Startseite Hearing loss and brain disorders: A review of multiple pathologies
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Hearing loss and brain disorders: A review of multiple pathologies

  • Oluwafemi Gabriel Oluwole EMAIL logo , Kili James , Abdoulaye Yalcouye und Ambroise Wonkam
Veröffentlicht/Copyright: 15. Dezember 2021
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Open Medicine
Aus der Zeitschrift Open Medicine Band 17 Heft 1

Abstract

Several causative factors are associated with hearing loss (HL) and brain disorders. However, there are many unidentified disease modifiers in these conditions. Our study summarised the most common brain disorders associated with HL and highlighted mechanisms of pathologies. We searched the literature for published articles on HL and brain disorders. Alzheimer’s disease/dementia, Parkinson’s disease, cognitive impairment, autism spectrum disorder, ataxia, epilepsy, stroke, and hypoxic-ischaemic encephalopathy majorly co-interact with HL. The estimated incidence rate was 113 per 10,000 person-years. Genetic, epigenetic, early life/neonatal stress, hypoxia, inflammation, nitric oxide infiltration, endoplasmic reticulum stress, and excess glutamate were the distinguished modifiers identified. Various mechanisms like adhesion molecules, transport proteins, hair cell apoptosis, and neurodegeneration have been implicated in these conditions and are serving as potential targets for therapies. To improve the quality of life of patients, these understandings will improve clinical diagnoses and management of HL and brain disorders.

Keywords: hearing loss; brain disorders; pathology; correlated risk factors

1 Introduction

Hearing loss (HL), deafness, or hearing impairment can be described as a total or partial inability to hear sounds. HL could be conductive, sensorineural, or mixed, depending on the parts of the auditory system being affected [1]. Globally, approximately 400 million people are diagnosed of HL [2,3] and millions of people suffered from one form of brain disorders. Environmental and genetic factors have been identified as the leading contributors. Syndromic HL is associated with numerous syndromes like Waardenburg syndrome, branchiootorenal syndrome, Usher syndrome, Pendred syndrome, keratitis-ichthyosis-deafness syndrome, and Alport syndrome [1,4]. Non-syndromic HL is a form of sensorineural HL that is not linked to a syndrome [5].

HL can cause several neurological and psychiatric complications that can reduce quality of life [6]. Some of the complications may include cognitive impairment, depression, dementia, and comorbidities like cardiovascular diseases and diabetes [4,7,8]. More so, the feelings of irritability, anxiety, and rage in patients with HL may emanate from undiagnosed brain disorders [2].

Physiologically, the brain is the true organ of hearing because the brain processes the sounds that are transmitted from the ears. Hearing is a complex process that requires connection between the peripheral and central auditory processing systems [9], this connectivity enables the sharing of aetiological factors. Impaired cochlear blood perfusion and microvascular damage in the ear can cause sensorineural HL, as well as certain brain disorders. This review aims to identify commonly associated brain disorders with sensorineural HL and explains the plausible mechanisms by which HL co-interacts with the brain disorders. The understanding of these multiple pathologies will contribute to the clinical management of patients.

2 Methods

2.1 Search method

We searched five electronic databases “PubMed, HubMed, Google Scholar, MEDLINE, and Embase” for published articles on HL and brain disorders between the years 2000 and 2021.

We used a combination of strings and MeSH terms (hearing loss) AND with OR (hearing impairment) AND with OR (deafness) AND with OR (brain) AND with OR (brain disorders) AND with OR (brain disease). The strings were adapted to each database entries.

