results: A total of 1114 patients were included. The rates of procedure-related major complications were comparable between the standard and modified processes (3.7% vs. 2.2%, p = 0.219), except for a higher incidence of respiratory depression in standard process group (0.9% vs 0%, p = 0.037), and between WATCHMAN and LACBES devices (2.4% vs. 3.3%, p = 0.535). The follow-up imaging evaluation revealed a high rate of satisfactory seals (99.7%) and a low rate of device related thrombus (1.9%), which were similar between two process groups and devices. The follow-up of over 1960 patient-years revealed low rates of mortality, thromboembolism, and nonprocedural major bleeding (1.8, 3.2, and 0.9 per 100 patient-years, respectively). Recurrent atrial tachyarrhythmias was observed in 23.9% patients.

Conclusions: The results supported the safety and long-term efficacy of the combined procedure of catheter ablation and LAAC. Fluoroscopy-guided LAAC device implantation may be considered in experienced centers.
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http://dx.doi.org/10.1016/j.ijcard.2022.08.007DOI Listing
August 2022

Research on the Integrated Development of Local Art Design and Art Design Education in the New Media Environment.

Authors:
Zhuo Wang Bo Liu

J Environ Public Health 2022 30;2022:1105679. Epub 2022 Jul 30.

ZhuHai City Polytechnic, Zhuhai 519000, China.

With the rapid development of the times, various industries have undergone earth-shaking changes in the face of development trends. The education industry is also making progress in development. Art design and new media technology can be better presented to the public, and it is also convenient for designers. This paper investigates the local art design and art design education. (1) The new media art design and the traditional art design are compared, and the advantages and disadvantages are analyzed. Both have advantages and disadvantages, and they should learn from each other and improve the disadvantages. (2) Conducted an investigation and analysis on art and design education, and the analysis results showed the defects of today's art and design education, and analyzed the methods of improving art and design education through the school's investigation and applied it to art and design education. (3) Artists and designers are very important for local art. This paper analyzes the genealogical relationship of art designers and the composition of local art designers, taking Yunnan as an example.
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http://dx.doi.org/10.1155/2022/1105679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356866PMC
August 2022

Comparative genomic analysis reveals cellulase plays an important role in the pathogenicity of f. sp. .

Front Microbiol 2022 22;13:925355. Epub 2022 Jul 22.

Institute of Plant Immunology, College of Plant Protection, Shenyang Agricultural University, Shenyang, China.

f. sp. and f. sp. , the two formae speciales of , cause northern leaf blight disease of corn and sorghum, respectively, and often cause serious economic losses. They have obvious physiological differentiation and show complete host specificity. Host specificity is often closely related to pathogen virulence factors, including secreted protein effectors and secondary metabolites. Genomic sequencing can provide more information for understanding the virulence mechanisms of pathogens. However, the complete genomic sequence of f. sp. has not yet been reported, and no comparative genomic information is available for the two formae speciales. In this study, f. sp. was predicted to have fewer secreted proteins, pathogen-host interaction (PHI) genes and carbohydrate-active enzymes (CAZys) than f. sp. . Fifteen and 20 polyketide synthase (PKS) genes were identified in f. sp. and f. sp. , respectively, which maintained high homology. There were eight functionally annotated effector protein-encoding genes specifically in f. sp. , among which the encoding gene of endo-1, 4-β-D-glucanase, an important component of cellulase, was significantly up-regulated during the interaction process. Finally, gluconolactone inhibited cellulase activity and decreased infection rate and pathogenicity, which indicates that cellulase is essential for maintaining virulence. These findings demonstrate that cellulase plays an important role in the pathogenicity of f. sp. . Our results also provide a theoretical basis for future research on the molecular mechanisms underlying the pathogenicity of the two formae speciales and for identifying any associated genes.
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http://dx.doi.org/10.3389/fmicb.2022.925355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355644PMC
July 2022

Impact of a phage cocktail targeting and as members of a gut bacterial consortium and .

Front Microbiol 2022 22;13:936083. Epub 2022 Jul 22.

APC Microbiome Ireland, University College Cork, Cork, Ireland.

Escherichia coli and have been implicated as important players in human gut health that have been associated with the onset of inflammatory bowel disease (IBD). Bacteriophage (phage) therapy has been used for decades to target pathogens as an alternative to antibiotics, but the ability of phage to shape complex bacterial consortia in the lower gastrointestinal tract is not clearly understood. We administered a cocktail of six phages (either viable or heat-inactivated) targeting pro-inflammatory LF82 and OG1RF as members of a defined community in both a continuous fermenter and a murine colitis model. The two target strains were members of a six species simplified human microbiome consortium (SIHUMI-6). In a 72-h continuous fermentation, the phage cocktail caused a 1.1 and 1.5 log (log genome copies/mL) reduction in and numbers, respectively. This interaction was accompanied by changes in the numbers of other SIHUMI-6 members, with an increase of (1.7 log) and (1.8 log). However, in germ-free mice colonized by the same bacterial consortium, the same phage cocktail administered twice a week over nine weeks did not cause a significant reduction of the target strains. Mice treated with active or inactive phage had similar levels of pro-inflammatory cytokines (IFN-y/IL12p40) in unstimulated colorectal colonic strip cultures. However, histology scores of the murine lower GIT (cecum and distal colon) were lower in the viable phage-treated mice, suggesting that the phage cocktail did influence the functionality of the SIHUMI-6 consortium. For this study, we conclude that the observed potential of phages to reduce host populations in models did not translate to a similar outcome in an setting, with this effect likely brought about by the reduction of phage numbers during transit of the mouse GIT.
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http://dx.doi.org/10.3389/fmicb.2022.936083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355613PMC
July 2022

Effects of adaptive left bundle branch-optimized cardiac resynchronization therapy: a single centre experience.

BMC Cardiovasc Disord 2022 08 6;22(1):360. Epub 2022 Aug 6.

