Publications by authors named "Shanshan Wang"

933 Publications

Aluminum inhibits non-amyloid pathways via retinoic acid receptor.

J Trace Elem Med Biol 2021 Nov 18;69:126902. Epub 2021 Nov 18.

Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Department of Occupational Health, School of Public Health, Xuzhou Medical University, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, China. Electronic address:

Background: Aluminium neurotoxicity has been widely confirmed and mainly manifests as cognitive impairment. Al can inhibit the expression of ADAM10, a key enzyme of the nonamyloid pathway, but its mechanism of toxicity has not been fully elucidated. Studies have shown that RARs can regulate ADAM10 expression.

Methods: We explored whether Al affects the expression of ADAM10 through RARs, thereby affecting the nonamyloid pathway.

Results: Al reduced the expressions of RARα, RARβ and ADAM10. The expression levels of the RARα, RARβ and ADAM10 proteins were upregulated in the RA group compared with the control group. In the RA + 200 μmol Al(mal) group, the downregulation of RARα, RARβ and ADAM10 was weaker than that of the 200 μmol Al(mal) group, which indicated that RA participated in and upregulated the expression of ADAM10 through RARα and RARβ.

Conclusion: Al inhibits ADAM10 expression through RARα and RARβ and results in a decrease in the nonamyloid pathway.
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http://dx.doi.org/10.1016/j.jtemb.2021.126902DOI Listing
November 2021

Comparative observation of aerosol vertical profiles in urban and suburban areas: Impacts of local and regional transport.

Sci Total Environ 2022 Jan 16;805:150363. Epub 2021 Sep 16.

Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Department of Environmental Science and Engineering, Fudan University, Shanghai 200433, China; Institute of Eco-Chongming (IEC), No. 20 Cuiniao Road, Shanghai 202162, China; Institute of Atmospheric Sciences, Fudan University, Shanghai 200433, China. Electronic address:

Ground-based Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) instruments were used to carry out observation of aerosol in the urban and suburban areas of Shanghai from October 17 to November 21, 2019. Fudan University (FDU) site is a typical urban environment, surrounded by residential areas, commercial areas and arterial roads, while Dianshan Lake (DSL) site is a suburban environment with high vegetation coverage and no pollutant emission sources. The aerosol retrieved by MAX-DOAS was in good correlation with the observation of sun photometer and the PM concentration of the corresponding site, which demonstrates that the aerosol retrieved by MAX-DOAS is reliable and feasible. Comparing the mean aerosol extinction coefficient (AEC) profiles during the observation period between urban and suburban areas, it was found that the occurrence of high aerosol concentration at FDU was nearly 3 h later than that of DSL at suburban site. And the aerosol at DSL was concentrated at an altitude of 0.3- 0.5 km, with a mean peak value of 0.486 km, which was slightly higher than the peak AEC of 0.453 km at FDU of 0.2- 0.4 km. The difference in aerosol characteristics between the two sites may be due to the fact that the influences of aerosol transport and boundary layer dynamics are different between the two sites. The backward trajectories analysis also presents that there were mutual transports of aerosol between urban and suburban areas, which affect the optical properties of the aerosol in these two sites. In a case of aerosol pollution, we visualized the transport pathway of aerosol from the western part of the North China Plain to Shanghai using AEC profiles and backward trajectories, providing the evidence that the local aerosol pollution in Shanghai was affected by long-distance transport.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150363DOI Listing
January 2022

Genome-Wide Analysis of H3K27me3 in Porcine Embryonic Muscle Development.

Front Cell Dev Biol 2021 5;9:739321. Epub 2021 Nov 5.

National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China.

The trimethylation of histone H3 lysine 27 (H3K27me3) is one of the most important chromatin modifications, which is generally presented as a repressive mark in various biological processes. However, the dynamic and global-scale distribution of H3K27me3 during porcine embryonic muscle development remains unclear. Here, our study provided a comprehensive genome-wide view of H3K27me3 and analyzed the matching transcriptome in the skeletal muscles on days 33, 65, and 90 post-coitus from Duroc fetuses. Transcriptome analysis identified 4,124 differentially expressed genes (DEGs) and revealed the key transcriptional properties in three stages. We found that the global H3K27me3 levels continually increased during embryonic development, and the H3K27me3 level was negatively correlated with gene expression. The loss of H3K27me3 in the promoter was associated with the transcriptional activation of 856 DEGs in various processes, including skeletal muscle development, calcium signaling, and multiple metabolic pathways. We also identified for the first time that H3K27me3 could enrich in the promoter of genes, such as , , , and , to negatively regulate gene expression in porcine satellite cells (PSCs). The loss of H3K27me3 could promote muscle cell differentiation. Taken together, this study provided the first genome-wide landscape of H3K27me3 in porcine embryonic muscle development. It revealed the complex and broad function of H3K27me3 in the regulation of embryonic muscle development from skeletal muscle morphogenesis to myofiber maturation.
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http://dx.doi.org/10.3389/fcell.2021.739321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602352PMC
November 2021

Lorcaserin Inhibit Glucose-Stimulated Insulin Secretion and Calcium Influx in Murine Pancreatic Islets.

Front Pharmacol 2021 5;12:761966. Epub 2021 Nov 5.

Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.

