Publications by authors named "Guang Wang"

382 Publications

A review of possible therapies for multiple sclerosis.

Mol Cell Biochem 2021 Apr 22. Epub 2021 Apr 22.

Hengyang Medical School, University of South China, Hengyang City, 421001, Hunan Province, China.

Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system with a wide range of symptoms, like executive function defect, cognitive dysfunction, blurred vision, decreased sensation, spasticity, fatigue, and other symptoms. This neurological disease is characterized by the destruction of the blood-brain barrier, loss of myelin, and damage to neurons. It is the result of immune cells crossing the blood-brain barrier into the central nervous system and attacking self-antigens. Heretofore, many treatments proved that they can retard the progression of the disease even though there is no cure. Therefore, treatments aimed at improving patients' quality of life and reducing adverse drug reactions and costs are essential. In this review, the treatment approaches to alleviate the progress of MS include the following: pharmacotherapy, antibody therapy, cell therapy, gene therapy, and surgery. The current treatment methods of MS are described in terms of the prevention of myelin shedding, the promotion of myelin regeneration, and the protection of neurons.
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http://dx.doi.org/10.1007/s11010-021-04119-zDOI Listing
April 2021

Relation of kidney function and homocysteine in patients with hypothyroidism.

Endocr Connect 2021 Apr 1. Epub 2021 Apr 1.

G Wang, Department of Endocrinology, Beijing Chao-Yang Hospital, Beijing, 100020, China.

Objective: It has been found that both serum homocysteine (Hcy) and serum creatinine levels were increased in hypothyroidism patients. The aim of this study was to investigate the correlation between serum Hcy and kidney function in patients with subclinical hypothyroidism or hypothyroidism.

Methods: A total of 448 subjects were enrolled and divided into three groups: hypothyroidism (n=129), subclinical hypothyroidism (n=141), and control group (n=168). Anthropometric information, metabolic parameters, serum Hcy and creatinine levels, and estimated glomerular filtration rate (eGFR) were analyzed.

Results: Compared with healthy subjects, patients with subclinical hypothyroidism or hypothyroidism had significantly higher serum Hcy and creatinine levels and lower eGFR level (all P<0.001). Serum Hcy was negatively correlated with eGFR in subclinical hypothyroidism patients (r =-0.220, P=0.009), and in hypothyroidism patients (r =-0.422, P<0.001). After adjusting for age, sex and body mass index, eGFR was still significantly correlated with serum Hcy in subclinical hypothyroidism or hypothyroidism patients (both P<0.05). Levothyroxine treatment resulted in significantly decreased Hcy and increased eGFR in hypothyroidism patients (both P<0.001). The decrease in Hcy was correlated with the increased eGFR after treatment (P=0.001).

Conclusion: Serum Hcy was negatively correlated with eGFR in subclinical hypothyroidism or hypothyroidism patients. After levothyroxine treatment, a correlation was found between the decrease in serum Hcy and the increase in eGFR in hypothyroidism patients.
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http://dx.doi.org/10.1530/EC-21-0069DOI Listing
April 2021

Substrate-Independent, Regenerable Anti-Biofouling Coating for Polymeric Membranes.

Membranes (Basel) 2021 Mar 13;11(3). Epub 2021 Mar 13.

Institute for Frontier Materials, Deakin University, Geelong, VIC 3216, Australia.

Biofouling is a common but significant issue in the membrane process as it reduces permeate flux, increases energy costs, and shortens the life span of membranes. As an effective antibacterial agent, a small amount of silver nanoparticles (AgNPs) immobilized on membrane surfaces will alleviate the membrane from biofouling. However, loading AgNPs on the membrane surface remains a challenge due to the low loading efficiency or the lack of bonding stability between AgNPs and the membrane surface. In this study, a substrate-independent method is reported to immobilize silver nanoparticles on polymeric membrane surfaces by firstly modifying the membrane surface with functional groups and then forming silver nanoparticles in situ. The obtained membranes had good anti-biofouling properties as demonstrated from disk diffusion and anti-biofouling tests. The silver nanoparticles were stably immobilized on the membrane surfaces and easily regenerated. This method is applicable to various polymeric micro-, ultra-, nano-filtration and reverse osmosis (RO) membranes.
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http://dx.doi.org/10.3390/membranes11030205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000734PMC
March 2021

Circulating prolactin level is increased in metabolically healthy obesity.

Endocr Connect 2021 Apr 29;10(4):484-491. Epub 2021 Apr 29.

Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, Chaoyang District, Beijing, China.

Objective: Prolactin (PRL) has been demonstrated as a metabolic hormone to regulate energy metabolism recently. The present study aims to investigate the association between PRL and metabolic alterations in different obesity phenotypes.

Methods: A total of 451 drug-naive participants were recruited, comprising 351 obese patients and 100 age- and sex-matched healthy participants with normal weight. PRL, anthropometric, and clinical parameters were measured.

Results: In the obesity group, 15.1% (53/351) were categorized as 'metabolically healthy obesity (MHO)'. Besides favorable blood pressure, glucose, and lipids profiles, the MHO group exhibited increased PRL, and lower levels of high-sensitivity C-reactive protein (hsCRP), homeostasis model assessment of insulin resistance (HOMA-IR), and adipose tissue insulin resistance (adipo-IR) than the metabolically unhealthy obesity (MUHO) group (PRL, HOMA-IR, and adipo-IR: P < 0.01; hsCRP: P < 0.05). The severe MUHO group showed significantly decreased PRL levels than the mild MUHO group (P < 0.05). Multivariate linear regression analysis indicated that fasting plasma glucose (FBG) and adipo-IR were significantly associated with PRL (FBG: β = -0.263, P < 0.05; adipo-IR: β = -0.464, P < 0.01). Multivariable logistic regression analysis showed that hsCRP (OR = 0.824) and PRL (OR = 1.211) were independent predictors of MHO (all P < 0.01).