Department of Cardiology, School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University, #1665, KongJiang Road, Shanghai, 200092, China.

Background: Adaptive cardiac resynchronization therapy (aCRT) is associated with improved clinical outcomes. Left bundle branch area pacing (LBBAP) has shown encouraging results as an alternative option for aCRT. A technique that can be accomplished effectively using LBBAP combined with coronary venous pacing (LOT-aCRT). We aimed to assess the feasibility and outcomes of LOT-aCRT.

Methods: LOT-aCRT, capable of providing two pacing modes, LBBAP alone or LBBAP combined with LV pacing, was attempted in patients with CRT indications. Patients were divided into two groups: those with LBBAP and LV pacing (LOT-aCRT) and those with conventional biventricular pacing (BVP-aCRT).

Results: A total of 21 patients were enrolled in the study (10 in the LOT-aCRT group, 11 in the BVP-aCRT group). In the LOT-aCRT group, the QRS duration (QRSd) via BVP was narrowed from 158.0 ± 13.0 ms at baseline to 132.0 ± 4.5 ms (P = 0.019) during the procedure, and further narrowed to 123.0 ± 5.7 ms (P < 0.01) via LBBAP. After the procedure, when LOT-aCRT implanted and worked, QRSd was further changed to 121.0 ± 3.8 ms, but the change was not significant (P > 0.05). In the BVP-aCRT group, BVP resulted in a significant reduction in the QRSd from 176.7 ± 19.7 ms at baseline to 133.3 ± 8.2 ms (P = 0.011). However, compared with LOT-aCRT, BVP has no advantage in reducing QRSd and the difference was statistically significant (P < 0.01). During 9 months of follow-up, patients in both groups showed improvements in the LVEF and NT-proBNP levels (all P < 0.01). However, compared with BVP-aCRT, LOT-aCRT showed more significant changes in these parameters (P < 0.01).

Conclusions: The study demonstrates that LOT-aCRT is clinically feasible in patients with systolic heart failure and LBBB. LOT-aCRT was associated with significant narrowing of the QRSd and improvement in LV function.
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http://dx.doi.org/10.1186/s12872-022-02742-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357303PMC
August 2022

Influence of land use changes on the remaining available aquifer storage (RAAS): A case study of the Taoerhe alluvial-proluvial fan.

Sci Total Environ 2022 Aug 3:157848. Epub 2022 Aug 3.

State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering, Hohai University, Nanjing 210098, China; College of Hydrology and Water Resources, Hohai University, Nanjing 210098, China.

Groundwater resources are important water sources for people living in arid-semiarid China. To solve the problem of continuously declining groundwater levels, groundwater artificial recharge has been widely conducted by using available aquifers. However, the effects of land use changes on the available aquifer storage, especially on the remaining available aquifer storage (RAAS), have not been fully explored. Here, we quantitatively evaluated the effects of land use changes on the RAAS, exemplifying the Taoerhe alluvial-proluvial fan. Independent component analysis (ICA) is used to determine precipitation- and groundwater extraction-affected RAASs, and regression equations are established for land use type areas and precipitation- and groundwater extraction-affected RAASs through stepwise regression and all-subsets regression. An integrated model combining the future land use simulation (FLUS) model and Markov-chain model is established to predict three land use change scenarios in 2036, and the impacts of land use changes on the precipitation- and groundwater extraction-affected RAASs are evaluated. The results show that land use changes were generally active from 2000 to 2018; during this time, the RAAS showed a fluctuating upward trend. Rational land use changes are critical to the RAAS. In the 2036 baseline scenario, the precipitation-affected RAAS is the smallest and the groundwater extraction-affected RAAS is the largest among the three scenarios, contrary to the economic development scenario results. The woodland conservation scenario shows that the groundwater level can be maintained at a stable level with appropriate woodland protection measures to ensure the stability of the RAAS, providing the most promising results for groundwater development and utilization in the study area. These results temporally quantify the effects of land use changes on the precipitation- and groundwater extraction-affected RAASs and provide a reference for developing artificial recharge schemes in arid-semiarid regions and studying the effects of land use changes on available aquifer storages.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157848DOI Listing
August 2022

Biomimetic material degradation for synergistic enhanced therapy by regulating endogenous energy metabolism imaging under hypothermia.

Nat Commun 2022 Aug 5;13(1):4567. Epub 2022 Aug 5.

Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, P. R. China.

Inefficient tumour treatment approaches often cause fatal tumour metastases. Here, we report a biomimetic multifunctional nanoplatform explicitly engineered with a Co-based metal organic framework polydopamine heterostructure (MOF-PDA), anethole trithione (ADT), and a macrophage membrane. Co-MOF degradation in the tumour microenvironment releases Co, which results in the downregulation of HSP90 expression and the inhibition of cellular heat resistance, thereby improving the photothermal therapy effect of PDA. HS secretion after the enzymatic hydrolysis of ADT leads to high-concentration gas therapy. Moreover, ADT changes the balance between nicotinamide adenine dinucleotide/flavin adenine dinucleotide (NADH/FAD) during tumour glycolysis. ATP synthesis is limited by NADH consumption, which triggers a certain degree of tumour growth inhibition and results in starvation therapy. Potentiated 2D/3D autofluorescence imaging of NADH/FAD is also achieved in liquid nitrogen and employed to efficiently monitor tumour therapy. The developed biomimetic nanoplatform provides an approach to treat orthotopic tumours and inhibit metastasis.
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http://dx.doi.org/10.1038/s41467-022-32349-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355994PMC
August 2022

O-GlcNAcylation stabilizes the autophagy-initiating kinase ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection.

J Biol Chem 2022 Aug 2:102341. Epub 2022 Aug 2.

