The accurate representation of sound in the central auditory pathway of mammals depends on the cochlea, the peripheral sensory organ, which is optimised to detect acoustic signals with unparalleled temporal precision. Beyond its role in converting acoustic stimuli into electrical signals, the cochlea also plays a key role in shaping the maturation of the auditory pathway during pre-hearing stages. This process is essential for creating the tonotopic maps used to identify a broad range of sound frequencies. To achieve this extraordinary task, the sensory hair cells and supporting cells of the pre-hearing cochlear sensory epithelium generate spontaneous, sensory-independent Ca2+ signals that propagate along the ascending auditory pathway. Here we review the current understanding of how the different Ca2+ signals are generated within the developing cochlea, how they interact to regulate the activation of the auditory afferent fibres, and how they ultimately contribute to the establishment of a mature auditory system pathway. Remarkably, a partial regression to an immature developmental stage occurs in the ageing cochlea, correlated with age-related hearing loss. Increasing our understanding of how the cochlear epithelium changes during all stage of life will inform future therapies for preventing and to reverse hearing loss.

Mutations in MYO7A, the gene encoding the unconventional myosin 7a, cause hereditary deafness in mice and humans. In the cochlea, MYO7A is present in the sensory hair cells from embryonic stages of development, and plays a critical role in the development and maintenance of the mechanosensitive hair bundles composed of actin-rich stereocilia. Shaker-1 mutant mice (Myo7aSh1/Sh1), the murine model of Usher 1B syndrome, exhibit a progressive loss of the stereocilia, subsequent degeneration of the sensory epithelium and ultimately profound deafness. In addition to the hair bundle defects, we found that the shaker-1 mutation prevented both inner hair cells (IHCs) and outer hair cells (OHCs) from acquiring their fully mature basolateral current profile. Delivering exogenous Myo7a to newborn Myo7aSh1/Sh1 mice using dual-adeno-associated virus 8 (AAV8)-Myo7a or dual-AAV9-PhP.eB-Myo7a, which primarily target IHCs, led to a substantial rescue of their hair bundle structure. The rescued bundles regained their ability to generate mechanoelectrical transducer (MET) currents in response to fluid jet displacement. Although the average MET current was smaller than in control IHCs, the normal resting open probability of the MET channel was fully restored. The IHCs of the treated cochlea also regained a mature basolateral membrane current profile. Functionally, rescue of the IHC structure and function, but not that of OHCs, leads to an average improvement of 20-30 dB in hearing thresholds across most frequencies. These results support dual AAV-induced gene replacement therapy as an effective strategy to recover hair-cell function in Myo7aSh1/Sh1 mice. KEY POINTS: Shaker-1 mutant mice (Myo7aSh1/Sh1), which carry a mutation in the unconventional myosin MYO7A and are the murine model of Usher 1B syndrome, become profoundly deaf at 1 month of age or soon after. In the mammalian cochlea, MYO7A is expressed in the hair cells, including within their actin-rich stereociliary bundles. We show that hair cells of Myo7aSh1/Sh1 mice progressively lose their transducing stereocilia and mechanoelectrical transduction, and fail to acquire their fully mature basolateral current profile. Delivering exogenous Myo7a to newborn Myo7aSh1/Sh1 mice using dual-adeno-associated virus (AAVs) led to a substantial rescue of the bundle structure and function of inner hair cells, including mechanoelectrical transduction. This functional rescue led to a 20-30 dB improvement in hearing thresholds across most frequencies. These results support dual AAV-induced gene replacement therapy as an effective strategy to recover the hair-cell function in Myo7aSh1/Sh1 mice.