Conclusion: The MHO group had significantly increased circulating PRL levels when compared with the control and MUHO groups, and multivariable logistic regression analysis showed that PRL was independent predictors of MHO. Our findings suggested that increased circulating PRL might be a compensatory response for favoring energy metabolism during obesity.
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http://dx.doi.org/10.1530/EC-21-0040DOI Listing
April 2021

Retinoic Acid Signaling Plays a Crucial Role in Excessive Caffeine Intake-Disturbed Apoptosis and Differentiation of Myogenic Progenitors.

Front Cell Dev Biol 2021 9;9:586767. Epub 2021 Mar 9.

Division of Histology and Embryology, International Joint Laboratory for Embryonic Development and Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.

Whether or not the process of somitogenesis and myogenesis is affected by excessive caffeine intake still remains ambiguous. In this study, we first showed that caffeine treatment results in chest wall deformities and simultaneously reduced mRNA expressions of genes involved in myogenesis in the developing chicken embryos. We then used embryo cultures to assess in further detail how caffeine exposure affects the earliest steps of myogenesis, and we demonstrated that the caffeine treatment suppressed somitogenesis of chicken embryos by interfering with the expressions of crucial genes modulating apoptosis, proliferation, and differentiation of myogenic progenitors in differentiating somites. These phenotypes were abrogated by a retinoic acid (RA) antagonist in embryo cultures, even at low caffeine doses in C2C12 cells, implying that excess RA levels are responsible for these phenotypes in cells and possibly . These findings highlight that excessive caffeine exposure is negatively involved in regulating the development of myogenic progenitors through interfering with RA signaling. The RA somitogenesis/myogenesis pathway might be directly impacted by caffeine signaling rather than reflecting an indirect effect of the toxicity of excess caffeine dosage.
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http://dx.doi.org/10.3389/fcell.2021.586767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006404PMC
March 2021

The Prevalence of Euthyroid Hypertriiodothyroninemia in Newly Diagnosed Multiple Myeloma and its Clinical Characteristics.

Endocr Pract 2021 Mar 13;27(3):236-240. Epub 2020 Dec 13.

Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China. Electronic address:

Objective: To evaluate the prevalence of euthyroid hypertriiodothyroninemia and/or hyperthyroxinemia and its clinical characteristics in multiple myeloma (MM) patients.

Methods: Previously untreated, newly diagnosed patients with MM were enrolled at the Beijing Chao-yang Hospital between January 2016 and December 2019. Thyroid function and clinical characteristics were analyzed.

Results: A total of 105 patients were enrolled in this study. Thirteen (12.38%) patients exhibited euthyroid hypertriiodothyroninemia with strikingly elevated total triiodothyronine (TT3) levels (>8 ng/mL). Among these 13 patients, 12 patients were immunoglobulin (Ig) G type (92.31%), and 1 patient was light-chain κ type (7.69%). Compared with other patients with MM, patients with hypertriiodothyroninemia were more likely to be IgG type and had higher serum globulin and lower albumin levels and more advanced International Staging System stage (all P < .05). Among the 13 euthyroid hypertriiodothyroninemia patients, 8 patients have been followed up and checked for thyroid function. The TT3 levels in all 8 patients were normalized to the reference range after antimyeloma chemotherapy.

Conclusion: About 12% of patients with MM had euthyroid hypertriiodothyroninemia. Their strikingly elevated TT3 was normalized after chemotherapy. Clinicians should be aware of the possibility of high TT3 levels in euthyroid patients with MM and the potential risk of MM in patients with strikingly elevated TT3.
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http://dx.doi.org/10.1016/j.eprac.2020.09.004DOI Listing
March 2021

[Overview on Habitat Monitoring Methods Under Watershed Ecological Space Management].

Huan Jing Ke Xue 2021 Mar;42(3):1581-1590

China National Environmental Monitoring Centre, Beijing 100012, China.

Habitat consist of the physical, chemical, and biological features that support the survival and growth of aquatic organisms, and the maintenance of biological processes and ecological function. However, habitat is spatially and temporally heterogeneous and displays spatial autocorrelation, mean that at large spatial scales, the maintenance of ecological function is complex. Consequently, it is difficult to characterize and interpret habitat characteristics, especially over large space-time scales. Although a wide variety of habitat monitoring methods have been proposed, there is still lack of well-developed methods for long-term tracking and monitoring of habitat changes at the watershed scale. Here, the characteristics of watershed habitats and the importance of monitoring in environmental management were explored based on the concept, purpose, and significance of habitat monitoring. Several monitoring methods were summarized and compared, and the key scientific limitations and requirements of habitat monitoring (e.g., spatial scale, survey scope, characteristic parameters, data acquisition, etc.) evaluated. Based on this, key aspects for successful habitat monitoring in China are proposed as baseline information for the research and application of habitat monitoring for watershed-scale ecological space management.
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http://dx.doi.org/10.13227/j.hjkx.202007287DOI Listing
March 2021

Association Between Body Mass Index and Thyroid Function in Euthyroid Chinese Adults.

Med Sci Monit 2021 Mar 19;27:e930865. Epub 2021 Mar 19.

Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China (mainland).

BACKGROUND Obesity can influence thyroid function through multiple routes, even in people who are euthyroid. The correlation between weight and thyroid function is a matter of debate. The present study investigated the relationship between body weight and thyroid function in euthyroid Chinese adults. MATERIAL AND METHODS A total of 1564 participants with serum thyrotropin (TSH) and thyroid hormone levels within the reference range were included. All of them were tested for thyroid function parameters and categorized, based on body mass index (BMI), into 3 groups: normal weight, overweight, and obese. The effects of BMI on thyroid function were examined using linear (continuous values) and logistic (dichotomous levels according to medians or means) regression and controlling for age and sex. RESULTS There were significant differences in free triiodothyronine (FT3) levels and FT3/free thyroxine (FT4) ratios among participants who were normal weight, overweight, and obese (both P<0.001). Multivariable regression analysis (P<0.001) showed that BMI was positively associated with FT3 levels and FT3/FT4 ratios. Compared with the normal weight group, the patients who were overweight or obese had significantly higher FT3 levels and FT3/FT4 ratios that were higher than average, according to logistic regression analyses. CONCLUSIONS We found that Chinese adults who are obese may have higher FT3 levels and FT3/FT4 ratios than those who are of normal weight, even if their thyroid function values are within the normal range.
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http://dx.doi.org/10.12659/MSM.930865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986724PMC
March 2021

Fermi Velocity Reduction of Dirac Fermions around the Brillouin Zone Center in In Se -Bilayer Graphene Heterostructures.

