Publications by authors named "Liping Zhao"

390 Publications

Elemental iron modifies the redox environment of the gastrointestinal tract: a novel therapeutic target and test for metabolic syndrome.

Free Radic Biol Med 2021 Apr 5. Epub 2021 Apr 5.

Department of Plant Biology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ, 08901.

Metabolic syndrome (MetS, i.e., type 2 diabetes and obesity) is often associated with dysbiosis, inflammation, and leaky gut syndrome, which increase the content of oxygen and reactive oxygen species (ROS) in the gastrointestinal (GI) tract. Using near-infrared fluorescent, in situ imaging of ROS, we evaluated the effects of oral administration of elemental iron powder (Fe) on luminal ROS in the GI tract and related these changes to glucose metabolism and the gut microbiome. C57Bl/6J mice fed low-fat or high-fat diets and gavaged with Fe (2.5 g per kg), in both single- and repeat-doses, demonstrated decreased levels of luminal ROS. Fourteen days of repeated Fe administration reduced hyperglycemia and improved glucose tolerance in the obese and hyperglycemic animals compared to the untreated obese controls and reduced the relative amount of iron oxides in the feces, which indicated an increased redox environment of the GI tract. We determined that Fe administration can also be used as a diagnostic assay to assess the GI microenvironment. Improved metabolic outcomes and decreased gastrointestinal ROS in Fe-treated, high-fat diet-fed animals correlated with the increase in a co-abundance group of beneficial bacteria, including Lactobacillus, and the suppression of detrimental populations, including Oscillibacter, Peptococcus, and Intestinimonas. Daily Fe treatment also increased the relative abundance of amplicon sequence variants that lacked functional enzymatic antioxidant systems, which is consistent with the ability of Fe to scavenge ROS and oxygen in the GI, thus favoring the growth of oxygen-sensitive bacteria. These findings delineate a functional role for antioxidants in modification of the GI microenvironment and subsequent reversal of metabolic dysfunction.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.03.032DOI Listing
April 2021

Socket Preservation Following Extraction of Molars with Severe Periodontitis.

Int J Periodontics Restorative Dent 2021 Mar-Apr;41(2):269-275

The efficacy of the socket preservation procedure using deproteinized bovine bone mineral, bioabsorbable collagen membrane, and collagen sponge on molar extraction sites with severe periodontitis was assessed at 6 postoperative months, before implant placement. Results revealed excellent soft tissue healing without loss of keratinized tissue and no statistically significant differences in socket marginal bone changes in 20 molar extraction sockets. High levels of primary implant stability were recorded. Socket preservation using a minimally invasive surgical technique provides good soft and hard tissue healing as well as anticipated stability of implant placement at sites of extracted molars with severe periodontitis.
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http://dx.doi.org/10.11607/prd.4444DOI Listing
April 2021

Carbonyl Cyanide 3-Chlorophenylhydrazone (CCCP) Exhibits Direct Antibacterial Activity Against .

Infect Drug Resist 2021 23;14:1199-1208. Epub 2021 Mar 23.

National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People's Republic of China.

Objective: Treatment choices for () infections are very limited, and the prognosis is generally poor. Effective new antibiotics or repurposing existing antibiotics against infection are urgently needed. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a member of the lipophilic weak acid class, is known as an efflux pump inhibitor for . The aim of this study was to determine the inhibitory activity of CCCP as a potential novel antibiotic against .

Methods: A total of 47 reference strains of different mycobacterial species and 60 clinical isolates of were enrolled. In vitro inhibitory activity of CCCP was accessed using microplates alamar blue method with the reference and clinical isolates. The activity of CCCP against intracellular residing within macrophage was also evaluated by intracellular colony numerating assay.

Results: CCCP exhibited good activity against clinical isolates in vitro, the minimum inhibitory concentration (MIC) ranged from 0.47 μg/mL to 3.75 μg/mL, with a MIC of 1.875 μg/mL and MIC of 3.75 μg/mL. At concentrations safe for the cells, CCCP exhibited highly intracellular bactericidal activities against and reference strains, with inhibitory rates of 84.8%±8.8% and 72.5%±13.7%, respectively. CCCP demonstrated bactericidal activity against intracellular that was comparable to clarithromycin, and concentration-dependent antimicrobial activity against in macrophages was observed. In addition, CCCP also exhibited good activities against most reference strains of rapidly growing mycobacterial species.

Conclusion: CCCP could be a potential candidate of novel antimicrobiological agent to treat infection.
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http://dx.doi.org/10.2147/IDR.S303113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001050PMC
March 2021

Ketogenic Diets Induced Glucose Intolerance and Lipid Accumulation in Mice with Alterations in Gut Microbiota and Metabolites.

mBio 2021 03 30;12(2). Epub 2021 Mar 30.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China

