Publications by authors named "Han Jiang"

261 Publications

MdKCS2 increased plant drought resistance by regulating wax biosynthesis.

Plant Cell Rep 2021 Sep 1. Epub 2021 Sep 1.

State Key Laboratory of Crop Biology, Shandong Collaborative Innovation Center of Fruit and Vegetable Quality and Efficient Production, College of Horticulture Science and Engineering, Shandong Agricultural University, Tai'an, 271018, Shandong, China.

Key Message: We found that the apple wax related gene played a role in changing plant epidermal permeability and enhancing plant resistance to drought stress by increasing wax accumulation. The content and composition of epidermal wax in plants are affected by genetic and environmental factors. The KCS gene encodes the β-ketoalionyl-CoA synthetase, which is a rate-limiting enzyme in the synthesis of very-long-chain fatty acids (VLCFAs). In this study, we identified the MdKCS2 gene from apple as a homolog of Arabidopsis AtKCS2. The KCS protein is localized on the endoplasmic reticulum membrane. MdKCS2 exhibited the highest expression in apple pericarp, and was induced by abiotic stresses, such as drought and salt. Transgenic analysis indicated that the MdKCS2 improved the resistance to abiotic stress in apple calli. Ectopic expression of MdKCS2 in Arabidopsis increased the content of wax in leaves and stems, changed the permeability of cuticle of leaves, and enhanced plant drought resistance.
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http://dx.doi.org/10.1007/s00299-021-02776-4DOI Listing
September 2021

Adrenergic Blockade by Nebivolol to Suppress Oral Squamous Cell Carcinoma Growth Endoplasmic Reticulum Stress and Mitochondria Dysfunction.

Front Pharmacol 2021 12;12:691998. Epub 2021 Aug 12.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Adrenergic nerve fibers in the tumor microenvironment promote tumor growth and represent a potential target for cancer therapy. However, the effectiveness of targeting adrenergic nerve fibers for oral squamous cell carcinoma (OSCC) therapy needs to be evaluated by preclinical data. Herein, the 4NQO-induced and orthotopic xenograft OSCC mice models were established. We demonstrated that using 6OHDA chemical denervation as well as using nebivolol adrenergic blockade could halt the oral mucosa carcinogenesis. Our preclinical studies suggested that nebivolol, which is widely used to treat cardiovascular diseases, can be repositioned as a potential candidate to treat OSCC. Remarkably, we revealed the precise effect and mechanism of nebivolol on OSCC cells proliferation, cell cycle, and cell death. Administration of nebivolol could activate the endoplasmic reticulum (ER) stress signaling pathway through increasing the expression of inducible nitric oxide synthase, which subsequently triggers the integrated stress response and cell growth arrest. Simultaneously, ER stress also induced mitochondrial dysfunction in OSCC cells. We found that the accumulation of dysfunctional mitochondria with the impaired electron transport chain caused increasing reactive oxygen species production, which ultimately resulted in OSCC cell death. Altogether, our finding suggested a novel therapeutic opportunity for OSCC by targeting adrenergic nerve fibers, and repurposing nebivolol to treat OSCC can be represented as an effective strategy.
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http://dx.doi.org/10.3389/fphar.2021.691998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387679PMC
August 2021

Simultaneous adrenal tuberculosis and renal oncocytoma mimicking malignant masses incidentally detected by F-FDG PET/CT in a patient with lymphoma.

Eur J Nucl Med Mol Imaging 2021 Aug 24. Epub 2021 Aug 24.

Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.

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http://dx.doi.org/10.1007/s00259-021-05533-7DOI Listing
August 2021

Seadragon genome analysis provides insights into its phenotype and sex determination locus.

Sci Adv 2021 Aug 18;7(34). Epub 2021 Aug 18.

CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 510301 Guangzhou, China.

The iconic phenotype of seadragons includes leaf-like appendages, a toothless tubular mouth, and male pregnancy involving incubation of fertilized eggs on an open "brood patch." We de novo-sequenced male and female genomes of the common seadragon () and its closely related species, the alligator pipefish (). Transcription profiles from an evolutionary novelty, the leaf-like appendages, show that a set of genes typically involved in fin development have been co-opted as well as an enrichment of transcripts for potential tissue repair and immune defense genes. The zebrafish mutants for , which is lost in all syngnathids, were found to lack or have deformed pharyngeal teeth, supporting the hypothesis that the loss of has contributed to the loss of teeth in syngnathids. A putative sex-determining locus encoding a male-specific gene shared by common seadragon and alligator pipefish was identified.
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http://dx.doi.org/10.1126/sciadv.abg5196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373133PMC
August 2021

Draft genome of a multidrug and multi-heavy metal resistant Vibrio parahaemolyticus ST165 strain of Penaeus vannamei from seawater farms in Zhejiang, China.

J Glob Antimicrob Resist 2021 Sep 5;26:323-325. Epub 2021 Aug 5.

Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China. Electronic address:

Objectives: Vibrio parahaemolyticus ST165 strain (FB-11) was first isolated in 2019 in China from Penaeus vannamei from seawater farms. The strain includes multidrug resistant (MDR) and multi-heavy metal resistant (MHMR) phenotypes. In this study, we aimed to determine the draft genome sequence of strain FB-11 and analyze the genetic features with a special focus on MDR and MHMR genes.

Methods: The genomic DNA was sequenced using Nanopore PromethION and the Illumina Novaseq6000 platform, and the reads were de novo assembled into contigs using Unicycler. Genome function elements were predicted, the coding sequences were annotated, and whole-genome sequencing (WGS) analysis was performed.

Results: WGS analysis revealed that the genome comprised two chromosomes of 3,328,286 bp (GC content, 45.37%) and 1,805,825 bp (GC content, 45.36%). It harbored 26 important drug resistant genes and six important heavy metal resistant genes; all of these were located on the chromosomes. Multilocus sequence type of the strain was ST165.

