10 research outputs found
Effects of protocol utilized for collection of whole saliva stimulated by TENS in healthy adult Indians
<p><strong>Objective: </strong>The objective of this study was to evaluate the effects of Transcutaneous Electric Nerve stimulation (TENS) on whole salivary flow rate in healthy adult subjects and to find out whether the protocol utilized for collection of saliva influence the quantity of saliva stimulated.</p> <p><strong>Materials and Methods: </strong>Using an extraoral TENS applied over parotid glands stimulated whole saliva flow rate in fifty healthy adult subjects was measured Collection of TENS stimulated saliva was performed on day 1 after collection of unstimulated saliva, on day 2 only TENS stimulated saliva was measured. The data obtained was subjected to statistical analysis using paired âtâ test.</p> <p><strong>Results:</strong> Thirty nine patients on day one and thirty six patients on day two out of 50 (75 % of the subjects tested) responded to TENS therapy with an increase of stimulated whole saliva flow rate .There was a reduction in quantity of TENS stimulated saliva on day one and two with a difference of 4% which statistically significant with p value 0.009.</p> <p><strong>Conclusions: </strong>Transcutaneous electric nerve stimulation (TENS) as an extra-oral device can be considered as a safe, non-pharmacological measure in order to achieve an increase of the rate of unstimulated saliva. Further studies should be conducted to evaluate the possibility of using TENS in relieving the symptoms of xerostomia.<strong></strong></p>
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Biophysical, Molecular and Proteomic Profiling of Human Retinal Organoid-Derived Exosomes
PurposeThere is a growing interest in extracellular vesicles (EVs) for ocular applications as therapeutics, biomarkers, and drug delivery vehicles. EVs secreted from mesenchymal stem cells (MSCs) have shown to provide therapeutic benefits in ocular conditions. However, very little is known about the properties of bioreactor cultured-3D human retinal organoids secreted EVs. This study provides a comprehensive morphological, nanomechanical, molecular, and proteomic characterization of retinal organoid EVs and compares it with human umbilical cord (hUC) MSCs.MethodsThe morphology and nanomechanical properties of retinal organoid EVs were assessed using Nanoparticle tracking analysis (NTA) and Atomic force microscopy (AFM). Gene expression analysis of exosome biogenesis of early and late retinal organoids were compared using qPCR. The protein profile of the EVs were analyzed with proteomic tools.ResultsNTA indicated the average size of EV as 100-250 nm. A high expression of exosome biogenesis genes was observed in late retinal organoids EVs. Immunoblot analysis showed highly expressed exosomal markers in late retinal organoids EVs compared to early retinal organoids EVs. Protein profiling of retinal organoid EVs displayed a higher differential expression of retinal function-related proteins and EV biogenesis proteins than hUCMSC EVs, implicating that the use of retinal organoid EVs may have a superior therapeutic effect on retinal disorders.ConclusionThis study provides supplementary knowledge on the properties of retinal organoid EVs and suggests their potential use in the diagnostic and therapeutic treatments for ocular diseases
Combined Transcriptomic and Proteomic Profiling to Unravel Osimertinib, CARP-1 Functional Mimetic (CFM 4.17) Formulation and Telmisartan Combo Treatment in NSCLC Tumor Xenografts
The epidermal growth factor receptor (EGFR) is highly expressed in many non-small cell lung cancers (NSCLC), necessitating the use of EGFR-tyrosine kinase inhibitors (TKIs) as first-line treatments. Osimertinib (OSM), a third-generation TKI, is routinely used in clinics, but T790M mutations in exon 20 of the EGFR receptor lead to resistance against OSM, necessitating the development of more effective therapeutics. Telmisartan (TLM), OSM, and cell cycle and apoptosis regulatory protein 1 (CARP-1) functional mimetic treatments (CFM4.17) were evaluated in this study against experimental H1975 tumor xenografts to ascertain their anti-cancer effects. Briefly, tumor growth was studied in H1975 xenografts in athymic nude mice, gene and protein expressions were analyzed using next-generation RNA sequencing, proteomics, RT-PCR, and Western blotting. TLM pre-treatment significantly reduced the tumor burden when combined with CFM-4.17 nanoformulation and OSM combination (TLM_CFM-F_OSM) than their respective single treatments or combination of OSM and TLM with CFM 4.17. Data from RNA sequencing and proteomics revealed that TLM_CFM-F_OSM decreased the expression of Lamin B2, STAT3, SOD, NFKB, MMP-1, TGF beta, Sox-2, and PD-L1 proteins while increasing the expression of AMPK proteins, which was also confirmed by RT-PCR, proteomics, and Western blotting. According to our findings, the TLM_CFM-F_OSM combination has a superior anti-cancer effect in the treatment of NSCLC by affecting multiple resistant markers that regulate mitochondrial homeostasis, inflammation, oxidative stress, and apoptosis
Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
In cancer patients, chronic paclitaxel (PTX) treatment causes excruciating pain, limiting its use in cancer chemotherapy. The neuroprotective potential of synthetic cannabidiol (CBD) and CBD formulated in extracellular vesicles (CBD-EVs) isolated from human umbilical cord derived mesenchymal stem cells was investigated in C57BL/6J mice with PTX-induced neuropathic pain (PIPN). The particle size of EVs and CBD-EVs, surface roughness, nanomechanical properties, stability, and release studies were all investigated. To develop neuropathy in mice, PTX (8 mg/kg, i.p.) was administered every other day (four doses). In terms of decreasing mechanical and thermal hypersensitivity, CBD-EVs treatment was superior to EVs treatment or CBD treatment alone (p < 0.001). CBD and CBD-EVs significantly reduced mitochondrial dysfunction in dorsal root ganglions and spinal homogenates of PTX-treated animals by modulating the AMPK pathway (p < 0.001). Studies inhibiting the AMPK and 5HT1A receptors found that CBD did not influence the neurobehavioral or mitochondrial function of PIPN. Based on these results, we hypothesize that CBD and CBD-EVs mitigated PIPN by modulating AMPK and mitochondrial function
Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
In cancer patients, chronic paclitaxel (PTX) treatment causes excruciating pain, limiting its use in cancer chemotherapy. The neuroprotective potential of synthetic cannabidiol (CBD) and CBD formulated in extracellular vesicles (CBD-EVs) isolated from human umbilical cord derived mesenchymal stem cells was investigated in C57BL/6J mice with PTX-induced neuropathic pain (PIPN). The particle size of EVs and CBD-EVs, surface roughness, nanomechanical properties, stability, and release studies were all investigated. To develop neuropathy in mice, PTX (8 mg/kg, i.p.) was administered every other day (four doses). In terms of decreasing mechanical and thermal hypersensitivity, CBD-EVs treatment was superior to EVs treatment or CBD treatment alone (p p < 0.001). Studies inhibiting the AMPK and 5HT1A receptors found that CBD did not influence the neurobehavioral or mitochondrial function of PIPN. Based on these results, we hypothesize that CBD and CBD-EVs mitigated PIPN by modulating AMPK and mitochondrial function
Correction: Kalvala et al. Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy. <i>Pharmaceutics</i> 2023, <i>15</i>, 554
âYan Liâ was not included as an author in the original publication [...
DIAPH1 mediates progression of atherosclerosis and regulates hepatic lipid metabolism in mice
Funding for this project included: U.S. Public Health Service (P01HL146367) to AMS, AS, and RR and 1P01HL131481 (EF, AMS, and RR). Support was also provided from the Diabetes Research Program, NYU Grossman School of Medicine.
Primary data are available in Supplementary Data 1â6. RNAseq data are deposited to NCBI GEO GSE156403. Any materials reported in this research are available through Material Transfer Agreement (MTA) with NYU Grossman School of Medicine.Atherosclerosis evolves through dysregulated lipid metabolism interwoven with exaggerated inflammation. Previous work implicating the receptor for advanced glycation end products (RAGE) in atherosclerosis prompted us to explore if Diaphanous 1 (DIAPH1), which binds to the RAGE cytoplasmic domain and is important for RAGE signaling, contributes to these processes. We intercrossed atherosclerosis-prone Ldlrâ/â mice with mice devoid of Diaph1 and fed them Western diet for 16 weeks. Compared to male Ldlrâ/â mice, male Ldlrâ/â Diaph1â/â mice displayed significantly less atherosclerosis, in parallel with lower plasma concentrations of cholesterol and triglycerides. Female Ldlrâ/â Diaph1â/â mice displayed significantly less atherosclerosis compared to Ldlrâ/â mice and demonstrated lower plasma concentrations of cholesterol, but not plasma triglycerides. Deletion of Diaph1 attenuated expression of genes regulating hepatic lipid metabolism, Acaca, Acacb, Gpat2, Lpin1, Lpin2 and Fasn, without effect on mRNA expression of upstream transcription factors Srebf1, Srebf2 or Mxlipl in male mice. We traced DIAPH1-dependent mechanisms to nuclear translocation of SREBP1 in a manner independent of carbohydrate- or insulin-regulated cues but, at least in part, through the actin cytoskeleton. This work unveils new regulators of atherosclerosis and lipid metabolism through DIAPH1.Depto. de GenĂ©tica, FisiologĂa y MicrobiologĂaFac. de Ciencias BiolĂłgicasTRUEpu