Publications by authors named "Xuezhong Liu"

108 Publications

Quercetin and Allicin Can Alleviate the Hepatotoxicity of Lead (Pb) through the PI3K Signaling Pathway.

J Agric Food Chem 2021 Aug 9;69(32):9451-9460. Epub 2021 Aug 9.

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China.

Lead (Pb) is a common toxic heavy metal pollutant in the environment that seriously endangers the health of animals. The liver is a key target organ affected by Pb toxicity. Plant extracts allicin and quercetin have a strong antioxidant capacity that can promote the excretion of heavy metals by improving the body's antioxidant defense and chelating heavy metal ions. To explore the preventive and therapeutic effects of allicin and quercetin on Pb poisoning in chickens, 96 chickens were randomly divided into eight groups: control, Pb, allicin, quercetin, allicin + quercetin, Pb + allicin, Pb + quercetin, and Pb + allicin + quercetin groups. The chickens were given feed containing the above treatments for 90 days. The results indicated that Pb can affect the growth and development of the liver, damage the circulatory system, destroy the structure of mitochondria and nuclei in liver cells, cause an imbalance in the oxidation system, inhibit PI3K protein, and activate the mitochondrial apoptotic pathway. Allicin and quercetin, alone or in combination, can improve the antioxidant capacity of the liver and alleviate liver tissue damage caused by Pb. In summary, allicin and quercetin could alleviate oxidative damage and apoptosis in the Pb-poisoned chicken liver through the PI3K signaling pathway, with stronger effects achieved by their combination.
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http://dx.doi.org/10.1021/acs.jafc.1c03794DOI Listing
August 2021

Ca transfer via the ER-mitochondria tethering complex in neuronal cells contribute to cadmium-induced autophagy.

Cell Biol Toxicol 2021 Jul 26. Epub 2021 Jul 26.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, People's Republic of China.

Mitochondrial-associated endoplasmic reticulum (ER) membranes (MAMs) play a key role in several physiological functions, including calcium ion (Ca) transfer and autophagy; however, the molecular mechanism controlling this interaction in cadmium (Cd)-induced neurotoxicity is unknown. This study shows that Cd induces alterations in MAMs and mitochondrial Ca levels in PC12 cells and primary neurons. Ablation or silencing of mitofusin 2 (Mfn2) in PC12 cells or primary neurons blocks the colocalization of ER and mitochondria while reducing the efficiency of mitochondrial Ca uptake. Moreover, Mfn2 defects reduce interactions or colocalization between GRP75 and VDAC1. Interestingly, the enhancement of autophagic protein levels, colocalization of LC3 and Lamp2, and GFP-LC3 puncta induced by Cd decreased in Mfn2 or Grp75 PC12 cells and Mfn2- or Grp75-silenced primary neurons. Notably, the specific Ca uniporter inhibitor RuR blocked both mitochondrial Ca uptake and autophagy induced by Cd. Finally, this study proves that the mechanism by which IP3R-Grp75-VDAC1 tethers in MAMs is associated with the regulation of autophagy by Mfn2 and involves their role in mediating mitochondrial Ca uptake from ER stores. These results give new evidence into the organelle metabolic process by demonstrating that Ca transport between ER-mitochondria is important in autophagosome formation in Cd-induced neurodegeneration.
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http://dx.doi.org/10.1007/s10565-021-09623-yDOI Listing
July 2021

Protective Effects of α-Lipoic Acid and Chlorogenic Acid on Cadmium-Induced Liver Injury in Three-Yellow Chickens.

Animals (Basel) 2021 May 29;11(6). Epub 2021 May 29.

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

Cadmium (Cd) is a type of noxious heavy metal that is distributed widely. It can severely injure the hepatocytes and cause liver dysfunction by inducing oxidative stress and mitochondrial damage. We evaluated the protective effects of α-lipoic acid (α-LA) or chlorogenic acid (CGA) and their combination on counteracting cadmium toxicity in vivo in three-yellow chickens. For three months, CdCl (50 mg/L) was administrated through their drinking water, α-LA (400 mg/kg) was added to feed and CGA (45 mg/kg) was employed by gavage. The administration of Cd led to variations in growth performance, biochemical markers (of the liver, kidney and heart), hematological parameters, liver histopathology (which suggested hepatic injury) and ultrastructure of hepatocytes. Some antioxidant enzymes and oxidative stress parameters showed significant differences in the Cd-exposure group when compared with the control group. The groups treated with Cd and administrated α-LA or CGA showed significant amelioration with inhibited mitochondrial pathway-induced apoptosis. Combining both drugs was the most effective in reducing Cd toxicity in the liver. In summary, the results demonstrated that α-LA and CGA may be beneficial in alleviating oxidative stress induced by oxygen free radicals and tissue injury resulting from Cd-triggered hepatotoxicity.
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http://dx.doi.org/10.3390/ani11061606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228482PMC
May 2021

Generation and Genetic Correction of USH2A c.2299delG Mutation in Patient-Derived Induced Pluripotent Stem Cells.

Genes (Basel) 2021 05 25;12(6). Epub 2021 May 25.

Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA.