Conclusions: This is the first report of the complete genome sequence of a V. parahaemolyticus ST165 strain isolated from P. vannamei in China. This genome sequence provides useful information on the genomic features associated with antimicrobial and heavy metal resistance in V. parahaemolyticus ST165.
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http://dx.doi.org/10.1016/j.jgar.2021.07.015DOI Listing
September 2021

A Progressive Generative Adversarial Method for Structurally Inadequate Medical Image Data Augmentation.

IEEE J Biomed Health Inform 2021 Aug 4;PP. Epub 2021 Aug 4.

The generation-based data augmentation method can overcome the challenge caused by the imbalance of medical image data to a certain extent. However, most of the current research focus on images with unified structure which are easy to learn. What is different is that ultrasound images are structurally inadequate, making it difficult for the structure to be captured by the generative network, resulting in the generated image lacks structural legitimacy. Therefore, a Progressive Generative Adversarial Method for Structurally Inadequate Medical Image Data Augmentation is proposed in this paper, including a network and a strategy. Our Progressive Texture Generative Adversarial Network alleviates the adverse effect of completely truncating the reconstruction of structure and texture during the generation process and enhances the implicit association between structure and texture. The Image Data Augmentation Strategy based on Mask-Reconstruction overcomes data imbalance from a novel perspective, maintains the legitimacy of the structure in the generated data, as well as increases the diversity of disease data interpretably. The experiments prove the effectiveness of our method on data augmentation and image reconstruction on Structurally Inadequate Medical Image both qualitatively and quantitatively. Finally, the weakly supervised segmentation of the lesion is the additional contribution of our method.
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http://dx.doi.org/10.1109/JBHI.2021.3101551DOI Listing
August 2021

Corrigendum: Immune Phenotyping of Patients With Acute Vogt-Koyanagi-Harada Syndrome Before and After Glucocorticoids Therapy.

Front Immunol 2021 16;12:731824. Epub 2021 Jul 16.

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

[This corrects the article DOI: 10.3389/fimmu.2021.659150.].
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http://dx.doi.org/10.3389/fimmu.2021.731824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323518PMC
July 2021

Highly Luminescent Metal-Free Perovskite Single Crystal for Biocompatible X-Ray Detector to Attain Highest Sensitivity.

Adv Mater 2021 Sep 26;33(36):e2102190. Epub 2021 Jul 26.

Key Laboratory of Applied Surface and Colloid Chemistry, National Ministry of Education, Shaanxi Key Laboratory for Advanced Energy Devices, Shaanxi Engineering Lab for Advanced Energy Technology, Institute for Advanced Energy Materials, School of Materials Science and Engineering, Shaanxi Normal University, Xi'an, 710119, China.

Solution-processed metal-based halide perovskites have taken a dominant position for perovskite optoelectronics including light emission and X-ray detection; however, the toxicity of the included heavy metals severely restricts their applications for wearable, lightweight, and transient optoelectronic devices. Here, the authors describe investigations of large (4 × 6 × 2 mm ) 3D metal-free perovskite MDABCO-NH I (MDBACO = methyl-N'-diazabicyclo[2.2.2]octonium) single crystal and its charge recombination and extraction behavior for light emission and X-ray detection. Unlike conventional 3D metal-based perovskites, this lightweight and biocompatible perovskite large crystal is processed from aqueous solution at room temperature, and can achieve both an extremely long carrier lifetime up to ≈1.03 µs and the formation of self-trapped excited states for luminescence. These features contribute to a photoluminescence quantum yield (PLQY) as high as ≈53% at room temperature and an X-ray sensitivity up to 1997 ± 80 μC Gy cm at 50 V bias (highest among all metal-free detectors). The ability to tune the perovskite band gap by modulating the structure under high pressure is also demonstrated, which opens up applications for the crystal as colored emitters. These attributes make it a molecular alternative to metal-based perovskites for biocompatible and transient optoelectronics.
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http://dx.doi.org/10.1002/adma.202102190DOI Listing
September 2021

Water jet as a novel technique for enamel drilling ex vivo.

PLoS One 2021 23;16(7):e0254787. Epub 2021 Jul 23.

School & Hospital of Stomatology, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, Peoples R China.

To investigate the usage of a water jet for enamel drilling ex vivo, 210 individual extracted molars without lesions or fillings were collected. Then, the specimens were drilled by a water jet or a high-speed dental drill. The cavities of 50 teeth were reconstructed digitally by micro-computed tomography (micro-CT) to measure the height and width. The cavities of 10 teeth were longitudinally incised and their surfaces were observed by scanning electronic microscopy (SEM). After the cavities were filled, 50 fillings were vertically incised. The bonding interface between tooth and filling was observed by SEM. 50 teeth with fillings were stained in 0.1% rhodamine B solution, and then the dye penetration between tooth and filling was observed under the stereomicroscope and confocal laser scanning microscopy (CLSM). The bonding strength between enamel and filling of 50 teeth was simulated and predicted with finite element analysis (FEA). At 140-150 MPa and for 2-3 s, cavities were made with a depth of approximately 764 μm in each tooth. SEM showed the cavity surface in the water jet group had a more irregular concave and convex structure than that in the high-speed dental drill group. There was a trend that the microleakage and bonding width was smaller in the water jet group than in the high-speed dental drill group. FEA indicated that the stress on the resin surface was greater than on the enamel surface in the water jet group. Compared with the tooth drilled by a high-speed dental drill, the tooth drilled by a water jet gained better retention of the filling material and suffered less bonding strength on the enamel surface. Water jet drilling is effective for enamel drilling.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254787PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301641PMC
July 2021

An Online Cross-Sectional Survey on Oral Healthcare Among School-Age Children During COVID-19 Epidemic in Wuhan, China.

