Publications by authors named "Dan Wang"

3,062 Publications

  • Page 1 of 1

Inhibition of exosome release augments neuroinflammation following intracerebral hemorrhage.

FASEB J 2021 Jun;35(6):e21617

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.

Intracerebral hemorrhage (ICH) is a severe stroke subtype without effective pharmacological treatment. Following ICH, peripheral leukocytes infiltrate into the brain and contribute to neuroinflammation and brain edema. However, the intercellular machinery controlling the initiation and propagation of leukocyte infiltration remains elusive. Exosomes are small extracellular vesicles released from donor cells and bridge intercellular communication. In this study, we investigated the effects of inhibition of exosome release on neuroinflammation and ICH injury. Using a mouse model of ICH induced by collagenase injection, we found that ICH induced an increase of exosome level in the brain. Inhibition of exosome release using GW4869 augmented neurological deficits and brain edema after ICH. The exacerbation of ICH injury was accompanied by increased barrier disruption and brain infiltration of leukocytes. The detrimental effects of GW4869 were ablated in ICH mice receiving antibody depletion of Gr-1 myeloid cells. Extracted exosomes from the ICH brains suppressed the production of inflammatory factors by splenocytes. Additionally, exosomes extracted from brain tissues of donor ICH mice reduced ICH injury in recipient mice. These results demonstrate that inhibition of exosome release augments neuroinflammation and ICH injury. The impact of exosomes released from the ICH brain on the immune system deserves further investigation.
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http://dx.doi.org/10.1096/fj.202002766RDOI Listing
June 2021

Single-cell sequencing reveals suppressive transcriptional programs regulated by MIS/AMH in neonatal ovaries.

Proc Natl Acad Sci U S A 2021 May;118(20)

Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114;

Müllerian inhibiting substance (MIS/AMH), produced by granulosa cells of growing follicles, is an important regulator of folliculogenesis and follicle development. Treatment with exogenous MIS in mice suppresses follicle development and prevents ovulation. To investigate the mechanisms by which MIS inhibits follicle development, we performed single-cell RNA sequencing of whole neonatal ovaries treated with MIS at birth and analyzed at postnatal day 6, coinciding with the first wave of follicle growth. We identified distinct transcriptional signatures associated with MIS responses in the ovarian cell types. MIS treatment inhibited proliferation in granulosa, surface epithelial, and stromal cell types of the ovary and elicited a unique signature of quiescence in granulosa cells. In addition to decreasing the number of growing preantral follicles, we found that MIS treatment uncoupled the maturation of germ cells and granulosa cells. In conclusion, MIS suppressed neonatal follicle development by inhibiting proliferation, imposing a quiescent cell state, and preventing granulosa cell differentiation.
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http://dx.doi.org/10.1073/pnas.2100920118DOI Listing
May 2021

Neoadjuvant radiotherapy for locoregional Siewert type II gastroesophageal junction adenocarcinoma: A propensity scores matching analysis.

PLoS One 2021 12;16(5):e0251555. Epub 2021 May 12.

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.

Objective: To analyze the effect of neoadjuvant radiotherapy (nRT) on prognosis in patients with locoregional Siewert type II gastroesophageal junction adenocarcinoma (GEA).

Method: All patients pathologically diagnosed as Siewert type II GEA between 2004 and 2015 were retrieved from the Surveillance, Epidemiology and Final Results (SEER) database. We analyzed the impact of different treatment regimens on the prognosis in each stage. Survival analysis was performed by Kaplan-Meier (K-M) method. Multivariate Cox model and propensity score matching was further used to verify the results.

Results: 4,160 patients were included in this study. The efficacy of nRT was superior to that of adjuvant radiotherapy (aRT) (p = 0.048), which was the same as that of surgery combined with chemotherapy (p = 0.836), but inferior to the overall survival (OS) of surgical treatment alone (p<0.001) in T1-2N0M0 patients. Patients receiving nRT had distinctly better survival than those receiving surgical treatment alone (p = 0.008), but had similar survival compared with patients treated with aRT (p = 0.989) or surgery combined with chemotherapy (p = 0.205) in the T3N0/T1-3N+M0 subgroup. The efficacy of nRT is clearly stronger than that of surgical therapy alone (p<0.001), surgery combined with chemotherapy (p<0.001), and aRT (p = 0.008) in patients with T4 stage. The survival analysis results were consistent before and after propensity score matching.

Conclusion: In these carefully selected patients, the present study made the following recommendations: nRT can improve the prognosis of patients with T3N0M0/T1-3N+M0 and T4 Siewert type II GEA, and it seems to be a better treatment for T4 patients. Surgery alone seems to be sufficient, and nRT is not conducive to prolonging the survival of Siewert II GEA patients with T1-2N0M0 stage. Of course, further prospective trials are needed to verify this conclusion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251555PLOS
May 2021

YAP promotes the activation of NLRP3 inflammasome via blocking K27-linked polyubiquitination of NLRP3.

Nat Commun 2021 May 11;12(1):2674. Epub 2021 May 11.

Department of Hematology and Key Laboratory of Non-resolving Inflammation and Cancer of Hunan Province, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, People's Republic of China.

The transcription coactivator YAP plays a vital role in Hippo pathway for organ-size control and tissue homeostasis. Recent studies have demonstrated YAP is closely related to immune disorders and inflammatory diseases, but the underlying mechanisms remain less defined. Here, we find that YAP promotes the activation of NLRP3 inflammasome, an intracellular multi-protein complex that orchestrates host immune responses to infections or sterile injuries. YAP deficiency in myeloid cells significantly attenuates LPS-induced systemic inflammation and monosodium urate (MSU) crystals-induced peritonitis. Mechanistically, YAP physically interacts with NLRP3 and maintains the stability of NLRP3 through blocking the association between NLRP3 and the E3 ligase β-TrCP1, the latter increases the proteasomal degradation of NLRP3 via K27-linked ubiquitination at lys380. Together, these findings establish a role of YAP in the activation of NLRP3 inflammasome, and provide potential therapeutic target to treat the NLRP3 inflammasome-related diseases.
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http://dx.doi.org/10.1038/s41467-021-22987-3DOI Listing
May 2021

Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia.

