Publications by authors named "Junjie Xu"

299 Publications

Willingness to receive COVID-19 vaccination among people living with HIV and AIDS in China: A nationwide cross-sectional online survey.

JMIR Public Health Surveill 2021 Sep 2. Epub 2021 Sep 2.

Clinical Research Academy, Peking University Shenzhen Hospital, Peking University, Shenzhen, CN.

Background: HIV infection is a significant independent risk for both severe COVID-19 presentation at hospital admission and in-hospital mortality. Available information suggested that people living with HIV and AIDS (PLWHA) could benefit from COVID-19 vaccination. However, there is a dearth of evidence on willingness to receive COVID-19 vaccination among PLWHA.

Objective: This study investigated willingness to receive COVID-19 vaccination among a national sample of PLWHA.

Methods: This cross-sectional online survey investigated factors associated with willingness to receive COVID-19 vaccination among PLWHA aged 18-65 years living in eight conveniently selected Chinese metropolitan cities between January and February 2021. Eight community-based organizations (CBO) providing services to PLWHA facilitated the recruitment. Eligible PLWHA completed an online survey developed using a widely used encrypted web-based survey platform in China. We fitted a single logistic regression model to obtain adjusted odds ratios (aOR), which involved one of the independent variables of interest and all significant background variables. Path analysis were also used in data analysis.

Results: Out of 10,845 PLWHA approached by the CBO, 2740 completed the survey, and 170 had received at least one dose of COVID-19 vaccination. This analysis was performed among 2570 participants who had never received COVID-19 vaccination. Over half of the participants reported willingness to receive COVID-19 vaccination (57.2%, 1470/2570). Perceptions related to COVID-19 vaccination were significantly associated with willingness to receive COVID-19 vaccination, including positive attitudes (aOR: 1.11, 95%CI: 1.09, 1.12, P<.001), negative attitudes (aOR: 0.96, 95%CI: 0.94, 0.97), perceived support from significant others (perceived subjective norm) (aOR: 1.53, 95%CI: 1.46, 1.61), and perceived higher behavioral control (aOR: 1.13, 95%CI: 1.11, 1.14). At the interpersonal level, receiving advice supportive of COVID-19 vaccination from doctors (aOR: 1.99, 95%CI: 1.65, 2.40), CBO staff (aOR: 1.89, 95%CI: 1.51, 2.36), friends and/or family members (aOR: 3.22, 95%CI: 1.93, 5.35), and PLWHA peers (aOR: 2.38, 95%CI: 1.85, 3.08) were associated with higher willingness to receive COVID-19 vaccination. Overall opinion supporting COVID-19 vaccination for PLWHA on Internet or social media was also positively associated with willingness to receive COVID-19 vaccination (aOR: 1.59, 95%CI: 1.31, 1.94). Path analysis indicated that interpersonal-level variables was indirectly associated with willingness to receive COVID-19 vaccination through perceptions (β=0.43, 95% CI=0.37, 0.51, P<.001).

Conclusions: As compared to PLWHA in other countries and general population in most part of the world, PLWHA in China reported a relatively low willingness to receive COVID-19 vaccination. Internet/social media and interpersonal communications may be a major source of influence on PLWHA's perceptions and willingness to receive COVID-19 vaccination.
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http://dx.doi.org/10.2196/31125DOI Listing
September 2021

Establishment of human induced pluripotent stem cell line (SDQLCHi040-A) from a patient with Infantile-onset inflammatory bowel disease carrying a homozygous mutation in IL10RA gene.

Stem Cell Res 2021 Sep 7;56:102533. Epub 2021 Sep 7.

Pediatric Research Institute, Qilu Children's Hospital of Shandong University, Jinan, Shandong 250022, China. Electronic address:

Infantile-onset inflammatory bowel diseases (IO-IBD) is a heterogeneous subgroup of IBD spectrum characterized by age of onset less than 2 years old. Mutations in interleukin-10 receptor A (IL10RA) is one of the major causes. Here, we generated a human induced pluripotent stem cell line SDQLCHi040-A from a 1-year-4-month-old girl with IO-IBD caused by homozygous mutation (c.301 C > T, p.R101W) in the IL10RA gene (OMIM*146933). The established iPSC line was validated by pluripotency markers, original gene mutation and demonstrated trilineage differentiation potential in vitro.
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http://dx.doi.org/10.1016/j.scr.2021.102533DOI Listing
September 2021

A nanocubicle-like 3D adsorbent fabricated by in situ growth of 2D heterostructures for removal of aromatic contaminants in water.

J Hazard Mater 2021 Aug 21;423(Pt A):127004. Epub 2021 Aug 21.

Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Focusing on the emergence of organic pollutants in aqueous environments, attempts to assemble two-dimensional (2D) materials into three-dimensional (3D) structures are expected to improve their pollution control performance. However, most 3D heterostructural nanomaterials are constructed by mechanical mixing methods, which result in structures that are randomly arranged and prone to collapse. Two typical 2D carbon materials, reduced graphene oxide (rGO) and covalent triazine frameworks (CTFs), have exhibited excellent effects in the fields of contaminant adsorption and photocatalysis, respectively. However, their regular packing structure could not provide an interconnected pore network suitable for the diffusion or adsorption of pollutants. In this study, a series of heterostructures named rGCs were fabricated by direct growth of 2D CTFs with different ratios on the surface of rGO layers. The rGCs were designed to remove trace concentrations of naphthalene (NAP) and benzophenone (BP) from water, which can be regenerated under sunlight. rGC-20, in which nanocubicle-like 3D heterostructures were successfully constructed, not only adsorbed NAP and BP with superb normalized adsorption capacities (5000-5300 μmol/g) but also could be regenerated with an exceptional percentage recovery of 90-95% in the 4th cycle. The microenvironment created in nanocubicle-like 3D heterostructures enhances the adsorption of pollutants, the excitation of electrons and utilization of radicals, which further promotes the adsorption and photocatalysis of rGCs. This work provides a promising adsorbent with outstanding adsorption-regeneration ability for aromatic contaminant removal from water. DATA AVAILABILITY: The main data that support the findings of this study are available from the article and its Supplementary Information. Extra data are available from the corresponding author on request.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127004DOI Listing
August 2021

The Appropriate Methodologies in Biomechanical Studies Regarding Lateral Extra-Articular Procedures: What We Really Need in the Controlled Laboratory Studies.

