Dietary lipoic acid alleviates autism-like behavior induced by acrylamide in adolescent mice: the potential involvement of the gut-brain axis.

Consuming fried foods has been associated with an increased susceptibility to mental health disorders. Nevertheless, the impact of alpha-lipoic acid (α-LA, LA) on fried food-induced autism-like behavior remains unclear. This study aimed to explore how LA affects autism-related behavior and cognitive deficits caused by acrylamide in mice, a representative food hazard found in fried foods. This improvement was accomplished by enhanced synaptic plasticity, increased neurotrophin expression, elevated calcium-binding protein D28k, and restored serotonin. Additionally, LA substantially influenced the abundance of bacteria linked to autism and depression, simultaneously boosted short-chain fatty acid (SCFA) levels in fecal samples, and induced changes in serum amino acid concentrations. In summary, these findings suggested that exposure to acrylamide in adolescent mice could induce the development of social disorders in adulthood. LA showed promise as a nutritional intervention strategy to tackle emotional disorders during adolescence.

Lactobacillus plantarum LLY-606 Supplementation Ameliorates the Cognitive Impairment of Natural Aging in Mice: The Potential Role of Gut Microbiota Homeostasis.

This work explored the effects of Lactobacillus plantarum LLY-606 (LLY-606) on cognitive function in aging mice. Our findings demonstrated that LLY-606 effectively prolonged the lifespan of mice and improved age-related cognitive impairments. Additionally, our study revealed that supplementation with LLY-606 resulted in the downregulation of inflammatory cytokine levels and the upregulation of antioxidant capacity. Furthermore, probiotic supplementation effectively mitigated the deterioration of the intestinal barrier function in aging mice. Amplicon analysis indicated the successful colonization of probiotics, facilitating the regulation of age-induced gut microbiota dysbiosis. Notably, the functional abundance prediction of microbiota indicated that tryptophan metabolism pathways, glutamatergic synapse pathways, propanoate metabolism pathways, and arginine and proline metabolism pathways were enriched after the LLY-606 intervention. In summary, LLY-606 emerged as a potential functional probiotic capable of influencing cognitive function in aging mice. This effect was achieved through the modulation of gut microbiota, the regulation of synaptic plasticity, and the enhancement of neurotrophic factor levels.

Sigmoido-rectal intussusception anastomosis in the Altemeier procedure for complete rectal prolapse: preliminary results of a new technique.

Purpose: Our research introduces an innovative surgical approach, combining the Altemeier Procedure with Sigmoido-rectal Intussusception Anastomosis, effectively reducing recurrence, minimizing complications, and improving postoperative anal function in rectal prolapse patients. Materials and methods: This retrospective study, conducted at tertiary referral hospitals including Shandong University of Traditional Chinese Medicine's Affiliated Hospital, Linyi People's Hospital, and Pingyi People's Hospital, examined data from patients undergoing conventional Altemeier surgery or Altemeier combined with Sigmoido-rectal Intussusception Anastomosis. Analyzing hospitalization and follow-up data from January 2009 to December 2022, the study focused on prolapse recurrence, complications, and anal function as primary outcome indicators across these three study centers. Results: In the study, both groups had an average follow-up of (12.5 ± 2.41) months, and only two traditional group patients experienced mortality. Recurrence rates significantly differed, with 26.47% in the traditional group and 1.54% in the modified group (P < 0.001). The modified group showed no perioperative anastomotic dehiscence, contrasting with a 13.24% occurrence in the conventional group (P = 0.003). Primary complications in the modified group included anastomotic hemorrhage, with rates of 17.65% and 6.15% in the traditional and modified groups, respectively (P = 0.077). At 12 months postoperatively, both groups improved in anal manometry parameters and the Wexner anal incontinence score. Resting pressure was significantly lower in the traditional group (32.50 ± 1.76 mmHg) than the modified group (33.24 ± 2.06 mmHg) (P = 0.027), while the extrusion pressure was higher in the modified group (64.78 ± 1.55 mmHg) than the traditional group (62.85 ± 2.30 mmHg) (P < 0.001). The Wexner anal incontinence score was significantly lower in the modified group (2.69 ± 1.65) than the traditional group (3.69 ± 1.58, P = 0.001). Conclusion: This retrospective study affirms that adding Sigmoido-rectal Intussusception Anastomosis to the Altemeier procedure reduces recurrence and complications. While both approaches enhance postoperative anal function in complete rectal prolapse patients, the combined method, particularly with Sigmoido-rectal Intussusception Anastomosis, proves more effective.