Accumulation of amyloid beta 42 (Aβ42) senile plaques is the most critical event leading to Alzheimer’s disease (AD). Currently approved drugs for AD have not been able to effectively modify the disease. This has caused increasing research interests in health beneficial nutritious plant foods as viable alternative therapy to prevent or manage AD. Sorghum bicolor presents strong antioxidants, anticancer, anti-inflammatory and antidiabetic properties. However, there is no published data on how this widely available and cost-effective food could benefit people living with AD. Polyphenols were extracted from three Sorghum varieties with black, reddish-brown, and red pericarp. The individual polyphenols compounds were identified using an Agilent 1290 infinity 2 UHPLC system coupled to an Agilent 6475 LC-QQQ LC-MS/MS. The polyphenol extracts were screened using in-silico , MC65 cell and Caenorhabditis elegans AD models. The activities of the extracts against Aβ42 aggregation were analyzed using molecular docking, fluorescence, toxicity, and healthspan assays. Through the application of molecular docking, polyphenols extracted from Sorghum bicolor grains were identified for their potential to inhibit Aβ42 aggregation. Positive interactions were observed between the polyphenols and Aβ42. Cell studies indicated increased viability of MC65 cells, possibly attributed to the inhibition of Aβ42 aggregation. In the Alzheimer’s disease model of Caenorhabditis elegans, enhanced body bending, and pharyngeal pumping were observed compared to controls, suggesting a reduction in pathology. The order of activities was found to be red pericarp < reddish-brown pericarp < black pericarp sorghum. The polyphenol extracts from black pericarp Sorghum bicolor grain could be a candidate ingredient in the development of complementary dietary supplement for AD therapy. Future investigation include lifespan, and fluorescence imaging to unravel the mechanisms underlying the observed health benefits prior to study in AD animal models.

Myosin-VIIA (MYO7A) is an unconventional myosin responsible for syndromic (Usher 1B) or nonsyndromic forms of deafness in humans when mutated. In the cochlea, MYO7A is expressed in hair cells, where it is believed to act as the motor protein tensioning the mechanoelectrical transducer (MET) channels, thus setting their resting open probability ( P o ). However, direct evidence for this unique role for an unconventional myosin in mature hair cells is lacking. Here, we show that MYO7A has a distinct role in hair cells, being crucial for the structural integrity of hair bundles. Postnatal deletion of Myo7a leads to 87 to 96% reduction in MYO7A from hair cells by postnatal day 20 (P20), without affecting hearing function. During the following week, mice showed progressive decline in both hearing function and MET current amplitude in hair cells without affecting the resting P o and calcium sensitivity of the MET channel. Hair-bundle stiffness was normal at P20 but halved at P30, despite it having a normal staircase morphology and tip links. The reduction of MYO7A in the stereocilia (>87%) increased their vulnerability to sound-induced damage, with significantly more hearing loss and hair bundle deterioration than in control mice. RNA-sequencing identified a downregulation of several stereociliary genes in the Myo7a -deficient cochlea, indicating the presence of indirect compensatory mechanisms. This study reveals that mature hair cells seem to use a MYO7A-independent mechanism to maintain the resting P o of the MET channels. Instead, MYO7A is essential for maintaining the structural and functional integrity of the hair bundles.

Abstract Millets, including sorghum grain, are gaining global interest for their rich nutritional profile and potential to develop healthy staple foods. They also have a propensity for low protein and starch digestibility and are high in polyphenolics. These properties provide challenges for designing nutritious and consumer-acceptable foods from sorghum that meet the needs of those under energy/protein malnourishment. In contrast, the high nutritional and polyphenolic profiles and low digestibility make sorghum the ideal grain food to assist those over-energy, malnourished and at risk of obesity and related chronic diseases, including those linked to oxidative stress. Sorghum lacks gluten-forming proteins; therefore, producing sorghum foods with desirable textures is challenging. Extrusion cooking of sorghum may be one processing solution to overcome these barriers and design staple ready-to-eat food products with consumer acceptability. This paper critically reviews the current state of knowledge on the influence of extrusion cooking on protein quality and starch digestibility of sorghum and millet-composite extruded foods.