CNS Neurosci Ther 2021 May 11. Epub 2021 May 11.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Aims: General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating.

Methods: Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst-suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods.

Results: We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5-HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5-HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons.

Conclusion: Our results demonstrate that 5-HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5-HT 1A and 2C receptors.
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http://dx.doi.org/10.1111/cns.13656DOI Listing
May 2021

Oral immunization with recombinant Lactobacillus plantarum expressing Nudix hydrolase and 43 kDa proteins confers protection against Trichinella spiralis in BALB/c mice.

Acta Trop 2021 May 7:105947. Epub 2021 May 7.

College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of animal production and product quality safety of Ministry of Education, Jilin Agricultural University, Changchun, China. Electronic address:

Trichinellosis is a significant food-borne zoonotic parasitic disease caused by parasite Trichinella. Given the side effects of anti-Trichinella drugs (e.g., Mebendazole) aroused in the course of treatments, an effective vaccine against the parasite is called for. The therapies available to date are in most instances targeting a single stage of Trichinella, resulting in an incomplete protective immunity against the parasite in terms of the complexity of its developmental stages. In this study, a recombinant dual-expression double anchor vector NC8-pLp-TsNd-S-pgsA'-gp43 was constructed carrying two antigen genes from Trichinella spiralis (T. spiralis), encoding the gp43 and T. spiralis Nudix hydrolase (TsNd) proteins which were mainly expressed in muscle larva (ML) and intestinal infective larva stages of the parasite respectively. These two proteins were to be expressed by Lactobacillus plantarum NC8 (L. plantarum NC8) which was designed to express the two anchored peptides, a truncated poly-γ-glutamic acid synthetase A (pgsA') and the surface layer protein of Lactobacillus acidophilus (SlpA), on its surface for attaching expressed foreign proteins. Oral immunization with the above recombinant vaccine induced higher levels of specific serum IgG and mucosal secretory IgA (SIgA) in BALB/c mice. In addition, cytokines, interferon-γ (IFN- γ), interleukin-4 (IL-4) and IL-17 released by lymphocytes, and CD4 levels displayed on the surfaces of splenic and mesenteric lymph cells were significantly enhanced by the vaccination. Moreover, after larval challenges, a 75.67 % reduction of adult worms (AW) at 7 days post-infection (dpi) and 57.14 % reduction of ML at 42 dpi were observed in mice immunized with the recombinant vaccine. Furthermore, this oral vaccination reduced the counts of encysted larvae presented in tongue and masseter muscles after infected with T. spiralis in mice. The overall results demonstrated that the recombinant vaccine developed in this study could induce specific humoral, mucosal, and cellular immune responses, and provides protections against different stages (adult worms and muscle larva) of T. spiralis infections in BALB/c mice, which could make it a promising oral vaccine candidate against trichinellosis.
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http://dx.doi.org/10.1016/j.actatropica.2021.105947DOI Listing
May 2021

The paraventricular thalamus input to central amygdala controls depression-related behaviors.

Exp Neurol 2021 May 6:113744. Epub 2021 May 6.

Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong, China. Electronic address:

The dysregulation of neuronal networks may contribute to the etiology of major depressive disorder (MDD). However, the neural connections underlying the symptoms of MDD have yet to be elucidated. Here, we observed that glutamatergic neurons in the paraventricular thalamus (PVT) were activated by chronic unpredictable stress (CUS) with higher expression numbers of ΔFosB-labeled neurons and protein expression levels, activation of PVT neurons caused depressive-like phenotypes, whereas suppression of PVT neuronal activity induced an antidepressant effect in male, but not female mice, which were achieved by using a chemogenetic approach. Moreover, we found that PVT glutamatergic neurons showed strong neuronal projections to the central amygdala (CeA), activation of the CeA-projecting neurons in PVT or the neuronal terminals of PVT-CeA projection neurons induced depression-related behaviors or showed enhanced stress-induced susceptibility. These results suggest that PVT is a key depression-controlling nucleus, and PVT-CeA projection regulates depression-related behaviors in a sex-dependent manner, which could be served as an essential pathway for morbidity and treatment of depression.
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http://dx.doi.org/10.1016/j.expneurol.2021.113744DOI Listing
May 2021

Primary ciliated muconodular papillary tumor: A rare pulmonary disease and literature review of 65 cases.

Thorac Cancer 2021 May 7. Epub 2021 May 7.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

A ciliated muconodular papillary tumor (CMPT) or bronchiolar adenoma (BA) is a rather rare and unique type of lung tumor characterized by tripartite cellular components with a papillary-predominant structure including ciliated columnar cells, mucinous cells, and basal cells. Here, we present the case of a 64-year-old woman who was diagnosed with CMPT in our center. In addition to reporting the clinicopathological characteristics of this case, we also conducted whole exome sequencing (WES) to explore the underlying mechanism. According to current evidence, CMPTs tends to be benign or of low grade malignancy. However, this requires further validation.
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http://dx.doi.org/10.1111/1759-7714.13963DOI Listing
May 2021

Shaoyao Decoction Inhibits Inflammation and Improves Intestinal Barrier Function in Mice With Dextran Sulfate Sodium-Induced Colitis.

Front Pharmacol 2021 20;12:524287. Epub 2021 Apr 20.

Department of Traditional Chinese Medicine, The Second Clinical Medical College, Guangdong Medical University, Dongguan, China.