Adv Mater 2021 Apr 19;33(17):e2007503. Epub 2021 Mar 19.

Shenzhen Institute for Quantum Science and Engineering (SIQSE) and Department of Physics, Southern University of Science and Technology (SUSTech), Shenzhen, 518055, China.

Emergent phenomena such as unconventional superconductivity, Mott-like insulators, and the peculiar quantum Hall effect in graphene-based heterostructures are proposed to stem from the superlattice-induced renormalization of (moiré) Dirac fermions at the graphene Brillouin zone corners. Understanding the corresponding band structure commonly demands photoemission spectroscopy with both sub-meV resolution and large-momentum coverage, beyond the capability of the current state-of-the-art. Here the realization of moiré Dirac cones around the Brillouin zone center in monolayer In Se /bilayer graphene heterostructure is reported. The renormalization is evidenced by reduced Fermi velocity (≈23%) of the moiré Dirac cones and the reshaped Dirac point at the Γ point where they intersect. While there have been many theoretical predictions and much indirect experimental evidence, the findings here are the first direct observation of Fermi velocity reduction of the moiré Dirac cones. These features suggest strong In Se /graphene interlayer coupling, which is comparable with that in twisted bilayer graphene. The strategy expands the choice of materials in the heterostructure design and stimulates subsequent broad investigations of emergent physics at the sub-meV energy scale.
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http://dx.doi.org/10.1002/adma.202007503DOI Listing
April 2021

Endoplasmic reticulum stress-related calcium imbalance plays an important role on Zinc oxide nanoparticles-induced failure of neural tube closure during embryogenesis.

Environ Int 2021 07 14;152:106495. Epub 2021 Mar 14.

Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China. Electronic address:

Zinc oxide nanoparticles (ZnO NPs) have been increasingly and widely utilized in various fields, such as agriculture, food and cosmetics. However, various levels of adverse impacts of ZnO NPs on the ecological environment and public health have been associated with each stage of their production, use and disposal. ZnO NPs can be ingested by pregnant women and transferred to developing embryos/foetus through the placental barrier, however, the potential toxicity of ZnO NPs to embryonic and foetal development is largely unclear. In this study, we discovered that ZnO NPs exposure caused growth proportional failure of neural tube closure in mouse and chicken embryos and a simultaneous increase in apoptosis in the developing neural tubes of chicken embryos, which was verified in an in vitro experiment using the SH-SY5Y cell line. Furthermore, removal of free Zn ions with EDTA or inhibition of Zn ion absorption by CaCl partially alleviated the neurotoxicity induced by ZnO NPs, implying that ZnO NPs-induced developmental neurotoxicity is probably due to both ZnO NPs and the Zn ions released from ZnO NPs. In addition, we found that ZnO NPs exposure caused endoplasmic reticulum stress-mediated apoptosis driven mainly by an increase in intracellular calcium (Ca) concentrations, rather than by the activation of three membrane protein receptors (ATF6, IRE-1 and PERK). Thus, Ca imbalance-mediated apoptosis in the context of ZnO NPs exposure may lead to cellular dysfunctions in developing neural precursors, such as, abnormalities involved in neural tube closure, ultimately leading to neural tube defects (NTDs) during embryogenesis. In sum, our results revealed that ZnO NPs exposure greatly increases the risk of failure of neural tube closure through endoplasmic reticulum stress-mediated neural cell death in the developing embryos, which may further lead to the NTD in fetal stage, including failure of neural tube closure.
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http://dx.doi.org/10.1016/j.envint.2021.106495DOI Listing
July 2021

Dysbacteriosis induces abnormal neurogenesis via LPS in a pathway requiring NF-κB/IL-6.

Pharmacol Res 2021 May 10;167:105543. Epub 2021 Mar 10.

Division of Histology and Embryology, International Joint Laboratory for Embryonic Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou 510632, China; Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou 510632, China. Electronic address:

In this study, we identified elevated levels of LPS and suppressed neurogenesis in a successfully established mouse model of gut microbiota dysbiosis. We mimicked these phenotypes using mouse and chicken embryos exposed to LPS and found that dramatic variation in gene expression was due to changes in the dorsal-ventral patterning of the neural tube. Cell survival and excess ROS were also involved in this process. Antioxidant administration alleviated LPS-activated NF-κB signaling, while directly blocking NF-κB signaling altered the LPS-induced inhibition of neurogenesis. Furthermore, IL-6 was proven to play a vital role in the expression of crucial neurogenesis-related genes and NF-κB. In summary, we found that the suppression of neurogenesis induced by dysbacteriosis-derived LPS was significantly reversed in mice with fecal microbiota transplantation. This study reveals that gut dysbacteriosis-derived LPS impairs embryonic neurogenesis, and that the NF-κB/IL-6 pathway could be one of the main factors triggering the downstream signaling cascade.
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http://dx.doi.org/10.1016/j.phrs.2021.105543DOI Listing
May 2021

Gut-Lung Dysbiosis Accompanied by Diabetes Mellitus Leads to Pulmonary Fibrotic Change through the NF-κB Signaling Pathway.

Am J Pathol 2021 05 9;191(5):838-856. Epub 2021 Mar 9.