2.1.1 Selection criteria

We prioritized the articles that have the searched terms in their title or abstract. Additionally, the articles that reported clinical, scientific, or technological findings on HL with brain disorders in humans were selected. The articles considered relevant had the following objectives:

  1. Reported the incidence or clinical diagnoses of HL with brain disorders.

  2. Evaluated the causative factors of HL with brain disorders.

  3. Investigated novel potential targets for therapy in HL with brain disorders.

2.1.2 Extraction and data presentation

The full texts of the selected articles were downloaded to Zotero electronic reference manager for reference. We retrieved meta-data like demographics, the number of study participants and cases. We estimated the incidence rates as a measure of new cases/total, that is, the number of study participants considered at risk. The findings were summarized in Table 1. We provided a diagrammatic illustration to explain the underlying multiple pathologies and the mechanisms of HL co-interaction with brain disorder by using the biorender app (https://app.biorender.com/).

Table 1

Studies on brain disorders and hearing loss

Type of diseases Methods Major findings Total number of cases References
Alzheimer's disease (AD) and dementia Studies that performed PTA, ABR, and central auditory processing tests on participants diagnosed with dementia/AD. Patients were compared with control groups There was a significant association between central auditory dysfunction and dementia/AD in the primary auditory cortex with evidence of abnormal blood glucose levels 1,045 [10,11,12,13,14]
Studies that performed longitudinal research on patients diagnosed with sensorineural HL and investigated association with dementia in participants During the average 5 year follow-up period, the incidence rate of dementia in the sensorineural hearing loss (SNHL) cohort was 6.5 per 1,000 person-years compared with 5.09 per 10,000 person-years in the comparison group. HL was independently associated with a high incident rate of dementia in mild, moderate, and severe HL 17,523 [15,16,17]
Parkinson's disease (PD) Assessments of HL were evaluated in PD patients with audiometric testing, and a battery of central auditory processing tests Compared to the control group, PD patients reported greater HL 184 [18,19,20,21,22,23,24]
Cognitive impairment Patients diagnosed with HL were recruited for the study and completed the modified Mini-Mental State Examination, cognitive test, and linear mixed models for correlation About one-sixth (15.7%) of the patients studied had cognitive decline; 10.1% had functional decline among individuals with HL. There was also an association with history of stroke 5,445 [17,25,26,27]
Autism spectrum disorder (ASD) Audiological evaluation was performed using PTA tests in children diagnosed with autism Mild-to-moderate HL was diagnosed in 7.9% and unilateral HL in 1.6%, profound bilateral HL was diagnosed in 3.5% of all cases 199 [28]
Epilepsy and ataxia A retrospective review of the detailed neurological and neuroradiological features were performed in nine children All children presented with tonic–clonic seizures in infancy. Later, with non-progressive, cerebellar ataxia and profound HL 9 children, 1 adult [29,30]
Hypoxic ischaemic encephalopathy (HLE) Dual-stage hearing screening tests, including automated otoacoustic emissions and ABR tests, were performed in new-borns suspected to have developed HL The study affirms a significant association between HL in term infants who have moderate/severe HLE with evidence of abnormal blood glucose and multi-organ dysfunction (p = 0.006) 42 [31]
Stroke Neurological and general examinations were performed. Followed by audiogram and MRI screening Acute stress was recognised and moderate sensorineural HL with the presence of bilateral temporal ischemic stroke lesions 1 [32]

3 Results

The search engines gave an output of 39,454 articles, of which 8,531 articles were initially considered as relevant articles. They include case reports, reviews, short communications, letters to the editor, and original articles. However, after the filtering processes by using stringent criteria to select case reports, reviews, and original articles that presented meta-data or detailed information on the topic of HL with brain disorder only, we identified 71 important articles, of which 45 articles were original articles (Figure 1). The focus of the 45 articles was on molecular pathology, diagnosis, incidence, or genetics.

Figure 1 Filtering processes and article selections in the study.
Figure 1

Filtering processes and article selections in the study.

The results of our analyses showed that Alzheimer’s disease/dementia, Parkinson’s disease (PD), cognitive impairment, autism spectrum disorder, ataxia, epilepsy, hypoxic-ischaemic encephalopathy, and stroke have been reported to co-interact with HL (Table 1). The overall number of cases was 2,765 of 24,447 participants, and the estimated incidence rate was 0.113 per person-year or 113 per 10,000 person-years.