Shaoyao decoction (SYD), a classical traditional Chinese medicine formula, is effective for the treatment of inflammatory bowel disease (IBD). This study was designed to investigate the therapeutic effects of SYD on IBD and possible mechanisms. Dextran sulfate sodium (DSS, 3.5%) was used to induce colitis in C57BL/6 mice. Disease phenotypes were investigated based on disease activity index (DAI), colon length, and microscopic and macroscopic scores. Additionally, the presence of proinflammatory cytokines, immune cell infiltrates, intestinal cell proliferation, apoptosis, epithelial permeability, signal transducer and activator of transcription 3 (STAT3), and nuclear factor-κB (NF-κB) signaling, as well as the intestinal mucosal barrier function, were investigated. The administration of SYD significantly ameliorated the clinical signs, suppressed the levels of proinflammatory cytokines, and reduced immune cell infiltrates into colonic tissues of DSS-induced colitis model mice. SYD also significantly reduced the DSS-induced activation of STAT3 and NF-κB signaling. Furthermore, SYD promoted epithelial integrity by regulating epithelial cell apoptosis and epithelial permeability. Finally, we demonstrated that SYD protected the intestinal barrier function by significantly regulating the mucus layer genes , , , and , as well as the epithelial barrier genes and . Our results indicate that SYD has a protective effect on DSS-induced colitis, which is attributable to its anti-inflammatory activity and intestinal barrier function-enhancing effects. These results provide valuable insights into the pharmacological actions of SYD for the treatment of IBD.
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http://dx.doi.org/10.3389/fphar.2021.524287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093868PMC
April 2021

Exenatide Attenuates Non-Alcoholic Steatohepatitis by Inhibiting the Pyroptosis Signaling Pathway.

Front Endocrinol (Lausanne) 2021 19;12:663039. Epub 2021 Apr 19.

Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Background/aims: Exenatide is a glucagon-like polypeptide-1 analog, whose main clinical use is to treat type 2 diabetes. However, the mechanism of exenatide in mitigating non-alcoholic steatohepatitis (NASH) remains unclear. This study aimed to investigate the and effect of exenatide on NASH.

Methods: Leptin receptor-deficient C57BL/KsJ- db/db male mice were fed with methionine-choline-deficient (MCD) diet for 4 weeks to induce NASH, while oleic acid/LPS-treated HepG2 cells were used as an cell model. Exenatide (20 µg/kg/day, subcutaneous) and specific exenatide inhibitors (20 µg/kg/day, intraperitoneal) were used to determine the effects of exenatide on NASH.

Results: Exenatide treatment inhibited the pyroptosis signaling pathway to attenuate NASH.

Conclusion: To the best of our knowledge, this report provides the first evidence showing that exenatide attenuated NASH by inhibiting the pyroptosis signaling pathway. Exenatide thus has important pathophysiological functions in NASH and may represent a useful new therapeutic target.
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http://dx.doi.org/10.3389/fendo.2021.663039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092357PMC
April 2021

High Burden of Subclinical and Cardiovascular Disease Risk in Adults with Metabolically Healthy Obesity: The Atherosclerosis Risk in Communities (ARIC) Study.

Diabetes Care 2021 May 5. Epub 2021 May 5.

Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

Objective: It is controversial whether adults who are obese but "metabolically healthy" have cardiovascular disease (CVD) risk comparable with that of normal-weight adults. High-sensitivity cardiac troponin T (hs-cTnT), a biomarker of myocardial damage, is useful in characterizing subclinical CVD. We categorized obesity phenotypes and studied their associations with subclinical and clinical CVD and CVD subtypes, including heart failure (HF).

Research Design And Methods: We conducted cross-sectional and prospective analyses of 9,477 adults in the Atherosclerosis Risk in Communities (ARIC) study. We used the Adult Treatment Panel III criteria and BMI to define obesity phenotypes as follows: metabolically healthy normal weight, metabolically healthy overweight, metabolically healthy obese, metabolically unhealthy normal weight, metabolically unhealthy overweight, and metabolically unhealthy obese.

Results: At baseline (1990-1992), mean age was 56 years, 56% were female, 23% were Black, and 25% had detectable hs-cTnT (≥6 ng/L). Over a median of 17 years of follow-up, there were 2,603 clinical CVD events. Those with the metabolically healthy obese (hazard ratio [HR] 1.38, 95% CI 1.15-1.67), metabolically unhealthy normal weight (HR 1.51, 95% CI 1.30-1.76), metabolically unhealthy overweight (HR 1.60, 95% CI 1.41-1.82), and metabolically unhealthy obese (HR 2.14, 95% CI 1.88-2.44) phenotypes had higher CVD risks in comparison with metabolically healthy normal weight. Detectable hs-cTnT (≥6 ng/L) was associated with higher CVD risk, even among metabolically healthy normal-weight adults. Metabolically healthy obese adults had higher HF risk (HR 1.65, 95% CI 1.30-2.09) in comparison with metabolically healthy normal weight.

Conclusions: The metabolically healthy obese phenotype was associated with excess burden of clinical CVD, primarily driven by an excess risk of HF. hs-cTnT was useful in stratifying CVD risk across all obesity phenotypes, even among obese individuals who appear otherwise metabolically healthy.
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http://dx.doi.org/10.2337/dc20-2227DOI Listing
May 2021

Antimony tin oxide/lead selenide composite as efficient counter electrode material for quantum dot-sensitized solar cells.

J Colloid Interface Sci 2021 Apr 17;598:492-499. Epub 2021 Apr 17.