Front Med (Lausanne) 2021 22;8:572217. Epub 2021 Jun 22.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Since the outbreak of Coronavirus disease 2019 (COVID-19), the government of China adopted many measures which changed people's lifestyle including oral health-related lifestyle to control the transmission. The aim of this study was to investigate oral health status, oral healthcare behaviors, and parental attitudes toward oral healthcare among school-age children in Wuhan during the COVID-19 outbreak and what the status would be when the outbreak is under control. This study was an online cross-sectional survey facing elementary school students in Wuhan. The questionnaire was completed by children's parents or other family members. The information on demographic data, oral health status, oral healthcare behaviors, and parental attitudes toward oral healthcare was collected at the end of school closure. The chi-square test was used to test the association of different questionnaire items. A total of 18,383 subjects aged 6-13 years with complete data were included in this investigation, and 44.2% of them suffered pain or discomfort related to teeth and gums during the epidemic. While there might be an increasing need and concern of oral healthcare during the outbreak and even when the outbreak was controlled, the worry of infection made it difficult for people to meet their demands of dental attendance. The risk of cross-infection during the treatment had a negative influence on parental attitudes toward dental attendance. Effective measures should be taken to meet people's demands of dental attendance.
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http://dx.doi.org/10.3389/fmed.2021.572217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258385PMC
June 2021

A non-cooperative game approach to the robust control design for a class of fuzzy dynamical systems.

ISA Trans 2021 Jun 28. Epub 2021 Jun 28.

Anhui Jiexun Optoelectronic Technology Co., Ltd, Hefei, Anhui, 230009, PR China.

Aiming at the time-varying bounded uncertainty in the mechanical system and the problem of excessive control gain caused by the "worst case", a robust control with tunable parameters that can be used to compensate for the uncertainty is proposed. The proposed control can guarantee that the system has uniform boundedness and uniform ultimate boundedness. Besides, the fuzzy set theory is used to describe the uncertainty to avoid introducing any IF-THEN fuzzy logic rules or probability theory. Based on the non-cooperative game theory, the parameters of the proposed control are optimized. We treat mutually independent parameters to be optimized as players, then design performance indexes for each parameter as its cost function, and solve the optimal result by the definition of Nash equilibrium. Finally, taking the trajectory tracking control of omnidirectional mobile platform as an example, the feasibility of the optimization method and the effectiveness of the control are verified by comparing with the other two control methods.
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http://dx.doi.org/10.1016/j.isatra.2021.06.031DOI Listing
June 2021

The Effect of Periodontitis on Dementia and Cognitive Impairment: A Meta-Analysis.

Int J Environ Res Public Health 2021 06 25;18(13). Epub 2021 Jun 25.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.

The association between periodontal disease and dementia/cognitive impairment continues to receive increasing attention. However, whether periodontal disease is a risk factor for dementia/cognitive impairment is still uncertain. This meta-analysis was conducted to comprehensively analyze the effect of periodontitis on dementia and cognitive impairment, and to assess the periodontal status of dementia patients at the same time. A literature search was undertaken on 19 October 2020 using PubMed, Web of Science, and Embase with different search terms. Two evaluators screened studies according to inclusion and exclusion criteria, and a third evaluator was involved if there were disagreements; this process was the same as that used for data extraction. Included studies were assessed with the Newcastle-Ottawa Scale (NOS), and results were analyzed using software Review Manager 5.2. Twenty observational studies were included. In the comparison between periodontitis and cognitive impairment, the odds ratio (OR) was 1.77 (95% confidence interval (CI), 1.31-2.38), which indicated that there was a strong relationship between periodontitis and cognitive impairment. There was no statistical significance in the effect of periodontitis on dementia (OR = 1.59; 95%CI, 0.92-2.76). The subgroup analysis revealed that moderate or severe periodontitis was significantly associated with dementia (OR = 2.13; 95%CI, 1.25-3.64). The mean difference (MD) of the community periodontal index (CPI) and clinical attachment level (CAL) was 0.25 (95%CI, 0.09-0.40) and 1.22 (95%CI, 0.61-1.83), respectively. In this meta-analysis, there was an association between periodontitis and cognitive impairment, and moderate or severe periodontitis was a risk factor for dementia. Additionally, the deterioration of periodontal status was observed among dementia patients.
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http://dx.doi.org/10.3390/ijerph18136823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297088PMC
June 2021

Application of medical magnifying loupes in diagnosis of oral mucosal diseases.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 04;50(2):205-211

Department of Oral Medicine.

: To evaluate the application of medical magnifying loupes in diagnosis of oral mucosal diseases. Twenty-four patients with plaque-type oral lichen planus or homogeneous oral leukoplakia were inspected by naked eyes or assistance with magnifying loupes. Histopathological results were used as the gold standard to evaluate the sensitivity, specificity and accuracy of the two methods in clinical diagnosis. Questionnaires were used to evaluate the subjective effect of magnifying loupes on the diagnosis efficiency of oral mucosal diseases and to explore the most suitable parameters for application. The sensitivity, specificity and accuracy of medical magnifying loupes for the identification of plaque-type oral lichen planus and homogeneous oral leukoplakia were 94.74%, 100.00% and 95.83%, respectively, which were significantly higher than those of naked eye inspection (89.47%, 80.00% and 87.50%). The effective rate of magnifying loupes assisted diagnosis was 91.76% according to physicians' subjective evaluation. The most suitable parameters were 3.5 times magnification and working distance. The medical magnifying loupes can effectively improve the efficiency of the inspection and diagnosis of oral mucosal diseases, and have the characteristics of convenience and real-time. The recommended clinical parameters are 3.5 times magnification and working distance.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0132DOI Listing
April 2021

Artificial Intelligence for Screening Chinese Electronic Medical Record and Biobank Information.

