Jeenu Mittal's research while affiliated with University of Miami Miller School of Medicine and other places
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Publications (61)
Background: Vestibular schwannoma (VS) is a benign tumor of the eighth cranial nerve formed from neoplastic Schwann cells. Although VS can cause a variety of symptoms, tinnitus is one of the most distressing symptoms for patients and can greatly impact quality of life. The objective of this systematic review is to comprehensively examine and compar...
Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Recent research has increasingly focused on the genetic underpinnings of ASD, with the Neurexin 1 (NRXN1) gene emerging as a key player. This comprehensive systematic review elucidates the c...
Objectives
Type 1 diabetes (T1D) has been associated with several comorbidities such as ocular, renal, and cardiovascular complications. However, the effect of T1D on the auditory system and sensorineural hearing loss (SNHL) is still not clear. The aim of this study was to conduct a systematic review to evaluate whether T1D is associated with heari...
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by stereotyped and repetitive behavior patterns. In addition to neurological and behavioral problems, individuals with ASD commonly experience otolaryngological comorbidities. Individuals with ASD often have auditory disorders including hearing loss and auditory processin...
The gut microbiome has been shown to play a pivotal role in health and disease. Recently, there has been increased interest within the auditory community to explore the role of the gut microbiome in the auditory system and its implications for hearing disorders such as sensorineural hearing loss (SNHL), otitis media, and tinnitus. Studies have sugg...
Deciphering the inner ear transcriptome has allowed major breakthroughs in therapeutic development for auditory disorders. Single-cell sequencing (SCS) technologies, through the analysis of cellular heterogeneity and the identification of novel gene markers, can significantly enhance our understanding about auditory disorders. The application of SC...
Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive etiology. Individuals with autism spectrum disorder show deficits in a variety of areas including cognition, memory, attention, emotion recognition, and social skills. With no definitive treatment or cure, the main interventions for indiv...
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that has a high prevalence and a significant economic impact. Our knowledge regarding neurosensory disorders and co-occurring medical conditions in the ASD population is limited, particularly for autistic women. Most of the studies include male participants or do not make comparisons w...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication, and social skills, as well as repetitive and/or restrictive interests and behaviors. The severity of ASD varies from mild to severe, drastically interfering with the quality of life of affected individuals. The current occurrence of ASD in th...
The gut microbiota, composed of numerous species of microbes, works in synergy with the various organ systems in the body to bolster our overall health and well-being. The most well-known function of the gut microbiome is to facilitate the metabolism and absorption of crucial nutrients, such as complex carbohydrates, while also generating vitamins....
Cell-based models are a promising tool in deciphering the molecular mechanisms underlying the pathogenesis of neurological disorders as well as aiding in the discovery and development of future drug therapies. The greatest challenge is creating cell-based models that encapsulate the vast phenotypic presentations as well as the underlying genotypic...
The gut microbiome and its dynamic association with organ systems beyond the gastrointestinal tract, such as the nervous and cardiovascular systems, is an emerging area of research. Although the role of the gut microbiome has been extensively characterized in the gut-brain axis, the implications of gut dysbiosis in inner ear inflammation and hearin...
Given the non-labile, terminal differentiation of inner-ear sensory cells, preserving their function is critical since sensory cell damage results in irreversible hearing loss. Gentamicin-induced cytotoxicity is one of the major causes of sensory cell damage and consequent sensorineural hearing loss. However, the precise molecular mechanisms and ta...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core symptoms, specifically impaired social behavior, stereotypic/repetitive behaviors, and sensory/communication deficits. Although the exact pathophysiology of ASD is still unknown, host genetics, oxidative stress, and compromised blood brain barrier (BBB) have...
Introduction: Cell-based models play an important role in understanding the pathophysiology and etiology of auditory disorders. For the auditory system, models have primarily focused on restoring inner and outer hair cells. However, they have largely underrepresented the surrounding structures and cells that support the function of the hair cells....
There is a potential association between gastrointestinal (GI) symptoms and the severity of autism spectrum disorder (ASD). Given this correlation, the possible impact of probiotics and prebiotics have been explored in research studies to modify the gut microbiome and ameliorate behavioral manifestations of ASD via modulating the gut-brain-microbio...
Exosomes are small extracellular membrane particles that play a crucial role in intracellular signaling. Research shows that exosomes have the potential to be used as biomarkers or drug delivery systems in specific organs, such as the neurological system and the inner ear. Exosomes in neurological and auditory systems release different molecules wh...