International Joint Laboratory for Embryonic Development and Prenatal Medicine, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou, China; Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China. Electronic address:

Growing evidence shows that the lungs are an unavoidable target organ of diabetic complications. However, the pathologic mechanisms of diabetic lung injury are still controversial. This study demonstrated the dysbiosis of the gut and lung microbiome, pulmonary alveolar wall thickening, and fibrotic change in streptozotocin-induced diabetic mice and antibiotic-induced gut dysbiosis mice compared with controls. In both animal models, the NF-κB signaling pathway was activated in the lungs. Enhanced pulmonary alveolar well thickening and fibrotic change appeared in the lungs of transgenic mice expressing a constitutively active NF-κB mutant compared with wild type. When lincomycin hydrochloride-induced gut dysbiosis was ameliorated by fecal microbiota transplant, enhanced inflammatory response in the intestine and pulmonary fibrotic change in the lungs were significantly decreased compared with lincomycin hydrochloride-treated mice. Furthermore, the application of fecal microbiota transplant and baicalin could also redress the microbial dysbiosis of the gut and lungs in streptozotocin-induced diabetic mice. Taken together, these data suggest that multiple as yet undefined factors related to microbial dysbiosis of gut and lungs cause pulmonary fibrogenesis associated with diabetes mellitus through an NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.ajpath.2021.02.019DOI Listing
May 2021

Pathogenesis of Proteus mirabilis in Catheter-Associated Urinary Tract Infections.

Urol Int 2021 10;105(5-6):354-361. Epub 2021 Mar 10.

Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China,

Proteus mirabilis (PM) is a Gram-negative rod-shaped bacterium and widely exists in the natural environment, and it is most noted for its swarming motility and urease activity. PM is the main pathogen causing complicated urinary tract infections (UTIs), especially catheter-associated urinary tract infections. Clinically, PM can form a crystalline biofilm on the outer surface and inner cavity of the urethral indwelling catheter owing to its ureolytic biomineralization. This leads to catheter encrustation and blockage and, in most cases, is accompanied by urine retention and ascending UTI, causing cystitis, pyelonephritis, and the development of bladder or kidney stones, or even fatal complications such as septicemia and endotoxic shock. In this review, we discuss how PM is mediated by a catheter into the urethra, bladder, and then rose to the kidney causing UTI and the main virulence factors associated with different stages of infection, including flagella, pili or adhesins, urease, hemolysin, metal intake, and immune escape, encompassing both historical perspectives and current advances.
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http://dx.doi.org/10.1159/000514097DOI Listing
March 2021

The effects of long-term extracurricular scientific research on the medical students: Insight from Jinan University Medical School.

Biochem Mol Biol Educ 2021 Mar 8. Epub 2021 Mar 8.

Division of Histology and Embryology, International Joint Laboratory for Embryonic Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.

The benefits and long-term effects of extracurricular scientific research on undergraduate students in many countries have been intensively investigated, but it remains obscure for Chinese medical students. In this study, we investigated the outcome of 60 medical students who have participated in extracurricular scientific research at Jinan University Medical School over a period of 7 years (2011-2018). The results revealed that these students have contributed to 31 biomedical science articles in reputable academic journals, as first- or co-authors. Furthermore, they also independently procured various funding based on their research achievements, and smaller awards for achievements in conferences and competitions. Assessment of the grade point average score of these students revealed that conducting extracurricular scientific research did not affect their routine medical study and exam grades (P>0.05). The students benefited from participating in extracurricular research, by acquiring the ability to think scientifically and enhancing their communication skills. In addition, the medical students were motivated to enlist for postgraduate studies so that they could further embark in scientific research. In sum, Chinese medical students are capable of participating in scientific research and make a significant contribution to science.
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http://dx.doi.org/10.1002/bmb.21499DOI Listing
March 2021

A study on the characteristics of coke in the hearth of a superlarge blast furnace.

PLoS One 2021 3;16(3):e0247051. Epub 2021 Mar 3.

School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, China.

An in-depth study on the characteristics of coke in the hearths of blast furnaces is of great significance for explaining the mechanism of coke deterioration in blast furnaces. In the present work, the changes in macromorphology, degree of graphitization, and microstructure of the coke taken from different hearth locations of a 5,800 m3 superlarge blast furnace during its intermediate repair period were systematically studied. Significant differences were found between cokes obtained from the edge ("edge coke") and from the center ("center coke") of the hearth in terms of properties and degradation mechanisms. Edge coke was severely eroded by liquid metal, and only a small amount of slag was detected in the coke porosity, whereas center coke was basically free from erosion by liquid metal, and a large amount of slag was detected in the coke porosity. The degree of graphitization of edge coke was higher than that of center coke. The carburizing effect of liquid metal was the main cause of the degradation of edge coke and made it smaller or even disappear. Center coke was degraded due to the combination of two factors: slag inserted into micropores on the surface of center coke loosened the surface structure; and graphite-like flakes that appeared on the center coke surface lowered the strength and caused cracks in the surface.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247051PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928459PMC
March 2021

Omega-3FAs Can Inhibit the Inflammation and Insulin Resistance of Adipose Tissue Caused by HHcy Induced Lipids Profile Changing in Mice.

Front Physiol 2021 12;12:628122. Epub 2021 Feb 12.

Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

The adipose Nod-like receptor protein 3 (NLRP3) inflammasome initiates insulin resistance; however, the mechanism of inflammasome activation in adipose tissue remains elusive. In this study, homocysteine (Hcy) was found to participate in insulin resistance a NLRP3 inflammasome-related process. Hcy-induced activation of NLRP3 inflammasomes were observed in adipose tissue during the generation of insulin resistance . This animal model suggests that diets high in omega-3 fatty acids alter serum and adipose lipid profiles, and in this way, omega-3 fatty acids may reduce adipose tissue inflammation and attenuate insulin resistance.
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http://dx.doi.org/10.3389/fphys.2021.628122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907609PMC
February 2021

Increased Prolactin is an Adaptive Response to Protect Against Metabolic Disorders in Obesity.

Endocr Pract 2021 Jan 15. Epub 2021 Jan 15.

Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China. Electronic address:

Objective: Prolactin (PRL) is a polypeptide hormone named for its crucial role in lactation. Recently, PRL has been recognized as a metabolic hormone that regulates energy metabolism. The current study aimed to investigate the relationship between circulating PRL and metabolic alterations in overweight/obese patients and the effect of weight loss through bariatric surgery on circulating PRL.