The ketogenic diet (KD), which can induce changes in gut microbiota, has shown benefits for epilepsy and several neurodegenerative diseases. However, the effects of a KD on glucose and lipid metabolism remain inconclusive. Using two formulas of ketogenic diets (KDR with 89.5% fat and KDH with 91.3% fat), which are commonly used in mouse trials, we found that KDR but not KDH induced insulin resistance and damaged glucose homeostasis, while KDH induced more fat accumulation in mice. Further study showed that KD impacted glucose metabolism, which was related to the sources of fat, while both the sources and proportions of fat affected lipid metabolism. And the KD widely used in human studies still induced insulin resistance and fat accumulation in mice. Moreover, KDs changed the gut microbiota and metabolites in mice, and the sources and proportions of fat in the diets respectively changed the abundance of specific bacteria and metabolites which were correlated with parameters related to glucose intolerance and lipid accumulation. Overall, our study demonstrated that the metabolic disorders induced by KDs are closely related to the source and proportion of fat in the diet, which may be associated with the changes of the gut microbiota and metabolites. The ketogenic diet with extremely high fat and very low carbohydrate levels is very popular in society today. Although it has beneficial effects on epilepsy and neurodegenerative diseases, how ketogenic diets impact host glucose and lipid metabolism and gut microbiota still needs further investigation. Here, we surveyed the effects of two ketogenic diets which are commonly used in mouse trials on metabolic phenotypes, gut microbiota, and metabolites in mice. We found that both ketogenic diets impaired glucose and lipid metabolism in mice, and this may be due to the sources and proportions of fat in the diets. This work highlights the potential risk of glucose and lipid metabolism disorders and the importance of evaluating the sources and proportions of fat in the diets, when using ketogenic diets for weight loss and the treatment of diseases.
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http://dx.doi.org/10.1128/mBio.03601-20DOI Listing
March 2021

Author Correction: Application of Whole Genome Resequencing in Mapping of a Tomato Yellow Leaf Curl Virus Resistance Gene.

Sci Rep 2021 Mar 19;11(1):6917. Epub 2021 Mar 19.

Institute of Vegetable Crop, Jiangsu Academy of Agricultural Science, Nanjing, Jiangsu, China.

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http://dx.doi.org/10.1038/s41598-021-86636-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979778PMC
March 2021

The DNA methylation inhibitor RG108 protects against noise-induced hearing loss.

Cell Biol Toxicol 2021 Mar 15. Epub 2021 Mar 15.

ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

Background: Noise-induced hearing loss represents a commonly diagnosed type of hearing disability, severely impacting the quality of life of individuals. The current work is aimed at assessing the effects of DNA methylation on noise-induced hearing loss.

Methods: Blocking DNA methyltransferase 1 (DNMT1) activity with a selective inhibitor RG108 or silencing DNMT1 with siRNA was used in this study. Auditory brainstem responses were measured at baseline and 2 days after trauma in mice to assess auditory functions. Whole-mount immunofluorescent staining and confocal microcopy of mouse inner ear specimens were performed to analyze noise-induced damage in cochleae and the auditory nerve at 2 days after noise exposure.

Results: The results showed that noise exposure caused threshold elevation of auditory brainstem responses and cochlear hair cell loss. Whole-mount cochlea staining revealed a reduction in the density of auditory ribbon synapses between inner hair cells and spiral ganglion neurons. Inhibition of DNA methyltransferase activity via a non-nucleoside specific pharmacological inhibitor, RG108, or silencing of DNA methyltransferase-1 with siRNA significantly attenuated ABR threshold elevation, hair cell damage, and the loss of auditory synapses.

Conclusions: This study suggests that inhibition of DNMT1 ameliorates noise-induced hearing loss and indicates that DNMT1 may be a promising therapeutic target. Graphical Headlights • RG108 protected against noise-induced hearing loss • RG108 administration protected against noise-induced hair cell loss and auditory neural damage. • RG108 administration attenuated oxidative stress-induced DNA damage and subsequent apoptosis-mediated cell loss in the cochlea after noise exposure.
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http://dx.doi.org/10.1007/s10565-021-09596-yDOI Listing
March 2021

RNA m6A reader IMP2/IGF2BP2 promotes pancreatic β-cell proliferation and insulin secretion by enhancing PDX1 expression.

Mol Metab 2021 Mar 9:101209. Epub 2021 Mar 9.

Department of Molecular Biology and Diabetes Unit of the Medical Services, Massachusetts General Hospital, Boston, 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. Electronic address:

Type 2 diabetes (T2D) is a common metabolic disease. Variants in IMP2 (IGF2BP2) associated with increased risk of T2D impair insulin secretion. However, the underlying mechanism is not known. IMP2 is an RNA-binding protein that preferentially recognizes N6-methyladenosine (m6A)-modified mRNAs. Here, we report that the deletion of IMP2 in pancreatic β-cells leads to reduced compensatory β-cell proliferation and function in mice. Mechanically, IMP2 directly binds to Pdx1 mRNA and stimulates its translation in an m6A-dependent manner. Additionally, IMP2 orchestrates IGF2-AKT-GSK3-PDX1 signaling to promote insulin secretion. In human EndoC-βH1 cells, the expression of IMP2 enhances cell proliferation, PDX1 expression, IGF2 signaling, and insulin secretion. Our work therefore reveals IMP2 as a critical regulator of β-cell function and highlights the importance of post-transcriptional gene expression in T2D pathology.
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http://dx.doi.org/10.1016/j.molmet.2021.101209DOI Listing
March 2021

Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome.

Nutrients 2021 Feb 16;13(2). Epub 2021 Feb 16.

Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USA.

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly , which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.
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http://dx.doi.org/10.3390/nu13020637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920311PMC
February 2021

Smell disorders in COVID-19 patients: role of olfactory training: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(8):e24862

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine.