Head movements are detected and signalled to primary sensory neurons by vestibular types I and II hair cells. Signal transmission involves glutamate exocytosis from hair cells, which is triggered by Ca2+ inflow through voltage-gated CaV1.3 Ca2+ channels. In a previous study on mice, we reported a Ca2+-dependent exocytosis in both hair cell types, measured as a sustained change in cell membrane capacitance (ΔCm) following cell depolarization, which was significantly smaller in type I than in type II hair cells. By contrast, only type I hair cells showed a large transient ΔCm, which was still present in CaV1.3-/- mouse type I hair cells. Here we investigated the nature of this transient ΔCm. We found that it was unaffected by 10 mm intracellular EGTA, which blocked most of the sustained exocytosis in these cells, demonstrating its insensitivity to intracellular Ca2+. Moreover the amplitude of the transient ΔCm correlated with the degree of activation of the low-voltage activated outward rectifying K+ conductance, GK,L, expressed by type I, but not type II hair cells. Finally the sign and kinetics of the transient ΔCm changed based on voltage steps activating or deactivating GK,L. These findings are consistent with the transient ΔCm arising from the mobilization of charges during the gating of K,L channels, while excluding fast transient neurotransmitter exocytosis. Its large amplitude can be explained by the high resistance of the calyceal synaptic cleft since it was significantly reduced in Caspr-/- mice, which show a significantly larger synaptic cleft compared to wild type mice. KEY POINTS: Vestibular type I and type II hair cells signal head movement to the central nervous system. Signal transmission from both hair cell types relies on Ca2+-dependent glutamate exocytosis, measured here as a sustained change in cell membrane capacitance (ΔCm). Type I hair cells exhibit also a large transient ΔCm, whose nature has not been elucidated. In this study we found that the transient ΔCm does not involve exocytosis, but it is generated by the gating of the low-voltage activated outward rectifying K+ conductance, specifically expressed in type I hair cells. Transient ΔCm analysis (also carried out in mice lacking the core protein of the septate-like junction) conclusively demonstrates that type I hair cells, like type II ones, do not elicit a transient release of neurotransmitter. Knowledge of the basic mechanisms of vestibular signalling is crucial in the study of pharmacological treatment for vestibular disorders and in the drug side effects targeted there.

BACKGROUND/OBJECTIVES: In vitro studies suggest that incorporating sorghum flour into staple foods including pasta reduces their starch digestibility and hence may suppress postprandial blood glucose levels, appetite and energy intake; however, these effects in humans have yet to be reported. Therefore, this study investigated the effect of red and white sorghum-containing pasta on blood glucose response, appetite and energy intake in humans. SUBJECTS/METHODS: In a randomised crossover design, healthy individuals (n = 20) consumed the following three iso-caloric test meals (each providing 50 g available carbohydrates) as breakfast: control pasta (CP) made from100% durum wheat; 30% red sorghum pasta (RSP) and; 30% white sorghum pasta (WSP). Blood glucose and subjective appetite were measured postprandially for 2 and 3 h, respectively. Energy intakes from ad libitum lunch consumed 3 h after breakfast and for the remainder of the day were also measured. Incremental areas under or over the curves (iAUCs/iAOCs) for blood glucose and appetite parameters were calculated. RESULTS: The RSP meal resulted in significantly lower blood glucose response (-0.35 +/- 0.09 mmol/l; 95% CI: -0.61 similar to -0.09; P = 0.005) and glucose iAUC over 120 min (-36.11 +/- 10.53 mmol/l x min; 95% CI: -67.11 similar to -5.11; P = 0.017) compared to CP meal. Compared to CP meal, the RSP meal resulted in significantly higher satiety iAUC (1219.46 +/- 383.26 mm x min; 95% 91.18 similar to 2347.75; P = 0.029), lower hunger iAOC (-1410.47 +/- 349.14 mm x min; 95% CI: -2438.30 similar to -382.63; P = 0.004) and lower prospective food intake iAOC (-1645.73 +/- 324.14 mm x min; 95% CI: -2599.97 similar to -691.49; P < 0.001). Energy intake at ad libitum lunch was significantly lower after the RSP meal than after the CP meal (-794.17 +/- 163.25 kJ; 95% CI: -1274.77 similar to -313.57; P = 0.001). CONCLUSION: The results indicate that red sorghum addition into pasta provides a product inducing reduced glycemia, favourably changed appetite parameters and decreased subsequent energy intake.