Stevioside Ameliorates Prenatal Obesity Induced Postpartum Depression: The Potential Role of Gut Barrier Homeostasis.

SCOPE: Postpartum depression and cognitive impairment are the common complications of prenatal obesity. Stevioside is a non-nutritive natural sweetener with antioxidant and anti-inflammatory. However, its effects on depression behaviors and cognitive impairment induced by a high-fat diet (HFD) remain unclear. METHODS AND RESULTS: An 8-week HFD is used to establish a prenatal obesity model in female C57BL/6J mice to explore the improvement effects of stevioside (0.5 mg mL-1 in drinking water) on maternal depression and cognitive dysfunction after weaning. The results demonstrated that stevioside improves behavioral performance of obese maternal mice, and inhibits neuronal damage and 5-hydroxytryptamine (5-HT) abnormality induced by HFD. In addition, stevioside inhibits oxidative stress by reducing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) and glutathione (GSH) activities in the brains of obese maternal mice. Additionally, stevioside improves gut barrier integrity and prevented lipopolysaccharide (LPS) extravasation, and alleviates neuroinflammation. Correlation analysis shows that gut barrier and serum LPS are closely related to behavioral performance and brain biochemical indicators. CONCLUSION: Stevioside is capable to prevent prenatal obesity-induced cognitive and mood disorders by restoring intestinal barrier damage and inhibiting inflammation.

Leucine-Restricted Diet Ameliorates Obesity-Linked Cognitive Deficits: Involvement of the Microbiota-Gut-Brain Axis.

Leucine restriction (LR) improves insulin resistance and promotes white adipose tissue browning. However, the effect of LR on obesity-associated cognitive impairment remains unclear. The present study found that an 8-week LR dramatically improved high-fat diet (HFD)-induced cognitive decline by preventing synaptic dysfunction, increasing the expressions of neurotrophic factors, and inhibiting neuroinflammation in memory-related brain regions. Moreover, LR notably reshaped the structure of gut microbiota, which was manifested by downregulating the Firmicutes/Bacteroidetes ratio, reducing the relative abundance of inflammation-related bacteria including Acetatifactor, Helicobacter, Mucispirillum, and Oscillibacter but increasing short-chain fatty acid (SCFA)-producing bacterial genera including Alistipes, Allobaculum, Odoribacter, and Olsenella. Notably, HFD-caused SCFA reduction, gut barrier damage, and LPS leakage were recovered by LR. Our findings suggested that LR could serve as an effective approach to attenuate obesity-induced cognitive deficits, which may be achieved by balancing gut microbiota homeostasis and enhancing SCFA production.

Lactobacillus plantarum LLY-606 supplementation ameliorates hyperuricemia via modulating intestinal homeostasis and relieving inflammation.

Gut microbiota is associated with hyperuricemia progression and can be regulated by Lactobacillus plantarum. However, the role of Lactobacillus plantarum in hyperuricemia is still unknown. Thus, we constructed the mouse model of hyperuricemia using potassium oxonate and hypoxanthine treatment to explore the effects of Lactobacillus plantarum LLY-606 supplementation on the development of hyperuricemia. The results showed that Lactobacillus plantarum LLY-606 significantly reduced the level of serum uric acid through inhibiting uric acid secretion and regulating uric acid transport. We also found that Lactobacillus plantarum LLY-606 supplementation inhibited the inflammatory response and the activation of the TLR4/MyD88/NF-κB signaling pathway in mice. Microbiome sequencing and analysis suggested the successful colonization of probiotics, which could regulate intestinal flora dysbiosis induced by hyperuricemia. The abundance of Lactobacillus plantarum was significantly negatively correlated with hyperuricemia-related indicators. Notably, the functional abundance prediction of microbiota indicated that lipopolysaccharide biosynthesis protein pathways and lipopolysaccharide biosynthesis pathways were inhibited after the probiotic intervention. In conclusion, Lactobacillus plantarum LLY-606 can serve as a potential functional probiotic to affect the development of hyperuricemia through modulating gut microbiota, downregulating renal inflammation, and regulating uric acid metabolism.