Background: As the coronavirus disease 2019 (COVID-19) spread around the world, a surge of evidence suggests that smell disorders are common symptoms in COVID-19 infection. This dysfunction may cause loss of appetite, malnutrition, poisoning, and depression. Obviously, the impairment has a strong impact on the quality of life. Therefore, there is an urgent need to identify effective treatments. Various therapies have been studied to treat smell disorders after infection, and olfactory training (OT) is considered a promising treatment option. Assessing the effectiveness and safety of olfactory training for COVID-19 patients with smell disorders is the main purpose of this systematic review protocol.

Methods: PubMed, EMBASE, MEDLINE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, ClinicalTrials.gov trials registry, and Chinese Clinical Trial Registry will be searched from January 2019 to January 2021. A combination of subject words and free text words will be applied in the searches. The language is limited to Chinese and English. The complete process will include study selection, data extraction, risk of bias assessment, and meta-analyses. Endnote X9.3 will be used to manage data screening. The statistical analysis will be completed by Review Manager V.5.3 (Cochrane Collaboration) or Stata V.16.0 software.

Results: This proposed study will assess the effectiveness and safety of OT for COVID-19 patients with smell disorders.

Conclusion: The conclusion of this study will provide evidence to prove the effectiveness and safety of olfactory training for COVID-19 patients with smell disorders.

Ethics And Dissemination: This protocol will not evaluate individual patient information or infringe patient rights and therefore does not require ethical approval.

Registration: PEROSPERO CRD42020218009.
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http://dx.doi.org/10.1097/MD.0000000000024862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909207PMC
February 2021

Kalman Filter for Spatial-Temporal Regularized Correlation Filters.

IEEE Trans Image Process 2021 2;30:3263-3278. Epub 2021 Mar 2.

We consider visual tracking in numerous applications of computer vision and seek to achieve optimal tracking accuracy and robustness based on various evaluation criteria for applications in intelligent monitoring during disaster recovery activities. We propose a novel framework to integrate a Kalman filter (KF) with spatial-temporal regularized correlation filters (STRCF) for visual tracking to overcome the instability problem due to large-scale application variation. To solve the problem of target loss caused by sudden acceleration and steering, we present a stride length control method to limit the maximum amplitude of the output state of the framework, which provides a reasonable constraint based on the laws of motion of objects in real-world scenarios. Moreover, we analyze the attributes influencing the performance of the proposed framework in large-scale experiments. The experimental results illustrate that the proposed framework outperforms STRCF on OTB-2013, OTB-2015 and Temple-Color datasets for some specific attributes and achieves optimal visual tracking for computer vision. Compared with STRCF, our framework achieves AUC gains of 2.8%, 2%, 1.8%, 1.3%, and 2.4% for the background clutter, illumination variation, occlusion, out-of-plane rotation, and out-of-view attributes on the OTB-2015 datasets, respectively. For sporting events, our framework presents much better performance and greater robustness than its competitors.
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http://dx.doi.org/10.1109/TIP.2021.3060164DOI Listing
March 2021

Guild-based analysis for understanding gut microbiome in human health and diseases.

Genome Med 2021 Feb 9;13(1):22. Epub 2021 Feb 9.

Center for Nutrition, Microbiome and Health, New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA.

To demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem's higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same "guild" if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of "guild" to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.
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http://dx.doi.org/10.1186/s13073-021-00840-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874449PMC
February 2021

The oral microbiome and inflammation in mild cognitive impairment.

Exp Gerontol 2021 May 5;147:111273. Epub 2021 Feb 5.

Emory University, School of Medicine, 1841 Clifton Road NE, Atlanta, GA 30329, United States of America.

Inflammation and immune mechanisms are believed to play important roles in Alzheimer's disease pathogenesis. Research supports the link between poor oral health and Alzheimer's disease. Periodontal disease and dental caries represent the two most common infections of the oral cavity. This study focused on a precursor to Alzheimer's disease, mild cognitive impairment (MCI). Using 16S rRNA sequencing, we characterized and compared the oral microbiome of 68 older adults who met the criteria for MCI or were cognitively normal, then explored relationships between the oral microbiome, diagnostic markers of MCI, and blood markers of systemic inflammation. Two taxa, Pasteurellacae and Lautropia mirabilis were identified to be differentially abundant in this cohort. Although systemic inflammatory markers did not differentiate the two groups, differences in five cerebrospinal fluid inflammatory mediators were identified and had significant associations with MCI. Because inflammatory markers may reflect CNS changes, pursuing this line of research could provide opportunities for new diagnostic tools and illuminate mechanisms for prevention and mitigation of Alzheimer's disease.
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http://dx.doi.org/10.1016/j.exger.2021.111273DOI Listing
May 2021

Tai Chi for the elderly patients with COVID-19 in recovery period: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jan;100(3):e24111

School of Acupuncture, Moxibustion and Tuina.

Background: The coronavirus disease 2019 (COVID-19) outbreak has caused a great impact in many countries. Older people are more susceptible to the virus than other people. As a good health exercise suitable for the elderly, Tai Chi has a positive impact on heart function, blood pressure, lung function, immunity, etc. It can enhance cardiopulmonary function, increase the elasticity of blood vessels, and improve the body's self-regulation function. For the elder patients with COVID-19, Tai Chi has outstanding merits.