Summary Empty carob pods, a by‐product of carob seed production, are abundant in D‐pinitol, dietary fibre and phenolics, offering diverse potential health benefits. However, they also contain high levels of sugars. This study evaluated the capacity of Saccharomyces cerevisiae in submerged fermentation of empty carob pods to enhance D‐pinitol to total carbohydrate ratio, and contents of dietary fibre, and phenolics. Empty carob pods were fermented at pH 5.0, 5.5, 6.0, 6.5, and 7.0 at 30 °C for 10, 20, 30 and 50 h. After 20 h of fermentation, the total carbohydrates decreased by 70% ( P < 0.001); the ratio of D‐pinitol to total carbohydrates increased by nearly fivefold ( P < 0.05); total phenolic and total flavonoid contents and antioxidant activity significantly increased ( P < 0.05), whereas condensed tannin content and α‐glucosidase inhibitory activity remained stable. Fermented carob pods may be potentially used as a functional food ingredient to help control blood glucose levels.

Spiral ganglion neurons (SGNs) are primary sensory afferent neurons that relay acoustic information from the cochlear inner hair cells (IHCs) to the brainstem. The response properties of different SGNs diverge to represent a wide range of sound intensities in an action-potential code. This biophysical heterogeneity is established during pre-hearing stages of development, a time when IHCs fire spontaneous Ca2+ action potentials that drive glutamate release from their ribbon synapses onto the SGN terminals. The role of spontaneous IHC activity in the refinement of SGN characteristics is still largely unknown. Using pre-hearing otoferlin knockout mice (Otof-/-), in which Ca2+-dependent exocytosis in IHCs is abolished, we found that developing SGNs fail to upregulate low-voltage-activated K+-channels and hyperpolarisation-activated cyclic-nucleotide-gated channels. This delayed maturation resulted in hyperexcitable SGNs with immature firing characteristics. We have also shown that SGNs that synapse with the pillar side of the IHCs selectively express a resurgent K+ current, highlighting a novel biophysical marker for these neurons. RNA-sequencing showed that several K+ channels are downregulated in Otof-/- mice, further supporting the electrophysiological recordings. Our data demonstrate that spontaneous Ca2+-dependent activity in pre-hearing IHCs regulates some of the key biophysical and molecular features of the developing SGNs. KEY POINTS: Ca2+-dependent exocytosis in inner hair cells (IHCs) is otoferlin-dependent as early as postnatal day 1. A lack of otoferlin in IHCs affects potassium channel expression in SGNs. The absence of otoferlin is associated with SGN hyperexcitability. We propose that type I spiral ganglion neuron functional maturation depends on IHC exocytosis.