Key Laboratory of Macromolecular Science of Shaanxi Province, School of Materials Science and Engineering, Shaanxi Normal University, Xi'an 710062, China. Electronic address:

Antimony tin oxide (ATO)/lead selenide (PbSe) composite was rationally designed and fabricated on fluorine doped tin oxide glass (FTO) for using as counter electrode (CE) of quantum dot sensitized solar cells (QDSSCs). The electrocatalytic activity of the CE is deeply investigated in the polysulfide electrolyte by employing the Tafel, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) of the symmetrical cells. The results confirm that the ATO/PbSe CE has better electrocatalytic activity and stability than that of PbSe CE obtained by pulse voltage electrodeposition (PVD). The enhanced electrocatalytic performance of ATO/PbSe CE can be attributed to its high specific surface area, excellent permeability, conductivity and interface connectivity, which provide more electrocatalytic active sites for the reduction of polysulfide species, as well as fast channels for ions diffusion and electron transport. As a result, the CdS QDSSCs and CdS/CdSe co-sensitized QDSSCs assembled by the ATO/PbSe CE exhibits better power conversion efficiency (η) of 1.72% and 5.59%, respectively than that of PbSe CE obtained by PVD. Furthermore, photovoltaic property of the ATO/PbSe CE in CdS/CdSe co-sensitized QDSSCs keeps stable for over 200 min. This present work provides a simple and effective strategy for the construction of high-performance CE materials of QDSSCs.
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http://dx.doi.org/10.1016/j.jcis.2021.04.073DOI Listing
April 2021

The long noncoding RNA AATBC promotes breast cancer migration and invasion by interacting with YBX1 and activating the YAP1/Hippo signaling pathway.

Cancer Lett 2021 May 2. Epub 2021 May 2.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

Long noncoding RNAs (lncRNAs) play an important role in the regulation of gene expression and are involved in several pathological responses. However, many important lncRNAs in breast cancer have not been identified and their expression levels and functions in breast cancer remain unknown. In this study, the lncRNA apoptosis-associated transcript in bladder cancer (AATBC) was found to be significantly highly expressed in breast cancer patients. In vitro and in vivo experiments indicated that AATBC promoted breast cancer metastasis. Further studies revealed that AATBC activated the YAP1/Hippo signaling pathway through the AATBC-YBX1-MST1 axis. This is also an important supplement to the composition of the YAP1/Hippo signaling pathway. The model of "AATBC-YAP1" may bring a new dawn to the treatment of breast cancer.
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http://dx.doi.org/10.1016/j.canlet.2021.04.025DOI Listing
May 2021

ANO7: Insights into topology, function, and potential applications as a biomarker and immunotherapy target.

Tissue Cell 2021 Apr 18;72:101546. Epub 2021 Apr 18.

College of Laboratory Medicine, Jilin Medical University, Jilin, 132013, China. Electronic address:

Anoctamin 7 (ANO7) is a member of the transmembrane protein TMEM16 family. It has a conservative topology similar to other members in this family, such as the typical eight-transmembrane domain, but it also has unique features. Although the ion channel role of ANO7 has been well accepted, evolutionary analyses and relevant studies suggest that ANO7 may be a multi-facet protein in function. Studies have shown that ANO7 may also function as a scramblase. ANO7 is highly expressed in prostate cancer as well as normal prostate tissues. A considerable amount of evidence has confirmed that ANO7 is associated with human physiology and pathology, particularly with the development of prostate cancer, which makes ANO7 a good candidate as a diagnostic and prognostic biomarker. In addition, ANO7 may be a potential target for prostate cancer immunotherapy. Antibody-based or T cell-mediated immunotherapies against prostate cancer by targeting ANO7 have been highly anticipated. ANO7 may also correlate with several other types of cancers or diseases, where further studies are warranted.
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http://dx.doi.org/10.1016/j.tice.2021.101546DOI Listing
April 2021

Differential diagnosis between small breast phyllodes tumors and fibroadenomas using artificial intelligence and ultrasound data.

Quant Imaging Med Surg 2021 May;11(5):2052-2061

Department of Ultrasound, Peking University People's Hospital, Beijing, China.

Background: It is challenging to differentiate between phyllodes tumors (PTs) and fibroadenomas (FAs). Artificial intelligence (AI) can provide quantitative information regarding the morphology and textural features of lesions. This study attempted to use AI to evaluate the ultrasonic images of PTs and FAs and to explore the diagnostic performance of AI features in the differential diagnosis of PTs and FAs.

Methods: A total of 40 PTs and 290 FAs <5 cm in maximum diameter found in female patients were retrospectively analyzed. All tumors were segmented by doctors, and the features of the lesions were collated, including circularity, height-to-width ratio, margin spicules, margin coarseness (MC), margin indistinctness, margin lobulation (ML), internal calcification, angle between the long axis of the lesion and skin, energy, grey entropy, and grey mean. The differences between PTs and FAs were analyzed, and the diagnostic performance of AI features in the differential diagnosis of PTs and FAs was evaluated.

Results: Statistically significant differences (P<0.05) were found in the height-to-width ratio, ML, energy, and grey entropy between the PTs and FAs. Receiver operating characteristic (ROC) curve analysis of single features showed that the area under the curve [(AUC) 0.759] of grey entropy was the largest among the four features with statistically significant differences, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.925, 0.459, 0.978, and 0.190, respectively. When considering the combinations of the features, the combination of height-to-width ratio, margin indistinctness, ML, energy, grey entropy, and internal calcification was the most optimal of the combinations of features with an AUC of 0.868, and a sensitivity, specificity, PPV, and NPV of 0.734, 0.900, 0.982, and 0.316, respectively.

Conclusions: Quantitative analysis of AI can identify subtle differences in the morphology and textural features between small PTs and FAs. Comprehensive consideration of multiple features is important for the differential diagnosis of PTs and FAs.
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http://dx.doi.org/10.21037/qims-20-919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047381PMC
May 2021

Response of Zebrina pendula leaves to enhanced UV-B radiation.

Funct Plant Biol 2021 May 3. Epub 2021 May 3.