Arthroscopy 2021 09;37(9):2726-2728

Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

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http://dx.doi.org/10.1016/j.arthro.2021.06.020DOI Listing
September 2021

Circular RNAs: characteristics, biogenesis, mechanisms and functions in liver cancer.

J Hematol Oncol 2021 08 30;14(1):134. Epub 2021 Aug 30.

Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies globally. Despite aggressive and multimodal treatment regimens, the overall survival of HCC patients remains poor. MAIN: Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with covalently closed structures and tissue- or organ-specific expression patterns in eukaryotes. They are highly stable and have important biological functions, including acting as microRNA sponges, protein scaffolds, transcription regulators, translation templates and interacting with RNA-binding protein. Recent advances have indicated that circRNAs present abnormal expression in HCC tissues and that their dysregulation contributes to HCC initiation and progression. Furthermore, researchers have revealed that some circRNAs might serve as diagnostic biomarkers or drug targets in clinical settings. In this review, we systematically evaluate the characteristics, biogenesis, mechanisms and functions of circRNAs in HCC and further discuss the current shortcomings and potential directions of prospective studies on liver cancer-related circRNAs.

Conclusion: CircRNAs are a novel class of ncRNAs that play a significant role in HCC initiation and progression, but their internal mechanisms and clinical applications need further investigation.
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http://dx.doi.org/10.1186/s13045-021-01145-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407006PMC
August 2021

A vaccine based on the receptor-binding domain of the spike protein expressed in glycoengineered targeting SARS-CoV-2 stimulates neutralizing and protective antibody responses.

Engineering (Beijing) 2021 Jul 13. Epub 2021 Jul 13.

Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China.

In 2020 and 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, caused a global pandemic. Vaccines are expected to reduce the pressure of prevention and control, and have become the most effective strategy to solve the pandemic crisis. SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2 (ACE2) via the receptor-binding domain (RBD) of the surface spike (S) glycoprotein. In this study, a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast expression system with characteristics of glycosylation modification similar to those of mammalian cells. The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody. Furthermore, the specific antibody titer and virus-neutralizing antibody (NAb) titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH) and CpG. Our results showed that the virus-NAb lasted for more than 6 months in mice. To summarize, we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered , which stimulates neutralizing and protective antibody responses. A technical route for fucose-free complex-type -glycosylation modified recombinant subunit vaccine preparation has been established.
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http://dx.doi.org/10.1016/j.eng.2021.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378774PMC
July 2021

Internet-Based HIV Self-Testing Among Men Who Have Sex With Men Through Pre-exposure Prophylaxis: 3-Month Prospective Cohort Analysis From China.

J Med Internet Res 2021 Aug 27;23(8):e23978. Epub 2021 Aug 27.

NHC Key Laboratory of AIDS Immunology, National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Routine HIV testing accompanied with pre-exposure prophylaxis (PrEP) requires innovative support in a real-world setting.

Objective: This study aimed to determine the usage of HIV self-testing (HIVST) kits and their secondary distribution to partners among men who have sex with men (MSM) in China, who use PrEP, in an observational study between 2018 and 2019.

Methods: In 4 major cities in China, we prospectively followed-up MSM from the China Real-world oral PrEP demonstration study, which provides daily or on-demand PrEP for 12 months, to assess the usage and secondary distribution of HIVST on quarterly follow-ups. Half of the PrEP users were randomized to receive 2 HIVSTs per month in addition to quarterly facility-based HIV testing. We evaluated the feasibility of providing HIVST to PrEP users.

Results: We recruited 939 MSM and randomized 471 to receive HIVST, among whom 235 (49.9%) were daily and 236 (50.1%) were on-demand PrEP users. At baseline, the median age was 29 years, 390 (82.0%) men had at least college-level education, and 119 (25.3%) had never undergone facility-based HIV testing before. Three months after PrEP initiation, 341 (74.5%) men had used the HIVST provided to them and found it very easy to use. Among them, 180 of 341 (52.8%) men had distributed the HIVST kits it to other MSM, and 132 (51.6%) among the 256 men who returned HIVST results reported that used it with their sexual partners at the onset of intercourse. Participants on daily PrEP were more likely to use HIVST (adjusted hazard ratio=1.3, 95% CI 1.0-1.6) and distribute HIVST kits (adjusted hazard ratio=1.3, 95% CI 1.1-1.7) than those using on-demand PrEP.

Conclusions: MSM who used PrEP had a high rate of usage and secondary distribution of HIVST kits, especially among those on daily PrEP, which suggested high feasibility and necessity for HIVST after PrEP initiation. Assuming that fourth-generation HIVST kits are available, HIVST may be able to replace facility-based HIV testing to a certain extent.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1800020374; https://www.chictr.org.cn/showprojen.aspx?proj=32481.

International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2019-036231.
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http://dx.doi.org/10.2196/23978DOI Listing
August 2021

IP-10 Promotes Latent HIV Infection in Resting Memory CD4 T Cells LIMK-Cofilin Pathway.

Front Immunol 2021 10;12:656663. Epub 2021 Aug 10.

NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

A major barrier to HIV eradication is the persistence of viral reservoirs. Resting CD4 T cells are thought to be one of the major viral reservoirs, However, the underlying mechanism regulating HIV infection and the establishment of viral reservoir in T cells remain poorly understood. We have investigated the role of IP-10 in the establishment of HIV reservoirs in CD4 T cells, and found that in HIV-infected individuals, plasma IP-10 was elevated, and positively correlated with HIV viral load and viral reservoir size. In addition, we found that binding of IP-10 to CXCR3 enhanced HIV latent infection of resting CD4 T cells Mechanistically, IP-10 stimulation promoted cofilin activity and actin dynamics, facilitating HIV entry and DNA integration. Moreover, treatment of resting CD4 T cells with a LIM kinase inhibitor R10015 blocked cofilin phosphorylation and abrogated IP-10-mediated enhancement of HIV latent infection. These results suggest that IP-10 is a critical factor involved in HIV latent infection, and that therapeutic targeting of IP-10 may be a potential strategy for inhibiting HIV latent infection.
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http://dx.doi.org/10.3389/fimmu.2021.656663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383741PMC
August 2021

The accumulation of plasma acylcarnitines are associated with poor immune recovery in HIV-infected individuals.

BMC Infect Dis 2021 Aug 12;21(1):808. Epub 2021 Aug 12.

NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.