Lorcaserin is a serotonergic agonist specific to the 5-hydroxytryptamine 2c receptor (5-HTR) that is FDA approved for the long-term management of obesity with or without at least one weight-related comorbidity. Lorcaserin can restrain patients' appetite and improve insulin sensitivity and hyperinsulinemia mainly through activating 5-HTR in the hypothalamus. It is known that the mCPP, a kind of 5-HTR agonist, decreases plasma insulin concentration in mice and previous research in our laboratory found that mCPP inhibited glucose-stimulated insulin secretion (GSIS) by activating 5-HTR on the β cells. However, the effect of lorcaserin on GSIS of pancreatic β cell has not been studied so far. The present study found that 5-HTR was expressed in both mouse pancreatic β cells and β-cell-derived MIN6 cells. Dose-dependent activation of 5-HTR by lorcaserin suppressed GSIS and SB242084 or knockdown of 5-HTR abolished lorcaserin's effect . Additionally, lorcaserin also suppressed GSIS in high-fat diet (HFD)-fed mice in dose-dependent manner. Lorcaserin did not change insulin synthesis ATP content, but lorcaserin decrease cytosolic free calcium level [(Ca)i] in MIN6 cells stimulated with glucose and also inhibit insulin secretion and (Ca)i in MIN6 treated with potassium chloride. Furthermore, stimulation with the L-type channel agonist, Bay K8644 did not restore GSIS in MIN6 exposed to lorcaserin. Lorcaserin inhibits the cAMP generation of MIN6 cells and pretreatment with the Gα i/o inhibitor pertussis toxin (PTX), abolished lorcaserin-induced suppression of GSIS in β cells, while membrane-permeable cAMP analogue db-cAMP had same effect as PTX. These date indicated lorcaserin coupled to PTX-sensitive Gα i/o proteins in β cells reduced intracellular cAMP level and Ca influx, thereby causing GSIS dysfunction of β cell. These results highlight a novel signaling mechanism of lorcaserin and provide valuable insights into the further investigation of 5-HTR functions in β-cell biology and it also provides guidance for the clinical application of lorcaserin.
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http://dx.doi.org/10.3389/fphar.2021.761966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602196PMC
November 2021

Effect of Fuzheng Qingdu Therapy for Metastatic Gastric Cancer is Associated With Improved Survival: A Multicenter Propensity-Matched Study.

Integr Cancer Ther 2021 Jan-Dec;20:15347354211058464

College of Medicine, Yangzhou University, Yangzhou, PR China.

Objective: To evaluate the therapeutic effect of Traditional Chinese Medicine (TCM), specifically Fuzheng Qingdu (FZQD) therapy, on the survival time of metastatic GC patients.

Patients And Methods: Databases of medical records of 6 hospitals showed that 432 patients with stage IV GC were enrolled from March 1, 2012 to October 31, 2020. Propensity score matching (PSM) was used to reduce the bias caused by confounding factors in the comparison between the TCM and the non-TCM users. We used a Cox multivariate regression model to compare the hazard ratio (HR) value for mortality risk, and Kaplan-Meier survival curve for the survival time of GC patients.

Results: The same number of subjects from the non-TCM group were matched with 122 TCM-treated patients after PSM to evaluate their overall survival (OS) and progression-free survival (PFS). Median time of OS of TCM and non-TCM users were 16.53 and 9.10 months, respectively. TCM and non-TCM groups demonstrated a 1-year survival rate of 68.5% and 34.5%, 2-year survival rate of 28.6% and 3.5%, and 3-year survival rate of 17.8% and 0.0%, respectively. A statistical difference exists in OS between the 2 groups (χ = 33.39 and  < .0001). The PFS of TCM users was also longer than that of non-TCM users (χ = 4.95 and  = 0.026). Notably, Chinese herbal decoction, Shenmai and compound Kushen injections were commonly used for FZQD therapy.

Conclusion: This propensity-matched study showed that FZQD therapy could improve the survival of metastatic GC patients.
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http://dx.doi.org/10.1177/15347354211058464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600555PMC
November 2021

PD-1 blockade improves the anti-tumor potency of exhausted CD3CD56 NKT-like cells in patients with primary hepatocellular carcinoma.

Oncoimmunology 2021 9;10(1):2002068. Epub 2021 Nov 9.

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China.

CD3CD56 NKT-like cells play pivotal roles in the anti-tumor immune defense response. However, little is known regarding circulating NKT-like cells in patients with primary hepatocellular carcinoma (HCC). In the present study, we demonstrate that circulating NKT-like cells in HCC patients are functionally impaired and anti-PD-1 blockade improves their anti-tumor potency. Circulating NKT cells were mainly comprised of CD8+ T cells. The frequencies and absolute counts of circulating NKT-like cells were comparable between HCC patents compared to healthy donors. NKT-like cells in HCC patients were impaired in their production of TNF-α and IFN-γ as well as cytotoxicity. The level of activating receptor NKG2D was significantly decreased on NKT-like cells in HCC patients. In contrast, the expression of inhibitory receptors PD-1, Tim-3, and CTLA-4 were markedly increased on NKT-like cells in HCC patients. Meanwhile, the expression of PD-L1 was also upregulated on NKT-like cells in HCC patients. In detail, PD-1 NKT-like cells expressed lower levels of NKG2D, higher levels of Tim-3, and CTLA-4, and less IFN-γ when compared with PD-1 NKT-like cells. Importantly, PD-1 blocked with anti-PD-1 antibody effectively improved the effector function of NKT-like cells from HCC patients or healthy donors. Our findings unveil the functional characterization of NKT-like cells in HCC patients and provide the potential targets to improve their function, which might benefit the optimization of HCC immunotherapy.
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http://dx.doi.org/10.1080/2162402X.2021.2002068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583083PMC
November 2021

Neuronatin gene expression levels affect foetal growth and development by regulating glucose transport in porcine placenta.

Gene 2021 Oct 29:146051. Epub 2021 Oct 29.

National Engineering Research Center for Breeding Swine Industry, Guangzhou, China & College of Animal Science, South China Agricultural University, Guangzhou, China. Electronic address:

Imprinted genes play important regulatory roles in the growth and development of placentas and foetuses during pregnancy. In a previous study, we found that the imprinted gene Neuronatin (NNAT) is involved in foetal development; NNAT expression was significantly lower in the placentas of piglets that died neonatally compared to the placentas of surviving piglets. However, the function and mechanism of NNAT in regulating porcine placental development is still unknown. In this study, we collected the placentas of high- and low-weight foetuses at gestational day (GD 65, 90), (n = 4-5 litters/GD) to investigate the role of NNAT in regulating foetal growth and development. We found that the mRNA and protein levels of NNAT were significantly higher in the placentas of high-weight than low-weight foetuses. We then overexpressed NNAT in porcine placental trophoblast cell lines (pTr2) and demonstrated that NNAT activated the PI3K-AKT pathway, and further promoted the expression of glucose transporter 1 (GLUT1) and increased cellular calcium ion levels, which improved glucose transport in placental trophoblast cells in vitro. To conclude, our study suggests that NNAT expression impacts porcine foetal development by regulating placental glucose transport.
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http://dx.doi.org/10.1016/j.gene.2021.146051DOI Listing
October 2021

Supporting caregivers of people with dementia: A systematic review of guidelines.

