Publications by authors named "Jie Jin"

863 Publications

SURPASS-ET: phase III study of ropeginterferon alfa-2b versus anagrelide as second-line therapy in essential thrombocythemia.

Future Oncol 2022 Aug 4. Epub 2022 Aug 4.

UT Health San Antonio Cancer Center, San Antonio, TX 78229, USA.

Patients diagnosed with high-risk essential thrombocythemia (ET) have limited treatment options to reduce the risk of thrombosis and lessen the progression of the disease by targeting the molecular source. Hydroxyurea is the recommended treatment, but many patients experience resistance or intolerance. Anagrelide is an approved second-line option for ET, but concerns of a higher frequency of disease transformation may affect its role as a suitable long-term option. Interferons have been evaluated in myeloproliferative neoplasms for over 30 years, but early formulations had safety and tolerability issues. SURPASS-ET (NCT04285086) is a phase III, open-label, multicenter, global, randomized, active-controlled trial that will evaluate the safety, efficacy, tolerability and pharmacokinetics of ropeginterferon alfa-2b compared with anagrelide as second-line therapy in high-risk ET.
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http://dx.doi.org/10.2217/fon-2022-0596DOI Listing
August 2022

Case Report: Pathogenesis With a Rare A161E Mutation in a Patient With Angioimmunoblastic T-Cell Lymphoma.

Front Genet 2022 14;13:948744. Epub 2022 Jul 14.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Angioimmunoblastic T-cell lymphoma (AITL) genomic abnormalities are highly disease-specific, and the ras homology family member A () gene is one of the most recurrent mutated genes, especially for G17V mutation site. Here, we identified a rare A161E mutation in an AITL patient through gene sequencing platforms. The patient presented with persistent hypereosinophilia, asymptomatic or symptomatic mildly for over 3 years. At diagnosis, this patient manifested night sweats, weight loss, multiple lymphadenopathies, and enlargement of the liver and spleen. We performed a retrospective genetic mutation analysis by whole-exome sequencing (WES) and droplet digital PCR (ddPCR) on serial gastric, intestinal, and lymph node specimens. The genetic mutation testing result demonstrated that a rare A161E mutation was found, which was elevated significantly on diagnosis related to AITL pathogenesis. Our case confirms that genetic mutation testing is helpful for diagnostic classification in AITL and dynamic monitoring of gene mutations at multiple time points may facilitate early detection of disease diagnosis.
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http://dx.doi.org/10.3389/fgene.2022.948744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330045PMC
July 2022

Efficacy and Safety of Generic Dasatinib in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase: A Multicenter Prospective Study in China.

Clin Lymphoma Myeloma Leuk 2022 May 21. Epub 2022 May 21.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Background: Brand-name dasatinib was approved for newly diagnosed chronic myeloid leukemia-chronic phase (CML-CP) patients due to its deeper and faster molecular response than imatinib. Generics, as the alternative, low-cost forms, are much in demand. This study aimed to evaluate the efficacy and safety of generic dasatinib (Yinishu) as a first-line treatment in CML-CP.

Materials And Methods: This was a prospective, multicenter, single-arm study from May 2016 to October 2018 with a 2-year follow-up analysis. All patients were given 100 mg/d (initial dose) of the generic dasatinib once a day. The primary endpoint was the major molecular response (MMR) calculated based on the BCR-ABL1 gene mutation rate of ≤ .1% at 12 months.

Results: Among 55 patients in CP observed for at least 3 months, 80.4% achieved MMR at 12 months. The cumulative MR4.5 was 58.2% by 24 months. Responses occurred rapidly, with 69.1% of patients achieving complete cytogenetic response (CCyR) by 3 months and 70.9% achieving CCyR by 6 months. The estimated 2-year PFS and OS were both 96%, with a median follow-up time of 24 months. Grade 3 neutropenia occurred in 8.5% of patients, and thrombocytopenia occurred in 11.9% of patients. Nonhematologic toxicity was usually mild and manageable. Pleural effusion occurred in 20.3% of patients, and only 1 patient (1.7%) had a grade 3 pleural effusion. No grade 4 adverse events were observed.

Conclusion: Generic dasatinib is an effective option for newly diagnosed CML-CP patients, producing an MMR early in a greater number of patients during their therapy.
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http://dx.doi.org/10.1016/j.clml.2022.05.002DOI Listing
May 2022

Real-world data on efficacy and safety of azacitidine therapy in chronic myelomonocytic leukemia in China: results from a multicenter, retrospective study.

Invest New Drugs 2022 Jul 14. Epub 2022 Jul 14.

Department of Hematology, First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou, 310003, China.

Chronic myelomonocytic leukemia (CMML) is a rare and aggressive myeloid malignancy with overlapped features of myelodysplastic syndromes/myeloproliferative neoplasms. Azacitidine (AZA), a hypomethylating agent, has been approved for the treatment of CMML in China, but real-world data are limited. Medical records of CMML patients who had received subcutaneously injected AZA were reviewed from January 2018 at five participating sites in China. Response was assessed according to the modified International Working Group (IWG 2006) criteria. Between January 2018 and November 2020, a total of 24 patients with CMML were included with a median age of 63 years. Patients received a median of 3 cycles of AZA treatment (range, 1-8). Overall response rate (ORR) was 37.5% (9 of 24); CR rate, PR rate, and mCR/HI rate were 8.3% (n = 2), 8.3% (n = 2), and 20.8% (n = 5), respectively. At a median duration of follow-up of 14.0 months (range 0.0-22.0 months), the median overall survival (OS) was 23.0 months. Univariate analysis revealed that ≥ 3 cycles of treatment was significantly associated with a higher 1-year OS rate compared with < 3 cycles of AZA treatment. Treatment was generally well-tolerated. The most common (> 10%) AEs were thrombocytopenia (n = 7, 29.2%), pneumonitis (n = 4, 16.7%) and fever (n = 3, 12.5%). This study provides valuable real-life data in China on the treatment schedules, efficacy and safety of AZA in the treatment of CMML.
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http://dx.doi.org/10.1007/s10637-022-01283-xDOI Listing
July 2022

A Novel Prognostic Scoring Model for Myelodysplastic Syndrome Patients With Mutation.