Biopreserv Biobank 2021 May 26. Epub 2021 May 26.

Department of Biobank, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To establish a structured and integrated platform of clinical data and biobank data, and a client to retrieve these data. Initially, the hospital information system (HIS) and biobank information system (BIS) were integrated through the patients' ID numbers. Then, natural language processing (NLP) was used to process the integrated unstructured clinical information. A query interface was designed for this system, which enabled researchers to retrieve clinical or biobank data. Finally, several queries were listed and manually checked to test the retrieval performance of the system. The construction of the biobank screening system (BSS) was completed, and the data were structured. The BSS took an average of 2 seconds to perform a search for target patients/samples. The retrieval results were consistent with the HIS and BIS. For complex queries, we manually checked the retrieved patients/samples, and the system's accuracy was 100%. This NLP-based system improved biological sample screening and using of clinical data. We will continue to improve this system, enhance resource sharing, and promote the development of translational medicine.
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http://dx.doi.org/10.1089/bio.2020.0151DOI Listing
May 2021

Immune Phenotyping of Patients With Acute Vogt-Koyanagi-Harada Syndrome Before and After Glucocorticoids Therapy.

Front Immunol 2021 28;12:659150. Epub 2021 Apr 28.

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Previous studies have established that disturbed lymphocytes are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) syndrome. Accordingly, glucocorticoids (GCs), with their well-recognized immune-suppressive function, have been widely used for treatment of VKH patients with acute relapses. However, the systemic response of diverse immune cells to GC therapy in VKH is poorly characterized. To address this issue, we analyzed immune cell subpopulations and their phenotype, as well as cytokine profiles in peripheral blood from VKH patients (n=25) and health controls (HCs, n=21) by flow cytometry and luminex technique, respectively. For 16 patients underwent GC therapy (methylprednisolone, MP), the aforementioned measurements as well as the transcriptome data from patients before and after one-week's GC therapy were also compared to interrogate the systemic immune response to GC therapy. Lymphocyte composition in the blood was different in VKH patients and HCs. VKH patients had significantly higher numbers of T cells with more activated, polarized and differentiated phenotype, more unswitched memory B cells and monocytes, as compared to HCs. MP treatment resulted in decreased frequencies of T cells and NK cells, inhibited NK cell activation and T cell differentiation, and more profoundly, a marked shift in the distribution of monocyte subsets. Collectively, our findings suggest that advanced activation and differentiation, as well as dysregulated numbers of peripheral lymphocytes are the major immunological features of VKH, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets, which might combinatorically result in the inhibition of the pathogenic immune response.
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http://dx.doi.org/10.3389/fimmu.2021.659150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113950PMC
April 2021

Chemical profile and potential mechanisms of Huo-Tan-Chu-Shi decoction in the treatment of coronary heart disease by UHPLC-Q/TOF-MS in combination with network pharmacology analysis and experimental verification.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jun 20;1175:122729. Epub 2021 Apr 20.

Department of Cardiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China; Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China. Electronic address:

Huo-Tan-Chu-Shi Decoction (HTCSD), a traditional Chinese medicine (TCM) prescription within Guangdong Provincial TCM Hospital (the largest TCM hospital in China), is used for effective clinical treatment of coronary heart disease (CHD) caused by phlegm-dampness syndrome with high incidence in the hot and humid climate of Lingnan region. However, its chemical components responsible for the therapeutic effects remain unclear, which restricts its application and further development. Hence, a detailed workflow, combing with UHPLC-Q/TOF-MS, network pharmacology analysis and experimental verification, was proposed and applied to characterize the chemical profile and potential mechanism of HTCSD against CHD. As a result, a total of 130 components from all six composed herbal medicines were characterized in a rapid and sensitive manner through UHPLC-Q/TOF-MS, of which 33 compounds were unambiguously confirmed with reference standards. Consequently, based on the integrated pharmacology network of "herbs-chemicals-targets-pathways-therapeutic effects", four chemicals (magnoflorine, menisperine, 13-hydroxyberberine, luteolin) with four CHD related targets (SRC, MAPK1, EGFR and AKT1) were considered as the key components and targets of HTCSD in the treatment of CHD. Furthermore, the effect of HTCSD was confirmed in animal experiments by enhancing the phosphorylation of MAPK, and the published literature and molecular binding results suggested that magnoflorine and luteolin tended to be the critical compounds involved in the process. Taken together, the characterization of chemical profile combined with network pharmacology analysis and experimental verification not only provided an efficient insight into the overall chemical profile of HTCSD but also revealed the potential pharmacological components and mechanisms of HTCSD against CHD, which laid a necessary chemical and biological basis for the discovery of in vivo bioactive components and the further revelation of functionary mechanism.
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http://dx.doi.org/10.1016/j.jchromb.2021.122729DOI Listing
June 2021

Identification and functional analysis of the MdLTPG gene family in apple.

Plant Physiol Biochem 2021 Jun 19;163:338-347. Epub 2021 Apr 19.

