Nervonic acid improves liver inflammation in a mouse model of Parkinson's disease by inhibiting proinflammatory signaling pathways and regulating metabolic pathways.

BACKGROUND: Nervonic acid (NA) - a type of bioactive fatty acid that is found in natural sources - can inhibit inflammatory reactions and regulate immune system balance. Therefore, the use of NA for the treatment of neurodegenerative diseases has received considerable attention. Our previous study found that NA inhibited inflammatory responses in the brain of Parkinson's disease (PD) mouse models. In addition to the brain, PD is also associated with visceral organ dysfunction, especially impaired liver function. Thus, studying the role of NA in PD-mediated inflammation of the liver is particularly important. METHODS: A combined transcriptome and metabolomic approach was utilized to investigate the anti-inflammatory effects of NA on the liver of PD mice. Inflammatory signaling molecules and metabolic pathway-related genes were examined in the liver using real-time PCR and western blotting. RESULTS: Liver transcriptome analysis revealed that NA exerted anti-inflammatory effects by controlling several pro-inflammatory signaling pathways, such as the down-regulation of the tumor necrosis factor and nuclear factor kappa B signaling pathways, both of which were essential in the development of inflammatory disease. In addition, liver metabolomic results revealed that metabolites related to steroid hormone biosynthesis, arachidonic acid metabolism, and linoleic acid metabolism were up-regulated and those related to valine, leucine, and isoleucine degradation pathways were down-regulated in NA treatment groups compared with the PD model. The integration of metabolomic and transcriptomic results showed NA significantly exerted its anti-inflammatory function by regulating the transcription and metabolic pathways of multiple genes. Particularly, linoleic acid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis were the crucial pathways of the anti-inflammatory action of NA. Key genes in these metabolic pathways and key molecules in inflammatory signaling pathways were also verified, which were consistent with transcriptomic results. CONCLUSION: These findings provide novel insights into the liver protective effects of NA against PD mice. This study also showed that NA could be a useful dietary element for improving and treating PD-induced liver inflammation.

Extraction Optimization and Antioxidant Activities of Ethanol Extract of the Brown Roll-Rim Mushroom Paxillus involutus (Agaricomycetes).

Box Behnken design (BBD) was used to optimize the extraction of Paxillus involutus (EPI) in ethanol. The optimum extraction conditions were as follows: temperature 45°C; solid:liquid ratio 1:35; time 5 h. Under these conditions, the yield of EPI was 13.57%. The antioxidant activity of EPI was evaluated in vitro, and DPPH free radical scavenging, ABTS free radical scavenging, and hydroxyl free radical scavenging effects were found to be equal to or close to that of the positive control vitamin C (VC). The antioxidant activity of EPI was next evaluated in vivo using aging mice; it was found to have appreciable effect on scavenging malonic dialdehyde (MDA) and could increase the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and total superoxide dismutase (T-SOD) in mice. Overall, EPI showed antioxidant effects in aging mice, thereby delaying aging, and has potential for application as a natural antioxidant and in medical applications.

Efficacy of ginseng oral administration and ginseng injections on cancer-related fatigue: A meta-analysis.

BACKGROUND: Up to 90% of patients who are under the active treatment suffer from cancer-related fatigue (CRF). CRF can persist about 10 years after diagnosis and/or treatment. Accumulating reports support that ginseng and ginseng injections are both potential drugs for the treatment of CRF but few studies put them together for analysis. METHODS: Two reviewers independently extracted data in 3 databases (PubMed, Cochrane Library and China National Knowledge Infrastructure) from their inception to May 24, 2021. The primary outcome was the effect of ginseng in alleviating CRF. The secondary outcome was ginseng in alleviating emotional or cognitive fatigue. Standardized mean difference (SMD) was employed. RESULTS: Twelve studies were included to evaluate efficacy of ginseng oral administration and ginseng injections on CRF. The pooled SMD was 0.40 (95% confidence Interval [95% CI] [0.29-0.51], P < .00001). Six studies were included to evaluate efficacy of ginseng oral administration on CRF and the SMD was 0.29 (95% CI [0.15-0.42], P < .0001). The order was 2000 mg/d, 3000 mg/d, 1000 mg/d and placebo from high efficacy to low. Ten studies were included to evaluate efficacy of ginseng injections on CRF and the SMD was 0.74 (95% CI [0.59-0.90], P < .00001). Emotional fatigue was reported in 4 studies, ginseng oral administration in 2 and ginseng injections in 2. The pooled SMD was 0.12 (95% CI [-0.04 to 0.29], P = .15). Cognitive fatigue was reported in 4 studies focusing on ginseng injections and the SMD was 0.72 (95% CI [0.48-0.96], P < .00001). CONCLUSION: Ginseng can improve CRF. Intravenous injection might be better than oral administration. Ginseng injections may alleviate cognitive fatigue. No evidence was found to support that ginseng could alleviate emotional fatigue.