Front Oncol 2022 27;12:905490. Epub 2022 Jun 27.

Department of Hematology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.

The outcomes of myelodysplastic syndrome (MDS) patients with mutation, despite identified as a favorable prognostic biomarker, are variable. To comprehend the heterogeneity in clinical characteristics and outcomes, we reviewed 140 MDS patients with mutation in Zhejiang province of China. Seventy-three (52.1%) patients diagnosed as MDS with ring sideroblasts (MDS-RS) following the 2016 World Health Organization (WHO) classification and 118 (84.3%) patients belonged to lower risk following the revised International Prognostic Scoring System (IPSS-R). Although clonal hematopoiesis-associated mutations containing , and were the most frequent co-mutant genes in these patients, and mutations had significant effects on overall survival (OS). Based on that we developed a risk scoring model as IPSS-R×0.4+×1.1+×0.6+×0.9+×1.6. Patients were categorized into two subgroups: low-risk (L-R, score <= 1.4) group and high risk (H-R, score > 1.4) group. The 3-year OS for the L-R and H-R groups was 91.88% (95% CI, 83.27%-100%) and 38.14% (95% CI, 24.08%-60.40%), respectively (P<0.001). This proposed model distinctly outperformed the widely used IPSS-R. In summary, we constructed and validated a personalized prediction model of MDS patients with mutation that can better predict the survival of these patients.
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http://dx.doi.org/10.3389/fonc.2022.905490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271788PMC
June 2022

Association between sensitivity to thyroid hormone indices and the risk of osteoarthritis: an NHANES study.

Eur J Med Res 2022 Jul 11;27(1):114. Epub 2022 Jul 11.

Department of Orthopaedics, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Objectives: Thyroid hormones play an instrumental role in chondrogenic differentiation and matrix maturation. However, studies investigating the relationship between thyroid function and the risk of osteoarthritis (OA) remain scarce. This study was designed to investigate the correlation between thyroid status and OA from a novel perspective of sensitivity to thyroid hormones.

Methods: The study included 8478 people from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. The sensitivity to thyroid hormone indices included Thyrotroph Thyroxine Resistance Index (TT4RI), Thyroid-stimulating hormone (TSHI), Thyroid Feedback Quantile-based Index (TFQI), and Free Triiodothyronine /Free thyroxine (FT3/FT4), which were calculated based on serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH). Considering the complex survey design and sample weights, we employed multivariate linear regression models and stratified analysis to evaluate the correlation between sensitivity to thyroid hormone indices and OA.

Results: Study results indicated that participants with OA had elevated TT4RI, TSHI, and TFQI levels, and lower FT3/FT4 levels compared to those with non-arthritis. After adjusting for other covariates, FT3/FT4 was negatively associated with the risk of OA (OR = 1.162, 95%CI 1.048-1.478, P = 0.021); (OR = 1.261, 95%CI 1.078-1.623, P = 0.042). In subgroup analyses stratified by gender and BMI, participants with OA had higher TFQI levels compared to those without OA in both genders. (OR = 1.491, 95%CI 1.070-2.077, P = 0.018); (OR = 2.548, 95%CI 1.929-3.365, P < 0.001). The higher TFQI levels were consistently associated with the increased prevalence of OA in the BMI (< 18.5 kg/m) group after adjusting for different covariates, but not in other BMI groups. In, addition, TFQI performed better than FT3/FT4, TSHI, and TT4RI on ROC analyses for OA prediction.

Conclusions: The levels of FT3/FT4, TSHI, TT4RI, and TFQI are strongly associated with the prevalence of OA, which illustrates the complex correlation between the thyroid system and chondrogenic differentiation. TFQI may be used as a helpful indicator to predict OA and provide novel ideas for the evaluation and treatment of OA.
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http://dx.doi.org/10.1186/s40001-022-00749-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275280PMC
July 2022

Arsenic(V) immobilization in fly ash and mine tailing-based geopolymers: Performance and mechanism insight.

Chemosphere 2022 Jul 7;306:135636. Epub 2022 Jul 7.

Collaborative Innovation Centre of Atmospheric Environment and Equipment Technology, Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, School of Environmental Science and Engineering, Nanjing University of Information Science and Technology (NUIST), 219 Ningliu Road, Nanjing, 210044, China. Electronic address:

Global mining activities produce thousands of millions of toxic-bearing mine tailing (MT) wastes each year. Storage of the mine tailings not only encroaches upon large areas of cropland but also arouses additional ecological and environmental risks. Herein we demonstrate that geopolymerization of a mixture of the toxic-bearing mine tailings and the coal fly ash (FA) can effectively immobilize exogenous arsenic (As) species in addition to inherent As from the raw materials. The geopolymers also possess high compressive strengths (e.g., >25 MPa for specimens with 54 wt% FA and activated with 10 M sodium hydroxide (NaOH)), allowing them to be further used as low-carbon, cement-free building materials. The geopolymer strength was found to depend clearly upon the NaOH concentration, the FA content, and the curing time, with the maximum being 37.07 MPa for a specimen with 54 wt% FA, 0.03 wt% As, activated with 10 M NaOH and cured for 28 days. Leaching tests showed that all specimens achieved an immobilization efficiency as high as 95.4% toward As, and that both the short-term and long-term leachabilities of all toxic elements are far below the standard maximum contaminant levels. Microstructural analyses indicate that calcite, calcium silicate, and calcium silicate hydroxide are likely to play a crucial role in immobilizing As species and heavy metals of concern in the geopolymer matrixes. Given the superior mechanical strengths and long-term stabilities, the FA/MT-based geopolymers demonstrate a promising low-carbon material for both the remediation of As-bearing lands and the construction industry.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135636DOI Listing
July 2022

Multiple chemical modifications and Cd adsorption characteristics of sludge-based activated carbon.

