Cognitive protection and brain entropy changes from omega-3 polyunsaturated fatty acids supplement in late-life depression: A 52-week randomized controlled trial.

BACKGROUND: Late-life depression (LLD) is associated with risk of dementia, yet intervention of LLD provides an opportunity to attenuate subsequent cognitive decline. Omega-3 polyunsaturated fatty acids (PUFAs) supplement is a potential intervention due to their beneficial effect in depressive symptoms and cognitive function. To explore the underlying neural mechanism, we used resting-state functional MRI (rs-fMRI) before and after omega-3 PUFAs supplement in older adults with LLD. METHODS: A 52-week double-blind randomized controlled trial was conducted. We used multi-scale sample entropy to analyze rs-fMRI data. Comprehensive cognitive tests and inflammatory markers were collected to correlate with brain entropy changes. RESULTS: A total of 20 patients completed the trial with 11 under omega-3 PUFAs and nine under placebo. While no significant global cognitive improvement was observed, a marginal enhancement in processing speed was noted in the omega-3 PUFAs group. Importantly, participants receiving omega-3 PUFAs exhibited decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. The brain entropy changes of the PCG in the omega-3 PUFAs group correlated with improvement of language function and attenuation of interleukin-6 levels. LIMITATIONS: Sample size is small with only marginal clinical effect. CONCLUSION: These findings suggest that omega-3 PUFAs supplement may mitigate cognitive decline in LLD through anti-inflammatory mechanisms and modulation of brain entropy. Larger clinical trials are warranted to validate the potential therapeutic implications of omega-3 PUFAs for deterring cognitive decline in patients with late-life depression.

Poricoic acid A induces mitophagy to ameliorate podocyte injury in diabetic kidney disease via downregulating FUNDC1.

Diabetic kidney disease (DKD) is a devastating complication of diabetes mellitus (DM) and is the most prevalent chronic kidney disease (CKD). Poricoic acid A (PAA), a component isolated from Traditional Chinese Medicine (TCM) Poria cocos, has hypoglycaemic and anti-fibrosis effects. However, the role of PAA in DKD remains largely unclear. To mimics an in vitro model of DKD, the mouse podocyte MPC5 cells were treated with high glucose (25 mM; HG) for 24 h. CCK-8 and flow cytometry assays were conducted for assessing MPC5 cell viability and apoptosis. Meanwhile, streptozotocin (STZ) was used to induce experimental DKD in mice by intraperitoneal injection. PAA notably inhibited the apoptosis and inflammation, reduced the generation of ROS, and elevated the MMP level in HG-treated MPC5 cells. Moreover, PAA obviously reduced blood glucose and urine protein levels, inhibited renal fibrosis in DKD mice. Meanwhile, PAA markedly increased LC3 and ATG5 levels and declined p62 and FUNDC1 levels in HG-treated MPC5 cells and in the kidney tissues of DKD mice, leading to the activation of cell mitophagy. Furthermore, the downregulation of FUNDC1 also inhibited apoptosis, inflammation, and promoted mitophagy in HG-treated MPC5 cells. As expected, the knockdown of FUNDC1 further enhanced the protective role of PAA in MPC5 cells following HG treatment, indicating that induction of mitophagy could attenuate podocyte injury. Collectively, PAA could exert beneficial effects on podocyte injury in DKD by promoting mitophagy via downregulating FUNDC1. These findings suggested that PAA may have great potential in alleviating kidney injury in DKD.

Human platelet lysate biotherapy for traumatic brain injury: preclinical assessment.