Methods: We will search PubMed, EMBASE, MEDLINE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Database, Wanfang Database, Clinical Trials and Chinese Clinical Trial Registry. The complete process will include study selection, data extraction, risk of bias assessment and meta-analyses. Endnote X9.3 will be used to manage data screening. The statistical analysis will be completed by Stata/SE 15.1 software.

Results: This proposed study will evaluate the effectiveness and safety of Tai Chi for the improvement of psychological pressure, cardiopulmonary function, and immunity in elderly COVID-19 patients during the recovery period.

Conclusion: The conclusion of this study will provide evidence to prove the safety and effectiveness of Tai Chi on elderly COVID-19 patients during the recovery period.

Ethics And Dissemination: This protocol will not evaluate individual patient information or infringe patient rights and therefore does not require ethical approval.

Registration: PEROSPERO CRD42020220128.
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http://dx.doi.org/10.1097/MD.0000000000024111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837887PMC
January 2021

The complete chloroplast genome of linnaeus and phylogenetic analysis of brassicaceae.

Mitochondrial DNA B Resour 2021 Jan 16;6(1):178-179. Epub 2021 Jan 16.

CCCC Water Transportation Consultants Co., Ltd, Beijing, China.

The complete chloroplast genome sequence of Linnaeus was assembled and characterized in the present study. The plastome is 153,989 bp in length, which is comprised of a large single-copy (LSC) region of 83,565 bp, a small single-copy (SSC) region of 17,526 bp, and two inverted repeat (IR) regions of 26,449 bp. The overall GC content of the plastome was 36.5%. The new sequence comprised 125 genes, including 84 protein-coding genes, 8 ribosomal RNA genes, and 33 tRNA genes. Phylogenetic analysis showed that L. was close to and .
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http://dx.doi.org/10.1080/23802359.2020.1860699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832579PMC
January 2021

Active phase prebiotic feeding alters gut microbiota, induces weight-independent alleviation of hepatic steatosis and serum cholesterol in high-fat diet-fed mice.

Comput Struct Biotechnol J 2021 24;19:448-458. Epub 2020 Dec 24.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Growing evidence suggests that prebiotics may induce weight loss and alleviate non-alcoholic fatty liver disease (NAFLD) via modulation of the gut microbiota. However, key members of the gut microbiota that may mediate the beneficial effects of prebiotics remain elusive. Here, we find that restricted prebiotic feeding during active phase (HF-ARP) induced weight-independent alleviation of liver steatosis and reduced serum cholesterol in high-fat diet (HF) fed mice more significantly than unrestricted feeding (HF-UP). HF-ARP mice also showed concomitantly altered gut microbiota structure that was different from HF-UP group along with significantly increased production of total short-chain fatty-acids (SCFAs). Amplicon sequence variants (ASVs) were clustered into co-abundant groups (CAGs) as potential functional groups that may respond distinctively to prebiotic consumption and prebiotic feeding regime. Prebiotic feeding induces significant alterations in CAG abundances by day 7. Eight of 32 CAGs were promoted by prebiotics, including CAG17 with the most abundant ASV from CAG22 with and CAG32 with and . Among the prebiotic-promoted CAGs, CAG20 with ASVs from Lachnospiraceae and CAG21 with ASVs from and Lachnospiraceae were significantly enhanced in HF-ARP compared to HF-UP. Moreover, most of the prebiotic-promoted CAGs were also significantly associated with improvements in hepatic steatosis, reduction in serum cholesterol and increased cecal propionate production. Together, these results suggest that the impact of prebiotics on weight-independent alleviation of liver steatosis and cholesterol-lowering effect can be optimized by restricting prebiotic intake to active phase and is associated with a distinct change of gut microbiota with increased SCFA production.
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http://dx.doi.org/10.1016/j.csbj.2020.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806547PMC
December 2020

Insulin-Like Growth Factor-1 Enhances Motoneuron Survival and Inhibits Neuroinflammation After Spinal Cord Transection in Zebrafish.

Cell Mol Neurobiol 2021 Jan 22. Epub 2021 Jan 22.

Wuxi Medical School, Jiangnan University, Wuxi, 214122, Jiangsu, China.

Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor produced locally in the central nervous system which can promote axonal regeneration, protect motoneurons, and inhibit neuroinflammation. In this study, we used the zebrafish spinal transection model to investigate whether IGF-1 plays an important role in the recovery of motor function. Unlike mammals, zebrafish can regenerate axons and restore mobility in remarkably short period after spinal cord transection. Quantitative real-time PCR and immunofluorescence showed decreased IGF-1 expression in the lesion site. Double immunostaining for IGF-1 and Islet-1 (motoneuron marker)/GFAP (astrocyte marker)/Iba-1 (microglia marker) showed that IGF-1 was mainly expressed in motoneurons and was surrounded by astrocyte and microglia. Following administration of IGF-1 morpholino at the lesion site of spinal-transected zebrafish, swimming test showed retarded recovery of mobility, the number of motoneurons was reduced, and increased immunofluorescence density of microglia was caused. Our data suggested that IGF-1 enhances motoneuron survival and inhibits neuroinflammation after spinal cord transection in zebrafish, which suggested that IGF-1 might be involved in the motor recovery.
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http://dx.doi.org/10.1007/s10571-020-01022-xDOI Listing
January 2021

The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome.