Methods: A total of 448 overweight/obese patients aged between 18 and 40 years and 120 age- and sex-matched healthy controls with normal weight were enrolled. Among all participants, 156 obese patients underwent bariatric surgery.

Results: Circulating PRL levels were significantly increased in the overweight (15.27 ± 9.58 μg/L) and obese (17.75 ± 9.15 μg/L) groups compared with the normal weight (13.57 ± 9.03 μg/L) group. Multiple regression analyses demonstrated that the adipose tissue insulin resistance (adipo-IR) level was an independent predictor for PRL (β = -0.451, P < .01). Despite comparable anthropometric parameters, the overweight/obese patients with a higher PRL tertile had decreased levels of triglycerides, nonesterified fatty acids, homeostasis model assessment of insulin resistance, and adipo-IR compared with the patients in the moderate and lower PRL tertiles. Serum PRL levels were significantly decreased following the alleviation of metabolic parameters after bariatric surgery (from 17.12 ± 8.27 to 13.00 ± 5.78 μg/L, P < .05), and the decrease in PRL levels was significantly greater in the lower adipo-IR group than in the higher adipo-IR group (P < .01).

Conclusion: An increased serum PRL level might be an adaptive response for protecting against metabolic disorders in obesity.
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http://dx.doi.org/10.1016/j.eprac.2021.01.002DOI Listing
January 2021

Effect of Sitagliptin on Serum Irisin Levels in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

Diabetes Ther 2021 Apr 24;12(4):1029-1039. Epub 2021 Feb 24.

Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100020, China.

Introduction: Irisin is a unique myokine with striking effects on regulating insulin sensitivity and energy metabolism. This study aimed to investigate the changes in serum irisin in patients with newly diagnosed type 2 diabetes mellitus (T2DM) following sitagliptin treatment.

Methods: Thirty-two patients with T2DM were treated with 100 mg/day sitagliptin for 16 weeks. Twenty age-, sex- and body mass index (BMI)-matched healthy subjects were enrolled as the control group. Irisin and metabolic parameters were measured at baseline and after treatment.

Results: Patients with T2DM had lower irisin levels than the controls (10.03 ± 2.06 vs. 13.06 ± 3.10 ng/ml, P < 0.01). Sitagliptin treatment significantly increased serum irisin levels in T2DM patients compared to baseline (11.18 ± 1.91 vs. 10.03 ± 2.06  ng/ml, P < 0.01). Increased irisin levels were associated with decreased fasting blood glucose (FBG) (β = - 0.24, P < 0.05) and glycosylated hemoglobin (HbA1c) (β = - 0.15, P < 0.05).

Conclusions: Sitagliptin treatment significantly increased serum irisin levels in patients with T2DM, and the increase of the irisin level was associated with decreases of FBG and HbA1c levels. These results suggest that irisin might be involved in the antidiabetic mechanisms of sitagliptin.

Trial Registration: ClinicalTrials.gov identifier NCT04495881.
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http://dx.doi.org/10.1007/s13300-021-01023-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994490PMC
April 2021

Vitamin D3 Supplement Attenuates Blood-Brain Barrier Disruption and Cognitive Impairments in a Rat Model of Traumatic Brain Injury.

Neuromolecular Med 2021 Feb 22. Epub 2021 Feb 22.

Division of Neurosurgery, The Affiliated Hospital, Chengde Medical College, Chengde, 067000, Hebei, China.

This study was designed to study the effects of vitamin D3 supplementation on the cognitive dysfunction and neurological function of traumatic brain injury (TBI) and the possible underlying mechanisms. To this purpose, different doses of vitamin D3 were intraperitoneally injection to TBI rats for one week before TBI surgery and three consecutive weeks after TBI. Brain edema evaluation was conducted on the third day and Evans blue staining for blood-brain barrier (BBB) permeability on the seventh day after TBI. Rat behavior was assessed by evaluation of neurological scores and morris water maze. It was revealed that vitamin D levels increased in serum after the administration of vitamin D3 for one week. TBI led to neurological deficit, together with brain edema, BBB disruption and inflammation. Vitamin D3 supplement ameliorated neurological deficit and cognitive impairments induced by TBI. Vitamin D3 administration reduced brain edema and impairments of blood-brain barrier induced by TBI, as well as decreased inflammatory response in TBI rat brain. Our results showed that vitamin D3 administration alleviated neurobehavioral deficits and improved brain edema after TBI. Vitamin D3 inhibited inflammatory cytokines and decreased BBB disruption in TBI rats. Vitamin D3 may be used for the treatment of TBI as a protective intervention.
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http://dx.doi.org/10.1007/s12017-021-08649-zDOI Listing
February 2021

Serum metabolomic patterns in young patients with ischemic stroke: a case study.

Metabolomics 2021 02 8;17(2):24. Epub 2021 Feb 8.

Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, NO. 8, Gongti South Road, Chaoyang District, Beijing, 100020, China.

Background: Ischemic stroke is one of the leading causes of death and adult disability. The incidence of ischemic stroke continues to rise in young adults. This study aimed to provide a comprehensive evaluation of metabolic changes and explore possible mechanisms in young ischemic stroke patients without common risk factors.

Methods: This study investigated serum metabolomics in 50 young patients with newly suffered ischemic stroke and 50 age-, sex-, and body mass index-matched healthy controls. Liquid chromatography coupled with a Waters Xevo TQ-S mass spectrometer with an electrospray ionization (ESI) source was used to analyze amino acid or bile acid, and free fatty acid or lipid was analyzed by liquid chromatography coupled with a Qtrap5500 mass spectrometer with an ESI source. The metabolomic data were analyzed by performing a multivariate statistical analysis.