RSC Adv 2022 Jun 23;12(29):18559-18571. Epub 2022 Jun 23.

School of Biology, Food and Environment, Anhui Key Laboratory of Sewage Purification and Eco-restoration Materials, Hefei University Hefei 230601 P. R. China +86 551 62158406 +86 551 62158405.

Sludge resource utilization is commonly realized through carbonization, but the use of direct carbonization to obtain sludge-based activated carbon (SAC) is not functional yet. The multiple chemical modifications were carried out to achieve N-doping and pore-making to modify SAC. The SAC was synthesized by activating sludge simultaneously with uric acid and potassium ferrate. Moreover, SAC, SAC, and SAC were prepared with no additives, uric acid, and potassium ferrate, respectively. The results indicated that the different modifications affected the chemical properties and structure of SAC. The BET of SAC was 56.73 m g, which was higher than that of SAC and SAC. SAC possessed abundant functional groups, such as C[double bond, length as m-dash]N and C-O. The adsorption capacity of SAC for Cd was 9.69 mg g, 5.5 times that of SAC, the adsorption process of Cd by SAC fitted well for the second-order kinetic model and Langmuir isothermal adsorption model. The XPS and chemical analysis revealed that SAC and Cd were bonded by functional groups, and the Cd removal by SAC was through complexation, anion exchange, electrostatic attraction, and pore filling. The SAC was exhibited different removal capacities for different metals, Pb and Mn correspond to adsorption capacities of 4.9 and 8.1 mg g. In addition, the adsorbed SAC can be regenerated by sodium hydroxide. The study highlights the importance of multiple chemical modifications performed on SAC, the double coupled chemical modifications to ensure its good performance in the treatment of heavy metals in wastewater treatment.
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http://dx.doi.org/10.1039/d2ra03268fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219043PMC
June 2022

Homoharringtonine is synergistically lethal with BCL-2 inhibitor APG-2575 in acute myeloid leukemia.

J Transl Med 2022 07 6;20(1):299. Epub 2022 Jul 6.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China.

Background: Despite advances in targeted agent development, effective treatment of acute myeloid leukemia (AML) remains a major clinical challenge. The B-cell lymphoma-2 (BCL-2) inhibitor exhibited promising clinical activity in AML, acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL) treatment. APG-2575 is a novel BCL-2 selective inhibitor, which has demonstrated anti-tumor activity in hematologic malignancies. Homoharringtonine (HHT), an alkaloid, exhibited anti-AML activity.

Methods: The synergistic effects of APG-2575 and HHT were studied in AML cell lines and primary samples. MTS was used to measure the cell viability. Annexin V/propidium iodide staining was used to measure the apoptosis rate by flow cytometry. AML cell xenografted mouse models were established to evaluate the anti-leukemic effect of BCL-2 inhibitor, HHT and their combination in vivo. Western blot was used to determine the expression of related proteins.

Results: APG-2575 showed comparable anti-leukemic effect to the FDA-approved BCL-2 inhibitor ABT-199 in vitro and in vivo. Combined treatment of HHT with APG-2575 synergistically inhibited AML cell growth and engraftment. Mechanistically, HHT promoted degradation of myeloid cell leukemia-1 (MCL-1), which was reported to induce BCL-2 inhibitor resistant, through the PI3K/AKT/GSK3β signaling pathway.

Conclusion: Our results provide an effective AML treatment strategy through combination of APG-2575 and HHT, which is worthy of further clinical research.
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http://dx.doi.org/10.1186/s12967-022-03497-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258085PMC
July 2022

Clinical features and next-generation sequencing landscape of essential thrombocythemia, prefibrotic primary myelofibrosis, and overt fibrotic primary myelofibrosis: a Chinese monocentric retrospective study.

J Cancer Res Clin Oncol 2022 Jun 22. Epub 2022 Jun 22.

Department of Hematology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, N1 Shangcheng Road, Yiwu, Zhejiang, People's Republic of China.

Objective: Since prefibrotic primary myelofibrosis (pre-PMF) was recognized as a separate entity in the 2016 revised classification of MPN differed from essential thrombocythemia (ET) or overt fibrotic primary myelofibrosis (overt PMF), it has been a subject of debate among experts due to its indefinite diagnosis.

Methods: We retrospectively reviewed the clinical parameters, haematologic information, and genetic mutations of patients who were diagnosed with myeloproliferative neoplasms (MPNs) according to the WHO 2016 criteria in China, including 56 ET patients, 19 pre-PMF patients, and 43 overt PMF patients.