Proc Natl Acad Sci U S A 2021 02;118(6)

Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada;

The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19-induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome's influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.
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http://dx.doi.org/10.1073/pnas.2010217118DOI Listing
February 2021

Serum-Derived Exosomal Proteins as Potential Candidate Biomarkers for Hepatocellular Carcinoma.

ACS Omega 2021 Jan 4;6(1):827-835. Epub 2021 Jan 4.

Medical School of Guizhou University, Jiaxiu South Road, Huaxi District, Guiyang 550025, China.

Hepatocellular carcinoma (HCC) is the most common form of hepatic malignancies. The diagnosis of HCC remains challenging due to the low sensitivity and specificity of the diagnostic method. Exosomes, which are abundant in various proteins from parent cells, play pivotal roles in intercellular communication and have been confirmed as promising sources of disease biomarkers. Herein, we performed a simple but robust proteomic profiling on exosomes derived from 1 μL of serum using a data-independent acquisition (DIA) method for the first time, to screen potential biomarkers for the diagnosis of HCC. Ten pivotal differentially expressed proteins (DEPs) (von Willebrand factor (VWF), LGALS3BP, TGFB1, SERPINC1, HPX, HP, HBA1, FGA, FGG, and FGB) were screened as a potential candidate biomarker panel, which could completely discriminate patients with HCC from normal control (NC). Interestingly, Gene Expression Profiling Interactive Analysis (GEPIA) revealed that the expression levels of four genes increased and those of six genes decreased in HCC tissues compared with normal tissues, which were in concordance with protein expression levels. In conclusion, we screened 10 exosomal proteins holding promise for acting as a potential candidate biomarker panel for detection of HCC through a simple but robust proteomic profiling.
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http://dx.doi.org/10.1021/acsomega.0c05408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808137PMC
January 2021

Evaluation of Middle Ear Function by Tympanometry and the Influence of Lower Barometric Pressure at High Altitude.

High Alt Med Biol 2021 Mar 31;22(1):70-76. Epub 2020 Dec 31.

ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, P.R. China.

Jiang, Tao, Liping Zhao, Yanbo Yin, Huiqian Yu, and Qingzhong Li. Evaluation of middle ear function by tympanometry and the influence of lower barometric pressure at high altitude. . 22:70-76, 2021. To evaluate middle ear function in residents of high-altitude areas in comparison to sea-level participants. Prospective observational study. All experiments were performed by experienced audiologists with a calibrated tympanometry machine. Young adults between the age of 17 and 23 were recruited. Seventy-five participants from Shanghai (altitude 4 m) and 133 participants from the Shigatse area (altitude 4,040 m) were recruited. Any participant with any otological disorder was excluded. Four indexes of the tympanogram were evaluated in the two groups from different altitudes. Our results showed that the peak of static compliance for the participants in Shigatse was smaller, but the absolute compliance of tympanic membrane remained the same. Similarly, the ear canal volume (ECV) from tympanometry was also affected by the elevated altitude in Tibet. In addition, the tympanometric peak pressure was decreased in high-altitude residents, which suggests a slightly declined function of the Eustachian tube at lower barometric pressure. However, no difference was found in the tympanometric width (TW). Our results indicate that tympanograms were affected by decreased atmospheric pressure at high altitude. Therefore, other than pressure-related indexes, TW is better for evaluating the function of the middle ear in high-altitude regions.
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http://dx.doi.org/10.1089/ham.2020.0042DOI Listing
March 2021

Phosphorus-doping-induced kinetics modulation for nitrogen-doped carbon mesoporous nanotubes as superior alkali metal anode beyond lithium for high-energy potassium-ion hybrid capacitors.

Nanoscale 2021 Jan 23;13(2):692-699. Epub 2020 Dec 23.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Materials for Energy Conversion, Department of Materials Science and Engineering, University of Science and Technology of China, Hefei 230026, China.

Alkali metal ion beyond lithium based energy storage systems have recently attracted increasing attention due to their unique advantages of high natural abundance and low cost. Herein, we report the fabrication of P,N-codoped carbon mesoporous nanotubes (denoted as PNC-MeNTs) through a facile two-step strategy with MnO nanowires as a dual-function sacrificing template, where the in situ oxidative polymerization formation of pyrrole-aniline-phytic acid composite nanotubes and a subsequent carbonization treatment are involved. The PNC-MeNTs exhibit outstanding electrochemical performance for both Na and K storage, respectively, where high specific capacities of 287.2 mA h g and 219.6 mA h g at 0.1 A g and remarkable cycling stability over 10 000 cycles at 10 A g and 3000 cycles at 1 A g can be achieved. More importantly, potassium-ion hybrid capacitors with a PNC-MeNT anode and an activated carbon cathode can deliver remarkable energy/power density of 175.1 W h kg/160.6 W kg, as well as a long cycling life. The possible origins and storage mechanisms are investigated with combined characterization methods including in situ Raman spectroscopy and a galvanostatic intermittent titration technique. This study may introduce a new avenue for designing carbonaceous electrode candidates for future high-performance energy storage devices.
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http://dx.doi.org/10.1039/d0nr06888hDOI Listing
January 2021

Demonstration of causality: back to cultures.