Results: A total of 197 metabolites, including amino acids, bile acids, free fatty acids, and lipids, were identified in all participants. Multivariate models showed significant differences in serum metabolomic patterns between young patients with ischemic stroke and healthy controls. The stroke patients had increased L-methionine, homocysteine, glutamine, uric acid, GCDCA, and PE (18:0/20:4, 16:0/22:5), and decreased levels of L-citrulline, taurine, PC (16:2/22:6, 16:2/20:5, 15:0/18:2), and SM (d18:1/23:0, d20:0/19:1, d18:1/22:0, d16:0/26:1, d16:0/18:0, d16:0/22:1, d18:1/19:1, d16:0/17:1, d16:1/24:1, d18:1/19:0). Based on the identified metabolites, the metabolic pathways of arginine biosynthesis, glycerophospholipid metabolism, and taurine and hypotaurine metabolism were significantly enriched in the young patients with ischemic stroke.

Conclusions: Serum metabolomic patterns were significantly different between young patients with ischemic stroke and healthy controls. Our study is beneficial in providing a further view into the pathophysiology of young patients with ischemic stroke.
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http://dx.doi.org/10.1007/s11306-021-01774-7DOI Listing
February 2021

Influence of Hyperproteinemia on Insect Innate Immune Function of the Circulatory System in .

Biology (Basel) 2021 Feb 3;10(2). Epub 2021 Feb 3.

School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China.

Metabolic disorders of the circulatory system of animals (e.g., hyperglycemia and hyperlipidemia) can significantly affect immune function; however, since there is currently no reliable animal model for hyperproteinemia, its effects on immunity remain unclear. In this study, we established an animal model for hyperproteinemia in an invertebrate silkworm model, with a controllable plasma protein concentration (PPC) and no primary disease effects. We evaluated the influence of hyperproteinemia on innate immunity. The results showed that high PPC enhanced hemolymph phagocytosis via inducing a rapid increase in granulocytes. Moreover, while oenocytoids increased, the plasmacytes quickly dwindled. High PPC inhibited hemolymph melanization due to decreased phenoloxidase (PO) activity in the hemolymph via inhibiting the expression of the prophenoloxidase-encoding genes, and . High PPC upregulated the gene expression of antimicrobial peptides via differential activation of the Toll and Imd signaling pathways associated with NF-κB signaling, followed by an induction of inconsistent antibacterial activity towards Gram-positive and Gram-negative bacteria in an animal model of high PPC. Therefore, high PPC has multiple significant effects on the innate immune function of the silkworm circulatory system.
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http://dx.doi.org/10.3390/biology10020112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913649PMC
February 2021

Effect of linagliptin, a dipeptidyl peptidase-4 inhibitor, compared with the sulfonylurea glimepiride on cardiovascular outcomes in Asians with type 2 diabetes: subgroup analysis of the randomized CAROLINA® trial.

Diabetol Int 2021 Jan 27;12(1):87-100. Epub 2020 Jun 27.

Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.

Objective: Linagliptin, a dipeptidyl peptidase-4 inhibitor, recently demonstrated cardiovascular (CV) safety versus placebo in Asians with advanced type 2 diabetes mellitus (T2DM) in the CARMELINA trial. We assessed its CV safety compared with the sulfonylurea glimepiride in Asians with relatively early T2DM in the CAROLINA trial.

Methods: Based on prespecified and post hoc subgroup analyses of the multinational CAROLINA trial in which adults with relatively early T2DM and elevated CV risk were randomized to linagliptin or glimepiride added to usual care, we analyzed data for participants from Asian countries. This included the primary outcome defined as time to first CV death, non-fatal myocardial infarction, or non-fatal stroke [three-point major adverse cardiovascular events (3P-MACE)].

Results: Of the 6033 participants, 933 (15.5%) were from Asia. During a median follow-up of 6.2 years, 3P-MACE occurred in 9.5% and 11.1% of the linagliptin and glimepiride groups, respectively (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.57-1.26]), consistent with the overall population (HR 0.98; 95% CI 0.84-1.13;  = 0.17 for treatment by region interaction). Similarly, there were no significant differences between groups for other outcomes, including CV death (HR 0.73; 95% CI 0.38-1.38), non-CV mortality (HR 0.76; 95% CI 0.37-1.57) and hospitalization for heart failure (HR 0.89; 95% CI 0.36-2.19). Hypoglycemia adverse events occurred in 13.1% of linagliptin patients versus 42.1% of glimepiride patients (HR 0.25; 95% CI 0.19-0.33;  < 0.0001) despite similar glycemic control. Body weight was slightly lower with linagliptin relative to glimepiride: weighted average mean difference over 256 weeks of - 1.82 kg (95% CI - 2.28 to - 1.35).

Conclusions: In Asian patients, linagliptin demonstrated similar CV safety to glimepiride with a markedly lower rate of hypoglycemia and modestly lower weight.
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http://dx.doi.org/10.1007/s13340-020-00447-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790983PMC
January 2021

RNA interference of trehalose-6-phosphate synthase and trehalase genes regulates chitin metabolism in two color morphs of Acyrthosiphon pisum Harris.

Sci Rep 2021 Jan 13;11(1):948. Epub 2021 Jan 13.

College of Plant Protection, Gansu Agricultural University, Lanzhou, 730070, Gansu, China.

Trehalose-6-phosphate synthase (TPS) and trehalase (TRE) directly regulate trehalose metabolism and indirectly regulate chitin metabolism in insects. Real-time quantitative PCR (RT-qPCR) and RNA interference (RNAi) were used to detect the expressions and functions of the ApTPS and ApTRE genes. Abnormal phenotypes were found after RNAi of ApTRE in the Acyrthosiphon pisum. The molting deformities were observed in two color morphs, while wing deformities were only observed in the red morphs. The RNAi of ApTPS significantly down-regulated the expression of chitin metabolism-related genes, UDP-N-acetyglucosamine pyrophosphorylase (ApUAP), chitin synthase 2 (Apchs-2), Chitinase 2, 5 (ApCht2, 5), endo-beta-N-acetylglucosaminidase (ApENGase) and chitin deacetylase (ApCDA) genes at 24 h and 48 h; The RNAi of ApTRE significantly down-regulated the expression of ApUAP, ApCht1, 2, 8 and ApCDA at 24 h and 48 h, and up-regulated the expression of glucose-6-phosphate isomerase (ApGPI) and Knickkopf protein (ApKNK) genes at 48 h. The RNAi of ApTRE and ApTPS not only altered the expression of chitin metabolism-related genes but also decreased the content of chitin. These results demonstrated that ApTPS and ApTRE can regulate the chitin metabolism, deepen our understanding of the biological functions, and provide a foundation for better understanding the molecular mechanism of insect metamorphosis.
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http://dx.doi.org/10.1038/s41598-020-80277-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806880PMC
January 2021

A comprehensive investigation of the reaction behaviorial features of coke with different CRIs in the simulated cohesive zone of a blast furnace.