Objective:
To systematically appraise the implementation of cochlear implantation (CI) in Usher Syndrome (USH) Types 1, 2, and 3 patients, and analyze who would benefit from CI.
Data sources:
A comprehensive search of PubMed, Embase, CINAHL, and Cochrane Library electronic databases from inception through June 2020 was performed. There were no l...
Diet has been shown to play an important role in maintaining normal homeostasis in the human body. Milk and milk products are a major component of the Western diet, but their consumption may predispose sensitive individuals to adverse health outcomes. Current literature about milk products recognizes various bioactive components including lactate,...
Cochlear implants (CIs) are widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (SNHL). However, insertion of electrode leads to inner trauma and activation of inflammatory and apoptotic signaling cascades resulting in loss of residual hearing in implanted individuals. Pharmaceutical in...
The use and utility of cochlear implantation has rapidly increased in recent years as technological advances in the field have expanded both the efficacy and eligible patient population for implantation. This review aims to serve as a general overview of the most common hearing disorders that have favorable auditory outcomes with cochlear implants...
Sensorineural deafness in mammals is most commonly caused by damage to inner ear sensory epithelia, or hair cells, and can be attributed to genetic and environmental causes. After undergoing trauma, many non-mammalian organisms, including reptiles, birds, and zebrafish, are capable of regenerating damaged hair cells. Mammals, however, are not capab...
Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not co...
Background:
Electrode insertion trauma (EIT) during cochlear implantation (CI) can cause loss of residual hearing. L-N-acetylcysteine (L-NAC) and dexamethasone (Dex) have been individually shown to provide otoprotection albeit at higher concentrations that may be associated with adverse effects. Objective/Aims: The aim of this study is to determin...
Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental disorder with considerable clinical heterogeneity. With no cure for the disorder, treatments commonly center around speech and behavioral therapies to improve the characteristic social, behavioral, and communicative symptoms of ASD. Gastrointestinal disturbances are comm...
Cochlear implantation (CI) is now widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (SNHL). However, CI can lead to electrode insertion trauma (EIT) that can cause damage to sensory cells in the inner ear resulting in loss of residual hearing. Even with soft surgical techniques where...
Noninvasive and targeted drug delivery to the cochlea is challenging due to anatomic inaccessibility of the inner ear and poor penetration of systemically-delivered drugs.
A method for targeted drug delivery that can be performed in an outpatient setting will provide less invasive approach and reduce complications associated with surgical approache...
Major advancements in targeted gene therapy have opened up avenues for the treatment of major neurological disorders through a range of versatile modalities varying from expression of exogenous to suppression of endogenous genes. Recent technological innovations for improved gene sequence delivery have focused on highly-specific viral vector design...
Hearing loss is the most common neurosensory impairment worldwide. While conductive hearing loss can be managed by surgery, the management of sensorineural hearing loss (SNHL), related to the damage of sensory cells of the inner ear is more challenging to manage medically. Many causes of SNHL such as sudden idiopathic SNHL, Meniere’s disease, noise...
Mesenchymal stem cell (MSC) therapy is an emerging treatment modality for various human diseases. Although induced pluripotent stem cells have been explored for the restoration of hearing, the potential of MSCs as a therapeutic strategy for various cochlear insults is not precisely known. MSCs possess anti‐inflammatory, anti‐apoptotic and neuroprot...
Before a lead compound goes through a clinical trial, preclinical studies utilize two‐dimensional (2D) in vitro models and animal models to study the pharmacodynamics and pharmacokinetics of that lead compound. However, these current preclinical studies may not accurately represent the efficacy and safety of a lead compound in humans, as there has...
Intercellular communication is essential for the development and maintenance of multicellular organisms. Tunneling nanotubes (TNTs) are a recently recognized means of long and short distance communication between a wide variety of cell types. TNTs are transient filamentous membrane protrusions that connect cytoplasm of neighboring or distant cells....
Otitis media (OM) is a common disease affecting humans, especially paediatric populations. OM refers to inflammation of the middle ear and can be broadly classified into two types, acute and chronic. Bacterial infection is one of the most common causes of OM. Despite the introduction of vaccines, the incidence of OM remains significantly high world...
Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. The underlying pathology for cardiovascular disease is largely atherosclerotic in nature and the steps include fatty streak formation, plaque progression and plaque rupture. While there is optimal drug therapy available for patients with CVD, there are also und...
Objective: The present study is aimed at determining the efficacy and exploring the mechanisms by which l-N-acetylcysteine (l-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative s...
Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Due to the significant impact of CVD on humans, there is a need to develop novel treatment modalities tailored to major classes of cardiac diseases including hypertension, coronary artery disease, cardiomyopathies, arrhythmias, valvular disease and inflammato...
Introduction: The emergent field of nanoparticles has presented a wealth of opportunities for improving the treatment of human diseases. Recent advances have allowed for promising developments in drug delivery, diagnostics, and therapeutics. Modified delivery systems allow improved drug delivery over traditional pH, microbe, or receptor dependent m...
Drug delivery is an important consideration in disease treatment. There are many opportunities for novel methods and technologies to hold promising roles in overcoming traditional obstacles. Delivery systems functionalized to boast synergistic antimicrobial effects, specific targeting, and enhanced bioavailability allow for improved therapeutic pot...
Zika virus (ZIKV) is an emerging healthcare threat. The presence of the mosquito Aedes species across South and Central America in combination with complementary climates have incited an epidemic of locally transmitted cases of ZIKV infection in Brazil. As one of the most significant current public health concerns in the Americas, ZIKV epidemic has...
Neurosensory responses of hearing and balance are mediated by receptors in specialized neuroepithelial sensory cells. Any disruption of the biochemical and molecular pathways that facilitate these responses can result in severe deficits, including hearing loss and vestibular dysfunction. Hearing is affected by both environmental and genetic factors...
The use of stem cells in cell-based therapy is an emerging concept for the treatment of ear disorders. Tympanic membrane perforation (TMP) and inner ear disorders are some of the most commonly presented otologic disorders that can benefit from advances in cell-based therapy. Studies have already demonstrated that stem cell-based therapy can potenti...
Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear is comprised of a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it...
Ear is a complex system where appropriate ionic composition is essential for maintaining the tissue homeostasis and hearing function. Ion transporters and channels present in the auditory system plays a crucial role in maintaining proper ionic composition in the ear. The extracellular fluid, called endolymph, found in the cochlea of the mammalian i...
Cover: The cover image, by Xue Liu et al., is based on the Review Article Molecular Structure and Regulation of P2X Receptors With a Special Emphasis on the Role of P2X2 in the Auditory System, DOI: 10.1002/jcp.25274.
Neurotransmitters including catecholamines and serotonin play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the “fight or flight” response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has...
Matrix metalloproteinases (MMPs) are a diverse group of proteolytic enzymes and play an important role in the degradation and remodeling of the extracellular matrix (ECM). In normal physiological conditions, MMPs are usually minimally expressed. Despite their low expression, MMPs have been implicated in many cellular processes ranging from embryolo...
Control group:
(1) untreated controls; (2) EIT. Experimental group: (1) EIT + L-NAC (5, 2, or 1 mM); (2) EIT + Mannitol (100, 50, or 10 mM); (3) EIT + Dex (20, 10, or 5 μg/mL); (4) EIT + L-NAC + Mannitol + Dex. After EIT was caused in an in-vitro model of CI, explants were cultured in media containing L-NAC alone, Mannitol alone, or Dex alone at d...
The P2X purinergic receptors are cation selective channels gated by extracellular adenosine 5'-triphosphate (ATP). These purinergic receptors are found in virtually all mammalian cell types and facilitate a number of important physiological processes. Within the past few years, the characterization of crystal structures of the zebrafish P2X4 recept...
Otitis media (OM) is an inflammation of the middle ear associated with infection. Despite appropriate therapy, acute OM (AOM) can progress to chronic suppurative OM (CSOM) associated with ear drum perforation and purulent discharge. The effusion prevents the middle ear ossicles from properly relaying sound vibrations from the ear drum to the oval w...
Phosphoribosylpyrophosphate synthetase 1 (PRPS1) codes for PRS-I enzyme that catalyzes the first step of nucleotide synthesis. PRPS1 gene mutations have been implicated in a number of human diseases. Recently, new mutations in PRPS1 have been identified that have been associated with novel phenotypes like diabetes insipidus expanding the spectrum o...
Programmed cell death (PCD) initially starts in the support cells (SCs) after electrode insertion trauma (EIT), followed by PCD in hair cells (HCs). Activation of caspase-3 was observed only in SCs. Protecting both SCs and HCs with selective otoprotective drugs at an early stage post implantation may help to preserve residual hearing.
Cochlear impl...
Objectives
(1) Describe the otoprotective mechanisms involved in common otoprotective drugs (ie, NAC, dexamethasone, and mannitol). (2) Describe the otoprotective effect of combining these drugs to prevent hair cell (HC) losses.