Beijing Key Laboratory of DNA Damage Response and College of Life Science, Capital Normal University, Beijing 100048, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China. Electronic address:

Human papillomaviruses (HPVs) cause a subset of cases of head and neck squamous cell carcinomas (HNSCCs). Previously, we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked GlcNAcylation (O-GlcNAc) transferase (OGT), but the OGT substrates and cellular pathways affected by this increase are unclear. Here, we focus on the effects of O-GlcNAcylation on HPV-positive HNSCCs. We found that upon HPV infection, ULK1, an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized, and linked with autophagy elevation. Through mass spectrometry, we identified that ULK1 is O-GlcNAcylated at Ser409, which is distinct from the previously reported Thr635/Thr754 sites. It has been demonstrated that PKCαmediates phosphorylation of ULK1 at Ser423, which attenuates its stability by shunting ULK1 to the chaperone-mediated autophagy (CMA) pathway. Using biochemical assays, we demonstrate that ULK1 Ser409Ser410 O-GlcNAcylation antagonizes its phosphorylation at Ser423. Moreover, we found that mutations of Ser409A and its neighboring site Ser410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperone Hsc70. Further, we determined that ULK1-2A mutants attenuate the association of ULK1 with STX17, which is vital for the fusion between autophagosomes and lysosomes. Analysis of The Cancer Genome Atlas (TCGA) database reveals that ULK1 is upregulated in HPV-positive HNSCCs and its level positively correlates with HNSCC patient survival. Overall, our work demonstrates that O-GlcNAcylation of ULK1 is altered in response to environmental changes. O-GlcNAcylation of ULK1 at Ser409 and perhaps at its neighboring Ser410 stabilizes ULK1, and this might underlie the molecular mechanism of HPV-positive HNSCC patient survival.
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http://dx.doi.org/10.1016/j.jbc.2022.102341DOI Listing
August 2022

Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation.

Cell 2022 Aug 4;185(16):2879-2898.e24. Epub 2022 Aug 4.

BiomX Ltd., 22 Einstein St., Ness Ziona, 7414001, Israel; BiomX Inc., 36 E Industrial Road, Branford, CT 06405, USA.

Human gut commensals are increasingly suggested to impact non-communicable diseases, such as inflammatory bowel diseases (IBD), yet their targeted suppression remains a daunting unmet challenge. In four geographically distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly associated with disease exacerbation and severity. Transfer of clinical IBD-associated Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation. Stepwise generation of a lytic five-phage combination, targeting sensitive and resistant IBD-associated Kp clade members through distinct mechanisms, enables effective Kp suppression in colitis-prone mice, driving an attenuated inflammation and disease severity. Proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers demonstrates gastric acid-dependent phage resilience, safety, and viability in the lower gut. Collectively, we demonstrate the feasibility of orally administered combination phage therapy in avoiding resistance, while effectively inhibiting non-communicable disease-contributing pathobionts.
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http://dx.doi.org/10.1016/j.cell.2022.07.003DOI Listing
August 2022

Visible-Light-Induced α-C(sp)-H Phosphinylation of Unactivated Ethers under Photocatalyst- and Additive-Free Conditions.

J Org Chem 2022 Aug 5. Epub 2022 Aug 5.

School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, P. R. China.

A photocatalyst- and additive-free visible-light-induced α-C(sp)-H phosphinylation of unactivated ethers involving a C-O bond cleavage with molecular oxygen as the sole oxidant at room temperature has been achieved. This method provides a sustainable access to α-hydroxyphosphine oxides in up to 88% yield with good functional group compatibility under mild and neutral conditions (34 examples). Moreover, the subsequent two-step conversion of the resulting dihydroxy diarylphosphine oxides afforded α-phosphinylated cyclic ethers in good overall yields (10 examples).
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http://dx.doi.org/10.1021/acs.joc.2c01502DOI Listing
August 2022

Where should Scoliometer and EOS Imaging be Applied when Evaluating Spinal Rotation in Adolescent Idiopathic Scoliosis -A Preliminary Study with Reference to CT Images.

Global Spine J 2022 Aug 5:21925682221116824. Epub 2022 Aug 5.

Department of Spine Surgery, 66526Beijing Jishuitan Hospital, Beijing, China.

Study Design: Retrospective study.

Objective: Our purpose was to evaluate spinal rotation measurement by scoliometer or EOS Imagings with reference to that by CT images, and to clarify their applicability in clinical practice.

Methods: Patients with adolescent idiopathic scoliosis (AIS) who were indicated for surgery were enrolled and the informed consents were obtained. The angle of trunk rotation (ATR) was measured by the scoliometer. Apical vertebral rotation (AVR) was measured with EOS Imaging and CT images. Paired T tests were used to compare the measurements between ATR or AVR-EOS and AVR-CT. Pearson correlation analysis was performed to explore the relationship between ATR or AVR-EOS and AVR-CT. Then subgroup analysis was performed.

Results: Forty-seven consecutive AIS patients with 62 curves were identified. In the whole group, the ATR, as well as AVR-EOS, was significantly smaller than the AVR-CT. Both ATR and AVR-EOS correlated with AVR-CT, although AVR-EOS correlated better. In thoracic group, there was no significant difference between ATR and AVR-CT ( = .236). A significant correlation was found between ATR and AVR-CT(r = .574, < .001). In TL/L group, no significant difference was noted between AVR-EOS and AVR-CT ( = .414), and a significant correlation was found between AVR-EOS and AVR-CT(r = .824, < .001).

Conclusion: ATR by scoliometer is numerically similar to AVR by CT and may evaluate the spinal rotation more appropriately in thoracic spine. AVR by EOS is numerically similar to AVR by CT and may be more applicable in TL/L spine. Appropriate methods could be selected according to the location of the curve.
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http://dx.doi.org/10.1177/21925682221116824DOI Listing
August 2022

The explorations of dynamic interactions of paxillin at the focal adhesions.

Biochim Biophys Acta Proteins Proteom 2022 Aug 1;1870(10):140825. Epub 2022 Aug 1.