Health Soc Care Community 2021 Nov 8. Epub 2021 Nov 8.

Office of Academic Studies, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Caregivers of people with dementia (PwD) frequently experience poor physical, mental and social health. Over the past decade, several guidelines have offered recommendations on supporting caregivers to improve their health outcomes. This systematic review aimed to assess the quality and evidence base of guidelines on supporting caregivers of PwD and review the content of their recommendations on caregiver support to facilitate the adoption and implementation of a specific guideline among policymakers and practitioners. A systematic search for guidelines on supporting caregivers of PwD was performed using journal databases, websites of guideline development organisations and professional dementia-related societies from inception to 30 June 2020. Four independent reviewers performed the quality assessment of the included guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. A thematic synthesis was used to analyse the content of recommendations on caregiver support extracted from the included guidelines by two independent reviewers. The strength of recommendations and level of evidence were reclassified and analysed. Literature searches identified nine guidelines. Their quality was variable. The applicability domain on AGREE II yielded the lowest median score (62.2%; range: 18.6%-86.6%), suggesting that some guidelines lacked applicability in certain fields, leaving them open to interpretation. Most evidence underlying the extracted recommendations was rated as Levels 3 (51.3%) and 4 (31.1%). High-quality evidence is required to fortify these recommendations. The nine guidelines covered six themes-assessment, education, skill training, information provision, psychosocial support and general support policies-which can guide future policies and interventions of caregiver support. The recommendations extracted were consistent across guidelines, but each guideline failed to cover all six themes. Thus, more applicable and comprehensive guidelines that fully address all themes of support for caregivers of PwD are needed.
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http://dx.doi.org/10.1111/hsc.13513DOI Listing
November 2021

Intranasal Dexmedetomidine Accompanied by Cartoon Video Preoperation for Reducing Emergence Delirium in Children Undergoing Strabismus Surgery: A Prospective Randomized Trial.

Front Surg 2021 22;8:754591. Epub 2021 Oct 22.

Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

After general anesthesia, many pediatric patients present with emergence delirium (ED). The aim of this study was to determine whether dexmedetomidine intranasal premedication accompanied by a cartoon video 30 min before general anesthesia would have an effect on reducing emergence delirium in preschool children. One hundred and forty children aged 3-6 year undergoing elective strabismus surgery were randomly to be premedicated with 2 μg kg intranasal dexmedetomidine accompanied by the viewing of a cartoon video (Group DV) or without any premedication as usual (Group C). The primary outcome was the incidence of emergence delirium at the postanesthesia care unit (PACU), evaluated by the Pediatric Anesthesia Emergence Delirium (PAED) scale. The secondary outcomes included: the Modified Yale Preoperative Anxiety Scale (mYPAS) upon separation from parents; the Induction Compliance Checklist score (ICC); the PACU discharge time; the parental satisfaction score; the incidences of the side effects and the Post-Hospital Behavior Questionnaire (PHBQ) score during the first day after surgery. The incidence of emergence agitation (PAED score ≥ 10) was reduced in Group DV compared with Group C [8 (11.4%) vs. 24 (34.3%); = 0.001]. None of the patients in the DV group experienced severe emergence agitation (PAED score ≥ 15), as compared with the C group ( = 0.006). The mYPAS score upon separation from parents ( < 0.001) and the incidence of poor coordination (ICC ≥ 4) during induction ( < 0.001) were significantly lower in Group DV than in Group C. In Group DV, the PACU discharge time was longer ( < 0.001), and the parental satisfaction score was higher ( < 0.001). However, during the first day after surgery, the PHBQ score was lower in Group DV compared with Group C ( = 0.001). Premedication with 2 μg kg intranasal dexmedetomidine accompanied by cartoon video viewing can dramatically reduce emergence delirium in preschool children undergoing strabismus surgery, relieve preoperative anxiety and improve the parental satisfaction and the postoperative behavior changes during the first day after surgery. ChiCTR2000030678.
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http://dx.doi.org/10.3389/fsurg.2021.754591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569138PMC
October 2021

Identification of Genetic Signature Associated With Aging in Pulmonary Fibrosis.

Front Med (Lausanne) 2021 20;8:744239. Epub 2021 Oct 20.

Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aging is a strong risk factor and an independent prognostic factor in idiopathic pulmonary fibrosis (IPF). In this study, we aimed to conduct a comprehensive analysis based on gene expression profiles for the role of aging in pulmonary fibrosis. Four datasets (GSE21411, GSE24206, GSE47460, and GSE101286) for patients with clinical IPF and one dataset for bleomycin (BLM)-induced pulmonary fibrosis (BIPF) mouse model (GSE123293) were obtained from Gene Expression Omnibus (GEO). According to different age ranges, both patients with IPF and BIPF mice were divided into young and aged groups. The differently expressed genes (DEGs) were systemically analyzed using Gene Ontology (GO) functional, Kyoto Encyclopedia of Genes and Genomes (KEGG), and hub genes analysis. Finally, we verified the role of age and core genes associated with age . the expression profile comparisons of aged and young patients with IPF, we identified 108 aging-associated DEGs, with 21 upregulated and 87 downregulated. The DEGs were associated with "response to glucocorticoid," "response to corticosteroid," and "rhythmic process" in GO biological process (BP). For KEGG analysis, the top three significantly enriched KEGG pathways of the DEGs included "IL-17 signaling pathway," "Mineral absorption," and "HIF-1-signaling pathway." Through the comparisons of aged and young BIPF mice, a total number of 778 aging-associated DEGs were identified, with 453 genes increased and 325 genes decreased. For GO and KEGG analysis, the DEGs were enriched in extracellular matrix (ECM) and collagen metabolism. The common DEGs of patients with IPF and BIPF mice were enriched in the BP category, including "induction of bacterial agglutination," "hyaluronan biosynthetic process," and "positive regulation of heterotypic cell-cell adhesion." We confirmed that aged BIPF mice developed more serious pulmonary fibrosis. Finally, the four aging-associated core genes (, and ) were verified . This study provides new insights into the impact of aging on pulmonary fibrosis. We also identified four aging-associated core genes (, and ) related to the development of pulmonary fibrosis.
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http://dx.doi.org/10.3389/fmed.2021.744239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564051PMC
October 2021

Fetal growth restriction impairs hippocampal neurogenesis and cognition via Tet1 in offspring.