Usher syndrome (USH) is the leading cause of inherited combined hearing and vision loss. As an autosomal recessive trait, it affects 15,000 people in the United States alone and is responsible for ~21% of inherited blindness and 3 to 6% of early childhood deafness. Approximately 2/3 of the patients with Usher syndrome suffer from USH2, of whom 85% have mutations in the USH2A gene. Patients affected by USH2 suffer from congenital bilateral progressive sensorineural hearing loss and retinitis pigmentosa which leads to progressive loss of vision. To study the molecular mechanisms of this disease and develop a gene therapy strategy, we generated human induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMCs) obtained from a patient carrying compound heterozygous variants of USH2A c.2299delG and c.1256G>T and the patient's healthy sibling. The pluripotency and stability were confirmed by pluripotency cell specific marker expression and molecular karyotyping. Subsequent CRISPR/Cas9 genome editing using a homology repair template was used to successfully correct the USH2A c.2299delG mutation back to normal c.2299G in the generated patient iPSCs to create an isogenic pair of lines. Importantly, this manuscript describes the first use of the recombinant Cas9 and synthetic gRNA ribonucleoprotein complex approach to correct the USH2A c.2299delG without additional genetic effects in patient-derived iPSCs, an approach that is amenable for therapeutic genome editing. This work lays a solid foundation for future ex vivo and in vivo gene therapy investigations and these patient's iPSCs also provide an unlimited resource for disease modeling and mechanistic studies.
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http://dx.doi.org/10.3390/genes12060805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227183PMC
May 2021

Activated AMPK promoted the decrease of lactate production in rat Sertoli cells exposed to Zearalenone.

Ecotoxicol Environ Saf 2021 Sep 27;220:112367. Epub 2021 May 27.

College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, Jiangsu, China. Electronic address:

Zearalenone, which is ubiquitous in grains and animal feed, is a mycotoxin that can cause serious damage to animals and humans. Sertoli cells (SCs) can be used to study ZEA male reproductive toxicity in vitro. SCs provide energy for germ cells, where AMPK regulates intracellular energy. In order to explore the regulatory effect of AMPK on ZEA-induced lactate decline, we activated AMPK by AICAR and then inhibited AMPK by Compound C with ZEA-treated SCs for 24 h to detect intracellular lactate production-related indicators. Cell viability in the presence of 20 μmol/L ZEA and either 50 μmol/L AICAR or 5 μmol/L Compound C, respectively, did not damage SCs, and could effectively either activate or inhibit AMPK. Inhibition of AMPK promoted the production of pyruvate and lactate via increased expression of the glycolysis-related genes Pgam1 and the lactate production-related proteins GLUT1, LDHA, and MCT4. Activating AMPK inhibited the production of lactate and pyruvate by suppressing the expression of glycolysis-related genes HK1, Pgam1, and Gpi1 and that of lactate production-related proteins LDHA and MCT4. Zearalenone destroys the energy balance in SCs, activates P-AMPK, which inhibit the production of lactate and pyruvate in SCs. This also leads to the decrease of energy supply of SCs to spermatogenic cells, damages to reproductive system.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112367DOI Listing
September 2021

A nonsense variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder.

Proc Natl Acad Sci U S A 2021 Jun;118(22)

Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, , mainly expressed in GLSs. We identify p.(Arg372Ter) of by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.
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http://dx.doi.org/10.1073/pnas.2019681118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179140PMC
June 2021

Review of Genotype-Phenotype Correlations in Usher Syndrome.

Ear Hear 2021 May 25. Epub 2021 May 25.

Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA; ENT Institute and Otorhinolaryngology Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China; Department of Otolaryngology-Head and Neck Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Unit Progressive Sensory Disorders, Institut Pasteur, Institut de l'Audition, INSERM-UMRS1120, Sorbonne Université, Paris, France; Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA; and Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida, USA; These authors contributed equally to this work.

Usher syndrome (USH) encompasses a group of clinically and genetically heterogenous disorders defined by the triad of sensorineural hearing loss (SNHL), vestibular dysfunction, and vision loss. USH is the most common cause of deaf blindness. USH is divided clinically into three subtypes-USH1, USH2, and USH3-based on symptom severity, progression, and age of onset. The underlying genetics of these USH forms are, however, significantly more complex, with over a dozen genes linked to the three primary clinical subtypes and other atypical USH phenotypes. Several of these genes are associated with other deaf-blindness syndromes that share significant clinical overlap with USH, pointing to the limits of a clinically based classification system. The genotype-phenotype relationships among USH forms also may vary significantly based on the location and type of mutation in the gene of interest. Understanding these genotype-phenotype relationships and associated natural disease histories is necessary for the successful development and application of gene-based therapies and precision medicine approaches to USH. Currently, the state of knowledge varies widely depending on the gene of interest. Recent studies utilizing next-generation sequencing technology have expanded the list of known pathogenic mutations in USH genes, identified new genes associated with USH-like phenotypes, and proposed algorithms to predict the phenotypic effects of specific categories of allelic variants. Further work is required to validate USH gene causality, and better define USH genotype-phenotype relationships and disease natural histories-particularly for rare mutations-to lay the groundwork for the future of USH treatment.
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http://dx.doi.org/10.1097/AUD.0000000000001066DOI Listing
May 2021

Usher Syndrome in the Inner Ear: Etiologies and Advances in Gene Therapy.

Int J Mol Sci 2021 Apr 10;22(8). Epub 2021 Apr 10.

Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Hearing loss is the most common sensory disorder with ~466 million people worldwide affected, representing about 5% of the population. A substantial portion of hearing loss is genetic. Hearing loss can either be non-syndromic, if hearing loss is the only clinical manifestation, or syndromic, if the hearing loss is accompanied by a collage of other clinical manifestations. Usher syndrome is a syndromic form of genetic hearing loss that is accompanied by impaired vision associated with retinitis pigmentosa and, in many cases, vestibular dysfunction. It is the most common cause of deaf-blindness. Currently cochlear implantation or hearing aids are the only treatments for Usher-related hearing loss. However, gene therapy has shown promise in treating Usher-related retinitis pigmentosa. Here we review how the etiologies of Usher-related hearing loss make it a good candidate for gene therapy and discuss how various forms of gene therapy could be applied to Usher-related hearing loss.
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http://dx.doi.org/10.3390/ijms22083910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068832PMC
April 2021

Transcription co-factor LBH is necessary for the survival of cochlear hair cells.

J Cell Sci 2021 04 13;134(7). Epub 2021 Apr 13.

Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.

Hearing loss affects ∼10% of adults worldwide. Most sensorineural hearing loss is caused by the progressive loss of mechanosensitive hair cells (HCs) in the cochlea. The molecular mechanisms underlying HC maintenance and loss remain poorly understood. LBH, a transcription co-factor implicated in development, is abundantly expressed in outer hair cells (OHCs). We used Lbh-null mice to identify its role in HCs. Surprisingly, Lbh deletion did not affect differentiation and the early development of HCs, as nascent HCs in Lbh knockout mice had normal looking stereocilia. The stereocilia bundle was mechanosensitive and OHCs exhibited the characteristic electromotility. However, Lbh-null mice displayed progressive hearing loss, with stereocilia bundle degeneration and OHC loss as early as postnatal day 12. RNA-seq analysis showed significant gene enrichment of biological processes related to transcriptional regulation, cell cycle, DNA damage/repair and autophagy in Lbh-null OHCs. In addition, Wnt and Notch pathway-related genes were found to be dysregulated in Lbh-deficient OHCs. Our study implicates, for the first time, loss of LBH function in progressive hearing loss, and demonstrates a critical requirement of LBH in promoting HC survival in adult mice.
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http://dx.doi.org/10.1242/jcs.254458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077238PMC
April 2021

Cadmium Toxicity on Chondrocytes and the Palliative Effects of 1α, 25-Dihydroxy Vitamin D in White Leghorns Chicken's Embryo.

Front Vet Sci 2021 10;8:637369. Epub 2021 Feb 10.

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

Cadmium (Cd) can causes osteoporosis and joint swelling. However, the mechanism of Cd toxicity in chondrocytes and how to alleviate Cd poisoning to chondrocytes are still unclear. Herein, we evaluated the toxicity of Cd to chicken chondrocytes, and whether vitamin D can relieve the toxicity of Cd to chondrocytes. Primary chondrocytes were collected from knee-joint cartilage of 15-day-old chicken embryos. They were treated with (0, 1, 2, and 4) μM Cd alone, 10 M 1α,25-(OH)D alone, or 2 μM Cd combined with 10 M 1α,25-(OH)D. We found that Cd significantly inhibited and mRNA expression, which are markers for chondrocyte differentiation, downregulated the mitochondrial membrane potential, upregulated the Bax/B-cell lymphoma 2 ratio. Furthermore, Cd significantly promoted matrix metalloproteinase (MMP)-9 expression, thus accelerating the degradation of extracellular matrix. And Cd also inhibited the expression of main macromolecular protein of extracellular matrix, Collagen type IIα1 (COL2A1) and acid mucopolysaccharide. However, 1α,25-(OH)D pretreatment significantly alleviated the toxicity effects of Cd on the differentiation, apoptosis and extracellular matrix gene expression in primary chondrocytes. Conclusively, Cd exposure could inhibited chicken embryo chondrocytes differentiation, extracellular matrix gene expression, and induced chondrocyte apoptosis. However, these toxic effects of Cd are alleviated by the pretreatment of chondrocytes with 1α,25-(OH)D.
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http://dx.doi.org/10.3389/fvets.2021.637369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902530PMC
February 2021

Genetics and the Individualized Therapy of Vestibular Disorders.

Front Neurol 2021 5;12:633207. Epub 2021 Feb 5.

Department of Otolaryngology, University of Miami, Coral Gables, FL, United States.

Vestibular disorders (VDs) are a clinically divergent group of conditions that stem from pathology at the level of the inner ear, vestibulocochlear nerve, or central vestibular pathway. No etiology can be identified in the majority of patients with VDs. Relatively few families have been reported with VD, and so far, no causative genes have been identified despite the fact that more than 100 genes have been identified for inherited hearing loss. Inherited VDs, similar to deafness, are genetically heterogeneous and follow Mendelian inheritance patterns with all modes of transmission, as well as multifactorial inheritance. With advances in genetic sequencing, evidence of familial clustering in VD has begun to highlight the genetic causes of these disorders, potentially opening up new avenues of treatment, particularly in Meniere's disease and disorders with comorbid hearing loss, such as Usher syndrome. In this review, we aim to present recent findings on the genetics of VDs, review the role of genetic sequencing tools, and explore the potential for individualized medicine in the treatment of these disorders. A search of the PubMed database was performed for English language studies relevant to the genetic basis of and therapies for vestibular disorders, using search terms including but not limited to: "genetics," "genomics," "vestibular disorders," "hearing loss with vestibular dysfunction," "individualized medicine," "genome-wide association studies," "precision medicine," and "Meniere's syndrome." Increasing numbers of studies on vestibular disorder genetics have been published in recent years. Next-generation sequencing and new genetic tools are being utilized to unearth the significance of the genomic findings in terms of understanding disease etiology and clinical utility, with growing research interest being shown for individualized gene therapy for some disorders. The genetic knowledge base for vestibular disorders is still in its infancy. Identifying the genetic causes of balance problems is imperative in our understanding of the biology of normal function of the vestibule and the disease etiology and process. There is an increasing effort to use new and efficient genetic sequencing tools to discover the genetic causes for these diseases, leading to the hope for precise and personalized treatment for these patients.
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http://dx.doi.org/10.3389/fneur.2021.633207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892966PMC
February 2021

Electrophysiology and genetic testing in the precision medicine of congenital deafness: A review.