Plants inevitably receive harmful UV-B radiation when exposed to solar energy, so they have developed a variety of strategies to protect against UV-B radiation damage during long-term evolution. In this study, Zebrina pendulaSchnizl. was used to investigate the plant defence against UV-B radiation because of its strong adaptability to sunlight changes, and the colour of its leaves changes significantly under different sunlight intensities. The experiment was carried out to study the changes of Z. pendula leaves under three light conditions: artificial daylight (control check); shading 50%; and artificial daylight + UV-B, aiming to explore the mechanism of defence against UV-B radiation by observing changes in leaf morphological structure, anthocyanin content and distribution. Results showed that the single leaf area increased but leaves became thinner, and the anthocyanin content in the epidermal cells decreased under 50% shading. In contrast, under daylight + UV-B, the single leaf area decreased but thickness increased (mainly due to the increase of the thickness of the upper epidermis and the palisade tissue), the trichomes increased. In addition, the anthocyanin content in the epidermal cells and phenylalanine ammonia-lyase (PAL) activity increased, and the leaf colour became redder, also, the photosynthetic pigment content in mesophyll cells and the biomass per unit volume increased significantly under daylight + UV-B. Thus, when UV-B radiation was enhanced, Z. pendula leaves reduced the exposure to UV-B radiation by reducing the area, and reflect some UV-B radiation by growing trichomes. The UV-B transmittance was effectively reduced by increasing the single leaf thickness and anthocyanin content to block or absorb partial UV-B. Through the above comprehensive defence strategies, Z. pendula effectively avoided the damage of UV-B radiation to mesophyll tissue.
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http://dx.doi.org/10.1071/FP20274DOI Listing
May 2021

Intermittent hypoxia preconditioning protects WRL68 cells against oxidative injury: Involvement of the PINK1/Parkin-mediated mitophagy regulated by nuclear respiratory factor 1.

Mitochondrion 2021 Apr 30;59:113-122. Epub 2021 Apr 30.

Institute of Special Environmental Medicine, Nantong University, Nantong 226019, China. Electronic address:

The protective effect of intermittent hypoxia (IH) preconditioning against oxidative injury in hepatic cells was investigated and the involvement of the PINK1/Parkin-mediated mitophagy regulated by nuclear respiratory factor 1 (NRF-1) was evaluated. The results showed that IH preconditioning protected HepG2 cells against oxygen and glucose deprivation/reperfusion (OGD/Rep)-induced injury and protected WRL68 cells against HO or AMA-induced oxidative injury. IH preconditioning up-regulated the protein level of NRF-1, PINK1, Parkin, and LC3 II, promoted the recruitment of the cytosolic Parkin, indicating the initiation of the PINK1/Parkin-mediated mitophagy in WRL68 cells. When NRF-1 was down-regulated by NRF-1 specific shRNA, the protein level of PINK1 and Parkin as well as the mitophagy level were significantly decreased. After IH preconditioning, the protein level of PINK1 and the recruitment of Parkin in CCCP-treated group were significantly higher than that of the control group, indicating the increased mitophagy capacity. And the increased mitophagy capacity induced by IH preconditioning was also reduced by down-regulation of NRF-1. Furthermore, the protective effect of IH preconditioning against HO-induced oxidative injury in WRL68 cells was inhibited when NRF-1 or PINK1 was down-regulated by specific shRNA. Mitochondrial ROS generation may be responsible for the increased expression of NRF-1 induced by IH preconditioning. In conclusion, the PINK1/Parkin-mediated mitophagy regulated by NRF-1 was involved in IH preconditioning-induced protective effect against oxidative cellular injury in hepatic cells.
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http://dx.doi.org/10.1016/j.mito.2021.04.012DOI Listing
April 2021

The General Population's Inappropriate Behaviors and Misunderstanding of Antibiotic Use in China: A Systematic Review and Meta-Analysis.

Antibiotics (Basel) 2021 Apr 26;10(5). Epub 2021 Apr 26.

School of Medicine and Health Management, Tongji Medical School, Huazhong University of Science and Technology, Wuhan 430030, China.

The general population has increasingly become the key contributor to irrational antibiotic use in China, which fuels the emergence of antibiotic resistance. This study aimed to estimate the prevalence of the general population's irrational use behaviors of antibiotics and identify the potential reasons behind them. A systematic review and meta-analysis were performed concerning four main behaviors relevant to easy access and irrational use of antibiotics and common misunderstandings among the population about antibiotics. Four databases were searched, and studies published before 28 February 2021 were retrieved. Medium and high-level quality studies were included. Random effects meta-analysis was performed to calculate the prevalence of the general population's irrational behaviors and misunderstandings relevant to antibiotic use. A total of 8468 studies were retrieved and 78 met the criteria and were included. The synthesis showed the public can easily obtain unnecessary antibiotics, with an estimated 37% (95% CI: 29-46) of the population demanding antibiotics from physicians and 47% (95% CI: 38-57) purchasing non-prescription antibiotics from pharmacies. This situation is severe in the western area of China. People also commonly inappropriately use antibiotics by not following antibiotic prescriptions (pooled estimate: 48%, 95% CI: 41-55) and preventatively use antibiotics for non-indicated diseases (pooled estimate: 35%, 95% CI: 29-42). Misunderstanding of antibiotic use was also popular among people, including incorrect antibiotic recognition, wrong antibiotic use indication, inappropriate usage, and ignorance of potential adverse outcomes. Over-and inappropriate use of antibiotics is evident in China and a multifaceted antibiotic strategy targeted at the general population is urgently required.
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http://dx.doi.org/10.3390/antibiotics10050497DOI Listing
April 2021

Where in the (lncRNA) World Is ?: Safeguarding Against Vascular Dysfunction.

Circ Res 2021 Apr 29;128(9):1276-1278. Epub 2021 Apr 29.

Division of Cardiology, Department of Medicine (D.W., T.S.), University of California, Los Angeles.

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http://dx.doi.org/10.1161/CIRCRESAHA.121.319150DOI Listing
April 2021

Identification of Two Novel Peptides That Inhibit α-Synuclein Toxicity and Aggregation.

Front Mol Neurosci 2021 12;14:659926. Epub 2021 Apr 12.

Department of Molecular Microbiology and Genetics, Institute for Microbiology and Genetics, University of Goettingen, Göttingen, Germany.