Cell Rep 2021 Nov;37(5):109912

Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, National Stem Cell Translational Resource Center, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address:

Fetal growth restriction (FGR) increases the risk for impaired cognitive function later in life. However, the precise mechanisms remain elusive. Using dexamethasone-induced FGR and protein restriction-influenced FGR mouse models, we observe learning and memory deficits in adult FGR offspring. FGR induces decreased hippocampal neurogenesis from the early post-natal period to adulthood by reducing the proliferation of neural stem cells (NSCs). We further find a persistent decrease of Tet1 expression in hippocampal NSCs of FGR mice. Mechanistically, Tet1 downregulation results in hypermethylation of the Dll3 and Notch1 promoters and inhibition of Notch signaling, leading to reduced NSC proliferation. Overexpression of Tet1 activates Notch signaling, offsets the decline in neurogenesis, and enhances learning and memory abilities in FGR offspring. Our data indicate that a long-term decrease in Tet1/Notch signaling in hippocampal NSCs contributes to impaired neurogenesis following FGR and could serve as potential targets for the intervention of FGR-related cognitive disorders.
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http://dx.doi.org/10.1016/j.celrep.2021.109912DOI Listing
November 2021

Association Between Family Structure and Anxiety Disorder Among Pre-schoolers: A Cross-Sectional Study in Urban Chongqing, China.

Front Psychiatry 2021 13;12:626377. Epub 2021 Oct 13.

Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing, China.

This study explores the current situation of anxiety disorder of pre-schoolers and assesses the association between family structure and anxiety disorder (AD) among pre-schoolers in Chongqing, China. This is a cross-sectional study of 499 main fosterers of children aged 3-6 years who completed the 28-item Chinese version of the Spence Pre-school Anxiety Scale (PAS). Multinomial logistic regression with three models was used to assess the association of the family structure with the different AD. The prevalence of AD was 31.46%, whose score of PAS were more than 48. Among the five different PAS sub-scales, the prevalence of obsessive-compulsive disorder (OCD) was the highest (50.10%), followed by separation anxiety disorder (SAD, 39.28%), fear of physical harm (FPH, 37.68%), generalized anxiety disorder (GAD, 33.47%), and social phobia (SP, 25.85%). Pre-schoolers from inter-generational families were more probably have AD than those from nuclear families (OR = 3.73, < 0.05). The participants from inter-generational families were more likely to have SAD (OR = 3.39, < 0.05), FPM (OR = 2.80, < 0.05), or OCD (OR = 2.40, < 0.05), in comparison with participants from other family structures. Anxiety disorder among pre-schoolers aged 3-6 in Chongqing is widespread. Pre-schoolers from inter-generational families were more probably have AD, SAD, FPM, and OR and pre-schoolers from stem families may be less likely to have SAD compared with those from nuclear families. Relieving the anxiety of pre-schoolers may be possible with additional interventional efforts in inter-generational families.
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http://dx.doi.org/10.3389/fpsyt.2021.626377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548734PMC
October 2021

The association between blood lymphocyte NMDAR, group I mGluRs and cognitive function changes in occupationally aluminum-exposed workers and verification in rats.

J Trace Elem Med Biol 2021 Oct 14;69:126875. Epub 2021 Oct 14.

Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, Taiyuan, Shanxi, 030001, China; Key Lab of Cellular Physiology of Education Ministry, Shanxi Medical University, Taiyuan, Shanxi, 030001, China. Electronic address:

Background: Many studies have shown that occupational aluminum (Al) exposure could affect the cognitive functions of workers and cause mild cognitive impairment (MCI). Glutamate receptors (GluRs) play an important role in learning and memory functions.

Methods: 352 workers in a large Al production enterprise were investigated in this research. MMSE, CDT, DST, VFT, FOM were used to evaluate the cognitive functions of workers. Plasma Al levels as exposure indices were measured by Graphite Furnace Atomic Absorption Method (GFAAS). The expression of GluRs was measured by ELISA. Cognitive function comprehensive scores were obtained through factor analysis. Then a rat model of chronic AlCl exposure was established. The detection method of Al levels and protein expression were the same as mentioned-above.

Results: Compared with the Q1 group, the DST, VFT, and comprehensive cognitive function scores of the Q4 group were lower(P < 0.05). For every 1μg/L increase in plasma Al concentration, the risk of cognitive impairment increases 1.051 times (95 %CI:1.031,1.072). Both NMDAR1 and NMDAR2A protein expression level of Q1 group were higher than those of Q2, Q3, Q4 group (all P < 0.05). The mediating effect ratio of NMDAR1 between plasma Al levels and cognitive function comprehensive scores was a1*b1/c=11.30 %, and the mediating effect ratio of NMDAR2A was |a2*b2/c|=21.77 %. Compared with control group, the escape latency of rats in the high Al dose group was longer day by day (P < 0.05). With the increase of Al dose, the relative expression of NMDAR1, NMDAR2A, NMDAR2B, GluR1 and mGluR5 in cerebral cortex and lymphocytes of rats were decreased (P < 0.05). The result of correlation analysis on NMDAR1 protein expression between brain cortex and lymphocyte showed that the correlation coefficient is r = 0.646(P < 0.05).

Conclusion: Taking together the results from both Al exposed workers and animal, there is a certain correlation between NMDAR1 protein contents of brain cortex and peripheral lymphocytes. We propose that lymphocyte NMDAR1 could be considered as a peripheral potential marker of cognitive impairment for further observation.
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http://dx.doi.org/10.1016/j.jtemb.2021.126875DOI Listing
October 2021

Moderate Freshwater Fish Intake, but Not n-3 Polyunsaturated Fatty Acids, Is Associated with a Reduced Risk of Small for Gestational Age in a Prospective Cohort of Chinese Pregnant Women.

J Acad Nutr Diet 2021 Oct 18. Epub 2021 Oct 18.

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Background: Although previous studies have found that maternal fish intake is associated with fetal growth, the role of freshwater fish intake remains unknown.