A Metabolomic Study of the Analgesic Effect of Lappaconitine Hydrobromide (LAH) on Inflammatory Pain.

Lappaconitine (LA) is a C-18 diterpene alkaloid isolated from Aconitum sinomontanum Nakai that has been shown to relieve mild to moderate discomfort. Various researchers have tried to explain the underlying mechanism of LA's effects on chronic pain. This article uses metabolomics technology to investigate the metabolite alterations in the dorsal root ganglion (DRG) when lappaconitine hydrobromide (LAH) was injected in an inflammatory pain model, to explain the molecular mechanism of its analgesia from a metabolomics perspective. The pain model used in this study was a complete Freund's adjuvant (CFA)-induced inflammatory pain model in rats. There were two treatment groups receiving different dosages of LAH (4 mg/kg LAH and 8 mg/kg LAH). The analgesic mechanism of LAH was investigated with an analgesic behavioral test, tissue sections, and metabolomics. The results of the analgesic behavioral experiment showed that both 4 mg/kg LAH and 8 mg/kg LAH could significantly improve the paw withdrawal latency (PWL) of rats. The tissue section results showed that LAH could reduce the inflammatory response and enlargement of the paw and ankle of rats and that there was no significant difference in the tissue sections of the DRG. The metabolomics results showed that retinol metabolism and glycerophospholipid metabolism in the CFA-induced inflammatory pain model were significantly affected and may exacerbate the inflammatory reactions and initiate persistent pain; in addition, the linoleic acid metabolism, arachidonic acid metabolism, and alanine, aspartate, and glutamate metabolism were also slightly affected. Among them, the alpha-linolenic acid metabolism was up-regulated after LAH treatment, while the retinol metabolism was down-regulated. These results suggest that LAH could effectively reduce inflammatory pain and might achieve this by regulating the lipid metabolism in the rat DRG.

Aronia melanocarpa (Michx.) Elliott. attenuates dextran sulfate sodium-induced Inflammatory Bowel Disease via regulation of inflammation-related signaling pathways and modulation of the gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Aronia melanocarpa (Michx.) Elliott. Is one of the most functional berries usually used in the preparation of juice and jams, but it has revealed its ethnopharmacological properties due to their richness in biologically active molecules with pharmaceutical and physiological effects. AIMS OF THE STUDY: The aim of this study was to assess the antioxidant and anti-inflammatory effects of Aronia melanocarpa ethanol-extract as well as the possible mechanisms of action involved and the modulation of gut microbiota in Dextran Sulfate Sodium (DSS)-induced Inflammatory bowel disease in mice. MATERIALS AND METHODS: Inflammatory bowel disease (IBD) were induced by DSS in drinking water for 7 days to evaluate the properties of A. melanocarpa ethanol-extract (AME) on the intestinal microflora. AME was administered orally to DSS-induced IBD mice for 21 days. Clinical, inflammatory, histopathological parameters, and different mRNA and proteins involved in its possible mechanism of action were determined as well as gut microbiota analysis via 16S high throughput sequencing. RESULTS: AME improved clinical symptoms and regulated histopathological parameters, pro- and anti-inflammatory cytokines and oxidative stress factors as well as mRNA and protein expressions of transcription factors involved in maintaining the intestinal barrier integrity. In addition, AME also reversed the DSS-induced intestinal dysbiosis effects promoting the production of cecal short chain fatty acids linked to signaling pathways inhibiting IBD. CONCLUSION: AME improved intestinal lesions induced by DSS suggesting that A. melanocarpa berries could have significant therapeutic potential against IBD due to their antioxidant and anti-inflammatory capacities as well as their ability to restore the gut microbiota balance.