Alternate-day fasting prevents non-alcoholic fatty liver disease and working memory impairment in diet-induced obese mice.

Alternate-day fasting (ADF) regimen has been reported to alleviate obesity and insulin resistance. However, the effects of ADF on preventing diet-induced non-alcoholic fatty liver disease (NAFLD) and related cognitive deficits are still elusive. In the present study, a high-fat diet (HFD)-induced obese (DIO) C57BL/6 mouse model was established. Mice were treated with a 4-week long ADF regimen and/or switching the diet to a standard diet. ADF reduced lipid accumulation, activated AMPK/ULK1 signaling, and suppressed the phosphorylation of mTOR. Also, ADF inhibited lipid accumulation and inflammatory responses in the white adipose tissue and down-regulated expressions of PPAR-γ and cytokines. Moreover, ADF improved the working memory and synaptic structure in the DIO mice and upregulated PSD-95 and BDNF in the hippocampus. ADF reduced oxidative stress and microglial over-activation in the CNS. These results suggest that ADF attenuates NAFLD development in the liver of DIO mice, which is related to the mediating effects of ADF on autophagy and energy metabolism. ADF also enhanced cognitive function, which could be partly explained by the down-regulated peripheral inflammatory responses. This study indicates that ADF could be a promising intervention for alleviating NAFLD development and cognitive decline.

Tryptophan-rich diet ameliorates chronic unpredictable mild stress induced depression- and anxiety-like behavior in mice: The potential involvement of gut-brain axis.

Tryptophan, an essential amino acid, has been reported that it has the potential to regulate depression-like behavior. Meanwhile, Chronic stress-induced depression also has a close relationship with gut microbiota structure and composition. In the current research, we demonstrated that a tryptophan-rich diet (0.6% tryptophan w/w) significantly attenuated depression- and anxiety-like behaviors in a chronic unpredictable mild stress (CUMS)-treated mouse model. Tryptophan supplementation improved neuroinflammation, increased expression of BDNF, and improved mitochondrial energy metabolism in the brain of CUMS-treated mice. Besides, CUMS also enhanced the kynurenine pathway, but repressed the serotonin pathway and indole pathway of tryptophan metabolism, leading to a decrease in 5-HT and indole in serum, whereas tryptophan supplementation might shift the tryptophan metabolism more toward the serotonin pathway in CUMS-treated mice. The gut microbiome was restructured by increasing the relative abundance of Lachnospiracea, Clostridium, Lactobacillus, Bifidobacterium in tryptophan-treated depressive mice. Moreover, tryptophan administration inhibited stress-induced gut barrier damage and decreased inflammatory responses in the colon. Together, our study purports the gut-brain axis as a mechanism for the potential of tryptophan to improve depression and anxiety-related behavior.

Sesamol ameliorates dextran sulfate sodium-induced depression-like and anxiety-like behaviors in colitis mice: the potential involvement of the gut-brain axis.