J Otol 2021 Jan 1;16(1):40-46. Epub 2020 Aug 1.

Department of Otolaryngology - Head & Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: Congenital hearing loss is remarkably heterogeneous, with over 130 deafness genes and thousands of variants, making for innumerable genotype/phenotype combinations. Understanding both the pathophysiology of hearing loss and molecular site of lesion along the auditory pathway permits for significantly individualized counseling. Electrophysiologic techniques such as electrocochleography (ECochG) and electrically-evoked compound action potentials (eCAP) are being studied to localize pathology and estimate residual cochlear vs. neural health. This review describes the expanding roles of genetic and electrophysiologic evaluation in the precision medicine of congenital hearing loss.The basics of genetic mutations in hearing loss and electrophysiologic testing (ECochG and eCAP) are reviewed, and how they complement each other in the diagnostics and prognostication of hearing outcomes. Used together, these measures improve the understanding of insults to the auditory system, allowing for individualized counseling for CI candidacy/outcomes or other habilitation strategies.

Conclusion: Despite tremendous discovery in deafness genes, the effects of individual genes on neural function remain poorly understood. Bridging the understanding between molecular genotype and neural and functional phenotype is paramount to interpreting genetic results in clinical practice. The future hearing healthcare provider must consolidate an ever-increasing amount of genetic and phenotypic information in the precision medicine of hearing loss.
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http://dx.doi.org/10.1016/j.joto.2020.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814082PMC
January 2021

Author Correction: Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells.

Sci Rep 2020 Jun 25;10(1):10658. Epub 2020 Jun 25.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-67552-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314833PMC
June 2020

COVID19: A Systematic Approach to Early Identification and Healthcare Worker Protection.

Front Public Health 2020 19;8:205. Epub 2020 May 19.

ENT Institute and Otorhinolaryngology Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

The COVID-19 outbreak spread rapidly throughout the globe, with worldwide infections and deaths continuing to increase dramatically. To control disease spread and protect healthcare workers, accurate information is necessary. We searched PubMed and Google Scholar for studies published from December 2019 to March 31, 2020 with the terms "COVID-19," "2019-nCoV," "SARS-CoV-2," or "Novel Coronavirus Pneumonia." The main symptoms of COVID-19 are fever (83-98.6%), cough (59.4-82%), and fatigue (38.1-69.6%). However, only 43.8% of patients have fever early in the disease course, despite still being infectious. These patients may present to clinics lacking proper precautions, leading to nosocomial transmission, and infection of workers. Potential COVID-19 cases must be identified early to initiate proper triage and distinguish them quickly from similar infections. Early identification, accurate triage, and standardized personal protection protocols can reduce the risk of cross infection. Containing disease spread will require protecting healthcare workers.
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http://dx.doi.org/10.3389/fpubh.2020.00205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248242PMC
January 2021

Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study.

Otolaryngol Head Neck Surg 2020 10 16;163(4):714-721. Epub 2020 Jun 16.

Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China.

Objective: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients.

Study Design: Multicenter case series.

Setting: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany).

Subjects And Methods: In total, 394 polymerase chain reaction (PCR)-confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing.

Results: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation.

Conclusions: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.
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http://dx.doi.org/10.1177/0194599820934376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298561PMC
October 2020

Olfactory and Gustatory Dysfunction as An Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study.

medRxiv 2020 May 16. Epub 2020 May 16.

Objective: Evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in COVID-19 patients Study Design: Multicenter Case Series Setting: 5 tertiary care hospitals (3 in China, 1 in France, 1 in Germany) Subjects and Methods: 394 PCR confirmed COVID-19 positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and Visual Analogue Scale (VAS) were used to quantify olfactory and gustatory dysfunction respectively. All subjects at one hospital (Shanghai) without subjective olfactory complaints underwent objective testing.

Results: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n=239), German (n=39) and French (n=116) cohorts were 32%, 69%, and 49% 138 respectively. The median age of included subjects was 39 years old, 92/161 (57%) were male, and 10/161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10/90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. 43% (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation.

Conclusions: Olfactory and/or gustatory disorders may represent early or isolated symptoms of SARS-CoV-2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.
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http://dx.doi.org/10.1101/2020.05.13.20100198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274227PMC
May 2020

Approaching Otolaryngology Patients During the COVID-19 Pandemic.

Otolaryngol Head Neck Surg 2020 07 12;163(1):121-131. Epub 2020 May 12.

Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USA.

