The Regenerative Potential of Donkey and Human Milk on the Redox-Sensitive and Proliferative Signaling Pathways of Skin Fibroblasts

The influence of milk bioactive peptides on skin regenerative potential and rejuvenation is very often limited because of allergic reactions. The current study is aimed at exploring the influence of donkey colostrum and mature milk, human colostrum and mature milk, and β-casein and β-casomorphine-7, on the growth and inflammatory response of the culture of cultured skin fibroblasts exposed to these conditions for twenty-four hours. Their effects on the growth-regulatory kinases and redox-sensitive, proinflammatory transcriptional factor NF-κB were detected by using specific primary antibodies against NF-κB p65, Akt-1, phospho-Akt-1, Erk-1, phospho-Erk-1, JNK, phospho-JNK, phospho-STAT-1, and CD26, while logarithmic integrated fluorescence intensity patterns were recorded by flow cytometry. The downregulation of NF-κB p65 was observed after the exposure of skin fibroblasts to donkey milk and human colostrum, while β-casein and β-casomorphine-7 exerted the opposite effect, which suggests that noncasein bioactive peptides of donkey and human milk may be responsible for anti-inflammatory properties. The exposure to all milk species examined and β-casein leads to the activation of growth-regulatory kinases (Akt1/2/3 kinase, Erk kinase, JNK kinase, and Stat-1 kinase), especially for the p-Erk pathway, which suggests that essential amino acids of casein may be responsible for Erk-induced cell cycle activation and proliferation. The opposite effect was observed when cells were exposed to β-casomorphine-7, which may affect the skin fibroblast survival and their proliferative and regenerative potential. Donkey milk did not significantly change the CD26 antigen expression. In conclusion, our results suggest that among cell signaling molecules, the most sensitive but nonspecific downstream effector is p-Erk kinase, which may point to donkey milk usefulness in wound healing, regenerative, and aesthetic dermatology. The noncasein bioactive peptides of donkey milk may be responsible for the anti-inflammatory property of donkey milk and colostrum, which may indicate the usefulness in the treatment of inflammatory skin diseases

Speech discrimination performance in multiple sclerosis dataset

The most complex interactions between human beings occur through speech, and often in the presence of background noise. Understanding speech in noisy environments requires the integrity of highly integrated and widespread auditory networks likely to be impacted by multiple sclerosis (MS) related neurogenic injury. Despite the impact auditory communication has on a person's ability to navigate the world, build relationships, and maintain employability; studies of speech-in-noise (SiN) perception in people with MS (pwMS) have been minimal to date. Thus, this paper presents a dataset related to the acquisition of pure-tone thresholds, SiN performance and questionnaire responses in age-matched controls and pwMS. Bilateral pure-tone hearing thresholds were obtained at frequencies of 250 hertz (Hz), 500 Hz, 750 Hz, 1000 Hz, 1500 Hz, 2000 Hz, 4000 Hz, 6000 Hz and 8000 Hz, and hearing thresholds were defined as the lowest level at which the tone was perceived 50% of the time. Thresholds at 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz were used to calculate the four-tone average for each participant, and only those with a bilateral four tone average of ≤ 25 dB HL were included in the analysis. To investigate SiN performance in pwMS, pre-recorded Bamford-Kowal-Bench (BKB) sentences were presented binaurally through headphones at five signal-to-noise ratios (SNR) in two noise conditions: speech-weighted noise and multi-talker babble. Participants were required to verbally repeat each sentence they had just heard; or indicate their inability to do so. A 33-item questionnaire, based on validated inventories for specific adult clinical populations with abnormal auditory processing, was used to evaluate auditory processing in daily life for pwMS. For analysis, pwMS were grouped according to their Expanded Disability Status Scale (EDSS) score as rated by a neurologist. PwMS with EDSS scores ≤ 1.5 were classified as 'mild' (n = 20); between 2 and 4.5 as 'moderate' (n = 16) and between 5 and 7 as 'advanced' (n = 10) and were compared to neurologically healthy controls (n = 38). The outcomes of the SiN task conducted in pwMS can be found in Iva et al., (2021). The present data has important implications for the timing and delivery of preparatory education to patients, family, and caregivers about communication abilities in pwMS. This dataset will also be valuable for the reuse/reanalysis required for future investigations into the clinical utility of SiN tasks to monitor disease progression

Speech discrimination impairments as a marker of disease severity in multiple sclerosis

BACKGROUND: Multiple Sclerosis (MS) pathology is likely to disrupt central auditory pathways, thereby affecting an individual's ability to discriminate speech from noise. Despite the importance of speech discrimination in daily communication, it's characterization in the context of MS remains limited. This cross-sectional study evaluated speech discrimination in MS under "real world" conditions where sentences were presented in ecologically valid multi-talker speech or broadband noise at several signal-to-noise ratios (SNRs). METHODS: Pre-recorded Bamford-Kowal-Bench sentences were presented at five signal-to-noise ratios (SNR) in one of two background noises: speech-weighted noise and eight-talker babble. All auditory stimuli were presented via headphones to control (n = 38) and MS listeners with mild (n = 20), moderate (n = 16) and advanced (n = 10) disability. Disability was quantified by the Kurtzke Expanded Disability Status Scale (EDSS) and scored by a neurologist. All participants passed a routine audiometric examination. RESULTS: Despite normal hearing, MS psychometric discrimination curves which model the relationship between signal-to-noise ratio (SNR) and sentence discrimination accuracy in speech-weighted noise and babble did not change in slope (sentences/dB) but shifted to higher SNRs (dB) compared to controls. The magnitude of the shift in the curve systematically increased with greater disability. Furthermore, mixed-effects models identified EDSS score as the most significant predictor of speech discrimination in noise (odds ratio = 0.81; p < 0.001). Neither age, sex, disease phenotype or disease duration were significantly associated with speech discrimination performance in noise. Only MS listeners with advanced disability self-reported audio-attentional difficulty in a questionnaire designed to reflect auditory processing behaviours in daily life. CONCLUSION: Speech discrimination performance worsened systematically with greater disability, independent of age, sex, education, disease duration or disease phenotype. These results identify novel auditory processing deficits in MS and highlight that speech discrimination tasks may provide a viable non-invasive and sensitive means for disease monitoring in MS

Functional and structural differences in fibroblasts from atria of patients with and without atrial fibrillation

Conclusion: This study, for the first time, identifies differences in fibroblasts from human atria between AR (atrial fibrillation) and non-AF patients with regard to size, shape, motility, and time to wound closure. Further investigation into the functional significance of these differences on cardiac repair after injury and progression of AF and its complications is warranted