Inflammatory bowel disease (IBD) is accompanied by some psychiatric disorders, including anxiety and depression. Sesamol has been reported to alleviate colitis symptoms and depression-like behaviors caused by chronic unpredictable mild stress, but its protective effect and underlying neurobiological mechanism on IBD induced by dextran sulfate sodium (DSS) accompanying depression-like and anxiety-like behaviors remains still unclear. Here, we found that a six-week sesamol treatment (100 mg per kg bodyweight per day) for DSS-induced mice predominantly prevented inflammatory response, epithelial barrier dysfunction and depression-like and anxiety-like behaviors via the gut-brain axis. Sesamol alleviated neuroinflammatory responses via suppressing the TLR-4/NF-κB pathway, protected against oxidative stress and upregulated the Nrf2 antioxidant signaling pathway. Moreover, sesamol treatment improved brain-derived neurotrophic factor (BDNF) by upregulating the BDNF/TrkB/CREB signaling pathway, restored synaptic impairments and enhanced norepinephrine (NE) and serotonin (5-HT) levels. Importantly, the correlation analysis showed that the gut barrier and lipopolysaccharide (LPS) content in the serum were highly associated with behavioral performance and the biochemical indexes of the brain. In summary, the present study indicates that sesamol is a novel nutritional intervention strategy for preventing IBD and its symptoms of anxiety and depression.

Dietary protein and amino acid restriction: Roles in metabolic health and aging-related diseases.

The prevalence of obesity is a worldwide phenomenon in all age groups and is associated with aging-related diseases such as type 2 diabetes, as well metabolic and cardiovascular diseases. The use of dietary restriction (DR) while avoiding malnutrition has many profound beneficial effects on aging and metabolic health, and dietary protein or specific amino acid (AA) restrictions, rather than overall calorie intake, are considered to play key roles in the effects of DR on host health. Whereas comprehensive reviews of the underlying mechanisms are limited, protein restriction and methionine (Met) restriction improve metabolic health and aging-related neurodegenerative diseases, and may be associated with FGF21, mTOR and autophagy, improved mitochondrial function and oxidative stress. Circulating branched-chain amino acids (BCAAs) are inversely correlated with metabolic health, and BCAAs and leucine (Leu) restriction promote metabolic homeostasis in rodents. Although tryptophan (Trp) restriction extends the lifespan of rodents, the Trp-restricted diet is reported to increase inflammation in aged mice, while severe Trp restriction has side effects such as anorexia. Furthermore, inadequate protein intake in the elderly increases the risk of muscle-centric health. Therefore, the restriction of specific AAs may be an effective and executable dietary manipulation for metabolic and aging-related health in humans, which warrants further investigation to elucidate the underlying mechanisms.

Sesamol Supplementation Attenuates DSS-Induced Colitis via Mediating Gut Barrier Integrity, Inflammatory Responses, and Reshaping Gut Microbiome.

Sesamol, a liposoluble lignan extract, has already been proved to possess potent anti-inflammatory properties, and it could also regulate gut dysfunction. The purpose of the present research is to explore the protective effect of sesamol on colitis mice. In the current research, sesamol treatment (100 mg/kg bodyweight/day) for 6 weeks inhibited the dextran sulphate sodium (DSS)-induced bodyweight loss of mice. Transmission electron microscopy and hematoxylin and eosin staining results showed that the DSS-induced histopathological changes of mice were also recovered by sesamol supplementation. In addition, DSS-induced inflammatory responses were inhibited by sesamol supplementation via the NF-κB signaling pathway in mice colon. Moreover, sesamol treatment prevented gut barrier damages by enhancing the expression of tight junction proteins (occludin, claudin-1, and ZO-1) and recovering the loss of gut mucus layer. Furthermore, sesamol supplementation also increased the short-chain fatty acid (SCFAs) contents of acetate, propionate, and butyrate. Furthermore, sesamol supplementation changed the gut microbiome structure by enhancing the relative abundance of Coprococcuscus, Butyricicoccus, Odoribacter, and AF12 in colitis mice. In conclusion, sesamol could effectively ameliorate DSS-induced colitis by promoting gut microecology.

Methionine Restriction Regulates Cognitive Function in High-Fat Diet-Fed Mice: Roles of Diurnal Rhythms of SCFAs Producing- and Inflammation-Related Microbes.