Background: Antiretroviral therapy (ART) can reduce opportunistic infections and mortality rates among individuals infected with human immunodeficiency virus (HIV); however, some HIV-infected individuals exhibit poor immune recovery after ART. Hence, we explored the association between metabolome profiles and immune recovery in HIV-infected individuals following ART.

Methods: An untargeted metabolomics approach was used to analyze plasma samples from 18 HIV-negative individuals and 20 HIV-infected individuals, including 10 immunological non-responders (INR, CD4 T cell rise < 100 cells/μl) and 10 immunological responders (IR, CD4 T cell rise > 300 cells/μl) after 2 years of ART. These individuals were followed for the next 6 years and viral loads and CD4 T cell count were measured regularly. Orthogonal projection on latent structures discriminant analysis (OPLS-DA), ANOVA, correlation, receiver operating characteristic (ROC), and survival analyses were used for selection of discriminant metabolites.

Results: Eighteen lipid metabolites were identified which could distinguish among control, INR, and IR groups. Among them, myristoylcarnitine (MC), palmitoylcarnitine (PC), stearoylcarnitine (SC), and oleoylcarnitine (OC) were significantly elevated in INR plasma samples compared with those from the IR and control groups and were negatively associated with CD4 T cell count. Additionally, ROC analysis using a combination of MC, PC, SC, and OC had high sensitivity and specificity for differentiating INR from IR (AUC = 0.94). Finally, survival analysis for the combination of MC, PC, SC, and OC demonstrated that it could predict CD4 T cell count in patients undergoing long-term ART.

Conclusions: High levels of lipid metabolites, MC, PC, SC, and OC are associated with poor immune recovery in patients receiving ART and these data provide potential new insights into immune recovery mechanisms.
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http://dx.doi.org/10.1186/s12879-021-06525-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362229PMC
August 2021

Rapid Clinical Progression and Its Correlates Among Acute HIV Infected Men Who Have Sex With Men in China: Findings From a 5-Year Multicenter Prospective Cohort Study.

Front Immunol 2021 22;12:712802. Epub 2021 Jul 22.

NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: In the "treat all" era, there are few data on the nature of HIV clinical progression in middle-income countries. The aim of the current study was to prospectively analyze the clinical progression of HIV and its indicators among men in China with acute HIV who have sex with men.

Methods: From 2009-2014 a total of 400 men with acute HIV infection (AHI) were identified among 7,893 men who have sex with men periodic pooled nucleic acid amplification testing, and they were assigned to an AHI prospective cohort in Beijing and Shenyang, China. Rapid progression was defined as two consecutive CD4 T cell counts < 350/µL within 3-24 months post-infection. Kaplan-Meier and Cox-regression analyses were conducted to identify predictors of rapid progression.

Results: Among 400 men with AHI 46.5% were rapid progressors, 35.1% reached rapid progressor status by 12 months post-infection, and 63.9% reached rapid progressor status by 24 months. Rapid progression was associated with herpes simplex-2 virus coinfection (adjusted hazard ratio [aHR] 1.7, 95% confidence interval [CI] 1.2-2.3], depression (aHR 1.9, 95% CI 1.5-2.6), baseline CD4 T cell count < 500/μL (aHR 3.5, 95% CI 2.4-5.1), higher baseline HIV viral load (aHR 1.6, 95% CI 1.2-2.3), acute symptoms lasting ≥ 2 weeks (aHR 1.6, 95% CI 1.1-2.2), higher body mass index (aHR 0.9, 95% CI 0.9-1.0), higher HIV viral load (aHR 1.7, 95% CI 1.4-2.1), set point viral load at 3 months (aHR 2.0, 95% CI 1.6-2.5), each 100-cell/μL decrease in CD4 T cell count at 3 months (aHR 2.2, 95% CI 1.9-2.5), and baseline routine blood tests including white blood cell count < 5.32, hemoglobin ≥ 151, mean corpuscular hemoglobin ≥ 30.5, hemoglobin concentration ≥ 342, mean platelet count ≥ 342, lymphocytes ≥ 1.98, and mixed cell count ≥ 0.4 (all < 0.05).

Conclusion: Almost half of the patients underwent rapid clinical progression within 2 years after HIV infection. A treat-all policy is necessary and should be strengthened globally. Rapid progression was correlated with herpes simplex-2 virus coinfection, depression, low CD4 T cell counts, and high set point viral load in acute infection stage. Rapid progression can be identified simple indicators such as body mass index and routine blood test parameters in low and middle-income countries.
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http://dx.doi.org/10.3389/fimmu.2021.712802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339583PMC
July 2021

Anterolateral Structure Reconstruction Similarly Improves the Stability and Causes Less Overconstraint in Anterior Cruciate Ligament-Reconstructed Knees Compared with Modified Lemaire Lateral Extra-articular Tenodesis: A Biomechanical Study.

Arthroscopy 2021 Aug 3. Epub 2021 Aug 3.

Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address:

Purpose: To compare the kinematics of anterolateral structure (ALS) reconstruction (ALSR) and lateral extra-articular tenodesis (LET) in ACL-ALS-deficient knees with anterior cruciate ligament (ACL) reconstruction.

Methods: Ten fresh-frozen cadaveric knees with the following conditions were tested: (1) intact, (2) ACL-ALS deficiency, (3) ACL reconstruction (ACLR), (4) ACLR combined with ALSR (ACL-ALSR) or LET (ACLR+LET). Anterior translation and tibial internal rotation were measured with 90-N anterior load and 5 N·m internal torque at 0°, 30°, 60°, and 90°. The anterolateral translation and internal rotation were also measured during a simulated pivot-shift test at 0°, 15°, 30°, and 45°. The knee kinematic changes in all reconstructions were compared with each other, with intact knees as the baseline.

Results: Isolated ACLR failed to restore native knee kinematics in ACL-ALS-deficient knees. Both ACL-ALSR and ACLR+LET procedures decreased the anterior instability of the ACLR. However, ACLR+LET caused overconstraints in internal rotation at 30° (-3.73° ± 2.60°, P = .023), 60° (-4.96° ± 2.22°, P = .001) and 90° (-6.14° ± 1.60°, P < .001). ACL-ALSR also overconstrained the knee at 60° (-3.65° ± 1.90°, P < .001) and 90° (-3.18° ± 2.53°, P < .001). For a simulated pivot-shift test, both combined procedures significantly reduced the ACLR instability, with anterolateral translation and internal rotation being overconstrained in ACLR+LET at 30° (-3.32 mm ± 3.89 mm, P = .005; -2.58° ± 1.61°, P < .001) and 45° (-3.02 mm ± 3.95 mm, P = .012; -3.44° ± 2.86°, P < .001). However, the ACL-ALSR overconstrained only the anterolateral translation at 30° (-1.51 mm ± 2.39 mm, P = .046) and internal rotation at 45° (-2.09° ± 1.70°, P < .001). There were no significant differences between the two combined procedures at most testing degrees in each testing state, except for the internal rotation at 30° (P = .007) and 90° (P = .032) in internal rotation torque.