School of Biomedical Engineering, Dalian University of Technology, Key Laboratory for Integrated Circuit and Biomedical Electronic System of Liaoning Province, Dalian 116024, China. Electronic address:

Paxillin is one of the most important adapters in integrin-mediated adhesions that performs numerous crucial functions relying on its dynamic interactions. Its structural behavior serves different purposes, providing a base for several activities. The various domains of paxillin display different functions in the whole process of cell movements and have a significant role in cell adhesion, migration, signal transmission, and protein-protein interactions. On the other hand, some paxillin-associated proteins provide a unique spatiotemporal mechanism for regulating its dynamic characteristics in the tissue homeostasis and make it a more complex and decisive protein at the focal adhesions. This review briefly describes the structural adaptations and molecular mechanisms of recruitment of paxillin into adhesions, explains paxillin's binding dynamics and impact on adhesion stability and turnover, and reveals a variety of paxillin-associated regulatory mechanisms and how paxillin is embedded into the signaling networks.
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http://dx.doi.org/10.1016/j.bbapap.2022.140825DOI Listing
August 2022

Corrigendum to "Hormone sensitive lipase ablation promotes bone regeneration" [Biochim. Biophys. Acta Mol. Basis Dis. Volume 1868, Issue 9, 1 September 2022, 166449].

Biochim Biophys Acta Mol Basis Dis 2022 Aug 1;1868(11):166506. Epub 2022 Aug 1.

Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Stanford Diabetes Research Center, Stanford, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bbadis.2022.166506DOI Listing
August 2022

Relationship between CYP2C8, UGT1A1, and ABCG2 gene polymorphisms and the exposure, efficacy, and toxicity of eltrombopag in the treatment of refractory aplastic anemia.

Eur J Clin Pharmacol 2022 Aug 3. Epub 2022 Aug 3.

Department of Hematology, Peking Union Medical Colleague Hospital, Chinese Academe of Medical Science, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China.

Purpose: Eltrombopag (ELT) is an effective drug for relapsed/refractory aplastic anemia (AA). Our previous study showed that ELT concentration was correlated with the effects of ELT. However, the factors affecting ELT concentration in patients with relapsed/refractory AA were not clarified. Therefore, we aimed to evaluate correlations between drug disposition-related gene polymorphisms and the concentration, efficacy, and toxicity of ELT.

Methods: Forty-five patients who underwent ELT administration from January 2018 to January 2019 at Peking Union Medical Colleague Hospital (PUMCH) were included. The corresponding clinical information was also collected. ELT plasma concentrations were detected by high-performance liquid chromatography-mass spectrometry (HPLC/MS). CYP2C8, (UGT)1A1, and ABCG21 were genotyped by polymerase chain reaction (PCR). The influence of gene polymorphisms on the plasma concentration, efficacy, and toxicity of ELT was analyzed.

Results: The mean dose required to obtain the optimal effects was significantly lower in the UGT1A1*6 variant carriers than in the UGT1A1*6 WT carriers. There was a significant correlation between the (UGT)1A1*6 polymorphism and higher ELT plasma concentrations (> 11.2 μg/mL). By logistic regression analysis, the efficacy of ELT was related to plasma concentration and a combined genotype of (UGT)1A1*6 and ABCG2. There were no significant associations between genotypes and adverse drug reactions (ADRs) or ELT concentrations and ADRs.

Conclusion: UGT1A1*6 is a predictor of the ELT plasma concentration and may help to determine the initial therapeutic dose in relapsed/refractory AA patients. Both drug exposure and patient genotype should be considered for better responses to ELT.
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http://dx.doi.org/10.1007/s00228-022-03367-2DOI Listing
August 2022

Effects of dietary threonine on growth and immune response of oriental river prawn (Macrobrachium nipponense).

Fish Shellfish Immunol 2022 Jul 31. Epub 2022 Jul 31.

Wuxi Fisheries College, Nanjing Agriculture University, Wuxi, 214081, PR China.

A 70-day feeding trial was conducted to ascertain the effects of threonine on immune response of juvenile oriental river prawn (Macrobrachium nipponense). Six isonitrogen and isolipidic feeds were formulated according to levels of dietary threonine (0.35%, 0.79%, 1.18%, 1.67%, 2.08% and 2.48% respectively). The juvenile prawns were divided into six groups with four replicates, and stocked into 24 tanks with 50 prawns per tank (initial weight 0.20 ± 0.02 g). The results showed a significant increasing trend of final body weight, specific growth rate, protein efficiency ratio, and weight gain rate when threonine levels increased to 1.67% (P < 0.05). However, feed intake, feed conversion ratio, and whole-body lipid composition significantly decreased as threonine levels in the feed increased up to 1.67% (P < 0.05). Moreover, haemolymph N-urea content was significantly lowest at 1.67% threonine level (P < 0.05), whereas glucose was highest at 0.79% followed by 1.67% of threonine levels in the feeds. Aspartate aminotransferase (AST) enzyme activities were significantly decreased by an imbalance (except 1.67%) of threonine in the feed (P < 0.05). Activities of Alanine aminotransferase (ALT) and albumen (ALB) were not significantly affected by threonine in the feed (P > 0.05). Excessive dietary threonine level (2.48%) significantly activated haemolymph catalase (CAT) activity (P < 0.05), whereas malondialdehyde (MDA) content was significantly affected by deficient (0.35% and 0.79%) dietary threonine levels (P < 0.05). Inducible nitric oxide synthase (iNOS) activity and haemolymph complement component 4 (C4) content were significantly decreased by deficient levels of threonine in the feed (P < 0.05). Excess threonine concentration significantly down-regulated Toll, Dorsal, Relish, and heat shock protein 60 (Hsp60) gene expressions in the hepatopancreas of M. nipponense (P < 0.05), while all genes were significantly up-regulated by the optimal (1.67%) threonine level (P < 0.05). The threonine level at which maximum specific growth rate of M. nipponense occurred was estimated by second degree polynomial regression analysis as 1.65% of threonine level, equivalent to 4.44% dry weight bases of protein in the feed.
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http://dx.doi.org/10.1016/j.fsi.2022.07.072DOI Listing
July 2022

Run! White blood cells cued by a motor brain under stress.