National Key Laboratory of Crop Biology, National Research Center for Apple Engineering and Technology, Shandong Collaborative Innovation Center of Fruit & Vegetable Quality and Efficient Production, College of Horticulture Science and Engineering, Shandong Agricultural University, Tai'an, 271018, Shandong, China. Electronic address:

Cuticular wax is synthesized from intracellular lipids that are exported by epidermal cells, and plant lipid transfer proteins (LTPs) play an important role in this process. The glycosylphosphatidylinositol (GPI)-anchored LTPs (LTPGs) are a large subgroup within the LTP family and function in lipid transport and wax formation. Although LTPG family members have been identified in several plant species, the LTPG gene family of apple (Malus domestica) remains uncharacterized. In this paper, we identified 26 potential LTPG genes by searching apple whole-genome annotation files using "GPI-anchored" and "lipid transferase" as keywords. Twenty of the 26 putative LTPG genes were confirmed as MdLTPG family members based on their subcellular localization predictions. The MdLTPGs were divided into four classes based on phylogenetic analysis and functional domain prediction. One member of each class was analyzed for subcellular localization, and all identified members were located on the plasma membrane. Most MdLTPG genes were induced by abiotic stress treatments such as low temperature, NaCl, and ABA. Finally, the MdLTPG17 protein was shown to interact with the lysine-rich arabinogalactan protein MdAGP18 to perform its function in wax transport during plant growth and development.
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http://dx.doi.org/10.1016/j.plaphy.2021.04.015DOI Listing
June 2021

Nanocatalytic Innate Immunity Activation by Mitochondrial DNA Oxidative Damage for Tumor-Specific Therapy.

Adv Mater 2021 May 2;33(20):e2008065. Epub 2021 Apr 2.

State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai, 200050, P. R. China.

The innate immune system plays a key role in protecting the human body from tumors, which, unfortunately, is largely counteracted by their immune-suppression function. Such an immune suppression has been reported to be induced by the immunosuppressive microenvironment, including the exhausted cytotoxic T lymphocytes (CTLs) and tumor-promoting M2-polarized macrophages. Here, a novel tumor-immunotherapeutic modality based on the nanocatalytic innate immunity activation by tumor-specific mitochondrial DNA (mtDNA) oxidative damage is proposed. In detail, a nanocatalytic medicine, Fe -Ru -loaded mesoporous silica nanoparticle named as MSN-Ru /Fe (MRF), is constructed to induce oxidative damage in the mtDNA of tumor cells. Such an oxidative mtDNA is able to escape from the tumor cells and acts as an immunogenic damage-associated molecular pattern to M1-polarize tumor-associated macrophages (TAMs), resulting in the reactivated immunoresponse of macrophages against cancer cells, and the subsequent inflammatory response of innate immunity. Most importantly, the treatment strategy based on regulating the innate immune response of TAMs not only stops the primary tumor progression, but also almost completely inhibits the growth of distant tumors in the periods of treatments.
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http://dx.doi.org/10.1002/adma.202008065DOI Listing
May 2021

Impact of COVID-19 on the oral health of adults in Wuhan and China: results of a nationwide online cross-sectional questionnaire survey.

BMC Oral Health 2021 Mar 26;21(1):162. Epub 2021 Mar 26.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.

Background: COVID-19 has seriously threatened the health and lives of people. This study aimed to investigate the impact of COVID-19 on the oral health of adults in Wuhan and other places of China amid the epidemic and to evaluate attitudes towards dental care in the post-epidemic period.

Methods: An online cross-sectional survey based on a questionnaire of 22 questions was conducted.

Results: A total of 3352 valid questionnaires were collected. Participants from Wuhan tended to be relatively psychologically affected and more concerned about future dental treatment. Toothbrushing frequency did not differ significantly between participants from Wuhan and other places and was associated with the prevalence of oral problems people encountered. Gingival bleeding, bad breath and oral ulcers were the three most common oral problems amid the epidemic, and significantly more participants in Wuhan experienced oral problems than other places in China.

Conclusion: The three most common oral problems amid the epidemic were gingival bleeding, bad breath and oral ulcers. Adults in Wuhan tended to be more seriously affected and suffered more oral problems than people from other places in China. Maintaining good oral health behaviours plays an important role in preventing dental problems. It is crucial to establish and to follow the standard guidelines for the provision of dental care during and after the epidemic.
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http://dx.doi.org/10.1186/s12903-021-01533-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994179PMC
March 2021

Aiding diagnosis of childhood attention-deficit/hyperactivity disorder of the inattentive presentation: Discriminant function analysis of multi-domain measures including EEG.

Biol Psychol 2021 04 17;161:108080. Epub 2021 Mar 17.

Peking University Sixth Hospital and Institute of Mental Health, Beijing, China; National Clinical Research Centre for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China.

Introduction: We developed a neurocognitive assessment tool (NCAT) in consultation with mental health professionals working with children with AD/HD as a diagnostic aid and screening tool. This study examines the predictive utility of NCAT in the classification of children with AD/HD Inattentive presentation.

Method: Fifty three children with AD/HD Inattentive presentation and 161 typically-developing children completed an NCAT assessment. Discriminant function analyses examined group membership prediction for separate components of NCAT and for the components combined.

Results: The combined model correctly classified 93.4 % of participants, with 91.4 % sensitivity and 93.9 % specificity. Contributions to classification were from SNAP-IV, psychological needs satisfaction, self-regulation, executive function performance, and EEG. The combined model resulted in a 9.3 % increase in specificity and 5.9 % increase in sensitivity compared to SNAP-IV alone.

Conclusions: NCAT provides good discrimination between children with and without AD/HD of the Inattentive presentation, and further investigation including other subtypes and comorbidities is warranted.
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http://dx.doi.org/10.1016/j.biopsycho.2021.108080DOI Listing
April 2021

VEGFA165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss.

JCI Insight 2021 Apr 22;6(8). Epub 2021 Apr 22.

Oregon Hearing Research Center, Department of Otolaryngology-Head & Neck Surgery, Oregon Health & Science University, Portland, Oregon, USA.