Sorghum grain contains high levels and a diverse profile of polyphenols (PPs), which are antioxidants known to reduce oxidative stress when consumed in the diet. Oxidative stress leading to amyloid-β (Aβ) aggregation, neurotoxicity, and mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer’s disease (AD). Thus, PPs have gained attention as possible therapeutic agents for combating AD. This study aimed to (a) quantify the phenolic compounds (PP) and antioxidant capacities in extracts from six different varieties of sorghum grain and (b) investigate whether these PP extracts exhibit any protective effects on human neuroblastoma (BE(2)-M17) cells against Aβ- and tau-induced toxicity, Aβ aggregation, mitochondrial dysfunction, and reactive oxygen species (ROS) induced by Aβ and tert-butyl hydroperoxide (TBHP). PP and antioxidant capacity were quantified using chemical assays. Aβ- and tau-induced toxicity was determined using the 3-(4,5-dimenthylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTS) assay. The thioflavin T (Th-T) assay assessed anti-Aβ aggregation. The dichlorodihydrofluorescein diacetate (DCFDA) assay determined the levels of general ROS and the MitoSOX assay determined the levels of mitochondrial superoxide. Sorghum varieties Shawaya short black-1 and IS1311C possessed the highest levels of total phenolics, total flavonoids, and antioxidant capacity, and sorghum varieties differed significantly in their profile of individual PPs. All extracts significantly increased cell viability compared to the control (minus extract). Variety QL33 (at 2000 µg sorghum flour equivalents/mL) showed the strongest protective effect with a 28% reduction in Aβ-toxicity cell death. The extracts of all sorghum varieties significantly reduced Aβ aggregation. All extracts except that from variety B923296 demonstrated a significant (p ≤ 0.05) downregulation of Aβ-induced and TBHP-induced ROS and mitochondrial superoxide relative to the control (minus extract) in a dose- and variety-dependent manner. We have demonstrated for the first time that sorghum polyphenolic extracts show promising neuroprotective effects against AD, which indicates the potential of sorghum foods to exert a similar beneficial property in the human diet. However, further analysis in other cellular models and in vivo is needed to confirm these effects.

Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming synapses with inner hair cells (IHCs) in the mammalian cochlea. The molecular mechanisms regulating the formation of the post-synaptic density (PSD) in the SGN afferent terminals are still unclear. Here, we demonstrate that brain-specific angiogenesis inhibitor 1 (BAI1) is required for the clustering of AMPA receptors GluR2-4 (glutamate receptors 2-4) at the PSD. Adult Bai1-deficient mice have functional IHCs but fail to transmit information to the SGNs, leading to highly raised hearing thresholds. Despite the almost complete absence of AMPA receptor subunits, the SGN fibers innervating the IHCs do not degenerate. Furthermore, we show that AMPA receptors are still expressed in the cochlea of Bai1-deficient mice, highlighting a role for BAI1 in trafficking or anchoring GluR2-4 to the PSDs. These findings identify molecular and functional mechanisms required for sound encoding at cochlear ribbon synapses.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and most common cause of dementia among older people. The main pathological hallmarks of AD are formation of insoluble amyloid beta senile plaques and paired helical filaments of neurofibrillary tangles. AD features gradual memory decline, mild to severe cognitive impairment, eventually total dependence of patients on caregivers. Currently available drugs have not been able to modify AD pathology. This has drawn increasing attention to plant food materials with high nutritional and bioactive constituents as potential complementary therapy for AD. Sorghum bicolor is a widely available cost-effective source of proteins, fats, crude fibres, biopeptides and polyphenols which are vital for human wellbeing. This review discussed the major mechanisms underlying AD pathology. The nutritional and bioactive constituents of Sorghum bicolor grains were extensively described. There is limited report on anti-AD activities of sorghum grains. Therefore, the pharmacological mechanisms of action including scavenging of reactive oxygen species, inhibition of oxidative stress, anti-acetylcholinesterase activity and modulation of mitophagy were only speculated. This comprehensive update suggests more robust innovative studies that will provide critical theoretical details necessary to promote utilization of sorghum grains as functional food or source of bioactive molecules for AD therapy.

In the mammalian cochlea, sensory hair cells are crucial for the transduction of acoustic stimuli into electrical signals, which are then relayed to the central auditory pathway via spiral ganglion neuron (SGN) afferent dendrites. The SGN output is directly modulated by inhibitory cholinergic axodendritic synapses from the efferent fibers originating in the superior olivary complex. When the adult cochlea is subjected to noxious stimuli or aging, the efferent system undergoes major rewiring, such that it reestablishes direct axosomatic contacts with the inner hair cells (IHCs), which occur only transiently during prehearing stages of development. The trigger, origin, and degree of efferent plasticity in the cochlea remains largely unknown. Using functional and morphological approaches, we demonstrate that efferent plasticity in the adult cochlea occurs as a direct consequence of mechanoelectrical transducer current dysfunction. We also show that, different from prehearing stages of development, the lateral olivocochlear - but not the medial olivocochlear - efferent fibers are those that form the axosomatic synapses with the IHCs. The study also demonstrates that in vivo restoration of IHC function using AAV-Myo7a rescue reestablishes the synaptic profile of adult IHCs and improves hearing, highlighting the potential of using gene-replacement therapy for progressive hearing loss.