. To describe coronavirus disease 2019 (COVID-19) patient presentations requiring otolaryngology consultation and provide recommendations for protective measures based on the experience of ear, nose, and throat (ENT) departments in 4 Chinese hospitals during the COVID-19 pandemic. . Retrospective case series. . Multicenter. . Twenty hospitalized COVID-19 patients requiring ENT consultation from 3 designated COVID-19 hospitals in Wuhan, Shanghai, and Shenzhen were identified. Data on demographics, comorbidities, COVID-19 symptoms and severity, consult reason, treatment, and personal protective equipment (PPE) use were collected and analyzed. Infection control strategies implemented for ENT outpatients and emergency room visits at the Eye and ENT Hospital of Fudan University were reported. . Median age was 63 years, 55% were male, and 95% were in severe or critical condition. Six tracheotomies were performed. Posttracheotomy outcomes were mixed (2 deaths, 2 patients comatose, all living patients still hospitalized). Other consults included epistaxis, pharyngitis, nasal congestion, hyposmia, rhinitis, otitis externa, dizziness, and tinnitus. At all hospitals, powered air-supply filter respirators (PAPRs) were used for tracheotomy or bleeding control. PAPR or N95-equivalent masks plus full protective clothing were used for other complaints. No inpatient ENT providers were infected. After implementation of infection control strategies for outpatient clinics, emergency visits, and surgeries, no providers were infected at the Eye and ENT Hospital of Fudan University. . COVID-19 patients require ENT consultation for many reasons, including tracheotomy. Otolaryngologists play an indispensable role in the treatment of COVID-19 patients but, due to their work, are at high risk of exposure. Appropriate protective strategies can prevent infection of otolaryngologists.
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http://dx.doi.org/10.1177/0194599820926144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218357PMC
July 2020

Otolaryngology Providers Must Be Alert for Patients with Mild and Asymptomatic COVID-19.

Otolaryngol Head Neck Surg 2020 06 14;162(6):809-810. Epub 2020 Apr 14.

ENT Institute and Otorhinolaryngology Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

More than half of COVID-19 patients are afebrile early in the disease course, yet mildly ill or asymptomatic patients can still spread SARS-CoV-2 with high efficiency. Atypically presenting patients may be seen in noninfectious disease settings such as otolaryngology, which is a specialty prone to occupational exposure. Otolaryngologists have been infected with COVID-19 at higher rates than other specialties in China and other countries. Otolaryngology providers should maintain high clinical suspicion for mild and asymptomatic COVID-19 patients. Protective strategies should be implemented including preappointment screening, triaging, restriction of nonurgent visits and surgeries, telemedicine, and appropriate personal protective equipment use.
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http://dx.doi.org/10.1177/0194599820920649DOI Listing
June 2020

Molecular Mechanism of Aflatoxin-Induced Hepatocellular Carcinoma Derived from a Bioinformatics Analysis.

Toxins (Basel) 2020 03 23;12(3). Epub 2020 Mar 23.

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

Exposure to aflatoxin is considered to be one of the causes of hepatocellular carcinoma (HCC). With the development of bioinformation, we sought to reveal the occurrence and development of aflatoxin-induced HCC through data research. We identified differentially expressed genes (DEGs) of datasets GSE127791 (Aflatoxin-treated pluripotent stem cell derived human hepatocytes vs. controls) and GSE64041 (liver carcinoma with unknown cause vs. non-cancerous tissue) by GEO2R to find the common DEGs. Gene ontology (GO) and KEGG path enrichment analysis were used to annotate the function of DEGs. Hub genes were screened from identified DEGs by protein-protein interaction (PPI) network analysis. The prognostic value of hub genes in cancer databases were evaluated. We obtained 132 common DEGs and 11 hub genes. According to cluster analysis and protein co-expression networks, we screened out the key genes, histidine-rich glycoprotein (HRG) and phosphoenolpyruvate carboxykinase 2 (PCK2). Oncomine database and survival curve analysis showed that the decline in HRG and PCK2 expression in the development of HCC indicated poor prognosis. We speculated that the decreased expression of HRG and PCK2 after aflatoxin exposure to hepatocyte may be related to aflatoxin induced hepatocyte injury and carcinogenesis. In addition, the decreased expression of HRG and PCK2 in the occurrence and development of HCC suggests a poor prognosis of HCC.
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http://dx.doi.org/10.3390/toxins12030203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150856PMC
March 2020

Effects of Cadmium and/or Lead on Autophagy and Liver Injury in Rats.

Biol Trace Elem Res 2020 Nov 31;198(1):206-215. Epub 2020 Jan 31.

College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, People's Republic of China.

Exposure to cadmium (Cd) and lead (Pb) can induce liver damage. However, the effects of the combined exposure to Cd and Pb on liver function have not been fully clarified. In the present study, we investigated the liver function in rats co-exposed to Cd and Pb. A total of 24 female SD rats were divided into 4 groups as follows: control group (DDW), Cd group (50 mg/l Cd), Pb group (300 mg/l Pb), Pb + Cd group (300 mg/l + 50 mg/l Cd). Following 12 weeks of continuous exposure, the results showed a large accumulation of Cd and Pb in the liver. The Liver weight and Liver coefficient were decreased, as well as liver structure and function was destroyed. In addition, Pb + Cd group exhibited additional pathological alterations. Moreover, the indices of oxidative stress and related trace elements were detected following treatment. The results showed that the single treatment of Pb or Cd and the combined Cd and Pb treatment could upregulate the contents of antioxidant enzymes and related trace elements. We further examined the expression levels of autophagy-related proteins and mRNAs, and we found that the single treatment of Pb or Cd and the combined Cd and Pb treatment could upregulate the expression of levels of autophagy-related proteins and mRNAs (Atg5, Atg7, Beclin-1, p62, and LC3). Transmission electron microscopy revealed the presence of autophagosomes in the exposed groups. All the results indicated that Cd and Pb may affect the level of oxidative stress and autophagy in hepatocytes, whereas the combination of Cd and Pb showed a tendency of escalation compared with the single treatment group.
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http://dx.doi.org/10.1007/s12011-020-02045-7DOI Listing
November 2020

Vitamin D Inhibition of TRPV5 Expression During Osteoclast Differentiation.

