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Kaleli, H. N.

Publications and source records attributed to Kaleli, H. N..

3 recordsLinked to original sources

Functional Human Retinohypothalamic Tract Assembloid Model for Circadian Rhythm Research

The retinohypothalamic tract (RHT) is the primary pathway for circadian photoentrainment. Rodent models exhibit a significant translational gap for human physiology due to their nocturnal nature. To overcome this, we developed a functional human RHT assembloid by fusing human pluripotent stem cell (hPSC) derived retinal and hypothalamus organoids. Characterization revealed mature retinal brush borders and the preservation of melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) integrated via excitatory glutamatergic synapses. Multielectrode array (MEA) analysis confirmed synchronized network activity across the interface. The development of the human RHT assembloid represents a significant leap forward in chronobiology. The "gold standard" for circadian models--self-sustained gene expression oscillations--was demonstrated using a PER2::Luciferase reporter, showing robust 20- 30 hour rhythms. This validates the hypothalamic component as a functional "clock in a dish". This platform provides a readout to screen drugs or test light-pulse effects on circadian phase, directly modeling jet lag or phase-shifting. Overall, this model offers a high-fidelity system for investigating human-specific chronobiological mechanisms in vitro. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/700761v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1327027org.highwire.dtl.DTLVardef@61183corg.highwire.dtl.DTLVardef@7e280eorg.highwire.dtl.DTLVardef@77e7ce_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Effects of Primed Adipose Mesenchymal Stem Cell-Derived Exosomes on Immunomodulation in Behcet Uveitis

PurposeThis study sought to investigate the potential role of exosomes of interferon-gamma (IFN-{gamma}) primed (IFN+Exo) and non-primed (IFN-Exo) adipose-derived mesenchymal stem cells (AdMSCs) for the treatment of Behcet Disease (BD) uveitis (BU). MethodsAdMSCs were isolated from adipose tissue. Characterization and multipotency analyses were performed. Exosomes were isolated from the media of AdMSCs and then characterized. Peripheral blood mononuclear cells (PBMC) were isolated from patients with BU and healthy individuals. AdMSCs were preincubated with or without IFN-{gamma} for 48 h. PBMC of patients with BU and healthy controls separately cultured with exosomes for 72 h. After the culture period, lymphocyte proliferation, viability, and apoptosis were carried out via flow cytometry. The expression of interleukin (IL)-10, IL-17, transforming growth factor (TGF)-{beta}, and interferon (IFN)-{gamma} levels were measured by real-time polymerase chain reaction (RT-PCR). ResultsIFN+Exo promoted lymphocyte apoptosis in patients with BU. IFN+Exo suppressed cell viability of T lymphocytes of BU. Exosomes alone did not affect on T lymphocyte proliferation. Additionally, exosomes increased anti-inflammatory cytokine levels and reduced pro-inflammatory cytokine levels of T lymphocytes in patients with BU. ConclusionThis studys findings can open a new pathway in MSCs/exosome therapy in BU.

immunology↗

A Retina-inspired Optoelectronic Synapse Using Quantum Dots for Neuromorphic Photostimulation of Neurons

Neuromorphic electronics, inspired by the functions of neurons, have the potential to enable biomimetic communication with cells. Such systems require operation in aqueous environments, generation of sufficient levels of ionic currents for neurostimulation, and plasticity. However, their implementation requires a combination of separate devices, such as sensors, organic synaptic transistors, and stimulation electrodes. Here, we present a compact neuromorphic synapse that combines photodetection, memory, and neurostimulation functionalities all-in-one. The artificial photoreception is facilitated by a photovoltaic device based on cell-interfacing InP/ZnS quantum dots, which induces photo-faradaic charge-transfer mediated plasticity. The device sends excitatory post-synaptic currents exhibiting paired-pulse facilitation and post-tetanic potentiation to the hippocampal neurons via the biohybrid synapse. The electrophysiological recordings indicate modulation of the probability of action potential firing due to biomimetic temporal summation of excitatory post-synaptic currents. Our results pave the way for the development of novel bioinspired neuroprosthetics and soft robotics and highlight the potential of quantum dots for achieving versatile neuromorphic functionality in aqueous environments.

bioengineering↗