Effectiveness of a Mindfulness-Based Group Intervention for Chinese University Students with Sleep Problems.

The increasing prevalence of sleep disorders among university students should be taken seriously. Group counseling involving a mindfulness-based strategy may help prevent students from developing insomnia and subsequent mental health disorders. This study aimed to evaluate the ameliorating effects of a mindfulness-based group intervention on sleep problems and emotional symptoms in university students in China. Twenty-one university students (16 females, 22.71 ± 4.28 years) who were not on medication were recruited and assigned to the intervention group based on the criterion of high levels of sleep problems. Additionally, twenty-four university students (19 females, 24.50 ± 0.93 years) were included as a nonrandomized control group. Individuals in the intervention group participated in a two-hour group intervention once a week for eight sessions. All participants completed self-reported questionnaire baseline tests, postintervention tests, and one-month follow-ups on mindfulness, sleep quality, anxiety and depressive symptoms. Repeated-measures ANOVA was performed. The results revealed significant intervention effects, with significant differences observed between the two groups in mindfulness and sleep quality. However, there was no significant effect of the intervention on anxiety and depressive symptoms. This study contributes to a better understanding of the effectiveness of mindfulness-based intervention in addressing sleep problems in university students.

Potential exploration of Fe3O4/biochar from sludge as the media of bioretention system and its comparison with conventional media.

The selection and configuration of soil media are a core issue of the bioretention system. A porous carbon material of Fe3O4/biochar (BSF) was prepared by adding pickling wastewater to modified sludge biochar, which could serve as a good adsorption performance and cheap media for bioretention system. Through the analytic hierarchy process (AHP), different media were evaluated according to their characteristics. By comparing the characteristics of BSF to bio-ceramic (BC), zeolite (ZE), and activated carbon (AC), it was found that BSF has a larger specific surface area and pore volume. The hydrological characteristics of the medium were also tested. The results show that BSF has better water-absorbing quality and hydraulic conductivity than the other three media, but the water-retention property of the medium seems to be inferior. BSF has stable adsorption performance for ammonia nitrogen (NH4+-N) and total phosphorus (TP) in rainwater. Its high adsorption capacity is maintained at 5-35°C, but it is very susceptible to pH factors. The adsorption process by BSF and other media conforms to pseudo-second-order kinetics and the Langmuir model in rainwater. In general, the performance of BSF is shown to be superior to BC, ZE, and AC, making it a potential medium for bioretention system.

[Effect of electroacupuncture on morphine-conditioned place preference and activation of glutamatergic neurons in the ventromedial prefrontal cortex in rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) and "Sanyinjiao"(SP6) on conditioned place preference (CPP) and activation of glutamatergic neurons in the ventromedial prefrontal cortex (VMPFC) of morphine-addiction rats, so as to explore its mechanisms underlying detoxification. METHODS: Thirty male SD rats were randomly and equally divided into control, model and EA groups. The rats with acquisition of morphine-induced CPP received intraperitoneal injection of morphine (10 mg/kg) in the morphine-paired chamber, once daily for 3 consecutive days, and those of the control group received intraperitoneal injection of the same dose of normal saline in saline-paired chamber. Thirty minutes before CPP acquisition training, EA (2 Hz/100 Hz, 0.5 to 1.0 mA) was applied to ST36 and SP6 for 20 min every day. The double-labeled neurons of Fos/vesicular glutamate transporter 2 (VGLUT2) in the VMPFC were detected by using fluorescent immunohistochemistry. The discharges of the VMPFC neurons were recorded by using a multi-channel microarray electrophysiological system, followed by performing a z-score standardized processing. The ratio of firing rate frequency of rats in the morphine-paired chamber/saline-paired chamber was calculated, and further statistical analysis was conducted on the data based on the standardized z-scores. The neuronal firing characteristic of glutamatergic neuron is low frequency and wide wave. RESULTS: Compared with the control group, the score of morphine-induced CPP and numbers of Fos, VGLUT2-positive and Fos-VGLUT2 double-labeled positive cells were significantly increased in the model group (P<0.01，P<0.05). After EA and in comparison with the model group, the morphine CPP score and numbers of Fos, VGLUT2-positive and Fos-VGLUT2 double-labeled cells were significantly reduced in the EA group (P<0.01，P<0.05). The ratio of firing rate of the VMPFC neurons in the preference chamber and the percentage of inhibitory neurons as well as the z-score were considerably lower in the EA group than in the model group (P<0.001). CONCLUSION: EA can suppress morphine-induced seeking behavior in rats, which may be related to its inhibitory effect on glutamatergic neurons in the VMPFC.