SCOPE: Methionine restriction (MR) is known to potently alleviate inflammation and improve gut microbiome in obese mice. The gut microbiome exhibits diurnal rhythmicity in composition and function, and this, in turn, drives oscillations in host metabolism. High-fat diet (HFD) strongly altered microbiome diurnal rhythmicity, however, the role of microbiome diurnal rhythmicity in mediating the improvement effects of MR on obesity-related metabolic disorders remains unclear. METHODS AND RESULTS: 10-week-old male C57BL/6J mice are fed a low-fat diet or HFD for 4 weeks, followed with a full diet (0.86% methionine, w/w) or a methionine-restricted diet (0.17% methionine, w/w) for 8 weeks. Analyzing microbiome diurnal rhythmicity at six time points, the results show that HFD disrupts the cyclical fluctuations of the gut microbiome in mice. MR partially restores these cyclical fluctuations, which lead to time-specifically enhance the abundance of short-chain fatty acids producing bacteria, increases the acetate and butyric, and dampens the oscillation of inflammation-related Desulfovibrionales and Staphylococcaceae over the course of 1 day. Notably, MR, which protects against systemic inflammation, influences brain function and synaptic plasticity. CONCLUSION: MR could serve as a potential nutritional intervention for attenuating obesity-induced cognitive impairments by balancing the circadian rhythm in microbiome-gut-brain homeostasis.

Paeonol exerts anti­tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/ß­catenin signaling pathway.

Paeonol is a simple phenolic compound isolated from herbal root bark, which has been reported to possess numerous biological and pharmacological characteristics, including a desirable anti­tumor effect. To date, the effect of paeonol against colorectal cancer (CRC) cells is yet to be fully elucidated. Therefore, the present study aimed to identify the underlying mechanism via which paeonol exerts its anti­tumor activity on HCT116 cells. After incubation with various concentrations of paeonol (7.8125, 15.625, 31.25, 62.5, 125, 250 and 500 µg/ml), the inhibitory effect of paeonol on cell viability was assessed using a Cell Counting Kit­8 assay. Cell apoptosis and cell cycle distribution were measured using flow cytometry. Moreover, caspase activity was measured using a colorimetric caspase assay. Luciferase assay was also used to determine the ß­catenin­mediated transcriptional activity of T­cell specific transcription factor/lymphoid­enhancer binding factor (TCF/LEF), and western blotting analysis was performed to measure the related expression of proteins. The results indicated that paeonol exhibited a notable effect against HCT116 cells by inducing G0/G1­phase arrest, as demonstrated by downregulation of the cell cycle regulators cyclin­dependent kinase 4 and cyclin D1 and upregulation of p21Cip1 in a dose­dependent manner. Furthermore, paeonol dose­dependently induced cell apoptosis, accompanied by an increase in the Bax/Bcl­2 ratio, release of cytochrome c and further activation of caspases. Paeonol also dose­dependently blocked the activation of the Wnt/ß­catenin signaling pathway by suppressing the expression of ß­catenin, resulting in a decrease in ß­catenin­mediated activity of TCF/LEF and downregulation of downstream target genes, including cyclin D1, survivin and c­Myc. Therefore, the present results suggested that paeonol exerted its anti­tumor effects on CRC cells, including the inhibition of cell proliferation, induction of cell cycle arrest and initiation of apoptosis, at least partly by suppressing the Wnt/ß­catenin pathway, which may offer a promising therapeutic strategy for CRC.

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment.

Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metabolism gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are observed between IF affected genes, microbiota and metabolites, as assessed by integrative modelling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metabolism-implicated cognitive pathophysiologies.

Mannan Oligosaccharide Suppresses Lipid Accumulation and Appetite in Western-Diet-Induced Obese Mice Via Reshaping Gut Microbiome and Enhancing Short-Chain Fatty Acids Production.