Aggregation of α-synuclein (αSyn) into proteinaceous deposits is a pathological hallmark of a range of neurodegenerative diseases including Parkinson's disease (PD). Numerous lines of evidence indicate that the accumulation of toxic oligomeric and prefibrillar αSyn species may underpin the cellular toxicity and spread of pathology between cells. Therefore, aggregation of αSyn is considered a priority target for drug development, as aggregation inhibitors are expected to reduce αSyn toxicity and serve as therapeutic agents. Here, we used the budding yeast as a platform for the identification of short peptides that inhibit αSyn aggregation and toxicity. A library consisting of approximately one million peptide variants was utilized in two high-throughput screening approaches for isolation of library representatives that reduce αSyn-associated toxicity and aggregation. Seven peptides were isolated that were able to suppress specifically αSyn toxicity and aggregation in living cells. Expression of the peptides in yeast reduced the accumulation of αSyn-induced reactive oxygen species and increased cell viability. Next, the peptides were chemically synthesized and probed for their ability to modulate αSyn aggregation . Two synthetic peptides, K84s and K102s, of 25 and 19 amino acids, respectively, significantly inhibited αSyn oligomerization and aggregation at sub-stoichiometric molar ratios. Importantly, K84s reduced αSyn aggregation in human cells. These peptides represent promising αSyn aggregation antagonists for the development of future therapeutic interventions.
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http://dx.doi.org/10.3389/fnmol.2021.659926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072481PMC
April 2021

Tricarboxylic-Ligand-Decorated Lanthanoid-Inserted Heteropolyoxometalates Built by Mixed-Heteroatom-Directing Polyoxotungstate Units: Syntheses, Structures, and Electrochemical Sensing for 17β-Estradiol.

Inorg Chem 2021 Apr 28. Epub 2021 Apr 28.

Henan Key Laboratory of Polyoxometalate Chemistry, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004, China.

Organic-inorganic hybrid metal-oxide clusters have been pursued for many years, benefiting from their abundant structures and prominent performances. Upon our exploration, a family of unusual mixed-heteroatom (Sb, P)-directing lanthanoid (Ln)-inserted heteropolyoxotungstates (Ln-HPOTs), [(CH)NH]NaH[Ln(HP)W(HO)(Hptca)O][SbWO]·27HO [Ln = Ce (), La (), Pr ()], functionalized by 1,2,3-propanetricarboxylic acid (Hptca) was achieved. The intriguing trimeric [Ln(HP)W(HO)(Hptca)O][SbWO] polyanion was established by two trivacant [B-α-SbWO] segments mounted on both sides and one rare [HPWO] segment at the bottom, which are bridged via an organic-inorganic hybrid [WLn(HO)O(Hptca)] central moiety. Such Ln-HPOTs involving dual-heteroatom-directing mixed building blocks, and even simultaneously modified by tricarboxylic ligands, are rather unseen in polyoxometalate chemistry. Moreover, the detection of 17β-estradiol through a -based electrochemical biosensor has been explored, demonstrating a low detection limit (7.08 × 10 M) and considerable stability.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00890DOI Listing
April 2021

Engineering a Second-Order DNA Logic-Gated Nanorobot to Sense-then-Release on Live Cell Membranes for Multiplexed Diagnosis and Synergistic Therapy.

Angew Chem Int Ed Engl 2021 Apr 27. Epub 2021 Apr 27.

Hunan University, College of Chemistry and Chemical Engineering, Department of Chemistry, 208 Yifu building, 410082, Changsha, CHINA.

Tumor biomarker-based theranostics has achieved broad interest and success in recent years. However, single biomarker-based recognition can cause false-positive feedback, including the on-target off-tumor phenomenon by the absence of tumor-specific antigen. Besides, multi-biomarker-based recognition molecules often elicit nonspecific and undesired internalization when they bind to ''bystander'' cells. Herein, we report a universal DNA tetrahedral scaffold (DTS) that anchors on the cell membrane to load multiple aptamers and therapeutics for precise and effective theranostics. This DNA logic-gated nanorobot (DLGN) not only facilitates the precise discrimination among five cell lines, but also triggers the synergistic killing of effector aptamer-tethered synergistic drugs (EASDs) to target cancer cells. Logic-gated recognition integrated in aptamer-functionalized molecular machines will prompt fast tumor profiling, in situ capture and isolation, and safe delivery of precise medicine.
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http://dx.doi.org/10.1002/anie.202103993DOI Listing
April 2021

Neighborhood Environment and Child Health in Immigrant Families: Using Nationally Representative Individual, Family, and Community Datasets.

Am J Health Promot 2021 Apr 28:8901171211012522. Epub 2021 Apr 28.

Department of School Psychology, 14719University of Nebraska-Lincoln, Lincoln, NE, USA.

Purpose: This study aimed to examine neighborhood effects on the physical and socioemotional health of children from immigrant families, after controlling for parents' demographic characteristics, socioeconomic status, acculturation, and health care issues.

Design: Pooled cross-sectional data were merged with community profiles.

Setting: The United States in 2013, 2014, and 2015.

Participants: 10,399 children from immigrant families in the 2013-2015 National Health Interview Surveys and the U.S. Census Data.

Measures: Both objective and subjective measures of neighborhood environments were assessed, including neighborhood physical disorder, socioeconomic status, demographic composition, community resources, and social trust.

Analysis: Descriptive statistics, logistic regression models.

Results: About half of the sampled children were male (51%); 68% were white; 56% were of Hispanic; and 34% were school-aged. Three neighborhood factors-neighborhood trust, area-level poverty rate, and the presence of primary care physician-were identified as significant predictors for child health outcomes. Foreign-born population, green space, and food desert were not significant. At the individual level, parents' racial and ethnic minority status, non-marital status, and healthcare issues were found to be risk factors. Families' financial resources and parental education were identified as protective factors of socioemotional health.

