Can pluripotent/multipotent stem cells reverse Parkinson's disease progression?

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by continuous and selective degeneration or death of dopamine neurons in the midbrain, leading to dysfunction of the nigrostriatal neural circuits. Current clinical treatments for PD include drug treatment and surgery, which provide short-term relief of symptoms but are associated with many side effects and cannot reverse the progression of PD. Pluripotent/multipotent stem cells possess a self-renewal capacity and the potential to differentiate into dopaminergic neurons. Transplantation of pluripotent/multipotent stem cells or dopaminergic neurons derived from these cells is a promising strategy for the complete repair of damaged neural circuits in PD. This article reviews and summarizes the current preclinical/clinical treatments for PD, their efficacies, and the advantages/disadvantages of various stem cells, including pluripotent and multipotent stem cells, to provide a detailed overview of how these cells can be applied in the treatment of PD, as well as the challenges and bottlenecks that need to be overcome in future translational studies.

Effect of Intermittent Fasting on Cardiometabolic Health in the Chinese Population: A Meta-Analysis of Randomized Controlled Trials.

The efficacy of intermittent fasting (IF), as an emerging weight management strategy, in improving cardiometabolic health has been evaluated in various populations, but that among Chinese individuals has not been systematically studied. A comprehensive search on multiple databases was performed to identify eligible randomized controlled trials (RCTs) up to October 2022. The primary outcome was post-intervention weight loss, and secondary outcomes included changes in cardiometabolic indicators. Effect estimates were meta-analyzed using a random-effects model. In total, nine RCTs with 899 Chinese participants were included. Time-restricted eating was the most adopted IF protocol in this study (six out of nine), followed by alternate-day fasting. The IF intervention significantly reduced body weight, body mass index, body fat mass, homeostatic model assessment of insulin resistance, low-density lipoprotein cholesterol, and triglycerides when compared with control groups. However, no statistically significant reductions in waist circumference, total cholesterol, high-density lipoprotein cholesterol, fasting glucose, systolic blood pressure, and diastolic blood pressure were found. To sum up, IF can be a weight management strategy and may improve the cardiometabolic health of Chinese adults, but more long-term trials using different IF strategies are required to generate robust evidence of its efficacy.

Time-restricted eating for chronodisruption-related chronic diseases.

The circadian timing system enables organisms to adapt their physiology and behavior to the cyclic environmental changes including light-dark cycle or food availability. Misalignment between the endogenous circadian rhythms and external cues is known as chronodisruption and is closely associated with the development of metabolic and gastrointestinal disorders, cardiovascular diseases, and cancer. Time-restricted eating (TRE, in human) is an emerging dietary approach for weight management. Recent studies have shown that TRE or time-restricted feeding (TRF, when referring to animals) has several beneficial health effects, which, however, are not limited to weight management. This review summarizes the effects of TRE/TRF on regulating energy metabolism, gut microbiota and homeostasis, development of cardiovascular diseases and cancer. Furthermore, we will address the role of circadian clocks in TRE/TRF and propose ways to optimize TRE as a dietary strategy to obtain maximal health benefits.

Linking circadian rhythms to microbiome-gut-brain axis in aging-associated neurodegenerative diseases.

Emerging evidence suggests that both disruption of circadian rhythms and gut dysbiosis are closely related to aging-associated neurodegenerative diseases. Over the last decade, the microbiota-gut-brain axis has been an emerging field and revolutionized studies in pathology, diagnosis, and treatment of neurological disorders. Crosstalk between the brain and gut microbiota can be accomplished via the endocrine, immune, and nervous system. Recent studies have shown that the composition and diurnal oscillation of gut microbiota are influenced by host circadian rhythms. This provides a new perspective for investigating the microbiome-gut-brain axis. We aim to review current understanding and research on the dynamic interaction between circadian rhythms and the microbiome-gut-brain axis. Furthermore, we will address the possible neurodegenerative disease contribution through circadian rhythms and microbiome-gut-brain axis crosstalk.

Circadian disruption-induced metabolic syndrome in mice is ameliorated by oat ß-glucan mediated by gut microbiota.

Circadian disruption-induced metabolic syndrome (CDIMS) involves body weight gain, changes in blood profile and gut microbiota. In this study, CDIMS was induced by shifted light dark cycle (SLDC) in C57BL/6J mice. Dietary intervention by oral administration of oat ß-glucan (a polymeric prebiotic) alleviated CDIMS when compared to chicory inulin/fructan (an oligomeric prebiotic) and melatonin (a chronobiotic). Oat ß-glucan reversed the increase in body weight, liver weight-to-body weight ratio and plasma leptin concentration as well as restored glucose tolerance. In altering gut microbiota, oat ß-glucan increased the species richness, reversed the populations of 7 bacterial genera and increased butyrate producers including Ruminococcaceae and Lachnospiraceae which enhance gut barrier protection and regulate glucose homeostasis. Correlation analysis demonstrated the linking of the alleviation of CDIMS by prebiotics and melatonin with different microbial metabolic pathways involved in energy metabolism, biosynthesis of metabolites, metabolism of cofactors and vitamins and endocrine synthesis.

Prebiotic supplementation (beta-glucan and inulin) attenuates circadian misalignment induced by shifted light-dark cycle in mice by modulating circadian gene expression.