Methods
Cochlear explants were dissected from P-3 rats and placed in serum-free media. Explants were divided into 3 grou...
Citations
... Three recent meta-analyses have demonstrated a close association between diabetes and Sensorineural Hearing Loss. [23][24][25] Another cohort study based on NHANES dataset has also shown that diabetes patients might be exposed to a higher risk of hearing loss 26 Further, Loprinzi et al studied the relationship between biomarkers for cardiovascular disease and hearing sensitivity with the NHANES database and ascertained a positive correlation between human insulin levels and high-frequency hearing thresholds. 27 Additionally, Braffett et al recruited 1150 participants for a hearing study in the Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and observed in follow-ups the relevance of higher HBA1c level to HL in speech and high frequencies in 2019. ...
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... The functioning of the GRM3 in human cochlear tissues remains elusive 75 . Single-cell transcriptomic studies in animals located GRM3 in supporting cells 76 . GRM3 activity in cochlear cells is downregulated following noise exposure 77 , a known risk factor for SIN deficits 78 . ...
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... ASD can vary in severity from mild to severe. It not only imposes social and personal challenges on the affected individuals and their families or caregivers but also leads to significant financial impacts on them and the healthcare system [5]. Individuals diagnosed with ASD often need comprehensive interventions from an early age, such as physical therapy, occupational therapy, behavioral therapy, medical treatments, specialized education, and assistive technology [6,7]. ...
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... The term ASD pertains to a number of sophisticated neurodevelopmental cognitive illnesses, including Asperger's disorder, autism, and developmental disintegrative conditions (Griff et al., 2023). The word "spectrum" indicates that these medical conditions have a wide range of signs and severity levels. ...
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... A marble was considered 'buried' if half of its size was covered with sawdust bedding and was counted by observers blind to treatment. The number of marbles buried was considered an index of compulsive behaviour (Eshraghi et al., 2022). ...
... These degenerative processes can have many causes, including genetic mutations and environmental toxins. Their origin could be caused by mitochondrial dysfunction, α-synuclein aggregation, impaired autophagy, endoplasmic reticulum (ER) stress, or deregulation of intracellular calcium homeostasis (Wiefels et al., 2024). The intestinal microbiota is an integral part of the human organism. ...
... This inflammatory response increases the permeability of BLB (Ichimiya et al., 2000). Recent studies postulate that the microbial metabolites and pathogens released from the gut increase BLB permeability, which allows the spreading of inflammatory processes to the inner ear, leading to hearing dysfunctions (Denton et al., 2022;Kociszewska and Vlajkovic, 2022b). The microbes we found in this study, Lachnospiraceae (UCG001), can produce acetic acid, one kind of short-chain fatty acid (SCFA) (Guo and Li, 2019) that has anti-inflammatory and immunomodulatory properties (Dalile et al., 2019). ...
... Современным перспективным направлением медицины является генно-инженерная терапия. Замена или корректирующее редактирование мутантных генетических последовательностей или дефектных генов представляется многообещающим методом, равно как и клеточная заместительная терапия для восстановления поврежденных клеток при нарушениях слуха [42,11]. Эксплантаты кортиева органа и диссоциированные культуры клеток спирального ганглия трансдуцировали векторами, содержащими человеческий ген Bcl-2, а затем подвергали воздействию неомицина, цисплатина или отменяли нейротрофин [37]. ...
... A selective CXCR2 antagonist, SB33223, was able to trigger an anti-inflammatory response by down-regulating inflammatory mediators and NF-kB/Notch inflammatory signaling in mice modeled with ASD (120), which could be a novel target for therapy. In addition, in individuals with ASD, the blood-brain barrier is impaired and permeability is increased (121), and high sensitivity C-reactive protein (hsCRP), prolactin (PRL), and serum reactive oxygen metabolites (ROM) are markedly elevated (122), accompanied by mitochondrial dysfunction and neuronal oxidative stress (123). Based on the neuroinflammatory theory, peripheral activation of immune-inflammatory pathways may lead to neuroinflammation and mitochondrial dysfunction in the CNS, resulting in abnormalities in transsynaptic transmission and brain neurodevelopment (124). ...
... The inherent challenges posed by the deep location and limited quantity of cochlear cells limit research investigating gene expression in cochlear SCs. Most previous studies on cochlear cells have inevitably mixed a variety of different cell types, and potentially important information may be lost in the context of data on complex SC populations (23)(24)(25). One of the biggest difficulties is obtaining enough cells of one single cochlear type for sequencing. ...