Authors:
Hai Qi Bo Liu

Cell Res 2022 Aug 1. Epub 2022 Aug 1.

Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China.

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http://dx.doi.org/10.1038/s41422-022-00704-zDOI Listing
August 2022

Time-restricted eating alters the 24-hour profile of adipose tissue transcriptome in men with obesity.

Obesity (Silver Spring) 2022 Aug 1. Epub 2022 Aug 1.

Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.

Objective: Time-restricted eating (TRE) restores circadian rhythms in mice, but the evidence to support this in humans is limited. The objective of this study was to investigate the effects of TRE on 24-hour profiles of plasma metabolites, glucoregulatory hormones, and the subcutaneous adipose tissue (SAT) transcriptome in humans.

Methods: Men (n = 15, age = 63 [4] years, BMI 30.5 [2.4] kg/m ) were recruited. A 35-hour metabolic ward stay was conducted at baseline and after 8 weeks of 10-hour TRE. Assessment included 24-hour profiles of plasma glucose, nonesterified fatty acid (NEFA), triglyceride, glucoregulatory hormones, and the SAT transcriptome. Dim light melatonin onset and cortisol area under the curve were calculated.

Results: TRE did not alter dim light melatonin onset but reduced morning cortisol area under the curve. TRE altered 24-hour profiles of insulin, NEFA, triglyceride, and glucose-dependent insulinotropic peptide and increased transcripts of circadian locomotor output cycles protein kaput (CLOCK) and nuclear receptor subfamily 1 group D member 2 (NR1D2) and decreased period circadian regulator 1 (PER1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) at 12:00 am. The rhythmicity of 450 genes was altered by TRE, which enriched in transcripts for transcription corepressor activity, DNA-binding transcription factor binding, regulation of chromatin organization, and small GTPase binding pathways. Weighted gene coexpression network analysis revealed eigengenes that were correlated with BMI, insulin, and NEFA.

Conclusions: TRE restored 24-hour profiles in hormones, metabolites, and genes controlling transcriptional regulation in SAT, which could underpin its metabolic health benefit.
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http://dx.doi.org/10.1002/oby.23499DOI Listing
August 2022

SApredictor: An Expert System for Screening Chemicals Against Structural Alerts.

Front Chem 2022 13;10:916614. Epub 2022 Jul 13.

Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.

The rapid and accurate evaluation of chemical toxicity is of great significance for estimation of chemical safety. In the past decades, a great number of excellent computational models have been developed for chemical toxicity prediction. But most machine learning models tend to be "black box", which bring about poor interpretability. In the present study, we focused on the identification and collection of structural alerts (SAs) responsible for a series of important toxicity endpoints. Then, we carried out effective storage of these structural alerts and developed a web-server named SApredictor (www.sapredictor.cn) for screening chemicals against structural alerts. People can quickly estimate the toxicity of chemicals with SApredictor, and the specific key substructures which cause the chemical toxicity will be intuitively displayed to provide valuable information for the structural optimization by medicinal chemists.
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http://dx.doi.org/10.3389/fchem.2022.916614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326022PMC
July 2022

Arthroscopic bone graft and fixation for proximal scaphoid nonunions.

Bone Joint J 2022 Aug;104-B(8):946-952

Department of Hand Surgery, Beijing Jishuitan Hospital, the fourth Clinical College of Peking University, Beijing, China.

Aims: This study aims to report the outcomes in the treatment of unstable proximal third scaphoid nonunions with arthroscopic curettage, non-vascularized bone grafting, and percutaneous fixation.

Methods: This was a retrospective analysis of 20 patients. All cases were delayed presentations (n = 15) or failed nonoperatively managed scaphoid fractures (n = 5). Surgery was performed at a mean duration of 27 months (7 to 120) following injury with arthroscopic debridement and arthroscopic iliac crest autograft. Fracture fixation was performed percutaneously with Kirschner (K)-wires in 12 wrists, a headless screw in six, and a combination of a headless screw and single K-wire in two. Clinical outcomes were assessed using grip strength, patient-reported outcome measures, and wrist range of motion (ROM) measurements.

Results: Intraoperatively, established avascular necrosis of the proximal fragment was identified in ten scaphoids. All fractures united within 16 weeks, confirmed by CT. At a mean follow-up of 31 months (12 to 64), there were significant improvements in the Patient-Rated Wrist Evaluation, Mayo Wrist Score, abbreviated Disabilities of the Arm, Shoulder and Hand score, wrist ROM, grip strength, and the patients' subjective pain score. No peri- or postoperative complications were encountered.

Conclusion: Our data indicate that arthroscopic bone grafting and fixation with cancellous autograft is a viable method in the treatment of proximal third scaphoid nonunions, regardless of the vascularity of the proximal fragment. Cite this article:  2022;104-B(8):946-952.
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http://dx.doi.org/10.1302/0301-620X.104B8.BJJ-2022-0198.R1DOI Listing
August 2022

A dRASSF-STRIPAK-Imd-JAK/STAT axis controls antiviral immune response in Drosophila.