Circadian rhythm governs multiple behavioural and physiological processes and its disruption is closely associated with various pathological conditions. In this study, the effects of dietary intervention by prebiotics including beta-glucan and inulin on attenuating circadian desynchrony in C57BL/6J mice subjected to weekly shifted light-dark cycle under a high fat diet was investigated. Using RT-qPCR and rhythmicity analysis, our study revealed that beta-glucan (0.2 g/day) and inulin (0.2 g/day) modulated the expression and phase of circadian-clock genes, explicitly reversed the phase delay of Period 1 and Period 3 in the hypothalamus, and reversed the phase delay of Period 2 in the liver of the mice. In the shifted mouse group, inulin also exhibited its reversal effects on the phase advance of Brain and muscle-Arnt-like 1 in the hypothalamus. These findings indicated that prebiotic supplementation can be a novel dietary approach for attenuating circadian misalignment.

Framework as a Service, FaaS: Personalized Prebiotic Development for Infants with the Elements of Time and Parametric Modelling of in vitro Fermentation.

We proposed a framework with parametric modeling to obtain biological relevant parameters from the total probiotic growth pattern and metabolite production curves. The lag phase, maximum increase rate, and maximum capacity were obtained via a 205-h exploratory in vitro fermentation of a library of 13 structural-characterized prebiotic candidates against an exclusively breastfed infant fecal inoculum. We also conducted 16S rRNA amplicon sequencing of the infant fecal inoculum. Moreover, we introduce a robust composite metabolite-based indicator that reflects the eubiosis/dysbiosis of microbiota to complement the conventional microbial markers. In terms of short-chain fatty acid, we discovered that polymeric beta-glucans from barley demonstrated potential as prebiotic candidates, while alpha-glucans as glycogen showed the least dissolved ammonia production. In terms of total probiotic, beta-glucans from oat and mushroom sclerotia of Pleurotus tuber-regium showed comparable sustainability when compared to alpha-glucans after 48 h. Being classical prebiotic, galacto-oligosaccharides gave the second-highest metabolite-based indicator, followed by lactose. While limited improvement could be made to lactose and oligosaccharides, polymeric beta-glucans from barley avails more capacity for novel prebiotic development, such as structural modification. We anticipate that more similar parallel screening with the element of time and parametric modeling will provide more novel insights.

In Vitro Infant Faecal Fermentation of Low Viscosity Barley ß-Glucan and Its Acid Hydrolyzed Derivatives: Evaluation of Their Potential as Novel Prebiotics.

Barley contains high level of ß-1,3-1,4-glucans (BBGs) which can be fermented by microbes and are a potential prebiotic. In the present study, native BBG with low viscosity and a MW of 319 kDa was depolymerized by acid hydrolysis to produce a series of four structurally characterized fragments with MWs ranging from 6⁻104 kDa. In vitro fermentation of these BBG samples by infant faecal microbiome was evaluated using a validated deep-well plate protocol as parallel miniature bioreactors. Microbial taxa were identified using 16S amplicon sequencing after 40 h of anaerobic fermentation. Bioinformatics analysis including diversity indexes, predicted metagenomic KEGG functions and predicted phenotypes were performed on the sequenced data. Short chain fatty acids and dissolved ammonia were quantified and the SCFAs/NH3 ratio was used to evaluate the eubiosis/dysbiosis potential. Correlation analysis showed that most of the parameters investigated showed a parabolic function instead of a monotonous function with the BBG samples having different MWs. Among the five BBGs, it was concluded that BBG with an intermediate MW of 28 kDa is the most promising candidate to be developed as a novel prebiotic.

Cosmetic and Skincare Benefits of Cultivated Mycelia from the Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes).

Mushrooms are potential sources of novel natural cosmeceutical ingredients. This study was conducted to evaluate the cosmetic (skincare) benefits of the valuable medicinal species Ophiocordyceps sinensis (=Cordyceps sinensis). The mycelial extracts of 2 O. sinensis strains, Cs-HK1 and Cs-4, prepared sequentially with ethyl acetate, ethanol, and hot water were tested with in vitro assays for tyrosinase-, collagenase-, and elastase-inhibitory activity. The ethyl acetate extracts of both fungal strains showed potent antityrosinase and antielastase activity, with low half-maximal inhibitory concentrations (0.14-0.47 mg/mL) comparable to those of the respective reference compounds (arbutin and epigallocatechin gallate). All mycelial extracts exhibited moderate or significant anticollagenase activity; most extracts showed a significant photoprotective effect with a sun protection factor up to 25. The results from this study show the potential use of O. sinensis as a source of cosmetic ingredients for skincare applications.

In Vitro and In Vivo Photothermal Cancer Therapeutic Effects of Gold Nanorods Modified with Mushroom ß-Glucan.

The photothermal cancer therapeutic effect of the AuNR-Glu nanohybrids produced by coating native gold nanorods (AuNRs) with a natural mushroom biopolymer from the Pleurotus tuber-regium sclerotia (Glu) were studied in the second near-infrared window (NIR-II). The AuNR-Glu exhibited low cytotoxicity and high biocompatibility due to the surface modification of Glu when compared with the native AuNRs. AuNR-Glu nanohybrids had a high photothermal transduction efficiency (η) of 43.12%, causing effective in vitro cell ablation in both HT-29 (94.2 ± 0.8% cell death) and SW480 (94.8 ± 1.1% cell death) colon cancer cells under 1064 nm NIR-II laser irradiation at 1.0 W/cm2. Intravenous injection of AuNR-Glu nanohybrids followed by irradiation from a NIR-II laser at a safe dose (1.0 W/cm2 for 5 min) in nude mice implanted with HT-29 tumors was effective in significantly reducing the tumor growth, with no obvious harmful side effects, as evidenced by histological analysis of major organs. The present results have shown that AuNRs modified by natural biopolymers from mushroom ß-glucans are novel nanomaterials with low cytotoxicity and effective photothermal anticancer agents with potential biomedical applications.