Results: Pre-PMF patients exhibited higher leukocyte counts [14.2(6.0-28.1) × 10/L vs 9.6(4.0-55.0) × 10/L, P = 0.003], LDH values [307(233-479)U/L vs 241(129-1182)U/L, P < 0.001], onset ages [67(32-76) years vs 50(16-79) years, P = 0.006], a higher frequency of splenomegaly(47.4% vs 16.7%, P = 0.018) and hypertension (57.9 vs 23.2%, P = 0.005) than ET patients. On the other hand, pre-PMF patients had higher platelet counts [960(500-2245) × 10/L vs 633(102-1720) × 10/L, P = 0.017], haemoglobin levels [152(115-174)g/L vs 119(71-200)g/L, P = 0.003], lower LDH values [307(233-479)U/L vs 439(134-8100)U/L, P = 0.007] and a lower frequency of splenomegaly(47.4 vs 75.6%, P = 0.031) than overt PMF patients. Next-generation sequencing landscape was performed in 50 patients, revealed the frequency of EP300 mutations was significantly increased in pre-PMF patients compared with ET and overt PMF patients (60 vs 10 vs 15.79%, P = 0.033), and WT1 was more often overexpressed (WT1/ABL1 copies ≥ 1.0%) in patients with overt PMF than in those with ET or pre-PMF(54.55 vs 16.67 vs 17.65%, P = 0.009). In terms of outcome, male sex, along with symptoms including MPN10, anaemia (haemoglobin < 120 g/L), thrombocytopenia (platelet count < 100 × 10/L), leucocytosis (leukocyte counts > 13 × 10/L), high LDH value (> 350U/L), splenomegaly, WT1 overexpression(WT1/ABL1 copies ≥ 1.0%), KMT2A, ASXL1 and TP53 mutations, indicated a poor prognosis for PMF patients.

Conclusion: The results of this study indicated that a comprehensive evaluation of BM features, clinical phenotypes, haematologic parameters, and molecular profiles is needed for the accurate diagnosis and treatment of ET, pre-PMF, and overt PMF patients.
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http://dx.doi.org/10.1007/s00432-022-04067-1DOI Listing
June 2022

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

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

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

Intervertebral disc degeneration (IVDD) is a complex process involving many factors, among which excessive senescence of nucleus pulposus cells is considered to be the main factor. Our previous study found that metformin can inhibit senescence in nucleus pulposus cells; however, the mechanism of such an action was still largely unknown. In the current study, we found that metformin inactivates the cGAS-STING pathway during oxidative stress. Furthermore, knockdown of STING (also known as STING1) suppresses senescence, indicating that metformin might exert its effect through the cGAS-STING pathway. Damaged DNA is a major inducer of the activation of the cGAS-STING pathway. Mechanistically, our study showed that DNA damage was reduced during metformin treatment; however, suppression of autophagy by 3-methyladenine (3-MA) treatment compromised the effect of metformin on DNA damage. In vivo studies also showed that 3-MA might diminish the therapeutic effect of metformin on IVDD. Taken together, our results reveal that metformin may suppress senescence via inactivating the cGAS-STING pathway through autophagy, implying a new application for metformin in cGAS-STING pathway-related diseases.
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http://dx.doi.org/10.1242/jcs.259738DOI Listing
August 2022

A Robust Predefined-Time Convergence Zeroing Neural Network for Dynamic Matrix Inversion.

IEEE Trans Cybern 2022 Jun 10;PP. Epub 2022 Jun 10.

As a classical and effective method for solving various time-varying problems, the zeroing neural network (ZNN) is widely applied in the scientific and industrial realms. In plentiful studies on the ZNN model, its robustness and convergence have been two essential criteria to evaluate the quality of the model. Improvements in the ZNN model have been focused on its convergence speed; however, the adjustability of its convergence speed has been neglected in most prior works, which restricts its extensive promotion in practical application. Considering the above-mentioned issue, a well-designed activation function (WDAF) is designed. Based on the WDAF, a robust predefined-time convergence ZNN (RPTCZNN) model with adjustable convergence speed is proposed to solve the dynamic matrix inversion problem. In addition, the upper bound of the RPTCZNN model's convergence time is theoretically validated by strict mathematical analysis in a noiseless and noisy environment. Finally, several simulation experiments of the proposed model are conducted to find solutions of dynamic matrix inversion with different dimensions. Moreover, the realization of the tracking control of the robotic manipulator further illustrates the model's superior convergence and robustness.
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http://dx.doi.org/10.1109/TCYB.2022.3179312DOI Listing
June 2022

Study on Corrosion Resistance and Conductivity of TiMoN Coatings with Different Mo Contents under Simulated PEMFC Cathode Environment.

Materials (Basel) 2022 May 25;15(11). Epub 2022 May 25.

College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310000, China.

TiMoN coatings with different Mo contents on a SS316L substrate are deposited by using closed field unbalanced magnetron sputtering ion plating (CFUMSIP) technology to enhance the corrosion resistance and durability of stainless steel (SS) bipolar plates (BPs) in proton exchange membrane fuel cell (PEMFC) during the start-up/shut-down process. The electrochemical test results illustrate that TiMoN-4A coating has extremely good corrosion resistance compared to other coatings. The potentiostat polarization (+0.6 V) tests indicate that the corrosion current density (I) of TiMoN-4A coating is 5.22 × 10A cm, which meets the department of energy 2020 targets (DOE, ≤1 × 10 A cm). Otherwise, TiMoN-4A coating also exhibits the best corrosion resistance and stability in potentiostatic polarization, electrochemical impedance spectroscopy (EIS), and high potential (+1.2V) polarization tests. The interfacial contact resistance (ICR) measurement results show that TiMoN-4A coating has the minimum ICR of 9.19 mΩ·cm, which meets the DOE 2020 targets (≤10 mΩ·cm).
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http://dx.doi.org/10.3390/ma15113766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181102PMC
May 2022

Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis.

Cell Death Dis 2022 Jun 7;13(6):533. Epub 2022 Jun 7.

Department of Urology, Peking University First Hospital, 100034, Beijing, China.

Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-β1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.
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http://dx.doi.org/10.1038/s41419-022-04979-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174491PMC
June 2022

Research Advances on Anti-Cancer Natural Products.

Front Oncol 2022 6;12:866154. Epub 2022 May 6.

College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China.

Malignant tumors seriously threaten people's health and life worldwide. Natural products, with definite pharmacological effects and known chemical structures, present dual advantages of Chinese herbs and chemotherapeutic drug. Some of them exhibit favorable anti-cancer activity. Natural products were categorized into eight classes according to their chemical structures, including alkaloids, terpenoids and volatile oils, inorganic salts, phenylpropanoids, flavonoids and isoflavones, quinone, saponins and polysaccharides. The review focused on the latest advances in anti-cancer activity of representative natural products for every class. Additionally, anti-cancer molecular mechanism and derivatization of natural products were summarized in detail, which would provide new core structures and new insights for anti-cancer new drug development.
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http://dx.doi.org/10.3389/fonc.2022.866154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135452PMC
May 2022

Improvement of the silver staining method for bacterial flagella.

J Microbiol Methods 2022 Jul 27;198:106495. Epub 2022 May 27.

School of Biology, Food and Environment, Hefei University, Hefei 230601, PR China; Anhui Key Laboratory of Sewage Purification and Eco-restoration Materials, Hefei 230088, PR China. Electronic address:

Flagella staining is a common method used in microbial research to identify and mark morphological features of bacteria. We improved the Blendon staining method by adding two steps to the usual procedure, viz. "preparation of a pre-atomized microscope slide" and "stretching flagella in situ". The staining effects were then comparatively studied for this new, improved method on Bacillus subtilis, under four different culture conditions: 1) liquid culture medium, 2) aqueous solution at the bottom of slant medium, 3) solid culture medium adding water for stretching after culture, and 4) semi-solid culture medium adding water for stretching after culture. The results revealed that after the addition of these two steps to the usual procedure, the order of the staining effects for the four culture conditions from best to worst was as follows: semi-solid culture medium > solid culture medium > aqueous solution at the bottom of slant medium > liquid culture medium. Hence, the semi-solid culture medium brought about the best staining effect, with flagella stretching freely and not entangled with each other, while the liquid culture medium had the worst staining, owing to the serious background interference. This improved method is simple, low cost, and worthy of promotion.
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http://dx.doi.org/10.1016/j.mimet.2022.106495DOI Listing
July 2022

Activating peroxymonosulfate using carbon from cyanobacteria as support for zero-valent iron.

Environ Sci Pollut Res Int 2022 May 27. Epub 2022 May 27.

School of Biology, Food and Environment, Hefei University, Hefei, 230601, People's Republic of China.

In the present study, the cyanobacterial char (ACC) prepared from Chaohu cyanobacteria was used as a nanoscale carrier for zero-valent iron (NZVI) to synthesize a highly efficient activation material designated as cyanobacterial char-supported nanoscale zero-valent iron ([email protected]), which was subsequently used for activating peroxymonosulfate (PMS) to degrade the orange II (OII) dye. The XRD and XPS results revealed that NZVI was anchored onto the ACC through coordination bonding, forming a stable structure. The SEM and TEM observations revealed that the NZVI was embedded in the sheet structure of the ACC. The [email protected] had a larger specific surface area (42.249 m/g) and also magnetism, due to which its components could be separated through an externally applied magnetic field. Using this [email protected]/PMS system, the rate of degradation of OII (100 mg/L) reached 98.32% within 14 min. The OII degradation reaction using the [email protected]/PMS system followed first-order kinetics. The activation energy of this degradation reaction was 17.34 kJ/(mol·K). Quenching and EPR experiments revealed that various free radicals (SO·, ·OH) were produced, with SO· playing the major role in the reaction. The theoretical calculations revealed that SO· attacked the 12 (N) of OII, thereby destroying and degrading both azo and hydrogenated azo structures of OII. The presence of halogen ions in the actual dye-containing wastewater samples inhibited the OII degradation by the [email protected] system to different degrees, and the inhibition effect followed the order I  > Br  > Cl.
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http://dx.doi.org/10.1007/s11356-022-20516-3DOI Listing
May 2022

MiR-103-3p promotes hepatic steatosis to aggravate nonalcoholic fatty liver disease by targeting of ACOX1.

Mol Biol Rep 2022 Aug 23;49(8):7297-7305. Epub 2022 May 23.

Department of Infectious Diseases, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, 310003, Zhejiang Province, China.

Background: Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for hepatocellular carcinoma, and alterations in miRNA expression are related to the development of NAFLD. However, the role of miRNAs in regulating the development of NAFLD is still poorly understood.

Methods: We used qRT-PCR to detect the level of miR-103-3p in both cell and mouse models of NAFLD. Biochemical assays, DCF-DA assays, Oil red O staining and HE staining were used to detect the role of miR-103-3p in NAFLD development. Target genes of miR-103-3p were predicted using the TargetScan database and verified by qRT-PCR, western blot and dual-luciferase assays.

Results: The expression of miR-103-3p increased in both NAFLD model cells and liver tissues from the NAFLD mouse model. Inhibition of miR-103-3p significantly alleviated the accumulation of lipid droplets in free fatty acid-treated L02 cells and liver tissues from mice with NAFLD. Inhibition of miR-103-3p reduced the contents of HO, TG, ALT, and AST and ROS production while increasing the ATP content. Moreover, the miR-103-3p antagomir alleviated liver tissue lesions in mice with NAFLD. Further studies identified ACOX1, a key enzyme for the oxidation and decomposition of fatty acids, as a direct target of miR-103-3p.