Cell Rep 2022 Jul;40(4):111143

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address:

Host antiviral immunity suffers strong pressure from rapidly evolving viruses. Identifying host antiviral immune mechanisms has profound implications for developing antiviral strategies. Here, we uncover an essential role for the tumor suppressor Ras-association domain family (RASSF) in Drosophila antiviral response. Loss of dRassf in fat body leads to increased vulnerability to viral infection and impaired Imd pathway activation accompanied by detrimental JAK/STAT signaling overactivation. Mechanistically, dRASSF protects TAK1, a key kinase of Imd pathway, from inhibition by the STRIPAK PP2A phosphatase complex. Activated Imd signaling then employs the effector Relish to interfere with the dimerization of JAK/STAT transmembrane receptor Domeless, therefore preventing excessive JAK/STAT signaling. Moreover, we find that RASSF and STRIPAK PP2A complex are also involved in antiviral response in human cell lines. Our study identifies an important role for RASSF in antiviral immunity and elucidates a dRASSF-STRIPAK-Imd-JAK/STAT signaling axis that ensures proper antiviral responses in Drosophila.
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http://dx.doi.org/10.1016/j.celrep.2022.111143DOI Listing
July 2022

A passive pump-assisted microfluidic assay for quantifying endothelial wound healing in response to fluid shear stress.

Electrophoresis 2022 Jul 27. Epub 2022 Jul 27.

School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian, Liaoning Province, P. R. China.

There as an urgent need to quantify the endothelial wound-healing process in response to fluid shear stress to improve the biological and clinical understanding of healing mechanisms, which is of great importance for preventing healing impairment, chronic wounds, and postoperative in-stent restenosis. However, current experimental platforms not only require expensive, cumbersome, and powered pumping devices (to, e.g., generate cell scratches and load shear stress stimulation) but also lack quantitative controls for quantitative analysis. In this paper, a passive pump-assisted microfluidic assay is developed to quantify endothelial wound healing in response to fluid shear stress. Our assay consists of passive constant-flow pumps based on the siphon principle and a three-inlet microfluidic chip for cell wound-healing experiments. We also propose a method for quantitatively adjusting cell scratch size by controlling trypsin flow. Both numerical simulations and fluorescein experiments validate the effectiveness of this method. Moreover, we use the designed microfluidic assay to successfully generate cell scratches, load a 12-h shear stress of 5 dyn/cm to the cells, and observe wound healing. The results indicate that the healing of a cell scratch is significantly accelerated under the stimulation of shear stress. In conclusion, our passive pump-assisted microfluidic assay shows versatility, applicability, and the potential for quantifying endothelial wound healing in response to fluid shear stress.
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http://dx.doi.org/10.1002/elps.202200104DOI Listing
July 2022

Evaluation of Laboratory Management Based on a Combination of TOPSIS and RSR Methods: A Study in 7 Provincial Laboratories of China.

Front Public Health 2022 11;10:883551. Epub 2022 Jul 11.

Department of Social Medicine and Health Management, School of Public Health, Jilin University, Changchun, China.

In this study, a comprehensive evaluation of management for pathogenic microbiology laboratories is performed based on a combination of Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) and Rank Sum Ratio (RSR) methods; in addition, the basis for improving laboratory management is provided. Using the laboratory evaluation tool developed by World Health Organization and a combination of TOPSIS and RSR methods, a system of evaluation indicators for the management of Chinese pathogenic microbiology laboratories is established for comprehensively evaluating the pathogenic microbiology laboratories of seven provincial Centers for Disease Control and Prevention. The evaluation system includes 12 primary indicators and 37 secondary indicators. In terms of laboratory management, the seven laboratories were ranked as D, G, E, C, F, B, and A in descending order. None of these laboratories were evaluated as "good" or "poor." One of the laboratories was marked as "relatively poor" (A), two as "medium" (B and F), and four as "relatively good" (C, E, G, and D). In this study, a method for evaluating laboratory management using the TOPSIS and RSR methods is proposed, and a basis for comprehensively evaluating laboratory management for pathogenic microbiology laboratories is provided to reflect management practices.
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http://dx.doi.org/10.3389/fpubh.2022.883551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309487PMC
July 2022

The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing.

J Inflamm Res 2022 20;15:4119-4138. Epub 2022 Jul 20.

Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China.

Poor wound healing in individuals with diabetes has long plagued clinicians, and immune cells play key roles in the inflammation, proliferation and remodeling that occur in wound healing. When skin integrity is damaged, immune cells migrate to the wound bed through the actions of chemokines and jointly restore tissue homeostasis and barrier function by exerting their respective biological functions. An imbalance of immune cells often leads to ineffective and disordered inflammatory responses. Due to the maladjusted microenvironment, the wound is unable to smoothly transition to the proliferation and remodeling stage, causing it to develop into a chronic refractory wound. However, chronic refractory wounds consistently lead to negative outcomes, such as long treatment cycles, high hospitalization rates, high medical costs, high disability rates, high mortality rates, and many adverse consequences. Therefore, strategies that promote the rational distribution and coordinated development of immune cells during wound healing are very important for the treatment of diabetic wounds (DW). Here, we explored the following aspects by performing a literature review: 1) the current situation of DW and an introduction to the biological functions of immune cells; 2) the role of immune cells in DW; and 3) existing (or undeveloped) therapies targeting immune cells to promote wound healing to provide new ideas for basic research, clinical treatment and nursing of DW.
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http://dx.doi.org/10.2147/JIR.S371939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309318PMC
July 2022

Characteristics of Gaseous/Liquid Hydrocarbon Adsorption Based on Numerical Simulation and Experimental Testing.

Molecules 2022 Jul 19;27(14). Epub 2022 Jul 19.

No.1 Geological Logging Company, Daqing 163318, China.