PLoS One 2021 11;16(1):e0245124. Epub 2021 Jan 11.

School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei, China.

The reaction characteristics and mechanism of coke with different coke reactivity indices (CRIs) in the high-temperature zone of a blast furnace should be fully understood to correctly evaluate the coke quality and optimize ironmaking. In this work, low-CRI coke (coke A) and high-CRI coke (coke B) were charged into a thermogravimetric analyzer to separately study their microstructural changes, gasification characteristics, and reaction mechanism under simulated cohesive zone conditions in a blast furnace. The results show that both coke A and coke B underwent pyrolysis, polycondensation, and graphitization during the heat treatment. The pyrolysis, polycondensation, gasification speed, and dissolution speed rates of coke B were higher than those of coke A. Direct and indirect reduction between sinter and coke occurred in the cohesive zone and had different stages. The consumption rate of coke B was faster than that of coke A during the coke-sinter reduction. The carbon molecules of coke A must absorb more energy to break away from the skeleton than those of coke B.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245124PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799840PMC
January 2021

[Multiple Organ Echinococcosis:Report of One Case and Literature Review].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2020 Dec;42(6):840-844

Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China.

A patient with multiple-organ echinococcosis suffered from liver echinococcosis,lung echinococcosis,and pelvic echinococcosis successively in the past three decades.From the first operation at 19 years-old,she underwent operations several times due to the recurrence of multiple organ involvement.Echinococcosis is a zoonotic disease.Although the liver usually is the primary site,the disease can also invade many other organs.Diagnosis is typically based on disease history and imaging findings.Thorough removal of the lesions during the first operation is particularly important.Comprehensive evaluations and multi-disciplinary team are helpful in the treatment of patients with multiple organ invasion.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12807DOI Listing
December 2020

The protective effects of trelagliptin on high-fat diet-induced nonalcoholic fatty liver disease in mice.

J Biochem Mol Toxicol 2021 Apr 9;35(4):e22696. Epub 2021 Jan 9.

Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, China.

Nonalcoholic fatty liver disease (NAFLD) occurs in patients with type 2 diabetes mellitus (T2DM). Trelagliptin is an important member of the Gliptins family, which has been recently licensed for the treatment of T2DM. However, the pharmacological function of trelagliptin in NAFLD has not been previously reported. In this study, we aimed to investigate the roles of trelagliptin in the development of NAFLD in a mouse model. To induce NAFLD disease, C57BL/6 mice were fed a high-fat diet for 10 weeks. Our results indicate that trelagliptin reduced plasma lipid levels in NAFLD mice by reducing triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Treatment with trelagliptin exhibited an improvement in insulin resistance. More important, trelagliptin improved liver function by reducing alanine transaminase, aspartate transaminase, lactate dehydrogenase, and total bile acid. In addition, trelagliptin ameliorated oxidative stress in the liver of NAFLD mice by reducing malondialdehyde and increasing the levels of reduced glutathione and superoxide dismutase activity. Also, the enzyme-linked immunosorbent assay results indicate that trelagliptin-treated mice displayed anti-inflammatory properties by reducing the levels of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α. Hematoxylin and eosin and Oil red O staining show that trelagliptin treatment ameliorates liver tissue damage and hepatic lipid deposition. Mechanistically, we found that the administration of trelagliptin reduced the activity of hepatic nuclear factor-κB but increased the activity of AMP-activated protein kinase. These findings suggest that trelagliptin might become a promising therapeutic agent for the treatment of NAFLD.
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http://dx.doi.org/10.1002/jbt.22696DOI Listing
April 2021

Hydrogen sulfide regulates insulin secretion and insulin resistance in diabetes mellitus, a new promising target for diabetes mellitus treatment? A review.

J Adv Res 2021 Jan 26;27:19-30. Epub 2020 Feb 26.

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

Background: Insulin resistance and impaired insulin secretion lead to disorders of glucose metabolism, which contributes to the development of diabetes. Hydrogen sulfide (H2S), a novel gasotransmitter, is found to play important roles in regulation of glucose metabolism homeostasis.

Aim Of Review: This study aimed to summarize and discuss current data about the function of H2S in insulin secretion and insulin resistance regulation as well as the underlying mechanisms.

Key Scientific Concepts Of Review: HS could be endogenously produced in islet β cells, liver, adipose, skeletal muscles, and the hypothalamus, and regulates local and systemic glucose metabolism. It is reported that HS suppresses insulin secretion, promotes or reduces the apoptosis of islet β cells. It plays important roles in the regulation of insulin sensitivity in insulin responsive tissues. HS inhibits glucose uptake and glycogen storage, and promotes or inhibits gluconeogenesis, mitochondrial biogenesis and mitochondrial bioenergetics in the liver. In adipose tissue, several investigators indicated that H2S promoted glucose uptake in adipocytes, while other studies reported that HS inhibits this process. HS has also been shown to promote adipogenesis, inhibit lipolysis, and regulate adiponectin and MCP-1 secretion from adipocytes. In skeletal muscle, HS increases glucose uptake and improves insulin sensitivity. It is also observed that HS modulates circadian-clock genes in muscle. Hypothalamic CBS/HS pathway reduces obesity and improves insulin sensitivity via the brain-adipose interaction. Most studies indicated plasma HS levels decreased in diabetic patients. However, the mechanisms by which HS regulates systemic glucose metabolism remain unclear. Whether HS acts as a new promising target for diabetes mellitus treatment merits further studies.
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http://dx.doi.org/10.1016/j.jare.2020.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728586PMC
January 2021

A multi-center randomized controlled trial of the LenoMed ATA-I-1-0 insulin pump for the intensive treatment of diabetic patients.