The demographic data derived from the studies imply that adult patients usually have Alzheimer’s disease, Parkinson’s disease, and cognitive impairment, whereas the infants and children had autism spectrum disorder (ASD), attention deficit hyperactivity disorder, and cerebral palsy with HL. Geographically, the studies were performed mainly in Europe and Asia. The researchers used different methods for diagnoses (Table 1), but generally the clinical presentations of the patients were similar. Likewise, the findings signified those complex mechanisms such as hereditary, acquired, or combination of factors including environmental and physical abnormalities in the causes of HL and brain disorders (Figure 2).

Figure 2 The description of intrinsic, extrinsic factors and disease modifiers underlying the pathologies of HL co-interactions with brain disorders.
Figure 2

The description of intrinsic, extrinsic factors and disease modifiers underlying the pathologies of HL co-interactions with brain disorders.

Furthermore, ten studies distinguished the roles of methylated genes and reported single nucleotide polymorphisms (SNPs), that overlap between HL and brain disorders (Table 2). We summarised, in Figure 3, the mechanisms involving the multiple pathologies of HL with brain disorders such as stress, inflammation, genetic factors, and environmental factors such as heavy metals, pesticides, bisphenol A; polybrominated diphenyl ethers; polychlorinated biphenyls; perfluorocarboxylic acids; and perfluorooctanesulfonate.

Table 2

Epigenetic studies involving HL and brain disorders genes

Methylated genes Brain disorders Proposed mechanisms Associated SNPs/mutations References
DNMT1 Autism, cerebellar ataxia, Huntington disease DNMT1 negatively impacts retrograde trafficking and autophagy rs10418707, rs10423341, rs2114724, and rs759920 [33,34,35]
NSD1 AD, and intellectual disability syndrome Most of the mutations identified are predicted to disrupt the reading frame in a way that causes early translational termination and/or activates non-sense-mediated decay Multiple mutations have been reported including the c.2314delG, c.2362C > T, c.5296C > A [36–38]
EZH2 Ataxia Enhanced nuclear H3K27me3 affects cell cycle and neuronal survival through reverse transcription mechanisms and complexes Ser652 and Ser734 sites methylation [39]
EHMT1 Intellectual disability, schizophrenia, and psychosis, autism, PD, and HD The addition of methyl groups to histone H3 lysine 9 linked to genomic imprinting, X-inactivation, and heterochromatin formation Multiple H3K9 dimethylation has been reported [40]
KMT2D Kabuki syndrome (intellectual disability) and multiple malformations syndrome Methylation leads to the truncation of C-terminal SET catalytic domain, likely resulting in the loss of enzymatic function Multiple mutations have been reported including the p.Cys1430Arg and p.Cys1471Tyr [41–43]
CHD7 ASD and sleep disorder Mechanisms not fully understood but were thought to control glia activation and causes hyperserotonemia Multiple mutations have been reported in non-human subjects [44]
Figure 3 A description of auditory signal pathway and possible insults to the auditory nervous system. The auditory nervous pathway originates from spiral ganglion cells in the cochlea. The pathological changes that occur in the cochlear, like inflammation can initiate peripheral immune responses and activations of inflammatory genes as well as over production of reactive oxygen species (ROS) and other inflammatory biomarkers that can affect the mitochondrial and diffuses to the central nervous system to cause neurodegeneration and cell apoptosis. Also, mtDNA mutations can cause mitochondrial dysfunction and cell apoptosis.
Figure 3

A description of auditory signal pathway and possible insults to the auditory nervous system. The auditory nervous pathway originates from spiral ganglion cells in the cochlea. The pathological changes that occur in the cochlear, like inflammation can initiate peripheral immune responses and activations of inflammatory genes as well as over production of reactive oxygen species (ROS) and other inflammatory biomarkers that can affect the mitochondrial and diffuses to the central nervous system to cause neurodegeneration and cell apoptosis. Also, mtDNA mutations can cause mitochondrial dysfunction and cell apoptosis.