Hydrocarbon vapor adsorption experiments (HVAs) are one of the most prevalent methods used to evaluate the proportion of adsorbed state oil, critical in understanding the recoverable resources of shale oil. HVAs have some limitations, which cannot be directly used to evaluate the proportion of adsorbed state oil. The proportion of adsorbed state oil from HVA is always smaller than that in shale oil reservoirs, which is caused by the difference in adsorption characteristics of liquid and gaseous hydrocarbons. The results of HVA need to be corrected. In this paper, HVA was conducted with kaolinite, an important component of shale. A new method is reported here to evaluate the proportion of adsorbed state oil. Molecular dynamics simulations (MDs) of gaseous/liquid hydrocarbons with the same temperature and pressure as the HVAs were used as a reference to reveal the errors in the HVAs evaluation from the molecular scale. We determine the amount of free state of hydrocarbons by HVAs, and then calculate the proportion of adsorbed state oil by the liquid hydrocarbon MD simulation under the same conditions. The results show that gaseous hydrocarbons adsorptions are monolayer at low relative pressures and bilayer at high relative pressures. The liquid hydrocarbons adsorption is multilayer adsorption. The adsorption capacity of liquid hydrocarbons is over 2.7 times higher than gaseous hydrocarbons. The new method will be more effective and accurate to evaluate the proportion of adsorbed state oil.
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http://dx.doi.org/10.3390/molecules27144590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317328PMC
July 2022

Reproductive Hormones Mediate Intestinal Microbiota Shifts during Estrus Synchronization in Grazing Simmental Cows.

Animals (Basel) 2022 Jul 7;12(14). Epub 2022 Jul 7.

College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China.

To study shifts in the intestinal microbiota during estrus synchronization in ruminants, we characterized the intestinal microbiota in grazing Simmental cows and the possible mechanism that mediates this shift. Fourteen postpartum Simmental beef cows were synchronized beginning on day 0 (D0) with a controlled internal release device (CIDR), and cloprostenol was injected on D9 when the CIDR was withdrawn. Synchronization ended with timed artificial insemination on D12. Serum and rectal samples harvested on D0, D9, and D12 were analyzed to assess the reproductive hormones and microbiota. Reproductive hormones in the serum of the host were measured using enzyme-linked immunosorbent assay. The microbiota was characterized using 16S rRNA sequencing of the V3-V4 hypervariable region, alpha diversity and beta diversity analyses (principal coordinate analysis, PCoA), cladogram of the linear discriminant analysis effect size (LEfSe) analysis, and microbiota function analysis. Levels of the reproductive hormones, except gonadotropin-releasing hormone ( > 0.05), shifted among D0, D9, and D12 ( < 0.05). Decreased community diversity (Chao1 and ACE) was observed on D12 compared with D0 ( < 0.05). The beta diversity (PCoA) of the microbiota shifted markedly among D0, D9, and D12 ( < 0.05). The LEfSe analysis revealed shifts in the intestinal microbiota communities among D0, D9, and D12 ( < 0.05 and LDA cutoff >3.0). The KEGG pathway analysis showed that carbohydrate metabolism, genetic information and processing, the excretory system, cellular processes and signaling, immune system diseases, and the metabolism were altered ( < 0.05). Reproductive hormones (especially estradiol) were correlated with the alpha diversity indices, beta diversity indices, and an abundance of biomarkers of the shifting intestinal microbiota ( < 0.05). In conclusion, the structure, composition, and function of the intestinal microbiota were shifted during estrus synchronization in a grazing Simmental cow model, and these shifts were mediated by reproductive hormones.
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http://dx.doi.org/10.3390/ani12141751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311722PMC
July 2022

Patulin Detoxification by Recombinant Manganese Peroxidase from Expressed by .

Toxins (Basel) 2022 Jun 29;14(7). Epub 2022 Jun 29.

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

The fungal secondary metabolite patulin is a mycotoxin widespread in foods and beverages which poses a serious threat to human health. However, no enzyme was known to be able to degrade this mycotoxin. For the first time, we discovered that a manganese peroxidase (MnP) from can efficiently degrade patulin. The MnP gene was cloned into pPICZα(A) and then the recombinant plasmid was transformed into X-33. The recombinant strain produced extracellular manganese peroxidase with an activity of up to 3659.5 U/L. The manganese peroxidase MnP was able to rapidly degrade patulin, with hydroascladiol appearing as a main degradation product. Five mg/L of pure patulin were completely degraded within 5 h. Moreover, up to 95% of the toxin was eliminated in a simulated patulin-contaminated apple juice after 24 h. Using as a model, it was demonstrated that the deconstruction of patulin led to detoxification. Collectively, these traits make MnP an intriguing candidate useful in enzymatic detoxification of patulin in foods and beverages.
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http://dx.doi.org/10.3390/toxins14070440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324453PMC
June 2022

The Secreted Ribonuclease SRE1 Contributes to Virulence and Activates Plant Immunity.

Front Microbiol 2022 8;13:941991. Epub 2022 Jul 8.

College of Plant Protection, Shenyang Agricultural University, Shenyang, China.

During the plant infection process, pathogens can secrete several effectors. Some of the effectors are well-known for their roles in regulating plant immunity and promoting successful pathogen colonization. However, there are few studies on the ribonuclease (RNase) effectors secreted by fungi. In the present study, we discovered a secretable RNase (SRE1) in the secretome of that was significantly upregulated during the early stages of infection in maize. Knockdown of significantly reduced the virulence of . SRE1 can induce cell death in maize and . However, unlike the conventional hypersensitive response (HR) caused by other effectors, SRE1 is not dependent on its signal peptide (SP) or plant receptor kinases (such as BAK1 and SOBIR1). SRE1-induced cell death depends upon its enzymatic activity and the N-terminal β-hairpin structure. SRE1 relies on its N-terminal β-hairpin structure to enter cells, and then degrades plant's RNA through its catalytic activity causing cytotoxic effects. Additionally, SRE1 enhances s resistance to pathogenic fungi and oomycetes. In summary, SRE1 promotes the virulence of , inducing plant cell death and activating plant immune responses.
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http://dx.doi.org/10.3389/fmicb.2022.941991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304870PMC
July 2022

Establishment of a Necroptosis Related Genes Signature to Predict Prognosis and Therapeutic Response in Colon Cancer.