Conclusion: Intervention approaches to build on neighborhood trust may have broad potential to improve child outcomes. Programs focusing on immigrant families with children in high poverty neighborhoods should be a high priority.
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http://dx.doi.org/10.1177/08901171211012522DOI Listing
April 2021

The value of glycosylated hemoglobin in the diagnosis of diabetic retinopathy: a systematic review and Meta-analysis.

BMC Endocr Disord 2021 Apr 26;21(1):82. Epub 2021 Apr 26.

Department of Ophthalmology, First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130021, Jilin, China.

Objective: Glycosylated hemoglobin (HbA1c) has obvious clinical value in the diagnosis of diabetes, but the conclusions on the diagnostic value of diabetic retinopathy (DR) are not consistent. This study aims to comprehensively evaluate the accuracy of glycosylated hemoglobin in the diagnosis of diabetic retinopathy through the meta-analysis of diagnostic tests.

Methods: Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Wanfang Database, Chinese Biomedical Literature Database (CBM) were searched until November, 2020. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of the included studies. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and areas under the receiver operating characteristic (ROC) curve were calculated by Stata 15.0 software.

Results: After screening, 18 high-quality papers were included. The results of meta-analysis showed that the combined DOR = 18.19 (95% CI: 10.99-30.11), the sensitivity= 0.81 (95% CI): 0.75 ~ 0.87), specificity = 0.81 (95%CI: 0.72 ~ 0.87), +LR = 4.2 (95%CI: 2.95 ~ 6.00), -LR = 0.23 (95%CI: 0.17 ~ 0.31), and the area under the Summary ROC curve was 0.88 (95%CI:  0.85 ~ 0.90).

Conclusion: The overall accuracy of HbA1cC forin diagnosing diabetic retinopathy is good. As it is more stable than blood sugar and is not affected by meals, it may be a suitable indicator for diabetic retinopathy.
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http://dx.doi.org/10.1186/s12902-021-00737-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073908PMC
April 2021

Pramipexole attenuates 6-OHDA-induced Parkinson's disease by mediating the Nurr1/NF-κB pathway.

Mol Biol Rep 2021 Apr 23. Epub 2021 Apr 23.

Department of Neurology, Second Hospital Affiliated of Xinjiang Medical University, No. 38, South Lake Road, Ürümqi, 830063, Xinjiang, China.

Neuroinflammation is the key factor associated with the progression of Parkinson's disease (PD). Pramipexole (PPX) has anti-inflammatory and antioxidant properties. This study explored the effects of PPX on PD and its related mechanisms. A PD rat model was established using 6-hydroxydopamine (6-OHDA). Thirty rats were divided into the following three groups: control, PD, and PD + PPX. The rats in the PD and PD + PPX groups were first administered 6-OHDA and then respectively treated with saline and PPX. Afterward, rotational behavior tests were performed to evaluate the efficiency of PPX. The level of tyrosine hydroxylase (TH) was measured using immunohistochemical staining. Subsequently, real-time quantitative PCR (RT-qPCR) and western blot were used to determine the expression of α-synuclein (α-syn), nuclear receptor subfamily 4 group A member 2 (Nurr1), and nuclear factor kappa B (NF-κB). PPX improved the motor behavior of PD rats caused by 6-OHDA. The number of TH-positive neurons in the PD group was significantly lower than that in the control group (P < 0.05), while PPX could rescue 6-OHDA-induced TH loss. RT-qPCR and western blot showed that Nurr1 expression was significantly downregulated in the PD group compared to that of the control group (P < 0.05), while after PPX treatment, its expression was significantly upregulated (P < 0.05). For α-syn and NF-κB, 6-OHDA significantly upregulated their expressions (P < 0.05), whereas PPX reversed them. PPX improved the motor behavior of PD through mediating the inflammatory response and regulating the Nurr1/NF-κB signaling pathway.
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http://dx.doi.org/10.1007/s11033-021-06343-8DOI Listing
April 2021

Long Non-coding RNA: A Key Regulator in the Pathogenesis of Diabetic Cardiomyopathy.

Front Cardiovasc Med 2021 6;8:655598. Epub 2021 Apr 6.

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

In recent years, diabetes mellitus has become a global issue with increasing incidence rate worldwide. Diabetic cardiomyopathy (DCM), one of the important complications of diabetes, refers to patients with type 1 and type 2 diabetes who have ventricular hypertrophy, fibrosis and even diastolic dysfunction. The pathogenesis of DCM is related to oxidative stress, inflammatory response, apoptosis, autophagy, myocardial fibrosis and, diabetic microangiopathy. Long non-coding RNAs (lncRNA) is a non-coding RNA with a length longer than 200 nucleotides which lack the ability of protein coding. With the development of molecular technology, massive evidence demonstrates that lncRNA play a critical role in the molecular mechanism of DCM. Moreover, it can also be used as potential diagnostic markers for DCM. In this review, we intend to summarize the pathological roles and molecular mechanism of lncRNA in the progression of diabetic cardiomyopathy, which may provide promising diagnosis and treatment strategies for DCM.
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http://dx.doi.org/10.3389/fcvm.2021.655598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057523PMC
April 2021

Diurnal and Seasonal Variations in the Photosynthetic Characteristics and the Gas Exchange Simulations of Two Rice Cultivars Grown at Ambient and Elevated CO.

Front Plant Sci 2021 6;12:651606. Epub 2021 Apr 6.

Department of Ecology, College of Applied Meteorology, Nanjing University of Information Science and Technology, Nanjing, China.