Conclusions: These findings identified a negative regulatory mechanism between ACOX1 and miR-103-3p that promotes the pathogenesis of NAFLD and suggested that inhibition of miR-103-3p may be a potential treatment strategy for NAFLD.
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http://dx.doi.org/10.1007/s11033-022-07515-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304065PMC
August 2022

A real-world study of infectious complications of venetoclax combined with decitabine or azacitidine in adult acute myeloid leukemia.

Support Care Cancer 2022 Aug 19;30(8):7031-7038. Epub 2022 May 19.

Department of Hematology, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Purpose: The purpose of this study was to identify the incidence, sites and main pathogens, and risk factors for infectious complications occurring in patients with adult acute myeloid leukemia (AML) during the first course of venetoclax combined with decitabine or azacitidine.

Methods: A retrospective cohort analysis was performed of 81 patients with AML older than 14 years who received the first cycle of venetoclax combined with a hypomethylating agent (HMA) between March 2018 and March 2021 at our institution. Infectious complications, if any, were documented.

Results: Among a total of 81 cases of AML, 59 (72.8%) patients occurred infections, including fever without an identifiable source (28.8%), clinically documented infections (40.7%), and microbiologically documented infections (30.5%). The most commonly isolated organism in culture was Candida albicans, followed by Klebsiella pneumonia, and Pseudomonas aeruginosa. The 4-week and 8-week mortality rates were 3.7% and 7.4%, respectively. In multivariate analysis, a high proportion of blasts in bone marrow, decreased hemoglobin level, and fever with or without a documented infection at baseline were significant independent risk factors for infectious complications.

Conclusion: Compared with conventional chemotherapy, the incidence of infectious complications of venetoclax combined with decitabine or azacitidine significantly decreased. Pretreatment high leukemia burden and fever were independent risk factors for infections.
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http://dx.doi.org/10.1007/s00520-022-07126-yDOI Listing
August 2022

Du13 encodes a C H zinc-finger protein that regulates Wx pre-mRNA splicing and microRNA biogenesis in rice endosperm.

Plant Biotechnol J 2022 07 13;20(7):1387-1401. Epub 2022 May 13.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing, China.

Amylose content is a crucial physicochemical property responsible for the eating and cooking quality of rice (Oryza sativa L.) grain and is mainly controlled by the Waxy (Wx) gene. Previous studies have identified several Dull genes that modulate the expression of the Wx allele in japonica rice by affecting the splicing efficiency of the Wx pre-mRNA. Here, we uncover dual roles for a novel Dull gene in pre-mRNA splicing and microRNA processing. We isolated the dull mutant, du13, with a dull endosperm and low amylose content. Map-based cloning showed that Du13 encodes a C H zinc-finger protein. Du13 coordinates with the nuclear cap-binding complex to regulate the splicing of Wx transcripts in rice endosperm. Moreover, Du13 also regulates alternative splicing of other protein-coding transcripts and affects the biogenesis of a subset of microRNAs. Our results reveal an evolutionarily conserved link between pre-mRNA splicing and microRNA biogenesis in rice endosperm. Our findings also provide new insights into the functions of Dull genes in rice and expand our knowledge of microRNA biogenesis in monocots.
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http://dx.doi.org/10.1111/pbi.13821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241381PMC
July 2022

Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial.

Lancet Haematol 2022 Jun 2;9(6):e415-e424. Epub 2022 May 2.

Department of Haematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Haematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Clinical Research Center for Haematological Disorders, Hangzhou, Zhejiang, China; Zhejiang University Cancer Center, Hangzhou, Zhejiang, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China. Electronic address:

Background: Adults with acute myeloid leukaemia have unsatisfactory clinical outcomes and rates of complete remission. Venetoclax combined with azacytidine or low-dose cytarabine has shown efficacy in adults aged 75 years or older (or 18-74 years with comorbidities precluding intensive chemotherapy) with acute myeloid leukaemia. We aimed to investigate the activity and safety of venetoclax plus 3+7 daunorubicin and cytarabine chemotherapy in adults with acute myeloid leukaemia.

Methods: We conducted a two-stage, single-arm, phase 2 trial at three public hospitals in China. We enrolled patients aged 18-60 years with previously untreated de novo acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received induction treatment with intravenous daunorubicin (60 mg/m on days 1-3), intravenous cytarabine (100 mg/m on days 1-7), and oral venetoclax (100 mg on day 4, 200 mg on day 5, and 400 mg on days 6-11; DAV regimen). For induction therapy, the length of the treatment was 28-35 days per cycle and the number of treatment cycles was one or two. The primary endpoint was the composite complete remission rate (complete remission plus complete remission with incomplete blood cell count recovery) after one cycle of induction treatment, assessed in the as-treated population. Secondary endpoints were bone marrow measurable residual disease by flow cytometry, event-free survival, overall survival, and adverse events. This trial is ongoing and is registered with Chinese Clinical Trial Registry, ChiCTR2000041509.

Findings: Between Dec 25, 2020, and July 7, 2021, 36 patients were assessed for eligibility and 33 were enrolled. 15 (45%) patients were men and 18 (55%) were women, and all were Asian. The composite complete remission rate after one cycle of DAV regimen was 91% (95% CI 76-98; 30 of 33 patients) in the entire cohort. 29 (97%) of 30 patients who reached complete remission had undetectable measurable residual disease (ie, <0·1%). Grade 3 or worse adverse events included neutropenia in 33 (100%) of 33 patients, thrombocytopenia in 33 (100%), anaemia in 33 (100%), febrile neutropenia in 18 (55%), pneumonia in seven (21%), and sepsis in four (12%). No treatment-related deaths occurred. With a median follow-up of 11 months (IQR 9-12), estimated 1-year overall survival was 97% (95% CI 91-100) and 1-year event-free survival was 72% (56-94).