SCOPE: Obesity is associated with gut microbiome dysbiosis. Mannose oligosaccharide (MOS) has been reported to be a potential prebiotic. The present study is aimed to determine the effects of MOS on western-diet-induced obesity and to uncover the mediating roles of the gut microbiota and microbial metabolites. METHODS AND RESULTS: Three-month-old male ICR mice are fed with a high-fat and high-fructose diet for 8 weeks. The diet-induced obese mice are then orally administrated with MOS (100 and 200 mg kg-1  d-1 ) for 4 weeks. MOS significantly reduces bodyweight gain, insulin resistance, fatty liver, and inflammatory responses in obese mice. MOS also stimulates lipolysis and inhibits lipogenesis in the adipose tissues. Moreover, MOS restructures the gut microbiome by enhancing the abundance of Bifidobacterium and Lactobacillus in obese mice. The microbial metabolite SCFAs are also increased in the feces and serum. Correlation analysis indicates that the appetite suppression and lipid-lowering effects of MOS are highly correlated with the butyrate levels. CONCLUSION: MOS suppresses the appetite, which results in less lipid deposition. The lower appetite is likely due to an altered gut microbiome and elevated SCFAs production. MOS may be a potential nutraceutical used in body weight management and gut health improvement.

[Postoperative acute urinary retention in anorectal diseases treated with acupuncture combined with grain-moxibustion: a randomized controlled trial].

OBJECTIVE: To observe the efficacy differences between acupuncture combined with grain-moxibustion and acupuncture on acute urinary retention after epidural anaesthesia for anorectal diseases. METHODS: A total of 60 patients were randomized into an acupuncture combined with grain-moxibustion group and an acupuncture group, 31 cases in each one. In the acupuncture group, acupuncture was applied at Zhongji (CV 3), Guanyuan (CV 4), Qihai (CV 6), Shuidao (ST 28), Pangguangshu (BL 28), Sanyinjiao (SP 6) and Yinlingquan (SP 9). In the acupuncture combined with grain-moxibustion group, grain-moxibustion was given at Zhongji (CV 3), Guanyuan (CV 4), Qihai (CV 6) and Shuidao (ST 28) on the basis of acupuncture. Those who failed to urinate 60 min after the first treatment received the second treatment. 30 min after the second treatment, the lower abdominal symptom scores before and after treatment as well as the bladder residual urine volume after the first urination after treatment were compared between the two groups. In addition, the clinical efficacy and security were evaluated. RESULTS: Compared before treatment, the symptom scores after treatment were reduced in the two groups (P<0.05), and the score in the acupuncture combined with grain-moxibustion group was lower than that in the acupuncture group after treatment (P<0.05). The bladder residual urine volume in the acupuncture combined with grain-moxibustion group was (26.71±17.01) mL, which was lower than (35.32±20.76) mL in the acupuncture group (P<0.05). The total effective rate was 93.5% (29/31) in the acupuncture combined with grain-moxibustion group, which was superior to 71.0% (22/31) in the acupuncture group (P<0.05). CONCLUSION: The efficacy of acupuncture combined with grain-moxibustion is superior to simple acupuncture on acute urinary retention after epidural anaesthesia for anorectal diseases, which is safe and reliable.

Tea polyphenols direct Bmal1-driven ameliorating of the redox imbalance and mitochondrial dysfunction in hepatocytes.

Circadian rhythms are intimately linked to cellular redox status homeostasis via the regulation of mitochondrial function. Tea polyphenols (TP) are nutraceuticals that possess powerful antioxidant properties, especially ameliorating oxidative stress. The objective of this study was to investigate whether circadian clock is involved in the protection effect of TP on oxidative stress cell models. TP ameliorate H2O2-triggered relatively shallow daily oscillations and phase shift of circadian clock genes transcription and protein expression. Meanwhile, TP attenuate H2O2-stimulated excessive secretions of reactive oxygen species (ROS) and restore the depletions of mitochondrial function in a Bmal1-dependent manner. Furthermore, TP treatment accelerates nuclear translocation of Nrf2 and modulates the downstream expressions of antioxidant enzymes. Intriguingly, knockdown of Bmal1 notably blocked Nrf2/ARE/HO-1 redox-sensitive transcription pathway. Our study revealed that TP, as a Bmal1-enhancing natural compound, alleviated redox imbalance via strengthening Keap1/Nrf2 antioxidant defense pathway and ameliorating mitochondrial dysfunction in a Bmal1-dependent manner.

Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts.

The aim of the present study was to investigate the underlying molecular mechanisms of the potent cell cycle inhibition and apoptotic effect of luteolin on LoVo human colon cancer cells. In the present study, Cell Counting kit-8 assay revealed that luteolin exerted notable cytotoxicity on LoVo cells in a dose- and time-dependent manner, with a 50% inhibitory concentration value of 66.70 and 30.47 µmol/l at the time points of 24 and 72 h, respectively. Flow cytometric analysis confirmed that luteolin promoted cell cycle arrest at the G2/M phase, and subsequently induced cell apoptosis. Western blot analysis further revealed that luteolin exhibited an inhibitory effect on the proliferation of LoVo cells by inhibiting cell cycle arrest at the G2/M phase transition, with an inactivation of cyclin B1/cell division cycle 2 and induction of cell apoptosis, in part via cytochrome c- and deoxyadenosine triphosphate-mediated activation of apoptotic protease activating factor 1. In vivo studies revealed that luteolin effectively decreased the colon tumor body weight of mice. Therefore, the evidence suggests that luteolin may be a potential chemopreventive and chemotherapeutic agent against human colon cancer.

Protective effects of lipoic acid against acrylamide-induced neurotoxicity: involvement of mitochondrial energy metabolism and autophagy.

Acrylamide (ACR) is a chronic neurotoxin that is generated in high-starch foods during heat processing. Alpha-lipoic acid (LA) is an antioxidant that occurs in most plants and animals. The objective of this study was to reveal the mechanism of ACR-triggered neurotoxicity and identify the protective role of LA in SH-SY5Y cells. In this study, LA restored ACR-stimulated depletion of glutathione content and mitochondrial membrane potential, moderated the activation of inflammatory pathways, and recovered the Keap1/Nrf2 pathway. Moreover, LA upregulated the activities of oxidative phosphorylation complexes and diminished ACR-induced variation in AMPK/GSK3ß, Ca2+ disturbance, and ATP depletion. The Sirt1/PGC-1α pathway was inhibited by ACR. Notably, autophagy was activated in the mitochondria-mediated apoptosis induced by ACR, which was also blocked by LA. Overall, our study demonstrated the pivotal roles of the mitochondrial energy metabolism and autophagy in the protective effects of LA and cytotoxicity of ACR in SH-SY5Y cells.

Root extractive from Daphne genkwa benefits in wound healing of anal fistula through up-regulation of collagen genes in human skin fibroblasts.

Wound healing is the main problem in the therapy of anal fistula (AF). Daphne genkwa root has been traditionally used as an agent to soak sutures in operation of AF patients, but its function in wound healing remains largely unclear. The aim of the present study was to illuminate mechanisms of D. genkwa root treatment on AF. In the present study, 60 AF patients after surgery were randomly divided into two groups, external applied with or without the D. genkwa extractive. Wound healing times were compared and granulation tissues were collected. In vitro, we constructed damaged human skin fibroblasts (HSFs) with the treatment of TNF-α (10 µg/ml). Cell Count Kit-8 (CCK-8) and flow cytometry analysis were used to determine the effects of D. genkwa root extractive on cell viability, cell cycle and apoptosis of damaged HSFs. Furthermore, protein levels of TGF-ß, COL1A1, COL3A1, Timp-1, matrix metalloproteinase (MMP)-3 (MMP-3) and MEK/ERK signalling pathways were investigated both in vivo and in vitro Results showed that D. genkwa root extractive greatly shortens the wound healing time in AF patients. In granulation tissues and HSFs, treatment with the extractive significantly elevated the expressions of COL1A1, COL3A1, Timp-1, c-fos and Cyclin D1, while reduced the expression of MMP-3 Further detection presented that MEK/ERK signalling was activated after the stimulation of extractive in HSFs. Our study demonstrated that extractive from D. genkwa root could effectively improve wound healing in patients with AF via the up-regulation of fibroblast proliferation and expressions of COL1A1 and COL3A1.