Millions of people are affected by hearing loss. Hearing loss is frequently caused by noise or aging and often associated with loss of pericytes. Pericytes populate the small vessels in the adult cochlea. However, their role in different types of hearing loss is largely unknown. Using an inducible and conditional pericyte depletion mouse model and noise-exposed mouse model, we show that loss of pericytes leads to marked changes in vascular structure, in turn leading to vascular degeneration and hearing loss. In vitro, using advanced tissue explants from pericyte fluorescence reporter models combined with exogenous donor pericytes, we show that pericytes, signaled by VEGF isoform A165 (VEGFA165), vigorously drive new vessel growth in both adult and neonatal mouse inner ear tissue. In vivo, the delivery of an adeno-associated virus serotype 1-mediated (AAV1-mediated) VEGFA165 viral vector to pericyte-depleted or noise-exposed animals prevented and regenerated lost pericytes, improved blood supply, and attenuated hearing loss. These studies provide the first clear-cut evidence that pericytes are critical for vascular regeneration, vascular stability, and hearing in adults. The restoration of vascular function in the damaged cochlea, including in noise-exposed animals, suggests that VEGFA165 gene therapy could be a new strategy for ameliorating vascular associated hearing disorders.
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http://dx.doi.org/10.1172/jci.insight.143285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119217PMC
April 2021

Qualitative and quantitative analysis of the chemical profile for Gualou-Xiebai-Banxia decoction, a classical traditional Chinese medicine formula for the treatment of coronary heart disease, by UPLC-Q/TOF-MS combined with chemometric analysis.

J Pharm Biomed Anal 2021 Apr 3;197:113950. Epub 2021 Feb 3.

College of Pharmacy, Jinan University, Guangzhou, 510632, PR China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), School of Pharmacy, Jinan University, Guangzhou, 510632, PR China. Electronic address:

Gualou-Xiebai-Banxia decoction (GXB) is one of the famous classical traditional Chinese Medicine (TCM) formula for the treatment of chest stuffiness and pains syndrome in Chinese medicine, i.e., coronary heart disease (CHD) in modern medicine. Being compared with Gualou-Xiebai Baijiu-decoction which only consists of Trichosanthis Pericarpium (TP), Allii Macrostemonis Bulbus (AMB) and wine, GXB is composed of another one additional herbal medicine, Pinellinae Rhizoma Praeparatum (PRP), and is more suitable to treat severe atherosclerosis and dyslipidemia. However, the comprehensive chemical composition of GXB is still unclear, which has seriously hindered the discovery of its effective components for improving the clinical symptoms of CHD. The present study aimed to investigate the overall chemical profile of GXB qualitatively and quantitatively by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS), and further explore the chemical contribution of PRP to this formula combined with chemometric approach. First, a total of 151 components, including steroidal saponins, flavonoids, triterpenoids, nitrogenous and other types components, were detected and characterized by UPLC-Q/TOF-MS in GXB. Then, flavonoids and nitrogenous could be qualitatively observed enrichment in GXB compared to those in GXB-dePRP (GXB deducted PRP in the formula). Furthermore, 19 characteristic components were selected for quantitative comparison between GXB and GXB-dePRP by UPLC-MS/MS combined with chemometric method. These findings indicated that steroidal saponins were the most abundant components in GXB, while the introduction of PRP could not only enrich the structural types of chemical compounds in this formula, but also increase the abundance of active components from other composed herbal medicines, TP and AMB. Taken together, this study developed and validated sensitive and practical methods for qualitative and quantitative analysis of GXB, and clarified the chemical contribution of PRP to this formula. These results laid a solid chemical foundation for further in vivo disposal investigation to screen out the potential effective components as well as therapeutic mechanism research of GXB.
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http://dx.doi.org/10.1016/j.jpba.2021.113950DOI Listing
April 2021

Low Serum-Free Testosterone Concentration in Chinese Male Patients with Uncomplicated Acute Type B Aortic Dissection.

Ann Vasc Surg 2021 Aug 4;75:324-331. Epub 2021 Feb 4.

Department of Vascular Surgery, The First Hospital, China Medical University, Shenyang, China. Electronic address:

Objective: Although aortic dissection occurs predominantly in men, its association with androgens is unknown. The aim of this study was to evaluate the androgen levels in Chinese male patients with uncomplicated, acute type B aortic dissection.

Study Design: Cross-sectional study.

Materials And Methods: A total of 192 age-matched male patients with uncomplicated, acute type B aortic dissection or essential hypertension were recruited between 2016 and 2018. The demographic and clinical data were analyzed.

Results: Male patients with uncomplicated, acute type B aortic dissection had lower serum total testosterone and free testosterone than male patients with essential hypertension (7.6 ± 3.7 nmol/L vs. 10.9 ± 3.8 nmol/L, P < 0.001; 36.0 ± 19.8 pmol/L vs. 56.4 ± 19.2 pmol/L, P < 0.001). Lower free testosterone level was significantly associated with uncomplicated, acute type B aortic dissection (univariate odds ratio 0.948, P < 0.001; multivariate odds ratio = 0.966, P = 0.002). No statistical difference was observed for free testosterone between younger patient groups (aged < 51 years; aged 51-60 years) and older patient groups (aged 61-70 years; aged >70 years) with uncomplicated, acute type B aortic dissection (33.7 ± 19.8 pmol/L vs. 38.5 ± 19.8 pmol/L, P = 0.239).

Conclusions: Lower free testosterone was independently associated with uncomplicated, acute type B aortic dissection in the Chinese male population with hypertension. Additional studies are needed to clarify whether earlier onset in Chinese patients with aortic dissection is associated with androgen deficiency.
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http://dx.doi.org/10.1016/j.avsg.2021.01.084DOI Listing
August 2021

The impact of coronavirus lockdown on oral healthcare and its associated issues of pre-schoolers in China: an online cross-sectional survey.

BMC Oral Health 2021 02 6;21(1):54. Epub 2021 Feb 6.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-Most) and Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, 430079, China.

Background: The sudden outbreak of coronavirus disease (COVID-19) epidemic influenced people's daily life. During lockdown of Wuhan city, the oral health and its associated issues of preschool children were investigated and guidance for dental clinics when the epidemic were controlled in the future were also provided.