Conclusion: ACL reconstruction alone did not restore intact knee kinematics in knees with concurrent ACL tears and severe ALS injury (ACL-ALS-deficient status). Both ACL-ALSR and ACLR+LET procedures restored knee stability at some flexion degrees, with less overconstraints in internal rotation resulting from ACL-ALSR.

Clinical Relevance: For patients with combined ACL tears and severe ALS deficiency, isolated ACLR probably results in residual rotational and pivot-shift instability. Both ACL-ALSR and ACLR+LET show promise for the improvement of knee stability, whereas ACL-ALSR has less propensity for knee overconstraint.
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http://dx.doi.org/10.1016/j.arthro.2021.06.023DOI Listing
August 2021

Recombinant human thymosin beta-4 (rhTβ4) improved scalp condition and microbiome homeostasis in seborrheic dermatitis.

Microb Biotechnol 2021 Sep 28;14(5):2152-2163. Epub 2021 Jul 28.

Beijing Institute of Biotechnology, Beijing, China.

Seborrheic dermatitis (SD) is a recurrent common inflammatory skin disease that affects all ethnic groups in all regions worldwide. However, no specific treatment or preventive measure is yet available. Identifying effective treatments with acceptable safety and tolerability is desirable. In this study, scalp microbiota alterations were measured in SD, showing significantly greater abundance of Malassezia and Staphylococcus and diminished fungal and bacterial diversity compared with healthy controls. We investigated the benefit of a 4-week treatment with 0.5 mg ml recombinant human thymosin β4 (rhTβ4) gel or 2% ketoconazole lotion on the scalp condition of 71 patients with SD compared with 21 healthy individuals. Clinical assessment (Adherent Scalp Flaking Score, and the Maximum Erythema Area) and physiological conditions (transepidermal water loss, hydration, and sebum secretion) were evaluated. The rhTβ4 treatment provided significantly greater efficacy than ketoconazole and a sustained effect in the treatment of scalp SD. More importantly, rhTβ4 dramatically improved the microbiome homeostasis and prompted a shift of scalp microflora towards healthy composition, helping symptoms and ameliorating physiological conditions more effectively and durably than ketoconazole. Our research demonstrated the scalp microbe dysbiosis of SD and highlighted rhTβ4 as a promising therapeutic strategy in the prevention and treatment of SD.
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http://dx.doi.org/10.1111/1751-7915.13897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449661PMC
September 2021

Targeting WD Repeat-Containing Protein 5 (WDR5): A Medicinal Chemistry Perspective.

J Med Chem 2021 Aug 20;64(15):10537-10556. Epub 2021 Jul 20.

Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.

WD repeat-containing protein 5 (WDR5) is a member of the WD40 protein family, and it is widely involved in various biological activities and not limited to epigenetic regulation . WDR5 is also involved in the initiation and development of many diseases and plays a key role in these diseases. Since WDR5 was discovered, it has been suggested as a potential disease treatment target, and a large number of inhibitors targeting WDR5 have been discovered. In this review, we discussed the development of inhibitors targeting WDR5 over the years, and the biological mechanisms of these inhibitors based on previous mechanistic studies were explored. Finally, we describe the development potential of inhibitors targeting WDR5 and prospects for further applications.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00037DOI Listing
August 2021

An integrated electrochemical POCT platform for ultrasensitive circRNA detection towards hepatocellular carcinoma diagnosis.

Biosens Bioelectron 2021 Nov 13;192:113500. Epub 2021 Jul 13.

Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Zhejiang Minimal Invasive Diagnosis and Treantment Thechnology Research Center of Severe Hepatobiliary Disease, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. Electronic address:

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. Circ-CDYL, one of the circular RNAs (circRNAs), is recognized as an independent marker for HCC early diagnosis. Point-of-care testing (POCT) of circRNA is essential and in great demand for clinical applications. Herein, we report a fully integrated electrochemical POCT platform for circRNA detection based on Au nanoflowers (AuNFs)/peptide nucleic acid (PNA) modified carbon-fiber microelectrode (CFME). PNA is applied as the recognition element, highly specified for a back-splice junction of circRNA. AuNFs increased active site for PNA probes, improving target-capturing efficiency at an ultralow level. The platform provides a linear range of 10 fM to 1 μM, with a detection limit as low as 3.29 fM. This biosensor demonstrates high specificity towards one-base mismatch and is stable for up to 24 days. The analytical performance has also been verified in human serum samples, demonstrating the potential utility in clinical POCT applications for HCC.
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http://dx.doi.org/10.1016/j.bios.2021.113500DOI Listing
November 2021

Acceleration of ligamentization and osseointegration processes after anterior cruciate ligament reconstruction with autologous tissue-engineered polyethylene terephthalate graft.

Ann Transl Med 2021 May;9(9):770

Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: Despite the advantages of excellent mechanical properties for rapid return to sports and early rehabilitation after anterior cruciate ligament (ACL) reconstruction with polyethylene terephthalate (PET) artificial ligament, the graft failure rate during long-term follow-up is relatively high due to poor graft-host incorporation. The purpose of the present study was to investigate the effect of autologous tissue-engineered PET (ATE-PET) grafts on osseointegration and ligamentization after ACL reconstruction.

Methods: Forty-eight New Zealand white rabbits were randomly divided into PET group (n=24) and ATE-PET group (n=24). In the ATE-PET group, the rabbits initially underwent subcutaneous implantation of the PET ligament. Two weeks later, unilateral ipsilateral ACL reconstruction was performed using an ATE-PET graft. In the PET group, the rabbits underwent ACL reconstruction using PET grafts as controls. Macroscopic observation, micro-computed tomography, histological and immunofluorescent staining, and biomechanical tests were conducted to evaluate the effects at 4 and 12 weeks postoperatively.