Nat Rev Gastroenterol Hepatol 2021 02;18(2):97-98

Center for Nutrition, Microbiome and Health, New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA.

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http://dx.doi.org/10.1038/s41575-020-00400-6DOI Listing
February 2021

Liproxstatin-1 Protects Hair Cell-Like HEI-OC1 Cells and Cochlear Hair Cells against Neomycin Ototoxicity.

Oxid Med Cell Longev 2020 1;2020:1782659. Epub 2020 Dec 1.

ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.

Ferroptosis is a recently discovered iron-dependent form of oxidative programmed cell death distinct from caspase-dependent apoptosis. In this study, we investigated the effect of ferroptosis in neomycin-induced hair cell loss by using selective ferroptosis inhibitor liproxstatin-1 (Lip-1). Cell viability was identified by CCK8 assay. The levels of reactive oxygen species (ROS) were determined by DCFH-DA and cellROX green staining. The mitochondrial membrane potential (ΔΨ) was evaluated by TMRM staining. Intracellular iron and lipid peroxides were detected with Mito-FerroGreen and Liperfluo probes. We found that ferroptosis can be induced in both HEI-OC1 cells and neonatal mouse cochlear explants, as evidenced by Mito-FerroGreen and Liperfluo staining. Further experiments showed that pretreatment with Lip-1 significantly alleviated neomycin-induced increased ROS generation and disruption in ΔΨ in the HEI-OC1 cells. In parallel, Lip-1 significantly attenuated neomycin-induced hair cell damage in neonatal mouse cochlear explants. Collectively, these results suggest a novel mechanism for neomycin-induced ototoxicity and suggest that ferroptosis inhibition may be a new clinical intervention to prevent hearing loss.
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http://dx.doi.org/10.1155/2020/1782659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725559PMC
December 2020

Anxiety Status and Influencing Factors of Rural Residents in Hunan During the Coronavirus Disease 2019 Epidemic: A Web-Based Cross-Sectional Survey.

Front Psychiatry 2020 24;11:564745. Epub 2020 Nov 24.

The Second Xiangya Hospital, Central South University, Changsha, China.

To explore the status quo of anxiety and its influencing factors among rural residents in Hunan Province during the coronavirus disease 2019 epidemic, and to provide an effective basis for prevention of and intervention for anxiety symptoms among rural residents. Convenience sampling was used. An online questionnaire was distributed to Hunan rural residents through the questionnaire star platform from February 26-29, 2020. The general data and anxiety of Hunan rural residents were investigated, and the data were analyzed using SPSS 18.0. The mean Self-Rating Anxiety Scale score of 179 rural residents in Hunan was 40.93 ± 9.36. Based on the cutoff criteria, 32 residents had anxiety, including 26 with mild anxiety, five with moderate anxiety, and one with severe anxiety. The detection rate of anxiety was 17.88%. Self-rated health status, level of concern about the epidemic, and self-rated impact of the epidemic on one's life were the factors influencing the anxiety score of rural residents in Hunan ( < 0.05). During the coronavirus disease 2019 epidemic, the detection rate of anxiety in rural residents in Hunan was higher than that of the general population in China. The relevant departments should pay attention to the mental health of rural residents and implement targeted mental health prevention and intervention measures during the epidemic situation.
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http://dx.doi.org/10.3389/fpsyt.2020.564745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732504PMC
November 2020

Selection and characterization of an ssDNA aptamer against thyroglobulin.

Talanta 2021 Feb 28;223(Pt 1):121690. Epub 2020 Sep 28.

Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, China. Electronic address:

Thyroglobulin (Tg) is a significant biomarker for the diagnose and postoperative monitoring of differentiated thyroid cancer, and its recognition is urgent due to the rising prevalence. In this study, an ssDNA aptamer against Tg was obtained by capillary electrophoresis-systematic evolution of ligands via exponential enrichment (CE-SELEX). Under the optimized conditions, the sub-library was enriched well through two selection rounds. After high-throughput sequencing, eight candidate sequences were picked out and their affinities towards Tg were observed not in accordance with the order of their frequencies, whereas sequence homology played a significant role in binding affinity. The high-affinity sequence Seq.T-2 with a dissociation constant (K) of 3.18 μM was finally selected as the aptamer, and its affinity was confirmed qualitatively by gold nanoparticles colorimetric and quantitatively by thin film interferometry (K, 4.51 nM). Besides, molecular docking and dynamics simulation were performed for their binding sites prediction and affinity confirmation. Furthermore, the aptamer was applied for Tg detection, which delivered a detection limit of 5.0 nM as well as with good selectivity, and showed a good linear relationship within a wide range of 10 nM-6.4 μM of Tg spiked into the serum matrix. This study first reported Tg's aptamer which also exhibited the potential in real applications.
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http://dx.doi.org/10.1016/j.talanta.2020.121690DOI Listing
February 2021

Gut Bacteria Shared by Children and Their Mothers Associate with Developmental Level and Social Deficits in Autism Spectrum Disorder.

mSphere 2020 12 2;5(6). Epub 2020 Dec 2.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China