Investigating the diurnal and seasonal variations of plant photosynthetic performance under future atmospheric CO conditions is essential for understanding plant adaptation to global change and for estimating parameters of ecophysiological models. In this study, diurnal changes of net photosynthetic rate (A), stomatal conductance (g), and photochemical efficiency of PSII (F'/F ') were measured in two rice cultivars grown in the open-top-chambers at ambient (∼450 μmol mol) and elevated (∼650 μmol mol) CO concentration [(CO)] throughout the growing season for 2 years. The results showed that elevated (CO) greatly increased A, especially at jointing stage. This stimulation was acclimated with the advance of growing season and was not affected by either stomatal limitations or Rubisco activity. Model parameters in photosynthesis model (V, J, and R) and two stomatal conductance models (m and g) varied across growing stages and m and g also varied across (CO) treatments and cultivars, which led to more accurate photosynthesis and stomatal conductance simulations when using these cultivar-, CO-, and stage- specific parameters. The results in the study suggested that further research is still needed to investigate the dominant factors contributing to the acclimation of photosynthetic capacity under future elevated CO conditions. The study also highlighted the need of investigating the impact of other environmental, such as nitrogen and O, and non-environmental factors, such as additional rice cultivars, on the variations of these parameters in photosynthesis and stomatal conductance models and their further impacts on simulations in large scale carbon and water cycles.
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http://dx.doi.org/10.3389/fpls.2021.651606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056013PMC
April 2021

Proteomics of protein trafficking by in vivo tissue-specific labeling.

Nat Commun 2021 04 22;12(1):2382. Epub 2021 Apr 22.

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

Conventional approaches to identify secreted factors that regulate homeostasis are limited in their abilities to identify the tissues/cells of origin and destination. We established a platform to identify secreted protein trafficking between organs using an engineered biotin ligase (BirA*G3) that biotinylates, promiscuously, proteins in a subcellular compartment of one tissue. Subsequently, biotinylated proteins are affinity-enriched and identified from distal organs using quantitative mass spectrometry. Applying this approach in Drosophila, we identify 51 muscle-secreted proteins from heads and 269 fat body-secreted proteins from legs/muscles, including CG2145 (human ortholog ENDOU) that binds directly to muscles and promotes activity. In addition, in mice, we identify 291 serum proteins secreted from conditional BirA*G3 embryo stem cell-derived teratomas, including low-abundance proteins with hormonal properties. Our findings indicate that the communication network of secreted proteins is vast. This approach has broad potential across different model systems to identify cell-specific secretomes and mediators of interorgan communication in health or disease.
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http://dx.doi.org/10.1038/s41467-021-22599-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062696PMC
April 2021

Sugar sweetened beverage consumption is positively associated with Klotho levels at two years of age in LatinX youth.

BMC Nutr 2021 Apr 23;7(1):22. Epub 2021 Apr 23.

Department of Pediatrics, University of California, 550 16th Street, San Francisco, USA.

Background: Klotho is an anti-aging protein mainly expressed in the kidneys with a smaller amount expressed in adipose tissue. Klotho effects include roles in reducing oxidative stress, insulin signaling, adipogenesis and glucose metabolism. Few studies have investigated the role of dietary factors such as sugar sweetened beverages (SSBs) on serum α-klotho levels in young children.

Methods: Data was collected from 60 low-income Latina pregnant women and their infants in San Francisco from birth until 2 years of life and examined for associations between dietary factors and child secreted α-klotho protein levels at 2 years.

Results: Mean α-klotho levels were 1782.96 ± 874.56 pg/mL at 2 years of age. Any consumption of SSBs was independently associated with increased α-klotho levels (Beta = 682.79, 95%CI 67.50, 1298.09; p = 0.03). Household income ranging from $25,000 to $50,000 was also correlated to higher levels of α-klotho in children compared with lower income levels (<$25,000) (Beta = 1613.35, 95%CI 527.37, 2699.33; p = 0.005).

Conclusions: The positive association between SSB intake and α-klotho levels at 2 years may reflect higher phosphate levels consistent with SSB intake. Higher socioeconomic status may be a proxy for reduced stress exposure in children, also associated with higher α-klotho levels. Future studies should evaluate the early impact of exposures to SSBs, stress and accelerated aging in children.
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http://dx.doi.org/10.1186/s40795-021-00423-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063295PMC
April 2021

Oxiracetam Mediates Neuroprotection Through the Regulation of Microglia Under Hypoxia-Ischemia Neonatal Brain Injury in Mice.

Mol Neurobiol 2021 Apr 22. Epub 2021 Apr 22.

Department of Histology and Embryology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.

In neonatal hypoxic-ischemic brain damage (HIBD), in addition to damage caused by hypoxia and ischemia, over-activation of inflammation leads to further deterioration of the condition, thus greatly shortening the optimal treatment time window. Ischemic penumbra, the edematous area encompassing the infarct core, is characterized by typical activation of microglia and overt inflammation, and prone to incorporate into the infarct core gradually after ischemia onset. If treated in time, the cells located in the penumbra can survive, thereby impeding the expansion of the infarction. We demonstrated for the first time that in the acute phase of HIBD in neonatal mice, treatment of Oxiracetam (ORC) significantly curtailed the size of ischemic penumbra together with drastic reduction of infarction. By staining various cellular markers, we found that the penumbra was defined and concentrated with activated microglia. We also analyzed transmission electron microscopy and Luminex assay results to elucidate the mechanisms involved. We further confirmed that ORC switched polarization of microglia from the inflammatory towards the alternatively activated phenotype, thus promoting microglia from being neurotoxic into neuroprotective. Meanwhile, ORC decreased proliferation of microglia; however, their functions of phagocytosis and autophagy were otherwise enhanced. Last, we clarified that ORC promoted autophagy through the AMPK/mTOR pathway, which further induced the transition of the inflammatory to the alternatively activated phenotype in microglia. The pro-inflammatory factors secretion was inhibited as well, thereby reducing the progression of the infarction. Taken together, it is concluded that Oxiracetam reduced the expansion of ischemic infarction in part via regulating the interplay between microglia activation and autophagy, which would delay the progression of HIBD and effectively prolong the time window for the clinical treatment of HIBD.
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http://dx.doi.org/10.1007/s12035-021-02376-zDOI Listing
April 2021