Preparation of sheep bone collagen peptide-calcium chelate using enzymolysis-fermentation methodology and its structural characterization and stability analysis.

In this study, enzymatic hydrolysis and Lactobacillus fermentation were used in combination to prepare collagen peptide with high free calcium content, followed by the addition of anhydrous ethanol to obtain peptide-calcium chelate. The optimal conditions for the fermentation of enzymatic hydrolysate (glucose 3%, inoculum size 6%, 24.5 h, 37 °C and pH 6.5) were determined by response surface methodology (RSM), under which a free calcium content of 2212.58 mg/100 g was obtained. The calcium-chelating capacity was 42.57 ± 0.09%. The results of ultraviolet absorption spectrum, Fourier transform infrared (FT-IR) spectra, differential scanning calorimeter (DSC), X-ray diffraction and amino acid analysis indicated that calcium could be chelated through carboxyl oxygen and amino nitrogen atoms of collagen peptides, forming peptide-calcium chelate. The chelate is stable at 30-80 °C of temperatures and during in simulated gastrointestinal digestion, which could promote calcium absorption in human. The test intended to provide a basis for developing a novel calcium supplement and promoting utilization of sheep bone.

A Sphingosine-1-Phosphate Modulator Ameliorates Polycystic Kidney Disease in Han:SPRD Rats.

BACKGROUND: Inflammation plays an important role in polycystic kidney disease (PKD). Cordyceps sinensis, a prized -Chinese medicinal herb, exerts anti-tumor, anti-inflammatory and anti-metastatic effects and benefits patients with kidney diseases. The aim of this study was to test the efficacy of FTY720, an immunosuppressant derived from C. sinensis, in a rat cystic kidney disease model, and explore its underlining mechanism. METHODS: Male wild type and Cy/+ Han:SPRD rats were treated with FTY720 at 3 and 10 mg/kg/day for 5 weeks and 12 weeks by gavage. Blood and kidney were collected for functional, morphological, RNA, and protein analysis. RESULTS: Inflammation is activated in Cy/+ Han:SPRD rats. Inflammatory cytokines including interleukin 6 and tumor necrosis factor alpha were upregulated and inflammation-related pathways were activated, such as nuclear factor κB and signal transducer and activator of transcription 3 (STAT3) pathways. Furthermore, the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), a regulator of inflammation, was accumulated in the Cy/+ Han:SPRD rats. FTY720 significantly reduced cyst growth and delayed disease progression by reducing the accumulation of S1P, thereby inhibiting inflammatory responses. CONCLUSION: FTY720 treatment reduced the expression of inflammatory cytokines and attenuated the activation of NK-κB and STAT3 pathways in Cy/+ Han:SPRD rats. It suggests that FTY720 may serve as a therapeutic agent for clinical autosomal dominant PKD treatment.

Genistein inhibits nasopharyngeal cancer stem cells through sonic hedgehog signaling.

Genistein, a soy derived isoflavanoid compound, exerts anticancer effects in various cancers. Nasopharyngeal cancer stem cells (NCSCs) are a small subpopulation of cancer cells which are responsible for initiation, progression, metastasis, and recurrence of nasopharyngeal cancer. The present study aimed to investigate the suppressive effects of genistein on NCSCs and its underlying mechanism. NCSCs were enriched from human nasopharyngeal cancer cell lines CNE2 and HONE1 through tumorsphere-forming assay. It was shown that genistein inhibited the tumorsphere formation capacity, decreased the number of EpCAM+ cells, downregulated the expression of NCSCs markers, suppressed cell proliferation, and induced apoptosis of NCSCs. Genistein suppressed the activity of Sonic hedgehog (SHH) signaling, which was important for the maintenance of NCSCs, while activation of SHH signaling by purmorphamine diminished the inhibitory effects of genistein on NCSCs. Our data suggested that genistein inhibited NCSCs through the suppression of SHH signaling. These findings support the use of genistein for targeting NCSCs.