The gut microbiota of autism spectrum disorder (ASD) children differs from that of children without ASD. The maternal gut microbiota impacts offspring gut microbiota. However, the relationship between the development of ASD and gut bacteria shared between children and their mothers remains elusive. Our study recruited 76 children with ASD and 47 age- and gender-matched children with typical development (TD), as well as the mothers of both groups, and investigated their gut microbiota using amplicon sequence variants (ASVs). The gut microbiota of ASD children was altered compared with that of children with TD, while no significant alterations were found in their mothers. We established 30 gut bacterial coabundance groups (CAGs) and found the relative abundances of CAG15 and CAG16 significantly decreased in ASD children. CAG15 showed a positive correlation with developmental level. The proportion of ASD children who shared either one of the two ASVs from CAG15 with their mothers was significantly lower than that of children with TD. Moreover, we found that CAG12, CAG13, and CAG18 negatively correlated with the severity of social deficits in ASD children. ASD children who shared any one of the four (two , one , and one ) ASVs in CAG13 and CAG18 with their mothers showed a lower level of social deficits than ASD children that did not share those with their mothers. These data demonstrate that these shared gut bacteria in ASD children are associated with their developmental level and social deficits. This work provides a new direction toward understanding the role of the gut microbiota in the pathogenesis and development of ASD. (This study has been registered in the Chinese Clinical Trial Registry under number ChiCTR-RPC-16008139.) Gut microbiota may contribute to the pathogenesis and development of autism spectrum disorder. The maternal gut microbiota influences offspring gut microbial structure and composition. However, the relationship between the clinical symptoms of autism spectrum disorder and the gut bacteria shared between children and their mothers is not yet known. In our study, the gut microbiota of children with autism spectrum disorder differed from that of children with typical development, but there were no differences in the gut microbiota of their mothers. More importantly, gut bacteria shared between children with autism spectrum disorder and their mothers were related to developmental disabilities and social deficits. Thus, our study suggests that these shared gut bacteria may play an important role in the development of autism spectrum disorder. This provides a new direction for future studies aiming to explore the role of the gut microbiota in autism spectrum disorder.
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http://dx.doi.org/10.1128/mSphere.01044-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716279PMC
December 2020

Aptamer-functionalized magnetic nanoparticles conjugated organic framework for immobilization of acetylcholinesterase and its application in inhibitors screening.

Anal Chim Acta 2020 Dec 16;1140:228-235. Epub 2020 Oct 16.

Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Beijing, 100081, China. Electronic address:

Construction of new enzyme reactor based on aptamer functionalized magnetic nanoparticles conjugated organic framework (COF) for acetylcholinesterase immobilization has been an enabling endeavor in this work. The aptamer against acetylcholinesterase was selected through a method based on capillary electrophoresis in one round. A new magnetic COF material rich of carboxyl groups was firstly synthesized, and its surface was then modified with the selected aptamer through covalently linking. Acetylcholinesterase was immobilized to fabricate the enzyme reactor FeO@COF-Apt-AChE through the high affinity and specificity with its binding aptamer. The as constructed enzyme reactor was comprehensively characterized and the key factors that affected its catalysis efficiency were investigated in detail. Owing to the surface modification of the magnetic COF materials by aptamer for acetylcholinesterase immobilization, the immobilized enzyme exhibited improved substrates affinity. What's more, good reusability (more than 8 times) and prolonged stability (enzyme activity still kept at 90% after 42 days) were also achieved. Finally, the enzyme reactor could be applied in AChE inhibitors screening, which expanded its application capability. The proposed protocol not only paves a new way for fabrication of novel aptamer functionalized magnetic COF materials as enzyme reactors, but also indicates a broadened application of the integration of aptamer and its enzyme.
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http://dx.doi.org/10.1016/j.aca.2020.10.024DOI Listing
December 2020

Combination of lysine-specific demethylase 6A (KDM6A) and mismatch repair (MMR) status is a potential prognostic factor in colorectal cancer.

Cancer Med 2021 Jan 11;10(1):317-324. Epub 2020 Nov 11.

College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.

Purpose: To evaluate the relationship between the DNA mismatch repair (MMR) status and histone lysine-specific demethylase 6A (KDM6A) on the prognosis of colorectal cancer (CRC).

Methods: About 594 patients with CRC from The Cancer Genome Atlas (TCGA) were enrolled in this retrospective study. Subsequently, a series of different classification tests for MMR status, cancer types, and target gene expression was conducted.

Results: After filtering out the KDMs group of genes, we selected KDM6A as the target gene. A significant difference in the performance of KDM6A in tumor and normal tissues were confirmed. Our results showed a lower KDM6A expression, lower KDM6A exon expression, and higher KDM6A DNA methylation than their corresponding normal tissues in colon adenocarcinoma (COAD). Notably, the main MMR genes were highly expressed in tumor tissues than normal tissues both in COAD and rectum adenocarcinoma (READ). Moreover, proficient DNA mismatch repair (pMMR) was found to be an important poor prognostic factor in COAD (p = 0.0064) and the low KDM6A expression was an important factor for poor prognosis in READ (p = 0.0217). Based on these results, we consequently relate MMR status with KDM6A expression in predicting the prognosis of patients with CRC. Moreover, patients with pMMR exhibited a low KDM6A expression in COAD (p = 0.0250). Samples were divided into two groups based on the KDM6A expression. Interestingly, the group with low KDM6A expression showed no difference between pMMR and deficient DNA mismatch repair (dMMR) in prognosis, whereas the group with high KDM6A expression was closely related to MMR status in OS (p = 0.0082). Besides, COAD patients with high KDM6A expression and pMMR status had poor OS (p = 0.0082).