4 Discussion

Complex biological pathways and modifiers are involved in the onset of HL and brain disorders. The anatomical structures of the cochlea of the ear, and the brain show that the cochlea consists of hair cells that allow the neural conduction with the brain by the auditory nerves at the synapses [1,9,45,46,47,48,49]. The damage(s) to the auditory nerves, cortex, or thalamus is/are capable of inducing HL and brain disorders. We identified studies that showed that a bilateral lesion of the superior temporal gyrus and the thalamic nuclei of the brain caused HL, motor, sensory, and neuropsychological impairments [50,51]. Also, a haemorrhagic lesion in the right thalamus due to an aneurysm was linked to the aetiology of bilateral HL in children [52,53]. More so, cerebral palsy co-interacts with childhood HL [54].

The damages to the thalamus and the central auditory system can be caused by a stroke, head injury, brain tumours, or neurodegeneration [52,53]. These damages may lead to loss of auditory cortex, and may contribute to the down regulation of neural activities in the brain [55].

In essence, our study advocate for the use of advanced technology such as magnetic resonance imaging (MRI) in the diagnosis and early detection of HL and brain disorders.

Furthermore, stress and inflammation contribute to the onset of HL and brain disorders. Stress has multiple effects that can be linked to the release of adrenaline and vasoconstrictors that may narrow blood flow into the tissues of inner ear [56]. Studies have shown a strong correlation (∼32% of 9,756 participants) between HL and different types of daily stressors like occupational, poverty, long-term illness, lack of sleep, and higher burnout [57]. Also, the responses to stress via the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in HL and various brain diseases [58]. The pathology may be linked to the release of cortisol and an imbalance of the N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the cochlea that can cause excess glutamate and glycine release, followed by excitotoxicity, and altered gene expression in the cochlea and the brain as described in Figure 2.

Stress can induce inflammation or hypoxia in the hair cell by affecting the epithelial cells in the brain to induce immune responses and cellular infiltration [46]. Stress-induced inflammation or hypoxia in the cochlea has been shown to be modulated by the macrophages [58]. Besides, virus-triggered inflammation of the meninges with subsequent spread to the cochlea could initiate the pathological processes that include cytokines (interleukin 1-beta [IL-1beta], IL-6,), overproduction of ROS, inducible nitric oxide synthase (iNOS), and tumour necrosis factor-alpha. The cytokines are known to enter the brain and cause neurodegeneration in the cortex and the thalamus to impair auditory processes [59,60,61]. And the iNOS has been linked to the cochlear pathology through blood flow to the middle ear, outer hair cell, and vestibular functions in sensorineural HL [62,63], as well as brain diseases like parkinson’s disease (PD), alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), huntington's disease (HD), autism spectrum disorder (ASD), and stroke [64].

Furthermore, there is genetic overlap between HL and AD pathology [65]. Studies have shown that genetic, environmental, and birth-related issues contribute largely to HL [66,67]. The environmental and genetic information of an individual can pose differences in the way diseases like HL and brain disorders co-interact. Mutated genes in HL share biological pathways with genes that regulate adhesion, transport, and synapses proteins peripherally and centrally [68], which have been implicated in the biological functions like adhesion, intracellular transport, neurotransmitter release, ionic homeostasis, and cytoskeletons. To date, mutations in over 150 genes have been linked to HL (http://hereditaryhearingloss.org/). The GJB2 and GJB6 genes are the most common in HL [69]. Perhaps, mutations in a single gene or combination of genes can result in the onset of the multiple pathologies in HL and brain disorders. Unlike the European and American populations that have been majorly investigated, research needs to focus more on the under-represented populations because they are known for genetic diversities that could play some important ramifications for diseases and treatment [70].