Ann Transl Med 2020 Nov;8(22):1485

Department of Endocrinology, The First Medical Center of PLA General Hospital, Beijing, China.

Background: Continuous subcutaneous insulin infusion (CSII) is an effective method for managing diabetes. The aim of this study was to evaluate the efficacy and safety of the LenoMed ATA-I-1-0 insulin pump for the treatment of patients with type 1 and type 2 diabetes, compared to the Medtronic MMT-712 insulin pump.

Methods: A total of 120 subjects with diabetes needing insulin treatment were recruited, and 104 completed the trial. The intervention and control group used the LenoMed and Medtronic insulin pump, respectively. The primary outcome was a reduction in fasting plasma glucose. Secondary outcomes included blood glucose control at 7 time points (before and after each meal, and before sleep), hemoglobin A1c (HbA1c) levels at 1 time point, and accuracy and safety of the pumps.

Results: In the per protocol set of 104 subjects, a significant drop in fasting plasma glucose levels was observed for 98.0% subjects in the intervention group and 92.7% in the control group. There was no statistically significant difference between groups [5.23%; 95% confidence interval (CI): -2.69% -13.2%]. Compared to baseline, levels of blood glucose and HbA1c dropped (P<0.001) at a similar magnitude in both groups. The accuracy and alarm effectiveness was 100%. No adverse event or severe adverse event related to the medication occurred in the study.

Conclusions: The novel injection equipment, the LenoMed ATA-I-1-0 insulin pump, demonstrated efficacy and a good safety profile, and was not inferior to the widely used Medtronic MMT-712 insulin pump. Thus, our study suggests that the LenoMed ATA-I-1-0 insulin pump can be widely used in clinical practice.
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http://dx.doi.org/10.21037/atm-20-6024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729342PMC
November 2020

The Inhibitory Effects of Juglanin on Adipogenesis in 3T3-L1 Adipocytes.

Drug Des Devel Ther 2020 2;14:5349-5357. Epub 2020 Dec 2.

Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin 130033, People's Republic of China.

Introduction: Deregulation of adipogenesis plays an important role in obesity and other metabolism disorders. PPAR, C/EBP and SREBP1c are key transcriptional factors involved in adipogenesis and lipogenesis. Juglanin is a natural compound belonging to flavonoids, and it has been reported that juglanin has a potent inhibitory effect on inflammation and certain type of cancers. However, the effects of juglanin in adipogenesis have not been reported before.

Materials And Methods: 3T3-L1 preadipocytes were incubated with differentiation induction medium in the presence or absence of 0.5, 2.5, or 5 µM juglanin for an 8-day differentiation period. The lipid droplets accumulated in the cytoplasm were monitored by Oil Red O staining on days 0, 2, 5, and 8. The regulatory effects of juglanin on adipogenesis-related genes and proteins were investigated by real-time polymerase chain reaction and Western blot analysis.

Results: Juglanin significantly decreased lipid accumulation in differentiated adipocytes. Our findings show that juglanin reduced the expression of C/EBPα, C/EBPβ, and SREBP-1c without affecting PPARα or PPARγ expression. Additionally, juglanin increased the activation of the SIRT1/AMPK signaling pathway through the phosphorylation of AMPKα. Finally, we performed an AMPK inhibitor experiment, which revealed that the inhibitory effects of juglanin on adipogenesis are mediated through AMPK.

Discussion: Juglanin can prevent adipogenesis by suppressing lipid accumulation and the differentiation of preadipocytes. The mechanism of juglanin regulating adipogenesis requires further investigation. Future clinical study in vivo could shed more light on its implication in modulating obesity and metabolic disorders.
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http://dx.doi.org/10.2147/DDDT.S256504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719332PMC
December 2020

miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer.

Cancer Cell Int 2020 Nov 3;20(1):534. Epub 2020 Nov 3.

Department of Histology and Embryology, Dalian Medical University, College of Basic Medicine Sciences, No 9 LvShun South Road-W, Dalian, 116044, China.

Background: Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to evaluate the prognostic and platinum-resistance predictive value of miR-206 in EOC patients and to investigate the functional roles of miR-206 in regulating the platinum resistance of EOC and the underlying mechanism.

Methods: MiRNA expression profiling in EOC specimens was performed using a TaqMan miRNA array. miR-206 expression was confirmed by quantitative real-time PCR (qRT-PCR) analysis. Overexpression of miR-206 in EOC cell lines was achieved by the stable transfection of a recombinant plasmid. In vitro assays of cisplatin cytotoxicity, cell cycle distribution, apoptosis, transwell invasion and cell scratching were employed. Connexin 43 (Cx43) expression was detected by Western blotting. Murine xenograft models were used to determine the effects of miR-206 on platinum resistance in vivo.

Results: miR-206 expression was increased in primary platinum-resistant EOC. High miR-206 expression was related to poor prognosis in EOC patients who received platinum-based chemotherapy and predicted chemoresistance to platinum treatment. Overexpression of miR-206 in cisplatin-sensitive EOC cell lines significantly increased cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis. Cx43, a target gene of miR-206, was negatively regulated by miR-206 in EOC cell lines and significantly related to better prognosis in patients who received platinum-based chemotherapy (KmPlot). miR-206 had high expression and Cx43 had low expression in platinum-sensitive EOC cell lines compared with resistant ones. In vivo murine xenograft models showed that miR-206 profoundly promoted the chemoresistance of EOC to cisplatin treatment.

Conclusion: miR-206 was highly expressed in primary platinum-resistant EOCs and functionally promoted platinum resistance in part by downregulating Cx43 expression, thereby providing a useful biomarker for prognostic and platinum-resistance prediction.
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http://dx.doi.org/10.1186/s12935-020-01623-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641844PMC
November 2020