Despite some evidence indicating diverse roles of whirlin in neurons, the functional corollary of whirlin gene function and behavior has not been investigated or broadly characterized. A single nucleotide variant was identified from our recessive ENU-mutagenesis screen at a donor-splice site in whirlin, a protein critical for proper sensorineural hearing function. The mutation (head-bob, hb) led to partial intron-retention causing a frameshift and introducing a premature termination codon. Mutant mice had a head-bobbing phenotype and significant hyperactivity across several phenotyping tests. Lack of complementation of head-bob with whirler mutant mice confirmed the head-bob mutation as functionally distinct with compound mutants having a mild-moderate hearing defect. Utilizing transgenics, we demonstrate rescue of the hyperactive phenotype and combined with the expression profiling data conclude whirlin plays an essential role in activity-related behaviors. These results highlight a pleiotropic role of whirlin within the brain and implicate alternative, central mediated pathways in its function.

SummaryFermentation may beneficially increase the bioaccessibility of minerals in legumes. In this study, the contents and in vitro bioaccessibilities of Ca, Mg, Fe and Zn were determined in lupin whole seed and dehulled seed during soaking, cooking and then fermentation with Bacillus subtilis into a natto analogue. For total mineral content, a significant loss (P < 0.05) of Mg was observed after cooking for both whole and dehulled seed. During pre‐processing, the Ca bioaccessibilities of whole and dehulled were highest (P < 0.05) in the soaked seed and for Mg was highest (P < 0.05) in the cooked samples. At all fermentation times, the bioaccessibility of all minerals was higher (P < 0.05) in the dehulled than the whole seed. Significant increases (P < 0.05) in bioaccessibility during fermentation were observed for Fe at 48 h and Zn 24 h in dehulled seed, providing the first evidence for the beneficial effect of lupin fermentation by B. subtilis in terms of Fe and Zn availability.

White rice is a high glycemic index food, and therefore different approaches are adopted to reduce its glycemic effect. The present study investigated the effect of adding fenugreek and Nigella sativa seed powder to white rice on glycemia, appetite, palatability, and gastrointestinal clinical manifestations in healthy subjects. In a randomized crossover design, 16 healthy subjects consumed white rice alone (control group), white rice with 2-g fenugreek seed powder, or white rice with 4-g nigella seed powder on different occasions. Each test meal provided 50 g of available carbohydrates. Blood glucose, subjective appetite, and gastrointestinal manifestations were measured at fasting and postprandially for 2 h. Palatability of the test meals was also measured using a 9-point hedonic scale. The nigella meal resulted in significantly lower blood glucose concentration (31.25 mg/dL) at 30 min (p = 0.022), compared to the control meal (43.88 mg/dL) whereas fenugreek meal showed no significant effect. Moreover, the nigella meal significantly increased satiety ratings at 30 and 90 min (p = 0.035 and 0.018, respectively). The results demonstrated that the addition of nigella powder to white rice reduced its glycemic response and increased satiety, compared to the control meal. All test meals were judged as acceptable by the subjects and their consumption didn’t cause any gastrointestinal discomfort. Results of the current study demonstrated promising implications for reducing glycemic response of white rice, a commonly consumed high-glycemic index food.