Lastly, the epigenetic factors contribute to the aetiology of HL and brain disorders. Epigenetic modifications and regulatory mechanisms are important biological events that switch on or off genes for hearing and brain functions. More than one hundred microRNAs are regulated by epigenetic mechanisms, and about 50% of them are modulated by DNA methylation and have been associated with different diseases [71]. Importantly, epigenetic factors can influence the transcriptomics during the developmental stage. Of which, the gene expression in the thalamus has been described to be susceptible to epigenetic changes [72]. Currently, resources like umgear (www.umgear.org) document epigenetic changes that influence gene expressions for further studies in this area.

In conclusion, there are limitations in our study which include that we only reviewed articles published in English between the years 2020 and 2021. Also, we analysed articles that have free full text. Nonetheless, the significance of our study is in the identification of various brain disorders that are co-interacting with HL, and the raw incidence rate to expect per population. Our study gave an overview of diseases that may present clinically with HL. We emphasised genetics, epigenetic, damaged cortical/thalamus, stress, inflammation, and immune system dysfunction as primary contributors to the onset of HL and brain disorders. The identification of the multiple pathologies strengthen research ideas in this area and will promote healthcare awareness, contribute to target discoveries and novel treatments, as well as improve the diagnosis and care for people affected with HL and brain disorders.

Abbreviations

ASD

autism spectrum disorders

HL

hearing loss

HPA-axis

hypothalamic-pituitary-adrenal axis

HLE

hypoxic ischaemic encephalopathy

IHC

inner hair cells

MRI

magnetic resonance imaging

NO

nitric oxide

NMDA

N-methyl-d-aspartate

NSHL

non-syndromic hearing loss

SGNs

spiral ganglion neurons

AMPA

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

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Acknowledgements

We acknowledge the University of Cape Town Library for making the articles on purchase available free of charge for this paper.

  1. Funding information: The study was funded by the National Institutes of Health, Bethesda, Maryland, USA. Grant number (U01-HG-009716) awarded to AW, and the African Academy of Science/Wellcome Trust, grant, number (H3A/18/001) awarded to AW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

  2. Author contributions: OGO conceptualised the idea, designed study, collected meta-data, analysed, prepared results, and drafted the manuscript. KJ, AY validated data. AW supervised, revised the manuscript and decision to submit it for publication.

  3. Conflict of interest: The authors declare that there is no commercial or financial influence that could be taken as a potential conflict of interest.

  4. Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Received: 2021-08-06
Revised: 2021-10-22
Accepted: 2021-11-05
Published Online: 2021-12-15

© 2022 Oluwafemi Gabriel Oluwole et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

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  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
https://doi.org/10.1515/med-2021-0402
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hearing loss; brain disorders; pathology; correlated risk factors
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Artikel in diesem Heft