Interpretation: The DAV regimen represents an effective induction therapy for newly diagnosed adults with acute myeloid leukaemia, which resulted in a high rate of complete remission. These findings are an important contribution to the field, showing a safe strategy to incorporate venetoclax into the most common induction regimen used to treat newly diagnosed acute myeloid leukaemia internationally.

Funding: Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang, National Natural Science Foundation of China, Key Research and Development Program of Zhejiang.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2352-3026(22)00106-5DOI Listing
June 2022

An analysis of the efficacy and safety of compound glycyrrhizin injections in the treatment of drug-induced liver injury using a nationwide database.

Int J Clin Pharm 2022 Jun 19;44(3):731-740. Epub 2022 Apr 19.

Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China.

Background Drug-induced liver injury (DILI) refers to liver damage caused by drugs. DILI poses a significant challenge in the development of new drugs. The management of DILI mainly involves the withdrawal of the offending drug, and there is a lack of specific therapy. This study sought to evaluate the efficacy and safety of compound glycyrrhizin (CG) injections in DILI patients. Aim To evaluate the efficacy and safety of compound glycyrrhizin injections in DILI treatment. Methods The clinical data of DILI patients were collected from a nationwide DILI database. Patients were divided into two groups: the compound glycyrrhizin (CG) group who received CG injections, and the control group who received no treatment. The propensity score matching (PSM) method was applied to obtain an even distribution of characteristics between the two groups. The efficacy of the CG injections was assessed by the analysis of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels between the two groups. Results There were 152 patients in the compound glycyrrhizin group and 512 patients in the control group. The PSM method was used to acquire 152 matched pairs. The compound glycyrrhizin group had a significantly higher overall ALT and AST normalization rate than the control group (43.42% vs. 24.34%, p = 0.0004 and 63.82% vs. 38.82%, p ≤ .0001). There was no difference in the levels of renal and serum biochemical parameters between the two groups. Conclusions CG injections are effective in reducing ALT and AST levels in DILI patients, and their safety is comparable to the control group.
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http://dx.doi.org/10.1007/s11096-022-01402-xDOI Listing
June 2022

Research Advances on Matrine.

Front Chem 2022 1;10:867318. Epub 2022 Apr 1.

College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China.

Matrine is an alkaloid extracted from traditional Chinese herbs including , , root, etc. It has the dual advantages of traditional Chinese herbs and chemotherapy drugs. It exhibits distinct benefits in preventing and improving chronic diseases such as cardiovascular disease and tumors. The review introduced recent research progresses on extraction, synthesis and derivatization of Matrine. The summary focused on the latest research advances of Matrine on anti-atherosclerosis, anti-hypertension, anti-ischemia reperfusion injury, anti-arrhythmia, anti-diabetic cardiovascular complications, anti-tumor, anti-inflammatory, anti-bacterium, anti-virus, which would provide new core structures and new insights for new drug development in related fields.
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http://dx.doi.org/10.3389/fchem.2022.867318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010661PMC
April 2022

Treatment of inadvertent cervical arterial catheterization: Single-center experience.

Vascular 2022 Apr 15:17085381221083161. Epub 2022 Apr 15.

Department of Vascular & Endovascular Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China.

Objectives: Inadvertent arterial catheterization can occur during transjugular central venous catheter insertion and should be promptly treated to prevent serious consequences. Although many treatment modalities are available, no exist guidelines regarding the selection of treatment. We aimed to describe our experience with the treatment of 11 patients who underwent inadvertent cervical arterial catheterization and propose an algorithm for the selection of treatment methods.

Methods: We retrospectively identified all patients who were treated for inadvertent arterial catheterization at our center between January 2016 and March 2021. We reviewed patient profiles, images, treatment methods, and follow-up data.

Results: Eleven patients were included (eight men and three women, age: 36-73 years). Ten catheter misplacements were in the right common carotid artery. The remaining catheter was inserted into the right subclavian artery after penetrating the right common carotid artery. Two catheters were 5-Fr and nine catheters were 11.5-Fr. Two patients underwent manual compressions, three underwent open surgery, three underwent stent-graft repairs, and four underwent Perclose Proglide closure. Clinical success was achieved in all 11 patients. Primary technical success was achieved in 10 patients. In one patient, unsuccessful manual compression was followed by successful stent-graft repair; the manual compression failed to prevent bleeding, possibly because of the long-term oral administration of aspirin for coronary heart disease. The mean follow-up was 5.4 months (range, 1-12 months). The overall mortality rate was zero, and no vascular or neurological events occurred.

Conclusions: The existing data show that the current protocol for the treatment of inadvertent cervical arterial catheterization at our center is safe and effective. However, the data are insufficient and require further clinical validation.
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http://dx.doi.org/10.1177/17085381221083161DOI Listing
April 2022

Predicted mouse interactome and network-based interpretation of differentially expressed genes.

PLoS One 2022 7;17(4):e0264174. Epub 2022 Apr 7.

Institute of Big Data and Artificial Intelligence in Medicine, School of Electronics & Information Engineering, Taizhou University, Taizhou, China.

The house mouse or Mus musculus has become a premier mammalian model for genetic research due to its genetic and physiological similarities to humans. It brought mechanistic insights into numerous human diseases and has been routinely used to assess drug efficiency and toxicity, as well as to predict patient responses. To facilitate molecular mechanism studies in mouse, we present the Mouse Interactome Database (MID, Version 1), which includes 155,887 putative functional associations between mouse protein-coding genes inferred from functional association evidence integrated from 9 public databases. These putative functional associations are expected to cover 19.32% of all mouse protein interactions, and 26.02% of these function associations may represent protein interactions. On top of MID, we developed a gene set linkage analysis (GSLA) web tool to annotate potential functional impacts from observed differentially expressed genes. Two case studies show that the MID/GSLA system provided precise and informative annotations that other widely used gene set annotation tools, such as PANTHER and DAVID, did not. Both MID and GSLA are accessible through the website http://mouse.biomedtzc.cn.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264174PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989236PMC
April 2022

Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.