Methods: A national online survey was conducted among preschool children and completed by their caregivers. The questionnaire related to children's oral health status and care behaviour, caregivers' attitudes. The information was statistically analyzed between Wuhan residents and others residents.

Results: 4495 valid questionnaires were collected. In oral health status, during Wuhan lockdown, 60.8%, 35.5% and 18.3% children had self-reported dental caries, toothache and halitosis respectively. In oral health attitudes, respondents who would increase attention to oral health was more than that would decrease. In oral hygiene behaviour, compared to non-Wuhan children, the children in Wuhan became more active in brushing their teeth. In utilization of dental services in the future, less Wuhan residents would choose to have dental visit directly, 28.5% Wuhan residents and 34.7% non-Wuhan residents agreed all of procedures could be done if proper protected.

Conclusions: Oral health status and associated issues of preschool children in Wuhan were significantly different from that of others during lockdown of Wuhan city and in the future. Effective measures should be taken as early as possible to protect children's oral health.
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http://dx.doi.org/10.1186/s12903-021-01410-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865116PMC
February 2021

The apple palmitoyltransferase MdPAT16 influences sugar content and salt tolerance via an MdCBL1-MdCIPK13-MdSUT2.2 pathway.

Plant J 2021 05 23;106(3):689-705. Epub 2021 Mar 23.

State Key Laboratory of Crop Biology, National Research Center for Apple Engineering and Technology, Shandong Collaborative Innovation Center of Fruit & Vegetable Quality and Efficient Production, College of Horticulture Science and Engineering, Shandong Agricultural University, Tai'an, Shandong, 271018, China.

Protein S-acyltransferases (PATs) are a category of eukaryotic transmembrane proteins that mediate the S-acylation of their target proteins. S-acylation, commonly known as palmitoylation, is a reversible protein modification that regulates the membrane association and function of target proteins. However, the functions and mechanisms of PATs in apple (Malus domestica) remain poorly understood. In this study, an MdPAT family member, MdPAT16, was identified and shown to have palmitoyltransferase activity. We demonstrated that this gene responds to salt stress and that its expression improves plant salt stress resistance. In addition, its overexpression significantly promotes the accumulation of soluble sugars. The same phenotypes were observed in transgenic tissue culture seedlings, transgenic roots, and Arabidopsis thaliana that ectopically expressed MdPAT16. MdPAT16 was shown to interact with MdCBL1 and stabilize MdCBL1 protein levels through palmitoylation. The N-terminal sequence of MdCBL1 contains a palmitoylation site, and its N-terminal deletion led to changes in MdCBL1 protein stability and subcellular localization. The phenotypes of MdCBL1 transgenic roots and transiently injected apple fruits were fully consistent with the sugar accumulation phenotype of MdPAT16. Mutation of the palmitoylation site interfered with this phenotype. These findings suggest that MdPAT16 palmitoylates its downstream target proteins, improving their stability. This may be a missing link in the plant salt stress response pathway and have an important impact on fruit quality.
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http://dx.doi.org/10.1111/tpj.15191DOI Listing
May 2021

Efficacy of topical administration for oral lichen planus: A network meta-analysis.

Oral Dis 2021 Feb 2. Epub 2021 Feb 2.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objective: To examine the comparative efficacy and safety of topical administration for oral lichen planus.

Materials And Methods: An electronic database search (1st January 1946 to 1st May 2020) for randomised controlled trials identified 34 studies involving eight interventions (clobetasol, betamethasone, triamcinolone, dexamethasone, fluocinolone, tacrolimus, pimecrolimus, and cyclosporine); these studies were subjected to network meta-analysis using direct and indirect comparisons [efficacy indicators: clinical response rate, symptom-reducing effect (visual analogue scale score), sign-reducing effect (Thongprasom-scale score) and relapse; safety indicator: adverse event occurrence].

Results: Compared with placebo, tacrolimus had the best clinical response rate (odds ratio (OR), 57.78 [95% CI 3.15-1060.52]; P-score, 0.8654) and cyclosporine had the worst (OR, 3.61[95% CI 0.20-66.62]; P-score, 0.2236); tacrolimus had the best symptom-reducing effect (standardised mean difference (SMD), 1.06 [95% CI 0.41-1.71]; P-score, 0.9323) and fluocinolone had the worst (SMD, -0.54 [95% CI -1.44-0.36]; P-score, 0.0157); dexamethasone had the best sign-reducing effect (SMD, 3.60 [95% CI 1.74-5.45]; P-score, 0.8306) and clobetasol had the worst (SMD, 2.63 [95% CI 1.66-3.61]; P-score, 0.2581); and pimecrolimus performed best (OR, 0.04 [95% CI 0.00-0.64]; P-score, 0.9227) and clobetasol performed the worst [OR, 0.60; 95% CI 0.15-2.45; P-score, 0.2545] in reducing relapse. Regarding safety, dexamethasone was the safest compared with placebo [OR, 0.37; 95% CI 0.05-2.57; P-score, 0.9337), whereas fluocinolone ranked low for safety [OR, 9.48; 95% CI 1.50- 60.03; P-score, 0.1189].

Conclusions: The relative ranking of topical administration varies according to the different indicators. Based on the joint consideration of clinical response rate and adverse event occurrence, dexamethasone, triamcinolone and betamethasone are recommended for better efficacy and safety. The optimal treatment for oral lichen patients varies under different conditions.
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http://dx.doi.org/10.1111/odi.13790DOI Listing
February 2021

The ankyrin repeat-containing protein MdANK2B regulates salt tolerance and ABA sensitivity in Malus domestica.

Plant Cell Rep 2021 Feb 17;40(2):405-419. Epub 2020 Dec 17.