  1. Research Articles
  2. AMBRA1 attenuates the proliferation of uveal melanoma cells
  3. A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma
  4. Differences in complications between hepatitis B-related cirrhosis and alcohol-related cirrhosis
  5. Effect of gestational diabetes mellitus on lipid profile: A systematic review and meta-analysis
  6. Long noncoding RNA NR2F1-AS1 stimulates the tumorigenic behavior of non-small cell lung cancer cells by sponging miR-363-3p to increase SOX4
  7. Promising novel biomarkers and candidate small-molecule drugs for lung adenocarcinoma: Evidence from bioinformatics analysis of high-throughput data
  8. Plasmapheresis: Is it a potential alternative treatment for chronic urticaria?
  9. The biomarkers of key miRNAs and gene targets associated with extranodal NK/T-cell lymphoma
  10. Gene signature to predict prognostic survival of hepatocellular carcinoma
  11. Effects of miRNA-199a-5p on cell proliferation and apoptosis of uterine leiomyoma by targeting MED12
  12. Does diabetes affect paraneoplastic thrombocytosis in colorectal cancer?
  13. Is there any effect on imprinted genes H19, PEG3, and SNRPN during AOA?
  14. Leptin and PCSK9 concentrations are associated with vascular endothelial cytokines in patients with stable coronary heart disease
  15. Pericentric inversion of chromosome 6 and male fertility problems
  16. Staple line reinforcement with nebulized cyanoacrylate glue in laparoscopic sleeve gastrectomy: A propensity score-matched study
  17. Retrospective analysis of crescent score in clinical prognosis of IgA nephropathy
  18. Expression of DNM3 is associated with good outcome in colorectal cancer
  19. Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation
  20. CRRT influences PICCO measurements in febrile critically ill patients
  21. SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis
  22. lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells
  23. circ_AKT3 knockdown suppresses cisplatin resistance in gastric cancer
  24. Prognostic value of nicotinamide N-methyltransferase in human cancers: Evidence from a meta-analysis and database validation
  25. GPC2 deficiency inhibits cell growth and metastasis in colon adenocarcinoma
  26. A pan-cancer analysis of the oncogenic role of Holliday junction recognition protein in human tumors
  27. Radiation increases COL1A1, COL3A1, and COL1A2 expression in breast cancer
  28. Association between preventable risk factors and metabolic syndrome
  29. miR-29c-5p knockdown reduces inflammation and blood–brain barrier disruption by upregulating LRP6
  30. Cardiac contractility modulation ameliorates myocardial metabolic remodeling in a rabbit model of chronic heart failure through activation of AMPK and PPAR-α pathway
  31. Quercitrin protects human bronchial epithelial cells from oxidative damage
  32. Smurf2 suppresses the metastasis of hepatocellular carcinoma via ubiquitin degradation of Smad2
  33. circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury
  34. Sonoclot’s usefulness in prediction of cardiopulmonary arrest prognosis: A proof of concept study
  35. Four drug metabolism-related subgroups of pancreatic adenocarcinoma in prognosis, immune infiltration, and gene mutation
  36. Decreased expression of miR-195 mediated by hypermethylation promotes osteosarcoma
  37. LMO3 promotes proliferation and metastasis of papillary thyroid carcinoma cells by regulating LIMK1-mediated cofilin and the β-catenin pathway
  38. Cx43 upregulation in HUVECs under stretch via TGF-β1 and cytoskeletal network
  39. Evaluation of menstrual irregularities after COVID-19 vaccination: Results of the MECOVAC survey
  40. Histopathologic findings on removed stomach after sleeve gastrectomy. Do they influence the outcome?
  41. Analysis of the expression and prognostic value of MT1-MMP, β1-integrin and YAP1 in glioma
  42. Optimal diagnosis of the skin cancer using a hybrid deep neural network and grasshopper optimization algorithm
  43. miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells
  44. Clinical value of SIRT1 as a prognostic biomarker in esophageal squamous cell carcinoma, a systematic meta-analysis
  45. circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8
  46. miR-22-5p regulates the self-renewal of spermatogonial stem cells by targeting EZH2
  47. hsa-miR-340-5p inhibits epithelial–mesenchymal transition in endometriosis by targeting MAP3K2 and inactivating MAPK/ERK signaling
  48. circ_0085296 inhibits the biological functions of trophoblast cells to promote the progression of preeclampsia via the miR-942-5p/THBS2 network
  49. TCD hemodynamics findings in the subacute phase of anterior circulation stroke patients treated with mechanical thrombectomy
  50. Development of a risk-stratification scoring system for predicting risk of breast cancer based on non-alcoholic fatty liver disease, non-alcoholic fatty pancreas disease, and uric acid
  51. Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway
  52. circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis
  53. Human amniotic fluid as a source of stem cells
  54. lncRNA NONRATT013819.2 promotes transforming growth factor-β1-induced myofibroblastic transition of hepatic stellate cells by miR24-3p/lox