Objective: Our aim was to examine the relationships of freshwater fish and n-3 polyunsaturated fatty acids (PUFAs) intake with the risk of small for gestational age (SGA) in Chinese pregnant women.

Design: This was a prospective analysis of data from the Tongji Birth cohort in Wuhan, China, from 2018 to 2021.

Participants/settings: This study included 1,701 pregnant women who had completed a food frequency questionnaire dietary assessment during mid-pregnancy.

Main Outcome Measures: Intake of fish was assessed by a semi-quantitative food frequency questionnaire. Total intake of n-3 PUFAs was the sum of data collected from both dietary and supplemental sources of n-3 PUFAs. Birth information was extracted from medical records.

Statistical Analyses: Multivariate logistic regression models were applied to estimate odds ratios and 95% CIs.

Results: The median (interquartile range) intake of freshwater fish and total n-3 PUFAs was 12.1 (4.3 to 26.4) g/d and 68.2 (24.5 to 370.0) mg/d, respectively. Moderate intake of freshwater fish was associated with reduced risk of SGA. Compared with the lowest quintile (0-3.2 g/d), the multivariable-adjusted odds ratio for women in the fourth quintile of freshwater fish intake (17.9 to 30.0 g/d) was 0.50 (95% CI 0.25 to 0.96). We found a nonlinear association between freshwater fish intake and SGA risk (P = .027). However, maternal n-3 PUFAs intake was not significantly associated with SGA risk, either from total intake or from dietary sources alone.

Conclusions: Moderate freshwater fish intake during pregnancy is associated with lower risk of SGA in a Chinese population. This finding provides supportive evidence for freshwater fish intake during pregnancy, particularly for the inland areas of developing countries.
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http://dx.doi.org/10.1016/j.jand.2021.10.016DOI Listing
October 2021

Nutrient Removal in Eutrophic Water Promotes Stability of Planktonic Bacterial and Protist Communities.

Microb Ecol 2021 Oct 20. Epub 2021 Oct 20.

School of Advanced Manufacturing, Fuzhou University, Jinjiang, 362200, China.

Nutrient (nitrogen and phosphorus) removal by using bioremediation technologies in eutrophic water alters bacterial and protist community structure and function, but how it changes the stability of community remains unclear. To fill this gap, in this study, bacterial and protist communities were investigated using 16S and 18S rRNA gene high-throughput sequencing during the nutrient removal by using ecological floating beds of Canna indica L. Our results showed that both bacterial and protist community compositions in the treatment group were similar to those in the control group at the beginning of the experiment (day 1 to day 11), but then bacterial and protist community compositions became more stable with the removal of nutrients in the treatment group than those in the control group (day 12 to day 18). We further explored the mechanisms for this increased stability and found that the contribution of the stochastic process to bacterial and protist community variations was higher in the control group than that in the treatment group. This suggests that the high nutrient concentration in the control group might increase the random colonization or extinction, and therefore resulted in the high temporal variability (i.e., unstable) of bacterial and protist communities. Our findings suggest that bioremediation for eutrophication can promote the stability of aquatic communities, and therefore potentially maintain aquatic ecosystem functions and services to humanity.
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http://dx.doi.org/10.1007/s00248-021-01898-2DOI Listing
October 2021

Mannose-modified liposome designed for epitope peptide drug delivery in cancer immunotherapy.

Int Immunopharmacol 2021 Oct 12;101(Pt A):108148. Epub 2021 Oct 12.

School of Pharmacy, China Medical University, Shenyang 110122, China. Electronic address:

Background: Based on the interaction between cytotoxic T lymphocyte (CTL) dominant epitopes and dendritic cells (DCs), CD8T cells are specifically activated into CTL cells. Targeted killing is a type of tumor vaccine for immunotherapy with great development potential. However, because of the disadvantages of poor stability in vivo and low uptake rate of DCs caused by single use of dominant epitope peptide drugs, its use is limited. Here, we investigated the antitumor potential of M-YL/LA-Lipo, a novel liposome drug delivery system.

Methods: We assembled mannose on the surface of liposome, which has a highly targeted effect on the mannose receptor on the surface of DCs. The dominant epitope peptide drugs were encapsulated into the liposome using membrane hydration method, and the encapsulation rate, release rate, in vitro stability, and microstructure were characterized using ultrafiltration method, dialysis method, and negative staining transmission electron microscopy. In addition, its targeting ability was verified by in vitro interaction with DCs, and its anticancer effect was verified by animal experiments.

Results: We have successfully prepared a liposome drug delivery system with stable physical and chemical properties. Moreover, we demonstrated that it was highly uptaken by DCs and promoted DC maturation in vitro. Furthermore, in vivo animal experiments indicated that M-YL/LA-Lipo specific CTL significantly inhibited the hematogenous spread of lung metastasis of triple negative breast cancer.

Conclusions: we successfully constructed a new polypeptide liposome drug delivery system by avoiding the disadvantages of single use of dominant epitope peptide drugs and accurate targeted therapy for tumors.
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http://dx.doi.org/10.1016/j.intimp.2021.108148DOI Listing
October 2021

SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection.

Signal Transduct Target Ther 2021 10 13;6(1):368. Epub 2021 Oct 13.

Department of Nephrology, Center of Nephrology and Urology, Sun Yat-sen University Seventh Hospital, Shenzhen, Guangdong, 518107, China.

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.
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http://dx.doi.org/10.1038/s41392-021-00777-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512652PMC
October 2021

Probing Atomic-Scale Fracture of Grain Boundaries in Low-symmetry 2D Materials.

Small 2021 Oct 13:e2102739. Epub 2021 Oct 13.

Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, P. R. China.