Phenethyl isothiocyanate inhibits colorectal cancer stem cells by suppressing Wnt/ß-catenin pathway.

Cancer stem cells (CSCs) are considered to play essential roles in the process of origination, proliferation, migration, and invasion of cancer, and their properties are regulated by Wnt/ß-catenin pathway. Phenethyl isothiocyanate (PEITC) is a natural product obtained from cruciferous vegetables with anticancer activities. The present study aimed to investigate the inhibitory effect and the underlying mechanisms of PEITC on colorectal CSCs. In this study, we found that PEITC can significantly reduce the size and number of colorectal cancer cell spheroids in serum-free medium. With increasing PEITC concentrations (10-40 µM), the number of spheroids was reduced to about 10% of the control group, and the percentage of CD133+ cells was decreased by about 3-16 folds. PEITC also decreased the expression of CSC markers. Meanwhile, inhibition of proliferation as well as induction of apoptosis of colorectal CSCs was observed after PEITC treatment. Furthermore, through activating Wnt/ß-catenin pathway with LiCl, the inhibitory effects of PEITC on colorectal CSCs were diminished. Our data suggested that PEITC can be an effective inhibitor of colorectal CSCs by targeting Wnt/ß-catenin pathway.

Electroacupuncture suppresses morphine reward-seeking behavior: Lateral hypothalamic orexin neurons implicated.

The orexin system specifically located in the lateral hypothalamus (LH) has been shown to play a unique role in reward seeking, drug relapse, and addiction. In this study, we investigated the effects of electroacupuncture (EA) on morphine conditioned place preference (CPP), reinstatement of extinguished CPP, and the expression of orexin in the LH. A two-chamber CPP model was used to measure the rewarding properties of morphine. 2Hz EA at points BL23 and ST36 was carried out for 30min daily before morphine injection on three conditioning days. The extinguished CPP was reinstated by systemic morphine injection. Immunohistochemistry was used to detect orexin-positive nuclei in the LH. The findings indicated that the expression of morphine-induced CPP can be effectively suppressed by EA. EA suppressed orexin-positive nuclei in the LH compared with morphine-conditioned rats. A combination of EA and orexin A antagonist (10mg/kg, i.p.) produced a significant decrease in the morphine reinstatement scores. The results indicate the possibility that orexin may be involved in the acupuncture effect on drug-seeking behavior and thereby has an important role in modulating acupuncture. The synergetic use of a protocol consisting of EA and low-dose orexin A antagonist may provide a novel treatment strategy for drug reward seeking and relapse.

Autosomal dominant polycystic kidney disease is associated with central and nephrogenic defects in osmoregulation.

Autosomal dominant polycystic kidney disease (ADPKD) is associated with a urine-concentrating defect attributed to renal cystic changes. As PKD genes are expressed in the brain, altered central release of arginine vasopressin could also play a role. In order to help determine this we measured central and nephrogenic components of osmoregulation in 10 adults and 10 children with ADPKD, all with normal renal function, and compared them to 20 age- and gender-matched controls. Overnight water deprivation caused a lower rise in urine osmolality in the patients with ADPKD than controls, reflecting an impaired release of vasopressin and a peripheral defect in the patients. The reactivity of plasma vasopressin to water deprivation, as found in controls, was blunted in the patients with the latter showing lower urine osmolality for the same range of plasma vasopressin. The maximal urine osmolality correlated negatively with total kidney volume. Defective osmoregulation was confirmed in the children with ADPKD but was unrelated to number of renal cysts or kidney size. Thus, patients with ADPKD have an early defect in osmoregulation, with a blunted release of arginine vasopressin. This reflects expression of polycystins in hypothalamic nuclei that synthesize vasopressin, and this should be considered when evaluating treatments targeting the vasopressin pathway in ADPKD.