Int J Endocrinol Metab 2019 Oct 14;17(4):e91583. Epub 2019 Oct 14.

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

Background: Vitamin D is an important steroid that can regulate bone metabolism including osteoclast (OC) differentiation. Transient receptor potential cation channel subfamily V member 5 (TRPV5), is a calcium channel protein involved in OC differentiation. However, the impact of vitamin D on TRPV5 expression during OC differentiation is not clear.

Objectives: To determine if 1,25-dihydroxyvitamin D3 (1,25(OH)D) regulates the expression of TRPV5 during OC differentiation.

Methods: Bone marrow mononuclear macrophage (BMMs) were induced to differentiate into OC with or without treatment with 10 nM 1,25(OH)D. The expression levels of vitamin D receptor (VDR) and TRPV5 were examined. The expression of several OC markers, including tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (Ca II), cathepsin K (CTSK), and vacuolar-type H-ATPase (V-ATPase) were also detected.

Results: We found that the VDR was expressed in murine bone marrow-derived macrophages at the early stage of OC differentiation. TRPV5 expression was increased during OC differentiation, which was down-regulated by 1,25(OH)D after a prolonged exposure. The 1,25(OH)D and TRPV5 inhibitors inhibited OC differentiation.

Conclusions: 1,25(OH)D can inhibit TRPV5 expression as well as TRPV5 inhibitors during OC differentiation. This suggests that 1,25(OH)D may suppress OC differentiation by inhibiting TRPV5 expression.
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http://dx.doi.org/10.5812/ijem.91583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948119PMC
October 2019

ZEA-induced autophagy in TM4 cells was mediated by the release of Ca activates CaMKKβ-AMPK signaling pathway in the endoplasmic reticulum.

Toxicol Lett 2020 May 23;323:1-9. Epub 2020 Jan 23.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious, Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, China. Electronic address:

Zearalenone (ZEA) is a prevalent non-steroidal estrogenic mycotoxin produced mainly by Fusarium contamination. Our previous study showed that ZEA induces the autophagy of Sertoli cells (SCs). However, the underlying mechanisms are still unknown. Several studies have indicated that the increasing level of cytoplasmic Ca could induce autophagy through CaMKKβ and AMPK pathways. Thus in order to investigate the potential mechanism underlying ZEA-induced autophagy, the activity of calmodulin-dependent kinase kinase β(CaMKKβ)and AMP-activated protein kinase (AMPK) signaling pathway in ZEA-infected TM4 cells was studied. In the present study, ZEA activated the CaMKKβ and AMPK signaling pathways. The AMPK inhibitor and activator significantly inhibited and stimulated the effect of ZEA on AMPK, the transformation from LC3I to LC3II, and the distribution of LC3 dots. In addition, cytosolic calcium (Ca) was increased gradually with the concentration of ZEA. After treatment of ZEA-infected cells with 1, 2-bis (2-aminophenoxy) ethane-N, N, N', N'- tetraacetic acid- tetraac etoxymethyl ester (BAPTA-AM) and 2-aminoethyl diphenylborinate (2-APB), the intracellular concentration of Ca reduced significantly. Also, the activities of CaMKKβ and AMPK and subsequent autophagy decreased. Moreover, the antioxidant NAC significantly decreased activities of AMPK and autophagy -related protein. Therefore, it can be speculated that ROS- mediated ER-stress induced by ZEA activates AMPK via Ca-CaMKKβ leading to autophagy in TM4 cells.
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http://dx.doi.org/10.1016/j.toxlet.2020.01.010DOI Listing
May 2020

Cadmium-induced cytotoxicity in mouse liver cells is associated with the disruption of autophagic flux via inhibiting the fusion of autophagosomes and lysosomes.

Toxicol Lett 2020 Mar 17;321:32-43. Epub 2019 Dec 17.

College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009, PR China. Electronic address:

Cadmium (Cd) is an important environmental pollutant. Previous studies have shown that Cd can induce liver cell injury; however, the toxicity mechanisms of Cd have not been fully elucidated. This study aimed to further confirm the hepatotoxic effects of Cd in mouse liver cells by various methods both in vivo and in vitro. In addition, it found that Cd induced autophagy but also caused autophagy blockade, and autophagy blockade intensified Cd-induced injury in liver cells. Subsequently, the study investigated the effects of Cd on lysosomes and found that Cd induced lysosomal acidification, promoted the expression of lysosomal-associated membrane protein 2 and lysosomal hydrolase cathepsin B both in vivo and in vitro, and enhanced the lysosomal degradation capacity. It indicated that Cd triggered lysosomal activation. However, the fusion of autophagosomes with lysosomes was inhibited by Cd both in vivo and in vitro. Next, the expression of Rab7, a key protein that regulates autophagosome-lysosome fusion, was examined. Cd was found to inhibit Rab7 expression both in vivo and in vitro. In conclusion, the results indicated that Cd obstructed the autophagic flux by inhibiting the fusion of autophagosomes with lysosomes, thus exacerbating the Cd-induced hepatotoxicity. Moreover, the molecular mechanism of Cd-induced inhibition of autophagosome-lysosome fusion is probably related to the Cd-induced downregulation of Rab7.
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http://dx.doi.org/10.1016/j.toxlet.2019.12.019DOI Listing
March 2020

Renewed proliferation in adult mouse cochlea and regeneration of hair cells.