Traumatic brain injury (TBI) leads to major brain anatomopathological damages underlined by neuroinflammation, oxidative stress and progressive neurodegeneration, ultimately leading to motor and cognitive deterioration. The multiple pathological events resulting from TBI can be addressed not by a single therapeutic approach, but rather by a synergistic biotherapy capable of activating a complementary set of signalling pathways and providing synergistic neuroprotective, anti-inflammatory, antioxidative, and neurorestorative activities. Human platelet lysate might fulfil these requirements as it is composed of a plethora of biomolecules readily accessible as a TBI biotherapy. In the present study, we tested the therapeutic potential of human platelet lysate using in vitro and in vivo models of TBI. We first prepared and characterized platelet lysate from clinical-grade human platelet concentrates. Platelets were pelletized, lysed by three freeze-thaw cycles, and centrifuged. The supernatant was purified by 56°C 30 min heat treatment and spun to obtain the heat-treated platelet pellet lysate that was characterized by ELISA and proteomic analyses. Two mouse models were used to investigate platelet lysate neuroprotective potential. The injury was induced by an in-house manual controlled scratching of the animals' cortex or by controlled cortical impact injury. The platelet lysate treatment was performed by topical application of 60 µl in the lesioned area, followed by daily 60 µl intranasal administration from Day 1 to 6 post-injury. Platelet lysate proteomics identified over 1000 proteins including growth factors, neurotrophins, and antioxidants. ELISA detected several neurotrophic and angiogenic factors at ∼1-50 ng/ml levels. We demonstrate, using two mouse models of TBI, that topical application and intranasal platelet lysate consistently improved mouse motor function in the beam and rotarod tests, mitigated cortical neuroinflammation, and oxidative stress in the injury area, as revealed by downregulation of pro-inflammatory genes and the reduction in reactive oxygen species levels. Moreover, platelet lysate treatment reduced the loss of cortical synaptic proteins. Unbiased proteomic analyses revealed that heat-treated platelet pellet lysate reversed several pathways promoted by both controlled cortical impact and cortical brain scratch and related to transport, postsynaptic density, mitochondria or lipid metabolism. The present data strongly support, for the first time, that human platelet lysate is a reliable and effective therapeutic source of neurorestorative factors. Therefore, brain administration of platelet lysate is a therapeutical strategy that deserves serious and urgent consideration for universal brain trauma treatment.

Changes in cerebral glucose metabolism after acupuncture at KI3 in spontaneously hypertensive rats: a positron emission tomography study.

OBJECTIVE: The aim of this study was to explore the effect of acupuncture stimulation at KI3 on brain glucose metabolism in spontaneously hypertensive rats (SHRs). METHODS: Brain glucose metabolism in SHRs after acupuncture stimulation at KI3 was detected using 18F-2-fluorodeoxy-D-glucose positron emission tomography (18F-FDG-PET). SHRs were randomly divided into three groups: no treatment (SHR group); acupuncture at KI3 (KI3 group); and sham acupuncture (Sham group). Wistar Kyoto (WKY) rats were used as a normal blood pressure (BP) control group. Rats were subjected to 10 min of acupuncture once a day for 7 days. BP and positron emission tomography-computed tomography (PET-CT) were measured after the first acupuncture session and after 7 days of treatment. RESULTS: The results showed that BP was lower in the KI3 group than in the SHR group, both 30-60 min after the first acupuncture session and 24-48 h after the 7-day treatment. Compared with the WKY group, the SHR group had lower glucose metabolism in the motor cortex, sensory cortex, basal ganglia, corpus callosum, caudate putamen, and visual cortex. Compared with the untreated/sham-treated SHR control groups, cerebral glucose metabolism was lower in the medulla oblongata, thalamus, dorsal thalamus, orbital cortex, and hypothalamus after acupuncture at KI3, while it was higher in the olfactory cortex and inferior phrenic muscle. CONCLUSION: Our results show that, in SHRs, needling at KI3 reduces high BP, most likely by altering the activation of cerebral regions.

Comparison of volatile profiles of nine litchi (Litchi chinensis Sonn.) cultivars from Southern China.

Volatile components of nine litchi cultivars (10 samples) with high commercial value from Southern China were investigated by means of gas chromatography-mass spectrometry combined with headspace solid phase microextraction. A total of 96 volatiles were detected, of which 43 were identified. Seventeen common volatiles in all the samples included linalool, cis-rose oxide, alpha-terpineol, beta-citronellol, geraniol, p-cymene, ethanol, 3-methyl-3-buten-1-ol, 3-methyl-2-buten-1-ol, 1-hexanol, (E)-2-hexen-1-ol, 2-ethyl-1-hexanol, 1-octen-3-ol, 1-octanol, ethyl acetate, p,alpha-dimethylstyrene and 3-tert-butyl-4-hydroxyanisole. Although the volatile composition and concentration varied between these cultivars, the components with the highest OAVs in most cultivars were still cis-rose oxide, trans-rose oxide, 1-octen-3-ol, and geraniol. Two Huaizhi samples from two producing areas exhibited similar volatile profiles, and significantly different from other cultivars according to cluster analysis performed on amounts of major volatile components.