Sensory‐independent Ca 2+ spiking regulates the development of mammalian sensory systems. In the immature cochlea, inner hair cells (IHCs) fire spontaneous Ca 2+ action potentials (APs) that are generated either intrinsically or by intercellular Ca 2+ waves in the nonsensory cells. The extent to which either or both of these Ca 2+ signalling mechansims are required for IHC maturation is unknown. We find that intrinsic Ca 2+ APs in IHCs, but not those elicited by Ca 2+ waves, regulate the maturation and maintenance of the stereociliary hair bundles. Using a mouse model in which the potassium channel Kir2.1 is reversibly overexpressed in IHCs ( Kir2.1‐ OE), we find that IHC membrane hyperpolarization prevents IHCs from generating intrinsic Ca 2+ APs but not APs induced by Ca 2+ waves. Absence of intrinsic Ca 2+ APs leads to the loss of mechanoelectrical transduction in IHCs prior to hearing onset due to progressive loss or fusion of stereocilia. RNA‐sequencing data show that pathways involved in morphogenesis, actin filament‐based processes, and Rho‐GTPase signaling are upregulated in Kir2.1‐ OE mice. By manipulating in vivo expression of Kir2.1 channels, we identify a “critical time period” during which intrinsic Ca 2+ APs in IHCs regulate hair‐bundle function.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that accounts for most dementia cases. It has become a serious international health and economic concern as there is no effective treatment. Naturally derived products, particularly polyphenols (PP), have become very popular for developing effective therapeutic strategies for AD. PP apply their neuroprotective actions through targeting various pathological hallmarks of the disease, such as Aβ and/or aggregation, oxidative stress and mitochondrial dysfunction. Aβ aggregation is majorly implicated in the pathogenesis of AD. Therefore, finding a way to attenuate Aβ-induced toxicity could be a potential approach for disease-modifying treatments of AD. In the current study, the effect of polyphenolic extract from different sorghum varieties was assessed against Aβ 42 -induced cytotoxicity. A cell viability assay (MTS) was utilized to assess the protective effect of the extracts on Aβ-induced cytotoxicity in human neuroblastoma BE (2)-M17 cells. Following that, a thioflavin T (Th-T) assay was performed to assess the anti-Aβ aggregation effect of the extracts. The sorghum extracts significantly increased the cell viability. Of the six different tested extracts, QL33(2000 µg/ml) and B923296(1000 µg/ml) demonstrated the strongest and weakest protective effect in decreasing Aβ-induced cell death (p < 0.01), respectively. In addition, the sorghum extracts were effective at inhibiting the Aβ aggregation. Sorghum polyphenolic extracts demonstrated a promising neuroprotective effect against Aβ-induced cytotoxicity and therefore can be considered as a potential naturally derived agent for AD treatment. However, further studies are required to confirm the anti-AD effects of these sorghum extracts.

The transduction of acoustic information by hair cells depends upon mechanosensitive stereociliary bundles that project from their apical surface. Mutations or absence of the stereociliary protein EPS8 cause deafness in humans and mice, respectively. Eps8 knockout mice (Eps8-'-) have hair cells with immature stereocilia and fail to become sensory receptors. Here, we show that exogenous delivery of Eps8 using Anc80L65 in P1-P2 Eps8-'- mice in vivo rescued the hair bundle structure of apical-coil hair cells. Rescued hair bundles correctly localize EPS8, WHIRLIN, MYO15, and BAIAP2L2, and generate normal mechanoelectrical transducer currents. Inner hair cells with normal-looking stereocilia re-expressed adult-like basolateral ion channels (BK and KCNQ4) and have normal exocytosis. The number of hair cells undergoing full recovery was not sufficient to rescue hearing in Eps8-'- mice. Adeno-associated virus (AAV)-transduction of P3 apical-coil and P1-P2 basalcoil hair cells does not rescue hair cells, nor does Anc80L65Eps8 delivery in adult Eps8-'- mice. We propose that AAV-induced gene-base therapy is an efficient strategy to recover the therapeutic approach may need to be performed in utero since, at postnatal ages, Eps8-'- hair cells appear to have matured or accumulated damage beyond the point of repair.