Conclusions: The KDM6A/MMR classification-based subtypes of low KDM6A expression/READ, high KDM6A expression/pMMR, and COAD/pMMR were associated with poor prognosis. This classification can be a novel prognostic approach in CRC.
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http://dx.doi.org/10.1002/cam4.3602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826484PMC
January 2021

[Exosomal proteomics study in the tumorigenesis, development and treatment of hepatocellular carcinoma].

Sheng Wu Gong Cheng Xue Bao 2020 Oct;36(10):1992-2000

School of Medicine, Guizhou University, Guiyang 550025, Guizhou, China.

Hepatocellular carcinoma (HCC) is one of the five most common malignant tumors. According to the latest statistics of the World Health Organization (WHO), the incident and mortality rates of HCC ranks the eighth and third in the world, respectively, which severely affect people's health. Exosomes are extracellular vesicles with a bilayer of phospholipids, which carry active substances such as proteins and nucleic acids derived from their mother cells. These exosomes greatly facilitate the exchange of substances and information between cells, and coordinate physiological and pathological processes in the body. In recent years, a large number of studies have shown that exosomal proteins play important roles in the tumorigenesis, development, diagnosis and treatment of HCC. Here we review the composition and functions of exosomes and the role of exosomal proteins in HCC.
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http://dx.doi.org/10.13345/j.cjb.200061DOI Listing
October 2020

From Best Evidence to Best Practice: Enteral Nutrition from Continuous Nasal Feeding in Stroke Patients.

Int J Gen Med 2020 22;13:927-936. Epub 2020 Oct 22.

Department of Nursing, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China.

Background: Best evidence regarding enteral nutrition from continuous nasal feeding in stroke patients is limited. The aim of this study was to explore the best evidence of continuous nasal feeding in stroke patients and translate the evidence into clinical practice.

Methods: This study utilized the standard procedures of the Joanna Briggs Institute (JBI) evidence-based nursing centers' clinical evidence-practice application system. The baseline assessment of stroke patients in the neurology ward was conducted. A pre- and post-implementation audit approach was used in this study and adopted the Getting Research into Practice program. We analyzed the compliance of nurses with best practice and its impact on patients' gastrointestinal function and complications, aspiration, aspiration pneumonia, nurses' daily workload of nasal feeding, and the length of hospitalization before and after implementing the evidence-based strategies.

Results: After application of the evidence-based strategies, nurses' compliance with best practice was improved. The incidence of patients' gastrointestinal complications including vomit ( 5.195, P=0.023), palirrhea ( 4.216, P=0.039), diarrhea ( 4.514, P=0.042), constipation ( 5.535, P=0.035) and gastric retention ( 4.541, P=0.042) decreased significantly after the application of the best evidence. The working time of nurses undergoing nasal feeding decreased from 23.71 ±3.22 min to 7.73 ±1.14 min (P =0.000) and the length of patient's hospitalization decreased from 35.63 ±4.45 days to 35.00 ±3.70 days (P=0.534). The rate of aspiration, aspiration pneumonia did not show a significant difference after implementation of the evidence-based strategies.

Conclusion: The results revealed that the evidence-based practice of continuous nasal feeding in stroke patients is an effective method to improve nursing quality and reduce gastrointestinal complications, which was worthy of clinical application.
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http://dx.doi.org/10.2147/IJGM.S269393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592149PMC
October 2020

Direct Functional Protein Delivery with a Peptide into Neonatal and Adult Mammalian Inner Ear .

Mol Ther Methods Clin Dev 2020 Sep 30;18:511-519. Epub 2020 Jun 30.

ENT Institute and Otorhinolaryngology Department, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, China.

The aim of this study was to study an antimicrobial peptide (AMP), aurein 1.2, which substantially increased protein delivery directly into multiple mammalian inner-ear cell types . Different concentrations of aurein 1.2 with superpositively charged GFP (+36 GFP) protein fused with Cre recombinase were delivered to postnatal day 1-2 (P1-2) and adult cochleae of Cre reporter transgenic mice with various delivery methods. By cochleostomy at different concentrations of aurein 1.2-+36 GFP (1 μM, 5 μM, 22.5 μM, and 50 μM, respectively), the tdTomato (tdT) expression was observed in outer hair cells (OHCs; 20.77%, 23.02%, 76.36%, and 92.47%, respectively) and inner hair cells (IHCs; 14.90%, 44.50%, 89.59%, and 96.13%, respectively) in the cochlea. The optimal concentration was 22.5 μM with the highest transfection efficiency and the lowest cytotoxicity. Wide-spread tdT signals were detected in the cochlear-supporting cells, utricular-supporting cells, auditory nerve, and spiral ligament in neonatal and adult mice. Compared to cochleostomy, injection through the round window membrane (RWM) also produced highly efficient tdT+ labeled cells with less cell loss. In summary, the peptide aurein 1.2 fused with +36 GFP dramatically expanded the target cells with increased efficiency in direct protein delivery in the inner ear. Aurein 1.2-+36 GFP has the potential to be developed as protein-based therapy in regeneration and genome editing in the mammalian inner ear.
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http://dx.doi.org/10.1016/j.omtm.2020.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477795PMC
September 2020