Nat Commun 2019 12 4;10(1):5530. Epub 2019 Dec 4.

Department of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Techology and Program in Neuroscience, Harvard Medical School, Boston, MA, 02115, USA.

The adult mammalian inner ear lacks the capacity to divide or regenerate. Damage to inner ear generally leads to permanent hearing loss in humans. Here, we present that reprogramming of the adult inner ear induces renewed proliferation and regeneration of inner ear cell types. Co-activation of cell cycle activator Myc and inner ear progenitor gene Notch1 induces robust proliferation of diverse adult cochlear sensory epithelial cell types. Transient MYC and NOTCH activities enable adult supporting cells to respond to transcription factor Atoh1 and efficiently transdifferentiate into hair cell-like cells. Furthermore, we uncover that mTOR pathway participates in MYC/NOTCH-mediated proliferation and regeneration. These regenerated hair cell-like cells take up the styryl dye FM1-43 and are likely to form connections with adult spiral ganglion neurons, supporting that Myc and Notch1 co-activation is sufficient to reprogram fully mature supporting cells to proliferate and regenerate hair cell-like cells in adult mammalian auditory organs.
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http://dx.doi.org/10.1038/s41467-019-13157-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892913PMC
December 2019

Elmod3 knockout leads to progressive hearing loss and abnormalities in cochlear hair cell stereocilia.

Hum Mol Genet 2019 12;28(24):4103-4112

Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

ELMOD3, an ARL2 GTPase-activating protein, is implicated in causing hearing impairment in humans. However, the specific role of ELMOD3 in auditory function is still far from being elucidated. In the present study, we used the CRISPR/Cas9 technology to establish an Elmod3 knockout mice line in the C57BL/6 background (hereinafter referred to as Elmod3-/- mice) and investigated the role of Elmod3 in the cochlea and auditory function. Elmod3-/- mice started to exhibit hearing loss from 2 months of age, and the deafness progressed with aging, while the vestibular function of Elmod3-/- mice was normal. We also observed that Elmod3-/- mice showed thinning and receding hair cells in the organ of Corti and much lower expression of F-actin cytoskeleton in the cochlea compared with wild-type mice. The deafness associated with the mutation may be caused by cochlear hair cells dysfunction, which manifests with shortening and fusion of inner hair cells stereocilia and progressive degeneration of outer hair cells stereocilia. Our finding associates Elmod3 deficiencies with stereocilia dysmorphologies and reveals that they might play roles in the actin cytoskeleton dynamics in cochlear hair cells, and thus relate to hearing impairment.
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http://dx.doi.org/10.1093/hmg/ddz240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305813PMC
December 2019

Optimization of ASE and SPE conditions for the HPLC-FLD detection of piperazine in chicken tissues and pork.

Chirality 2019 10 6;31(10):845-854. Epub 2019 Aug 6.

College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

Accelerated solvent extraction (ASE) and solid-phase extraction (SPE) conditions were optimized by a high-performance liquid chromatography-fluorescence detector (HPLC-FLD) method for the detection of piperazine in chicken tissues and pork. Piperazine residues were determined by precolumn derivatization with trimethylamine and dansyl chloride. Samples were extracted with 2% formic acid in acetonitrile using an ASE apparatus and purified using a Strata-X-C SPE column. The monosubstituted product of the reaction of piperazine with dansyl chloride was 1-dansyl piperazine (1-DNS-piperazine). Chromatographic separations were performed on an Athena C column (250 × 4.6 mm, id: 5 μm) with gradient elution using ultrapure water and acetonitrile (5:95, V/V) as the mobile phase. The calibration curves showed good linearity over a concentration range of LOQ-200.0 μg/kg with a coefficient of determination (R ) ≥ .9992. The recoveries and relative standard deviations (RSD values) ranged from 78.49% to 97.56% and 1.19% to 5.32%, respectively, across the limit of quantification (LOQ) and 0.5, 1, and 2.0 times the maximum residue limit (MRL; μg/kg). The limits of detection (LODs) and LOQs were 0.96 to 1.85 μg/kg and 3.20 to 5.50 μg/kg, respectively. The method was successfully applied for the validation of animal products in the laboratory.
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http://dx.doi.org/10.1002/chir.23117DOI Listing
October 2019

Proband Whole-Exome Sequencing Identified Genes Responsible for Autosomal Recessive Non-Syndromic Hearing Loss in 33 Chinese Nuclear Families.

Front Genet 2019 17;10:639. Epub 2019 Jul 17.

Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China.

Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous disease involving more than 70 pathogenic genes. However, most ARNSHL families have small-sized pedigrees with limited genetic information, rendering challenges for the molecular diagnosis of these patients. Therefore, we attempted to establish a strategy for identifying deleterious variants associated with ARNSHL by applying proband whole-exome sequencing (proband-WES). Aside from desiring to improve molecular diagnostic rates, we also aimed to search for novel deafness genes shared by patients with similar phenotype, making up for the deficiency of small ARNSHL families. In this study, 48.5% (16/33) families were detected the pathogenic variants in eight known deafness genes, including 10 novel variants identified in (MIM 605551), (MIM 602666), (MIM 606706), (MIM 602851), and (MIM 603317). Apart from six novel variants with a truncating effect (nonsense, deletion, insertion, and splice-site), four novel missense variants were not found in 200 unrelated control population by using Sanger sequencing. It is important to note that none of novel genes were shared across different pedigrees, indicating that a larger sample size might be needed. Proband-WES is a cost-effective and precise way of identifying causative variants in nuclear families with ARNSHL. This economical strategy may be appropriated as a clinical application to provide molecular diagnostics, genetic counseling, and individualized health maintenance measures for patients with ARNSHL at hearing clinics.
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http://dx.doi.org/10.3389/fgene.2019.00639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650584PMC
July 2019

Treatment with, Resveratrol, a SIRT1 Activator, Prevents Zearalenone-Induced Lactic Acid Metabolism Disorder in Rat Sertoli Cells.

Molecules 2019 Jul 5;24(13). Epub 2019 Jul 5.

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China.

Zearalenone (ZEA) interferes with the function of the male reproductive system, but its molecular mechanism has yet to be completely elucidated. Sertoli cells (SCs) are important in the male reproductive system. Silencing information regulator 1 (SIRT1) is a cell metabolism sensor and resveratrol (RSV) is an activator of SIRT1. In this study we investigated whether SIRT1 is involved in the regulation of ZEA-induced lactate metabolism disorder in SCs. The results showed that the cytotoxicity of ZEA toward SCs increased with increasing ZEA concentration. Moreover, ZEA induced a decrease in the production of lactic acid and pyruvate of SCs and inhibited the expression of glycolytic genes and lactic acid production-related proteins. ZEA also led to a decreased expression of SIRT1 in energy receptors and decreased ATP levels in SCs. However, the ZEA-induced cytotoxicity and decline in lactic acid production in SCs were alleviated by the use of RSV, which is an activator of SIRT1. In summary, ZEA decreased lactic acid production in SCs, while the treatment with an SIRT1 activator, RSV, restored the inhibition of lactic acid production in SCs and reduced cytotoxicity of ZEA toward SCs.
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http://dx.doi.org/10.3390/molecules24132474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651738PMC
July 2019

Extrusion pump ABCC1 was first linked with nonsyndromic hearing loss in humans by stepwise genetic analysis.

Genet Med 2019 12 5;21(12):2744-2754. Epub 2019 Jul 5.

Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Purpose: To determine the genetic etiology of deafness in a family (HN-SD01) with autosomal dominant nonsyndromic hearing loss (NSHL).

Methods: Stepwise genetic analysis was performed on family HN-SD01, including hotspot variant screening, exome sequencing, virtual hearing loss gene panel, and genome-wide linkage analysis. Targeted region sequencing was used to screen ABCC1 in additional cases. Cochlear expression of Abcc1 was evaluated by messenger RNA (mRNA) and protein levels. Computational prediction, immunofluorescence, real-time quantitative polymerase chain reaction, and flow cytometry were conducted to uncover functional consequences of candidate variants.

Results: Stepwise genetic analysis identified a heterozygous missense variant, ABCC1:c.1769A>G (p.Asn590Ser), cosegregating with phenotype in HN-SD01. Screening of ABCC1 in an additional 217 cases identified candidate pathogenic variants c.692G>A (p.Gly231Asp) in a sporadic case and c.887A>T (p.Glu296Val) in a familial proband. Abcc1 expressed in stria vascularis and auditory nerve of mouse cochlea. Immunofluorescence showed p.Asn590Ser distributed in cytomembrane and cytoplasm, while wild type was shown only in cytomembrane. Besides, it generated unstable mRNA and decreased efflux capacity of ABCC1.

Conclusion: Stepwise genetic analysis is efficient to analyze the genetic etiology of NSHL. Variants in ABCC1 are linked with NSHL and suggest an important role of extruding pumps in maintaining cochlea function.
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http://dx.doi.org/10.1038/s41436-019-0594-yDOI Listing
December 2019

Genetic screening as an adjunct to universal newborn hearing screening: literature review and implications for non-congenital pre-lingual hearing loss.

Int J Audiol 2019 12 2;58(12):834-850. Epub 2019 Jul 2.

Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA.

Universal newborn hearing screening (UNHS) uses otoacoustic emissions testing (OAE) and auditory brainstem response testing (ABR) to screen all newborn infants for hearing loss (HL), but may not identify infants with mild HL at birth or delayed onset HL. The purpose of this review is to examine the role of genetic screening to diagnose children with pre-lingual HL that is not detected at birth by determining the rate of children who pass UNHS but have a positive genetic screening. This includes a summary of the current UNHS and its limitations and a review of genetic mutations and screening technologies used to detect patients with an increased risk of undiagnosed pre-lingual HL. Literature review of studies that compare UNHS with concurrent genetic screening. Infants and children with HL Sixteen studies were included encompassing 137,895 infants. Pathogenic mutations were detected in 8.66% of patients. In total, 545 patients passed the UNHS but had a positive genetic screening. The average percentage of patients who passed UNHS but had a positive genetic screening was 1.4%. This review demonstrates the positive impact of concurrent genetic screening with UNHS to identify patients with pre-lingual HL.
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http://dx.doi.org/10.1080/14992027.2019.1632499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244215PMC
December 2019
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