Grain boundaries (GBs) play a central role in the fracture of polycrystals. However, the complexity of GBs and the difficulty in monitoring the atomic structure evolution during fracture greatly limit the understanding of the GB mechanics. Here, in situ aberration-corrected scanning transmission electron microscopy and density functional theory calculations are combined to investigate the fracture mechanics in low-symmetry, polycrystalline, 2D rhenium disulfide (ReS ), unveiling the distinctive crack behaviors at different GBs with atomic resolution. Brittle intergranular fracture prefers to rip through the GBs that are parallel to the Re chains of at least one side of the GBs. In contrast, those GBs, which do not align with Re chains on either side of the GBs, are highly resistant to fracture, impeding or deflecting the crack propagation. These results disclose the GB type-dependent mechanical failure of anisotropic 2D polycrystals, providing new ideas for material reinforcement and controllable cutting via GB engineering.
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http://dx.doi.org/10.1002/smll.202102739DOI Listing
October 2021

Label-Free Immunoassay for Sensitive and Rapid Detection of the SARS-CoV-2 Antigen Based on Functionalized Magnetic Nanobeads with Chemiluminescence and Immunoactivity.

Anal Chem 2021 10 12;93(42):14238-14246. Epub 2021 Oct 12.

CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.

Direct detection of SARS-CoV-2 in biological specimens is often challenging due to the low abundance of viral components and lack of enough sensitivity. Herein, we developed a new type of chemiluminescent functionalized magnetic nanomaterial for sensitive detection of the SARS-CoV-2 antigen. First, HAuCl was reduced by -(aminobutyl)--(ethylisoluminol) (ABEI) in the presence of amino magnetic beads (MB-NH) to generate ABEI-AuNPs, which were directly assembled on the surface of MB-NH. Then, Co was modified onto the surface to form [email protected]/Co (MAA/Co). MAA/Co exhibited good chemiluminescence (CL) and magnetic properties. It was also found that it was easy for the antibody to be connected with MAA/Co. Accordingly, MAA/Co was used as a sensing interface to construct a label-free immunoassay for rapid detection of the N protein in SARS-CoV-2. The immunoassay showed a linear range from 0.1 pg/mL to 10 ng/mL and a low detection limit of 69 fg/mL, which was superior to previously reported methods for N protein detection. It also demonstrated good selectivity by virtue of magnetic separation, which effectively removed a sample matrix after immunoreactions. It was successfully applied for the detection of the N protein in spiked human serum and saliva samples. Furthermore, the immunoassay was integrated with an automatic CL analyzer with magnetic separation to detect the N protein in patient serums and rehabilitation patient serums with satisfactory results. Thus, the CL immunoassay without a complicated labeling procedure is sensitive, selective, fast, simple, and cost-effective, which may be used to combat the COVID-19 pandemic. Finally, the CL quenching mechanism of the N protein in the immunoassay was also explored.
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http://dx.doi.org/10.1021/acs.analchem.1c03208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524964PMC
October 2021

Integrated Cobaloxime and Mesoporous Silica-Supported Ruthenium/Diamine Co-Catalysis for One-Pot Hydration/Reduction Enantioselective Sequential Reaction of Alkynes.

Front Chem 2021 22;9:732542. Epub 2021 Sep 22.

Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai, China.

This study developed a cost-efficient hydration/asymmetric transfer hydrogenation (ATH) process for the one-pot synthesis of valuable chiral alcohols from alkynes. During this process, the initial homogeneous cobaloxime-catalyzed hydration of alkynes was followed by heterogeneous Ru/diamine-catalyzed ATH transformation of the generated ketones, which provided varieties of chiral alcohols in good yields with up to 99% values. The immobilized Ru/diamine catalyst could be recycled at least three times before its deactivation in the sequential reaction system. This work shows a general method for developing one-pot asymmetric sequential catalysis towards sustainable organic synthesis.
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http://dx.doi.org/10.3389/fchem.2021.732542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493125PMC
September 2021

Mechanism of Baicalein in Brain Injury After Intracerebral Hemorrhage by Inhibiting the ROS/NLRP3 Inflammasome Pathway.

Inflammation 2021 Oct 8. Epub 2021 Oct 8.

Department of Neurology, The Fourth Affiliated Hospital of China Medical University, 4 Chongshan East Street, Shenyang, 110032, China.

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high disability/mortality. Baicalein has strong anti-inflammatory activity. This study aims to explore the mechanism of baicalein on brain injury after ICH. The model of brain injury after ICH was established by collagenase induction, followed by the evaluation of neurological severity, brain water content, the degenerated neurons, neuronal apoptosis, and reactive oxygen species (ROS). The ICH model was treated with baicalein or silencing NLRP3 to detect brain injury. The expression of NLRP3 inflammasome was detected after treatment with ROS scavenger. The expressions of oxidative stress markers and inflammatory factors were detected, and the levels of components in NLRP3 inflammasome were detected. Baicalein reduced the damage of nervous system, lesion surface, brain water content, and apoptosis. Baicalein inhibited malondialdehyde and increased IL-10 by inhibiting ROS in brain tissue after ICH. Baicalein inhibited the high expression of NLRP3 inflammasome in ICH. ROS scavenger inhibited the NLRP3 inflammatory response by inhibiting ROS levels. Silencing NLRP3 alleviated the brain injury after ICH by inhibiting excessive oxidative stress and inflammatory factors. Overall, baicalein alleviated the brain injury after ICH by inhibiting ROS and NLRP3 inflammasome.
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http://dx.doi.org/10.1007/s10753-021-01569-xDOI Listing
October 2021

Annotation-efficient deep learning for automatic medical image segmentation.

Nat Commun 2021 10 8;12(1):5915. Epub 2021 Oct 8.

Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.

Automatic medical image segmentation plays a critical role in scientific research and medical care. Existing high-performance deep learning methods typically rely on large training datasets with high-quality manual annotations, which are difficult to obtain in many clinical applications. Here, we introduce Annotation-effIcient Deep lEarning (AIDE), an open-source framework to handle imperfect training datasets. Methodological analyses and empirical evaluations are conducted, and we demonstrate that AIDE surpasses conventional fully-supervised models by presenting better performance on open datasets possessing scarce or noisy annotations. We further test AIDE in a real-life case study for breast tumor segmentation. Three datasets containing 11,852 breast images from three medical centers are employed, and AIDE, utilizing 10% training annotations, consistently produces segmentation maps comparable to those generated by fully-supervised counterparts or provided by independent radiologists. The 10-fold enhanced efficiency in utilizing expert labels has the potential to promote a wide range of biomedical applications.
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http://dx.doi.org/10.1038/s41467-021-26216-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501087PMC
October 2021

CircDTL Functions as an Oncogene and Regulates Both Apoptosis and Ferroptosis in Non-small Cell Lung Cancer Cells.