Results: The ATE-PET graft was highly pre-vascularized with myofibroblast aggregation after two weeks of subcutaneous implantation. With regard to the intraosseous part of the graft, the ATE-PET group had significantly higher bone mineral density and bone volume/total volume ratio at 12 weeks. Histologically, the width of the interface between the graft and bone was smaller. Regarding the intra-articular part, thicker tissue coverage with a glossy appearance was observed in the ATE-PET group at 12 weeks on macroscopic observation. Histological staining also showed more collagen fibers grew in the grafts with fewer inflammatory reactions of the ATE-PET group at both 4 and 12 weeks. Immunofluorescently, both α-SMA-positive vessels and α-SMA-positive myofibroblasts were found to be significantly greater around the graft in the ATE-PET group at 4 weeks and markedly declined at 12 weeks. Moreover, the ATE-PET group presented significantly greater failure load and stiffness than the PET group at 12 weeks (53.7±5.4 42.5±4.5 N, P<0.01; 12.9±3.0 9.8±1.3 N/mm, P=0.04).

Conclusions: The ATE-PET artificial ligament with pre-vascularization and myofibroblast aggregation could effectively accelerate intra-articular graft ligamentization and intraosseous graft osseointegration, thus enhancing the biomechanical properties after ACL reconstruction in a rabbit model.
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http://dx.doi.org/10.21037/atm-20-8048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246152PMC
May 2021

CD27CD38 B cells accumulated in early HIV infection exhibit transitional profile and promote HIV disease progression.

Cell Rep 2021 Jul;36(2):109344

NHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, China; National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou 310003, China. Electronic address:

Although peripheral B cell dysfunction in early HIV infection is established, how B cell subsets are altered by HIV infection is poorly understood. While investigating B cell subsets among individuals recently infected with HIV, we observe an accumulation of CD27CD38 B cells and find that these cells can directly facilitate HIV infection of primary CD4 T cells in vitro. Comprehensive analyses of the phenotype, function, and transcriptome of the CD27CD38 B cell subset is conducted compared with memory and naive B cells. We find that the CD27CD38 B cells exhibit a transitional B cell phenotype and an extremely high turnover rate. Importantly, individuals with higher proportions of CD27CD38 B cells during early HIV infection tend to become rapid progressors in the chronic infection stage. In this study, we identify a peripheral transitional B cell subset that accumulates during early HIV infection and may contribute to disease progression.
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http://dx.doi.org/10.1016/j.celrep.2021.109344DOI Listing
July 2021

Pterostilbene inhibits hepatocellular carcinoma proliferation and HBV replication by targeting ribonucleotide reductase M2 protein.

Am J Cancer Res 2021 15;11(6):2975-2989. Epub 2021 Jun 15.

Department of Pathology & Pathophysiology, and Cancer Institute of The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, China.

Hepatocellular carcinoma (HCC), one of the most deadly diseases all around the world. HBV infection is a causative factor of HCC and closely associated with HCC development. Ribonucleotide reductase (RR) is a key enzyme for cellular DNA synthesis and RR small subunit M2 (RRM2) is highly upregulated in HCC with poor survival rates. We have previously shown that HBV can activate the expression of RRM2 and the activity of RR enzyme for the viral DNA replication in host liver cells. Thus, RRM2 may be an important therapeutic target for HCC and HBV-related HCC. Pterostilbene, a natural plant component, potently inhibited RR enzyme activity with the IC of about 0.62 μM through interacting with RRM2 protein, which was much higher than current RRM2 inhibitory drugs. Pterostilbine inhibited cell proliferation with an MTT IC of about 20-40 μM in various HCC cell lines, causing DNA synthesis inhibition, cell cycle arrest at S phase, and accordingly apoptosis. On the other hand, the compound significantly inhibited HBV DNA replication in HBV genome integrated and newly transfected HCC cells, and the EC for inhibiting HBV replication was significantly lower than the IC for inhibiting HCC proliferation. Notably, pterostilbene possessed a similar inhibitory activity in sorafenib and lamivudine resistant HCC cells. Moreover, the inhibitory effects of pterostilbine against HCC proliferation and HBV replication were significantly reversed by addition of dNTP precursors, suggesting that RR was the intracellular target of the compound. Finally, pterostilbine effectively inhibited HCC xenograft growth with a relatively low toxicity in nude mouse experiments. This study demonstrates that pterostilbene is a novel potent RR inhibitor by targeting RRM2. It can simultaneously inhibit HCC proliferation and HBV replication with a potential new use for treatment of HCC and HBV-related HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263682PMC
June 2021

Radiomics Analysis of Gd-EOB-DTPA Enhanced Hepatic MRI for Assessment of Functional Liver Reserve.

Acad Radiol 2021 Jun 25. Epub 2021 Jun 25.

Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Rationale and Objectives To evaluate the effectiveness of radiomics analysis based on Gd-EOB-DTPA enhanced hepatic MRI for functional liver reserve assessment in HCC patients. Materials and Methods Radiomics features were extracted from Gd-EOB-DTPA enhanced MRI images in 60 HCC patients. Boruta algorithm was performed to select features associated with indocyanine green retention rate at 15 min (ICG R15). Prediction and classification model were built by performing Random Forest regression analysis. Pearson correlation analysis and AUC of ROC were used to assess performance of the two models. Results A total of 165 radiomics features were extracted. Six radiomics features were selected to build the prediction model. A Predicted value of ICG R15 for each patient was calculated by the prediction model. Pearson correlation analysis revealed that predicted values were significantly associated with actual values of ICG R15 (R value = 0.90, p < 0.001). Nine radiomics features were selected to build the classification model. AUC of ROC revealed favorable performance of the classification model for identifying patients with ICG R15 <10% (AUC: 0.906, 95%CI: 0.900-0.913), <15% (AUC: 0.954, 95%CI: 0.950-0.958), and <20% (AUC: 0.996, 95%CI: 0.995-0.996). Conclusion Radiomics analysis of Gd-EOB-DTPA enhanced hepatic MRI can be used for assessment of functional liver reserve in HCC patients.
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http://dx.doi.org/10.1016/j.acra.2021.04.019DOI Listing
June 2021

Factors Influencing Clinicians' Willingness to Prescribe Pre-exposure Prophylaxis for Persons at High Risk of HIV in China: Cross-sectional Online Survey Study.

JMIR Public Health Surveill 2021 Jun 4;7(6):e24235. Epub 2021 Jun 4.

NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.

Background: Pre-exposure prophylaxis (PrEP) is an effective HIV prevention measure. Clinicians play a crucial role in PrEP implementation, and their knowledge, attitudes, and career experience may affect their willingness to prescribe PrEP. However, little is known about the attitudes and willingness of clinicians to prescribe PrEP in countries without PrEP-specific guidelines.

Objective: We aimed to determine the factors associated with clinicians being willing to prescribe PrEP in China.

Methods: Between May and June 2019, we conducted an online cross-sectional survey of clinicians in 31 provinces across the six administrative regions in China on the WeChat smartphone app platform. Multivariable logistic regression was used to determine factors associated with willingness to prescribe PrEP.

Results: Overall, 777 HIV clinicians completed the survey. Most of the respondents had heard of PrEP (563/777, 72.5%), 31.9% (248/777) thought that PrEP was extremely effective for reducing the risk of HIV infection, and 47.2% (367/777) thought that it was necessary to provide PrEP to high-risk groups. After adjusting for age, gender, ethnicity, and educational background of the clinicians, the following factors significantly increased the odds of the clinicians being willing to prescribe PrEP: having worked for more than 10 years, compared to 5 years or less (adjusted odds ratio [aOR] 2.82, 95% CI 1.96-4.05); having treated more than 100 patients living with HIV per month, compared to 50 patients or fewer (aOR 4.16, 95% CI 2.85-6.08); and having heard of PrEP (aOR 7.32, 95% CI 4.88-10.97). Clinicians were less likely to be willing to prescribe PrEP if they were concerned about poor adherence to PrEP (aOR 0.66, 95% CI 0.50-0.88), the lack of PrEP clinical guidelines (aOR 0.47, 95% CI 0.32-0.70), and the lack of drug indications for PrEP (aOR 0.49, 95% CI 0.32-0.76).

Conclusions: About half of all clinicians surveyed were willing to prescribe PrEP, but most surveyed had a low understanding of PrEP. Lack of PrEP clinical guidelines, lack of drug indications, and less than 11 years of work experience were the main barriers to the surveyed clinicians' willingness to prescribe PrEP. Development of PrEP clinical guidelines and drug indications, as well as increasing the availability of PrEP training, could help improve understanding of PrEP among clinicians and, thus, increase the number willing to prescribe PrEP.
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http://dx.doi.org/10.2196/24235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214180PMC
June 2021

Safety and Immunogenicity of a Recombinant Tetanus Vaccine in Healthy Adults in China: A Randomized, Double-Blind, Dose Escalation, Placebo- and Positive-Controlled, Phase 1/2 Trial.

Adv Sci (Weinh) 2021 08 3;8(15):e2002751. Epub 2021 Jun 3.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

Tetanus is a fatal but vaccine-preventable disease. The currently available tetanus vaccines are tetanus toxoid (TT)-based. Although these vaccines are generally effective, challenges in vaccine development and access remain. A randomized, double-blind, dose escalation, placebo- and positive-controlled, phase 1/2 trial (ChiCTR1800015865) is performed to evaluate the safety and immunogenicity of an alternative recombinant tetanus vaccine based on the Hc domain of tetanus neurotoxin (TeNT-Hc) in healthy adult volunteers. The primary outcome is the safety profile of the recombinant tetanus vaccine, and immunogenicity is the secondary outcome. 150 eligible participants were enrolled and randomly assigned to receive one of the three doses of recombinant tetanus vaccine (TeNT-Hc 10/20/30 µg), TT vaccine, or placebo. The recombinant tetanus vaccine shows a good safety profile. The frequency of any solicited and unsolicited adverse events after each vaccination does not differ across the vaccine and placebo recipients. No serious treatment-related adverse events occur. The recombinant tetanus vaccine shows strong immune responses (seroconversion rates, geometric mean titer, and antigen-specific CD4+/CD8+ T-cell responses), which are roughly comparable to those of the TT vaccine. In conclusion, the findings from this study support that recombinant tetanus vaccine is safe and immunogenic; thereby, it represents a novel vaccine candidate against tetanus.
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http://dx.doi.org/10.1002/advs.202002751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336487PMC
August 2021

Screening of potential vaccine candidates against pathogenic Brucella spp. using compositive reverse vaccinology.

Vet Res 2021 Jun 2;52(1):75. Epub 2021 Jun 2.

Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, China.

Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and various animals. The threat of brucellosis has increased, yet currently available live attenuated vaccines still have drawbacks. Therefore, subunit vaccines, produced using protein antigens and having the advantage of being safe, cost-effective and efficacious, are urgently needed. In this study, we used core proteome analysis and a compositive RV methodology to screen potential broad-spectrum antigens against 213 pathogenic strains of Brucella spp. with worldwide geographic distribution. Candidate proteins were scored according to six biological features: subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability. In the RV analysis, a total 32 candidate antigens were picked out. Of these, three proteins were selected for assessment of immunogenicity and preliminary protection in a mouse model: outer membrane protein Omp19 (used as a positive control), type IV secretion system (T4SS) protein VirB8, and type I secretion system (T1SS) protein HlyD. These three antigens with a high degree of conservation could induce specific humoral and cellular immune responses. Omp19, VirB8 and HlyD could substantially reduce the organ bacterial load of B. abortus S19 in mice and provide varying degrees of protection. In this study, we demonstrated the effectiveness of this unique strategy for the screening of potential broad-spectrum antigens against Brucella. Further evaluation is needed to identify the levels of protection conferred by the vaccine antigens against wild-type pathogenic Brucella species challenge.
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http://dx.doi.org/10.1186/s13567-021-00939-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170439PMC
June 2021

UBQLN1 mediates sorafenib resistance through regulating mitochondrial biogenesis and ROS homeostasis by targeting PGC1β in hepatocellular carcinoma.

Signal Transduct Target Ther 2021 May 18;6(1):190. Epub 2021 May 18.