  55. NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage
  56. Idiopathic pulmonary fibrosis telemedicine management during COVID-19 outbreak
  57. Risk factors for adverse drug reactions associated with clopidogrel therapy
  58. Serum zinc associated with immunity and inflammatory markers in Covid-19
  59. The relationship between night shift work and breast cancer incidence: A systematic review and meta-analysis of observational studies
  60. LncRNA expression in idiopathic achalasia: New insight and preliminary exploration into pathogenesis
  61. Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway
  62. Moscatilin suppresses the inflammation from macrophages and T cells
  63. Zoledronate promotes ECM degradation and apoptosis via Wnt/β-catenin
  64. Epithelial-mesenchymal transition-related genes in coronary artery disease
  65. The effect evaluation of traditional vaginal surgery and transvaginal mesh surgery for severe pelvic organ prolapse: 5 years follow-up
  66. Repeated partial splenic artery embolization for hypersplenism improves platelet count
  67. Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR
  68. Exosomal hsa_circ_0000519 modulates the NSCLC cell growth and metastasis via miR-1258/RHOV axis
  69. miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1
  70. The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
  71. Isocitrate dehydrogenase 1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis
  72. Artemisinin protects against cerebral ischemia and reperfusion injury via inhibiting the NF-κB pathway
  73. A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer
  74. Lidocaine ameliorates chronic constriction injury-induced neuropathic pain through regulating M1/M2 microglia polarization
  75. MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model
  76. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis
  77. Clinical characteristics of pneumonia patients of long course of illness infected with SARS-CoV-2
  78. circRNF20 aggravates the malignancy of retinoblastoma depending on the regulation of miR-132-3p/PAX6 axis
  79. Linezolid for resistant Gram-positive bacterial infections in children under 12 years: A meta-analysis
  80. Rack1 regulates pro-inflammatory cytokines by NF-κB in diabetic nephropathy
  81. Comprehensive analysis of molecular mechanism and a novel prognostic signature based on small nuclear RNA biomarkers in gastric cancer patients
  82. Smog and risk of maternal and fetal birth outcomes: A retrospective study in Baoding, China
  83. Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1
  84. β2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis
  85. Possible impact of COVID-19 pandemic and lockdown on suicide behavior among patients in Southeast Serbia
  86. In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria
  87. Potential biomarkers for inflammatory response in acute lung injury
  88. A low serum uric acid concentration predicts a poor prognosis in adult patients with candidemia
  89. Antitumor activity of recombinant oncolytic vaccinia virus with human IL2
  90. ALKBH5 inhibits TNF-α-induced apoptosis of HUVECs through Bcl-2 pathway
  91. Risk prediction of cardiovascular disease using machine learning classifiers
  92. Value of ultrasonography parameters in diagnosing polycystic ovary syndrome
  93. Bioinformatics analysis reveals three key genes and four survival genes associated with youth-onset NSCLC
  94. Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis
  95. Protective effects of glaucocalyxin A on the airway of asthmatic mice
  96. Overexpression of miR-100-5p inhibits papillary thyroid cancer progression via targeting FZD8
  97. Bioinformatics-based analysis of SUMOylation-related genes in hepatocellular carcinoma reveals a role of upregulated SAE1 in promoting cell proliferation
  98. Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience
  99. Identification of osteoporosis based on gene biomarkers using support vector machine
  100. Tanshinone IIA reverses oxaliplatin resistance in colorectal cancer through microRNA-30b-5p/AVEN axis
  101. miR-212-5p inhibits nasopharyngeal carcinoma progression by targeting METTL3
  102. Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas
  103. LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma
  104. The perinatal factors that influence the excretion of fecal calprotectin in premature-born children
  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
  110. Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis
  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
  118. Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland
  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
  197. Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma
  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
  200. Trismus during tracheal extubation as a complication of general anaesthesia – A case report
  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
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Heruntergeladen am 1.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2021-0402/html
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