Front Cell Dev Biol 2022 8;10:921320. Epub 2022 Jul 8.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Necroptosis, as a form of programmed cell death, is involved in many physiological and pathological processes. However, its role in cancer progression and therapeutic response remains controversial. Colon cancer is one of the leading causes of cancer death and patients' response to immune checkpoint blockade vary to a large degree. In this study, we investigated necroptosis related genes (NRGs) alterations in colon cancer by bioinformatics analysis. Colon cancer patients were classified into two subtypes with distinct clinical and molecular features based on NRGs. After finding differentially expressed genes and lasso regression, a prognostic model based on four necroptosis signature genes was constructed. The necroptosis signature was also a good predictor in the field of chemotherapy and immunotherapy in colon cancer. Altogether, this study illustrates the relationship between necroptosis and colon cancer, and establishes a novel scoring method to predict prognosis and therapeutic response in colon cancer patients.
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http://dx.doi.org/10.3389/fcell.2022.921320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305485PMC
July 2022

Effects of hsa-miR-28-5p on Adriamycin Sensitivity in Diffuse Large B-Cell Lymphoma.

Evid Based Complement Alternat Med 2022 13;2022:4290994. Epub 2022 Jul 13.

Department of Hematology Oncology of Karamay Central Hospital, Number 67, Junggar Road, Karamay Region, Karamay 834000, The Xinjiang Uygur Autonomous Region of China, China.

Background: Adriamycin (doxorubicin) is an important traditional drug that exhibits cytotoxicity in Diffuse Large B-cell Lymphoma (DLBCL). Doxorubicin affects the DLBCL cells at all stages of their cell cycle. Combined with our previous results, this study discovered that the overexpression of hsa-miR-28-5p inhibited the proliferation, promoted apoptosis, and triggered cell cycle arrest at the S-phase in DLBCL cells. However, the effect of (Homo sapiens, hsa)-microRNA (miR)-28-5p on doxorubicin sensitivity in DLBCL has not been investigated. This study aims to reveal the effects of hsa-miR-28-5p on doxorubicin sensitivity at the level of DLBCL cells.

Methods: To determine the optimal concentration of doxorubicin, different concentrations of doxorubicin were used to treat DLBCL cells. CCK-8 assay was used to detect the proliferation of DLBCL cells. The hsa-miR-28-5p-mimic NC and hsa-miR-28-5p mimic were transfected to doxorubicin-mediated DLBCL cells. Simultaneously, blank control groups were set up. The cells were cultured and transfected for 24 h. Next, each group was administered with different concentrations of doxorubicin and cultured again for 24 h to observe the effects of hsa-miR-28-5p on doxorubicin sensitivity at different times. The proliferation, early apoptosis, and late apoptosis in DLBCL cells were determined using soft agar colony-forming assay, mitochondrial membrane potential assay, and caspase-3 activity assay, respectively. The apoptosis and cell cycle were explored using Annexin V-PE/7-AAD and PI/RNase staining buffer, respectively. We speculated that PD-L1 might be involved in the effect of hsa-miR-28-5p on the sensitivity of adriamycin (doxorubicin) in the DLBCL cells. Hence, we performed immunohistochemistry (IHC) to determine PD-L1 expression within formalin-fixed paraffin-embedded (FFPE) samples from 52 DLBCL cases.

Results: The optimal concentration of doxorubicin targeting DLBCL cells was found to be 3.028 mol/l. The effect of doxorubicin on DLBCL cells was time- and concentration-dependent. hsa-miR-28-5p mimic + doxorubicin remarkably decreased proliferation of DLBCL. DLBCL cell apoptosis rate was the highest in hsa-miR-28-5p mimic + doxorubicin group. Apart from that, hsa-miR-28-5p mimic plus doxorubicin had the best effect in promoting DLBCL cell apoptosis. After the intervention of hsa-miR-28-5p mimic + doxorubicin on DLBCL cells, the cell cycle was arrested in the S-phase and DNA synthesis was blocked. hsa-miR-28-5p mimic + doxorubicin could regulate the cycle of DLBCL cells. As a result, overexpression of hsa-miR-28-5p combined with doxorubicin is possibly involved in the development of DLBCL by affecting the proliferation, apoptosis, and cycle of DLBCL cells. PD-L1 showed an association with the prognosis of DLBCL patients. Combining with the literature, this suggested hsa-miR-28-5p may influence DLBCL occurrence and therapeutic effect by regulating the PD-L1 level.

Conclusion: The combination of hsa-miR-28-5p mimic and doxorubicin may be considered more effective in inhibiting growth, arresting the cell cycle, and promoting cell apoptosis of DLBCL cells compared to using doxorubicin alone. The effects of doxorubicin on DLBCL cells were found to be time- and concentration-dependent. The overexpression of hsa-miR-28-5p enhanced the effect of doxorubicin on DLBCL cells, which may be attributed to the regulation of PD-L1 levels.
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http://dx.doi.org/10.1155/2022/4290994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300279PMC
July 2022

Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray.

Front Pharmacol 2022 7;13:910629. Epub 2022 Jul 7.

Clinical Pharmacology Research Center, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

This study aimed to build a nasal semi-physiologically based pharmacokinetic (PBPK) model to predict the intranasal pharmacokinetic (PK) of the OC-01(varenicline) nasal spray and accelerate the development of this drug. Based on the physiology of the human upper respiratory system, the semi-PBPK model was established and validated using systemic plasma PK data of varenicline previously observed in Americans and Chinese. Drug concentrations, both in respiratory tissue and plasma circulation system, were well simulated, and it was indicated that local concentration at the target site (nasal cavity) was significantly higher than that of plasma when OC-01 nasal spray was administered. The nasal semi-PBPK model successfully depicted the absorption and distribution of intranasal varenicline in the respiratory tissues and provided an alternative to clinical PK study of OC-01 nasal spray in Chinese. Meanwhile the current study presented a viable framework for predicting respiratory concentrations for other novel nasal spray drugs by semi-PBPK modeling.
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http://dx.doi.org/10.3389/fphar.2022.910629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301199PMC
July 2022
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