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

The treatment for hepatocellular carcinoma (HCC) is promising in recent years, but still facing critical challenges. The first targeted therapy, sorafenib, prolonged the overall survival by months. However, resistance often occurs, largely limits its efficacy. Sorafenib was found to target the electron transport chain complexes, which results in the generation of reactive oxygen species (ROS). To maintain sorafenib resistance and further facilitate tumor progression, cancer cells develop strategies to overcome excessive ROS production and obtain resistance to oxidative stress-induced cell death. In the present study, we investigated the roles of ROS in sorafenib resistance, and found suppressed ROS levels and reductive redox states in sorafenib-resistant HCC cells. Mitochondria in sorafenib-resistant cells maintained greater functional and morphological integrity under the treatment of sorafenib. However, cellular oxygen consumption rate and mitochondria DNA content analyses revealed fewer numbers of mitochondria in sorafenib-resistant cells. Further investigation attributed this finding to decreased mitochondrial biogenesis, likely caused by the accelerated degradation of peroxisome proliferator-activated receptor γ coactivator 1β (PGC1β). Mechanistic dissection showed that upregulated UBQLN1 induced PGC1β degradation in a ubiquitination-independent manner to attenuate mitochondrial biogenesis and ROS production in sorafenib-resistant cells under sorafenib treatment. Furthermore, clinical investigations further indicated that the patients with higher UBQLN1 levels experienced worse recurrence-free survival. In conclusion, we propose a novel mechanism involving mitochondrial biogenesis and ROS homeostasis in sorafenib resistance, which may offer new therapeutic targets and strategies for HCC patients.
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http://dx.doi.org/10.1038/s41392-021-00594-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129126PMC
May 2021

The Effect of Antiosteoporosis Therapy With Risedronate on Rotator Cuff Healing in an Osteoporotic Rat Model.

Am J Sports Med 2021 07 17;49(8):2074-2084. Epub 2021 May 17.

Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: Osteoporosis increases the revision rate of rotator cuff repair (RCR). Weak fixation might not be the only cause of high RCR failure rates. The biological mechanism associated with tendon-to-bone healing after RCR in osteoporosis should be investigated.

Hypothesis: (1) Osteoporosis would impair rotator cuff healing through the high osteoclastic activity at the repaired interface. (2) Risedronate would promote rotator cuff healing by reducing osteoclastic activity at the repaired interface.

Study Design: Controlled laboratory study.

Methods: A total of 84 female Sprague Dawley rats were randomly treated using ovariectomy or sham surgeries to establish osteoporotic and nonosteoporotic rat models. After confirming osteoporosis, a chronic rotator cuff tear model was created and RCR was performed. Postoperatively, osteoporotic rats were randomly divided into osteoporosis (OP) and osteoporosis with risedronate administration (OP+RIS) groups. Nonosteoporotic rats were used as the control (CON) group. Osteoclastic activity was measured at 1 and 3 weeks after RCR, and histologic analysis of the tendon-to-bone interface, bone morphometric evaluation, and biomechanical tests were performed at 4 and 8 weeks.

Results: At the early healing stages of 1 and 3 weeks after RCR, the OP group showed the highest osteoclast density at the repaired interface. Compared with the OP group, risedronate administration significantly decreased osteoclast density in the OP+RIS group. At 8 weeks, histologic scores were greater in the OP+RIS group than in the OP group but still lower than in the CON group. Histologic scores at 8 weeks were negatively correlated with osteoclast density at the early healing stage. Additionally, the OP+RIS group showed better bone morphometric parameters and biomechanical properties than did the OP group.

Conclusion: Osteoporosis impaired rotator cuff healing, which might be related to the high osteoclast density at the repaired interface at the early healing stage. Postoperative risedronate administration decreased osteoclast density and enhanced rotator cuff healing in osteoporotic rats, although the effect was inferior to that in nonosteoporotic rats.

Clinical Relevance: Postoperative risedronate administration can be considered a potential therapy to enhance rotator cuff healing in patients with postmenopausal osteoporosis. However, this needs to be verified in a clinical setting.
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http://dx.doi.org/10.1177/03635465211011748DOI Listing
July 2021

Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection.

Mediators Inflamm 2021 21;2021:9979032. Epub 2021 Apr 21.

Beijing Institute of Biotechnology, Beijing 100071, China.

Coronaviruses (CoVs) are enveloped and harbor an unusually large (30-32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mouse hepatitis virus (MHV) infects mice and serves as an ideal model of viral pathogenesis, mainly because experiments can be conducted using animal-biosafety level-2 (A-BSL2) containment. Human thymosin beta-4 (T4), a 43-residue peptide with an acetylated N-terminus, is widely expressed in human tissues. T4 regulates actin polymerization and functions as an anti-inflammatory molecule and an antioxidant as well as a promoter of wound healing and angiogenesis. These activities led us to test whether T4 serves to treat coronavirus infections of humans. To test this possibility, here, we established a BALB/c mouse model of coronavirus infection using mouse CoV MHV-A59 to evaluate the potential protective effect of recombinant human T4 (rhT4). Such a system can be employed under A-BSL2 containment instead of A-BSL3 that is required to study coronaviruses infectious for humans. We found that rhT4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host's immune response, alleviating pathological damage, and promoting repair of the liver. These results will serve as the basis for further application of rhT4 to the treatment of human CoV diseases such as COVID-19.
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http://dx.doi.org/10.1155/2021/9979032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081638PMC
May 2021

TAK1 Is a Novel Target in Hepatocellular Carcinoma and Contributes to Sorafenib Resistance.

Cell Mol Gastroenterol Hepatol 2021 5;12(3):1121-1143. Epub 2021 May 5.

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, China; Zhejiang University Cancer Center, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China. Electronic address:

Background & Aims: Identifying novel and actionable targets in hepatocellular carcinoma (HCC) remains an unmet medical need. TAK1 was originally identified as a transforming growth factor-β-activated kinase and was further proved to phosphorylate and activate numerous downstream targets and promote cancer progression. However, the role of TAK1 in developed HCC progression and targeted therapy resistance is poorly understood.

Methods: The expression of TAK1 or MTDH in HCC cell lines, tumor tissues, and sorafenib-resistant models was analyzed by in silico analysis, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. In vivo and in vitro experiments were introduced to examine the function of TAK1 or MTDH in HCC and sorafenib resistance using small interfering RNA and pharmacologic inhibitors in combination with or without sorafenib. Co-immunoprecipitation and RNA immunoprecipitation were carried out to determine the binding between TAK1 and FBXW2 or between MTDH and FBXW2 mRNA. Protein half-life and in vitro ubiquitination experiment was performed to validate whether FBXW2 regulates TAK1 degradation.