National Key Laboratory of Crop Biology, College of Horticulture Science and Engineering, National Research Center for Apple Engineering and Technology, Shandong Agricultural University, Tai-An, 271018, Shandong, China.

Key Message: The ankyrin repeat-containing protein MdANK2B was identified to contribute to increasing resistance to salt stress and decreasing sensitivity to ABA in Malus domestica. Ankyrin (ANK) repeat-containing proteins occur widely in prokaryotes, eukaryotes, and even in some viruses and play a critical role in plant growth and development, as well as the response to biotic and abiotic stress. However, the function of ANK repeat-containing proteins in apple (Malus domestica) has not yet been investigated. Here, we identified apple MdANK2B based on homology analysis with the Arabidopsis ANK repeat-containing proteins AtAKR2A and AtAKR2B. MdANK2B was found to be localized in the cytoplasm, and its encoding gene was highly expressed in both apple leaves and fruits. In addition, MdANK2B gene expression was highly induced by salt stresses and abscisic acid (ABA). Overexpression of MdANK2B increased resistance to salt stress and decreased sensitivity to ABA in both transgenic apple calli and seedlings. In addition, overexpression of MdANK2B reduced the accumulation of reactive oxygen species (ROS) by enhancing the activity of antioxidant enzymes in response to salt stress. Our data revealed the role of MdANK2B in response to salt stress and ABA treatment in apple, which widens the known functions of ANK repeat-containing proteins in response to abiotic stress.
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http://dx.doi.org/10.1007/s00299-020-02642-9DOI Listing
February 2021

Altered Salivary Microbiome in the Early Stage of HIV Infections among Young Chinese Men Who Have Sex with Men (MSM).

Pathogens 2020 Nov 19;9(11). Epub 2020 Nov 19.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.

Human immunodeficiency virus (HIV) infections are spiking in Chinese young men who have sex with men (MSM). To explore alterations in the salivary microbiome and its correlation with demographic characteristics, CD4+ T cell count and viral load (VL) in HIV infections, samples of unstimulated whole saliva were analyzed by 16S rRNA gene sequencing using the Illumina MiSeq platform in 20 HIV newly infected patients before the initiation of antiretroviral therapy (ART) and at three and six months after, and in 20 age- and gender-paired healthy Chinese people. The results showed that the alpha diversity of salivary microbiota in HIV infections did not show differences from the healthy controls, but was reduced after six months under ART treatment. Comparative analysis revealed that was enriched in HIV-infected individuals, while was enriched in the healthy control group. After effective ART, the salivary microbiota composition was not completely restored, although some microbiota recovered. In addition, we found , and were correlated negatively with CD4+ T cell count, while was correlated positively with VL. We conclude that HIV infections experience a dysbiosis of the salivary microbiome. The salivary microbiome test could be a substitute for the blood tests in the diagnosis and prognosis of diseases.
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http://dx.doi.org/10.3390/pathogens9110960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699166PMC
November 2020

Therapeutic effect of curcumin on oral diseases: A literature review.

Phytother Res 2020 Nov 17. Epub 2020 Nov 17.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Curcumin (diferuloylmethane) is a polyphenol compound extracted from the rhizome of the plant Curcuma longa. It has the feature of being a yellow or orange pigment with a variety of biological properties, including anti-inflammation, antioxidation, anti-tumor, anti-bacteria, anti-fungus, and wound healing. Previous studies have reported the role of curcumin in treating different inflammatory diseases and tumors in vitro and in vivo. Recently, it has been demonstrated that curcumin has therapeutic benefits in oral mucosal diseases, periodontal diseases, and mouth neoplasms. In this review, we will focus on the therapeutic effects of curcumin on oral diseases.
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http://dx.doi.org/10.1002/ptr.6943DOI Listing
November 2020

Paroxetine combined with fluorouracil plays a therapeutic role in mouse models of colorectal cancer with depression through inhibiting IL-22 expression to regulate the MAPK signaling pathway.

Exp Ther Med 2020 Dec 22;20(6):240. Epub 2020 Oct 22.

Department of Psychiatry, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

The objective of the present study was to observe the therapeutic effect of paroxetine combined with fluorouracil on mice with colorectal cancer (CRC) complicated with depression and to explore its mechanism of action. Using chronic mild stress and xenograft tumor methods to model CRC complicated with depression, 60 BALB/c mice were randomly divided into control, tumor model, tumor depression model, tumor depression antidepressant, tumor depression chemotherapy and tumor depression antidepressant plus chemotherapeutic drug groups. Changes in mouse sucrose preference and forced swimming tests were tracked. Changes in tumor volume and weight were compared, the tumor inhibition rate was calculated, Ki-67 expression in tumor tissues was detected using immunohistochemistry and IL-22 levels in peripheral blood were detected using ELISAs. Additionally, protein expression levels of IL-22, Bcl-2, Bax, caspase-3, p38, phosphorylated (p)-p38, ERK, p-ERK, JNK and p-JNK in tumor tissue were detected using western blotting. Following treatment with paroxetine and chemotherapy drugs, the sucrose preference index was increased, autonomic behavior dysfunction was alleviated and tumor growth was significantly inhibited. Furthermore, the expression levels of Ki-67 and apoptosis-related proteins, Bax and caspase-3, increased in tumor tissues, anti-apoptosis protein Bcl2 expression levels decreased significantly, IL-22 levels in the blood and tumor tissues were reduced and p-p38, p-ERK and p-JNK proteins were significantly reduced. It was concluded that paroxetine combined with chemotherapy drugs improved depressive behavior and promoted the survival state in a mouse model of CRC and depression, possibly through inhibiting IL-22 expression to regulate the activity of the MAPK signaling pathway.
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http://dx.doi.org/10.3892/etm.2020.9370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7651781PMC
December 2020
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