Proc Natl Acad Sci U S A 2022 04 6;119(15):e2120787119. Epub 2022 Apr 6.

Department of Hematology, Second Hospital of Dalian Medical University, 116027 Leaoning, People's Republic of China.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1–G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1–G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7–G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9–G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.
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http://dx.doi.org/10.1073/pnas.2120787119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169777PMC
April 2022

[Isolation and culture of type 2 innate lymphoid cells (ILC2) in lungs of newborn mice].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2022 Mar;38(3):199-203

Department of Pediatrics, the Fourth People's Hospital of Zhenjiang, Zhenjiang 212000, China.

Objective To investigate the isolation and culture of the type 2 innate lymphoid cell (ILC2) in the lungs of newborn mice. Methods Immunomagnetic bead enrichment and fluorescence activated cell sorting (FACS) were used to isolate ILC2s. Flow cytometry was used to identify the purity of ILC2s. Inverted microscope was used to observe the growth of cells. ELISA was used to detect the expression levels of interleukin 5 (IL-5) and IL-13. Results The purity of the isolated ILC2s reached more than 95%. The isolated ILC2s were round or oval, and suspended in cell culture medium. After stimulation with IL-2 and IL-7 combined with IL-33, the contents of IL-5 and IL-13 produced by ILC2s and the proliferation ability of ILC2s increased significantly. Conclusion A rapid and efficient method for isolation and culture of ILC2s in the lung of newborn mice has been found.
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March 2022

Molecular weight tuning optimizes poly(2-methoxyethyl acrylate) dispersion to enhance the aging resistance and anti-fouling behavior of denture base resin.

Biomater Sci 2022 May 4;10(9):2224-2236. Epub 2022 May 4.

Department of Orthodontics, Institute of Craniofacial Deformity, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Poly(methyl methacrylate) (PMMA)-based denture base resins easily develop oral bacterial and fungal biofilms, which may constitute a significant health risk. Conventional bacterial-resistant additives and coatings often cause undesirable changes in the resin. Reduced bacterial resistance over time in the harsh oral environment is a major challenge in resin development. Poly(2-methoxyethyl acrylate) (PMEA) has anti-fouling properties; however, due to the oily/rubbery state of this polymer, and its surface aggregation tendency in a resin mixture, its direct use as a resin additive is limited. This study aimed to optimize the use of PMEA in dental resins. Acrylic resins containing a series of PMEA polymers with various molecular weights (MWs) at different concentrations were prepared, and the mechanical properties, surface gloss, direct transmittance, and cytotoxicity were evaluated, along with the distribution of PMEA in the resin. Resins with low-MW PMEA (2000 g mol) (PMEA-1) at low concentrations satisfied the clinical requirements for denture resins, and the PMEA was homogeneously distributed. The anti-fouling performance of the resin was evaluated for protein adsorption, bacterial and fungal attachment, and saliva-derived biofilm formation. The PMEA-1 resin most effectively inhibited biofilm formation (∼50% reduction in biofilm mass and thickness compared to those of the control). Post-aged resins maintained their mechanical properties and anti-fouling activity, and polished surfaces had the same anti-biofilm behavior. Based on wettability and tribological results, we propose that the PMEA additive creates a non-stick surface to inhibit biofilm formation. This study demonstrated that PMEA additives can provide a stable and biocompatible anti-fouling surface, without sacrificing the mechanical properties and aesthetics of denture resins.
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http://dx.doi.org/10.1039/d2bm00053aDOI Listing
May 2022

Ganoderic acid A ameliorates non-alcoholic streatohepatitis (NASH) induced by high-fat high-cholesterol diet in mice.

Exp Ther Med 2022 Apr 24;23(4):308. Epub 2022 Feb 24.

Department of Infectious Diseases, The Fourth Clinical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.

Non-alcoholic steatohepatitis (NASH) is becoming a huge global health problem. Previous studies have revealed that ganoderic acids have hepatoprotective and hypocholesterolemic effects. In the present study, to evaluate the anti-NASH activity of ganoderic acid A (GAA), male 6-week-old C57BL/6J mice were divided into the following four groups, which were administered different diets: Normal diet (ND group), high-fat high-cholesterol diet (HFHC group), HFHC diet supplemented with 25 mg/kg/day (GAAL group) or 50 mg/kg/day of GAA (GAAH group). After 12 weeks of GAA treatment, histopathological results revealed that compared with that of the HFHC group, GAA significantly inhibited fat accumulation, steatosis, inflammation and fibrosis in the liver. GAA effectively reduced serum aspartate transaminase and alanine transaminase levels compared with the HFHC model. Furthermore, the endoplasmic reticulum (ER) stress-responsive proteins, including glucose-regulated protein 78, phosphorylated (p)-eukaryotic initiation factor-2α and p-JNK, were significantly suppressed by GAA, while ERp57, p-MAPK and p-AKT were significantly increased after GAA treatment. Taken together, it was concluded that GAA could resist HFHC diet-induced NASH. In terms of its underlying mechanism, GAA could improve liver inflammation and fibrosis by inhibiting hepatic oxidative stress and the ER stress response induced by HFHC.
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http://dx.doi.org/10.3892/etm.2022.11237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931630PMC
April 2022
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