Results: Our findings unraveled the clinical significance of TAK1 in promoting HCC and sorafenib resistance. We identified a novel E3 ubiquitin ligase, FBXW2, targeting TAK1 for K48-linked polyubiquitylation and subsequent degradation. We also found that MTDH contributes to TAK1 up-regulation in HCC and sorafenib resistance through binding to FBXW2 mRNA and accelerates its degradation. Moreover, combination of TAK1 inhibitor and sorafenib suppressed the growth of sorafenib-resistant HCCLM3 xenograft in mouse models.

Conclusions: These results revealed novel mechanism underlying TAK1 protein degradation and highlighted the therapeutic value of targeting TAK1 in suppressing HCC and overcoming sorafenib resistance.
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http://dx.doi.org/10.1016/j.jcmgh.2021.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350196PMC
May 2021

Comparison of curative effect between cold knife resection and electrosurgical resection of posterior urethral valve (PUV) in children.

Asian J Surg 2021 May 22;44(5):802. Epub 2021 Apr 22.

Children's Medicine Affiliated to Chongqing Medical University, Chongqing, 400000, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.02.029DOI Listing
May 2021

Correction to: Effects of continuous cropping of sweet potatoes on the bacterial community structure in rhizospheric soil.

BMC Microbiol 2021 Apr 20;21(1):121. Epub 2021 Apr 20.

Institute of Cereal and Oil Crops, Hebei Academy of Agriculture and Forestry Sciences, The Key Laboratory of Crop Genetics and Breeding of Hebei, Shijiazhuang, China.

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http://dx.doi.org/10.1186/s12866-021-02194-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058960PMC
April 2021

Improving the Acceptability of Human Papillomavirus Vaccines Among Men Who Have Sex With Men According to the Associated Factors: A Systematic Review and Meta-analysis.

Front Pharmacol 2021 24;12:600273. Epub 2021 Mar 24.

Department of Dermatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

: To investigate the acceptability of human papillomavirus (HPV) vaccination among men who have sex with men (MSM) and its associated factors. : We searched studies written in English in PubMed, EMBASE, and Web of Science with no geographical or time restrictions. We evaluated the quality of the included literature. We calculated the pooled acceptability and performed meta-analysis of selected studies, including factors associated with the acceptability among MSM, using Review Manager (v5.3). : The acceptability among the 15 studies ( = 8,658) was 50% (95% CI: 0.27-0.72). The meta-analysis of seven articles ( = 4,200) indicated that having a college or higher degree (OR = 1.62, 95% CI: 1.35-1.95), disclosure of sexual orientation to healthcare professionals (HCPs; OR = 2.38, 95% CI: 1.47-3.86), vaccination with at least one dose for hepatitis A or B (OR = 2.10, 95% CI: 1.42-3.10), awareness of HPV (OR = 1.85, 95% CI: 1.21-2.83), knowledge of HPV (SMD = 0.28, 95% CI: 0.16-0.39), perceived susceptibility to HPV infection (SMD = 0.31, 95% CI: 0.11-0.50), and perceived severity of HPV-related disease (SMD = 0.40, 95% CI: 0.28-0.51) can promote acceptance of HPV vaccines. Meanwhile, people who have had unprotected anal sex or have more sex partners tend to have low acceptance of HPV vaccines. : HPV education should be actively promoted according to the factors that influence the acceptability of HPV vaccines among the MSM population. HPV education should be especially aimed at people with low academic qualifications and people with risky sexual behaviors, and should emphasize the aspects of susceptibility to and severity of HPV-related disease. More intervention trials should be conducted to increase the credibility of the results.
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http://dx.doi.org/10.3389/fphar.2021.600273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044753PMC
March 2021

Mobile Phone Intervention Based on an HIV Risk Prediction Tool for HIV Prevention Among Men Who Have Sex With Men in China: Randomized Controlled Trial.

JMIR Mhealth Uhealth 2021 04 13;9(4):e19511. Epub 2021 Apr 13.

NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: eHealth interventions based on risk stratification have not been extensively applied for HIV behavioral interventions among HIV-negative men who have sex with men (MSM).

Objective: This study aimed to evaluate the efficacy of a mobile phone intervention based on an HIV risk prediction tool in promoting HIV testing and reducing high-risk behavior among HIV-negative MSM in China.

Methods: We performed a mobile phone-based randomized controlled clinical trial for 12 weeks. A comprehensive intervention package deployed on Jinshuju-an online survey platform-was developed and consisted of 4 components: (1) a validated HIV risk prediction tool that provides information on personalized risk reduction interventions; (2) a map of individualized HIV testing facilities based on their geographic location; (3) a QR code for free resources on HIV prevention, including condoms and HIV self-testing kits; and (4) general resources for HIV health education. MSM participants recruited from WeChat/QQ groups were randomly assigned to the intervention or control group at a 1:1 ratio. The staff sent the QR code for the comprehensive intervention package to MSM in the intervention group over WeChat and sent the QR code only for the resources on HIV health education to those in the control group. At baseline and 12-week follow-up, data on HIV-related risk behavior and HIV testing behavior were collected through the Jinshuju online survey platform.

Results: In total, 192 MSM were recruited and assigned to the intervention or control group (n=96 each). At week 12, the total clinical trial retention rate was 87.5%. The number of male sexual partners of the MSM in the past 3 months was significantly lower in the intervention group than in the control group (3.51, SD 4.1 vs 6.01, SD 11.4, respectively; mean difference -2.5; 95% CI -5.12 to 0.12; P=.05); the rate of condom use with casual sexual partners was higher in the intervention group than in the control group (87%, n=66/76 vs 70%, n=54/77 respectively; odds ratio 2.81, 95% CI 1.23-6.39; P=.01). The proportion of individuals intending to undergo HIV testing after in the following 30 days was marginally higher in the intervention group than in the control group (90%, n=77/86 vs 79%, n=65/82 respectively; odds ratio 2.20, 95% CI 0.90-5.35; P=.07). The incremental cost-effectiveness ratio of eHealth intervention was US $131.60 on reducing 1 sexual partner and US $19.70 for a 1% increment in condom usage with casual partners.

Conclusions: A comprehensive intervention based on an HIV risk prediction tool can reduce the number of male sexual partners among MSM and increase the rate of condom use with casual partners. Hence, this intervention is a very promising preventive strategy for HIV among MSM, especially in areas with a prominent HIV epidemic.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1800017268; http://www.chictr.org.cn/showprojen.aspx?proj=29271.
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http://dx.doi.org/10.2196/19511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080142PMC
April 2021
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