Front Genet 2021 21;12:743505. Epub 2021 Sep 21.

Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, China.

Circular RNAs (circRNA) play an essential role in the tumorigenesis of non-small cell lung cancer (NSCLC). CircDTL is a novel identified circRNA with little information regarding its biological role. However, the role of circDTL in NSCLC has not been investigated yet. In this study, the levels of circDTL in tissues and cells were measured by RT-PCR. Cell viability was measured by the CCK-8 assay. Cell migration and invasion were evaluated using the wound healing assay and transwell assay, respectively. Cell death was measured by the cell death ELISA kit. The levels of Fe, ROS, MDA and GSH were measured using the commercial kits. The interactions between miR-1287-5p and circDTL/3'UTR GPX4 were verified by dual-luciferase activity assay. The effects of circDTL on tumor growth were evaluated CircDTL was found to be upregulated and acted as an oncogene in NSCLC cells. Knockdown of circDTL promoted both apoptosis and ferroptosis of NSCLC cells. It was identified that circDTL exerts its oncogenic effects via the circDTL/miR-1287-5p/GPX4 axis and GPX4 inhibits both ferroptosis and apoptosis. Finally, this study showed that silencing of circDTL promoted the sensitivity of NSCLC cells to chemotherapeutic agents and inhibited the growth of tumors . CircDTL acts as an oncogene and exerts its effects via the miR-1287-5p/GPX4 axis in NSCLC, providing a potential therapeutic target for NSCLC cancer therapy.
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http://dx.doi.org/10.3389/fgene.2021.743505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490767PMC
September 2021

Automatic label-free immunoassay with high sensitivity for rapid detection of SARS-CoV-2 nucleocapsid protein based on chemiluminescent magnetic beads.

Sens Actuators B Chem 2021 Dec 30;349:130739. Epub 2021 Sep 30.

CAS Key Laboratory of Soft Matter Chemistry, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, PR China.

Accurate and efficient early diagnosis is crucial for the control of COVID-19 pandemic. However, methods that can balance sensitivity, high throughput, detection speed and automation simultaneously are still scarce. Here, we report an automatic label-free chemiluminescence immunoassay (CLIA) for rapid SARS-CoV-2 nucleocapsid protein (NP) detection with high sensitivity and throughput. N-(4-aminobutyl)-N-ethylisoluminol and Co dual-functionalized chemiluminescent magnetic beads (dfCL-MB) were first applied to the detection of protein by a novel and simple strategy. Sulphydryl polyethylene glycol was coated on the surface of dfCL-MB so as to assemble dfCL-MB and antibody conjugated gold nanoparticles through Au-S bond. Considering the high-risk application scenarios, the immunosensor was integrated with an automatic chemiluminescence analyzer so that the whole testing procedure could be carried out automatically without manual operation. A linear correlation between CL intensities and the logarithm of NP concentration was obtained in the range of 0.1-10,000 pg/mL with a detection limit of 21 fg/mL. The whole process cost 25 min and the sample compartment can bear 24 samples simultaneously. The spiked human serum samples and serum samples from COVID-19 patients were determined with satisfactory recoveries of 91.1-109.4%, suggesting that the proposed label-free CLIA is of great potential for SARS-CoV-2 NP detection in practice.
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http://dx.doi.org/10.1016/j.snb.2021.130739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481120PMC
December 2021

Integrated lipidomics, transcriptomics and network pharmacology analysis to reveal the mechanisms of Danggui Buxue Decoction in the treatment of diabetic nephropathy in type 2 diabetes mellitus.

J Ethnopharmacol 2022 Jan 2;283:114699. Epub 2021 Oct 2.

School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China.

Ethnopharmacological Relevance: Danggui Buxue Decoction (DBT) is classical prescriptions, which contains two Traditional Chinese Medicines of Angelicae sinensis radix and Astragali radix. According to the preliminary work of our laboratory and numerous studies, it has been found that DBT has a therapeutic effect on diabetic nephropathy (DN). However, the mechanisms underlying its action remain unclear.

Aim Of The Study: The aim of this study was to evaluate the impact of DBT on kidney disease in diabetic mice and further explore its protective mechanism.

Methods: DN mice model was induced by high-fat fodder and streptozotocin (STZ). Qualitative and quantitative analysis of 6 compounds in DBT was carried out by HPLC, including calycosin-7-glucoside, ferulic acid, ononin, calycosin, formononetin, and levostilide A. Hematoxylin-Eosin (HE) staining was used to determine the degree of kidney pathological damage. The UPLC-Q Exactive MS technique was used to analyze the lipids metabolism profile of kidneys samples and multiple statistical analysis methods were used to screen and identify biomarkers. Transcriptomics analyses were carried out using RNAseq. The possible molecular mechanism was unraveled by network pharmacology.

Results: Thirty-one significantly altered lipid metabolites were identified in the model group comparing with the control group. DBT improved aberrant expression of several pathways related to lipidomics, including glycerophospholipid metabolism and sphingolipid metabolism. Comprehensive analysis indicated that DBT intervention reduced the content of Cers, phosphatidylethanolamines and phosphatidylcholines in mouse kidneys by downregulating the transcription level of Degs2 and Cers, reducing lipid accumulation and promoting Akt phosphorylation by upregulating the expression of Acers and Pdk1. Network pharmacology analysis showed that components in DBT, such as kaempferol, ferulic acid and astragaloside IV, could be responsible for the pharmacological activity of DN by regulating the AGE-RAGE, PI3K/Akt, MAPK and NF-κB signaling pathways in diabetic complications.

Conclusions: These results showed that DBT may improve DN by affecting insulin resistance, chronic inflammation and lipid accumulation.
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http://dx.doi.org/10.1016/j.jep.2021.114699DOI Listing
January 2022

The Application of the CRISPR/Cas9 System in the Treatment of Hepatitis B Liver Cancer.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211045206

36639The First Affiliated Hospital of Anhui Medical University, Hefei, China.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system was originally discovered in prokaryotes and functions as part of the adaptive immune system. The experimental research of many scholars, as well as scientific and technological advancements, has allowed prokaryote-derived CRISPR/Cas genome-editing systems to transform our ability to manipulate, detect, image, and annotate specific DNA and RNA sequences in the living cells of diverse species. Through modern genetic engineering editing technology and high-throughput gene sequencing, we can edit and splice covalently closed circular DNA to silence it, and correct the mutation and deletion of liver cancer genes to achieve precise in situ repair of defective genes and prohibit viral infection or replication. Such manipulations do not destroy the structure of the entire genome and facilitate the cure of diseases. In this review, we discussed the possibility that CRISPR/Cas could be used as a treatment for patients with liver cancer caused by hepatitis B virus infection, and reviewed the challenges incurred by this effective gene-editing technology.
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http://dx.doi.org/10.1177/15330338211045206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493308PMC
October 2021

Effects of Oral Vitamin C Supplementation on Liver Health and Associated Parameters in Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial.

Front Nutr 2021 14;8:745609. Epub 2021 Sep 14.

Department of Nutrition and Food Safety of School of Public Health, Xi'an Jiaotong University, Xi'an, China.

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18-60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, = 26), medium (1,000 mg/day, = 30), or high (2,000 mg/day, = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, -5.00 (-10.25, -1.75) vs. High, -2.50 (-7.75, 0.00), = 0.02] and alanine aminotransferase [Medium, -8.00 (-18.00, -1.75) vs. High, -3.50 (-13.75, 4.25), = 0.05; Medium vs. Low, -3.00 (-9.00, 5.50), = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.
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http://dx.doi.org/10.3389/fnut.2021.745609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478121PMC
September 2021

Assessing psychosocial interventions for informal caregivers of older people with early dementia: a systematic review of randomized controlled evidence.

Front Biosci (Landmark Ed) 2021 Sep;26(9):556-571

LUCAS - Centre for Care Research & Consultancy KU Leuven, 3000 Leuven, Belgium.

Dementia affects not only the patients, but also the caregivers. Timely targeted supporting for informal caregivers of people with dementia can improve their health and life quality, as well as contribute to sustainable healthcare. However, which interventions could efficiently support them and why still remains unclear. This systematic review aims to close this gap by critically assessing the current state of randomized controlled evidence concerning informal caregivers of older people with early dementia. We searched the electronic databases PubMed, CINAHL, Embase, Cochrane and Web of Science and assessed the methodological quality of the selected studies using the validated PEDro scale. A total of 2067 studies were identified in the initial searching, and 29 randomized controlled studies were finally selected based on the rigorous inclusion and exclusion criteria. Through completely assessing the methodological quality of studies, and the essentials and effectiveness of the 22 different types of interventions, we identified which interventions were effective and why. Timely targeted interventions for this caregiver group remains scarce. Furthermore, we highlight that there is a lack of systematic caregiver needs assessments prior to or when delivering the interventions.
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http://dx.doi.org/10.52586/4967DOI Listing
September 2021

Synapsin-Promoted Caveolin-1 Overexpression Maintains Mitochondrial Morphology and Function in PSAPP Alzheimer's Disease Mice.

Cells 2021 09 20;10(9). Epub 2021 Sep 20.

Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.

Mitochondrial dysfunction plays a pivotal role in the Alzheimer's Disease (AD) pathology. Disrupted mitochondrial dynamics (i.e., fusion/fission balance), which are essential for normal mitochondria structure and function, are documented in AD. Caveolin-1 (Cav-1), a membrane/lipid raft (MLR) scaffolding protein regulates metabolic pathways in several different cell types such as hepatocytes and cancer cells. Previously, we have shown decreased expression of Cav-1 in the hippocampus of 9-month (m) old PSAPP mice, while hippocampal overexpression of neuron-targeted Cav-1 using the synapsin promoter (i.e., ) preserved cognitive function, neuronal morphology, and synaptic ultrastructure in 9 and 12 m PSAPP mice. Considering the central role of energy production in maintaining normal neuronal and synaptic function and survival, the present study reveals that PSAPP mice exhibit disrupted mitochondrial distribution, morphometry, and respiration. In contrast, mitigates mitochondrial damage and loss and enhances mitochondrial respiration. Furthermore, by examining mitochondrial dynamics, we found that PSAPP mice showed a significant increase in the phosphorylation of mitochondrial dynamin-related GTPase protein (DRP1), resulting in excessive mitochondria fragmentation and dysfunction. In contrast, hippocampal delivery of significantly decreased p-DRP1 and augmented the level of the mitochondrial fusion protein, mitofusin1 (Mfn1) in PSAPP mice, a molecular event, which may mechanistically explain for the preserved balance of mitochondria fission/fusion and metabolic resilience in 12 m PSAPP- mice. Our data demonstrate the critical role for Cav-1 in maintaining normal mitochondrial morphology and function through affecting mitochondrial dynamics and explain a molecular and cellular mechanism underlying the previously reported neuroprotective and cognitive preservation induced by in PSAPP mouse model of AD.
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http://dx.doi.org/10.3390/cells10092487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467690PMC
September 2021

Progression on the Roles and Mechanisms of Tumor-Infiltrating T Lymphocytes in Patients With Hepatocellular Carcinoma.

Front Immunol 2021 3;12:729705. Epub 2021 Sep 3.

Department of Gastrointestinal and Hepatology, Beijing You'An Hospital, Capital Medical University, Beijing, China.

Primary liver cancer (PLC) is one of the most common malignancies in China, where it ranks second in mortality and fifth in morbidity. Currently, liver transplantation, hepatic tumor resection, radiofrequency ablation, and molecular-targeted agents are the major treatments for hepatocellular carcinoma (HCC). Overall, HCC has a poor survival rate and a high recurrence rate. Tumor-infiltrating lymphocytes (TILs) have been discovered to play essential roles in the development, prognosis, and immunotherapy treatment of HCC. As the major component cells of TILs, T cells are also proved to show antitumor and protumor effects in HCC. Foxp3+, CD8+, CD3+, and CD4+ T lymphocytes are the broadly studied subgroups of TILs. This article reviews the roles and mechanisms of different tumor-infiltrating T lymphocyte subtypes in HCC.
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http://dx.doi.org/10.3389/fimmu.2021.729705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462294PMC
September 2021
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