Mechanisms underlying palmitic acid-induced disruption of locomotor activity and sleep behavior in Drosophila.

The globally prevalent of sleep disorders is partly attributed to unhealthy dietary habits. This study investigated the underlying mechanisms of elevated palmitic acid (PA) intake on locomotor activity and sleep behavior in Drosophila. Our results indicate that exposure to PA significantly elevated Drosophila's daytime and nighttime locomotor activity while concurrently reducing overall sleep duration. Utilizing 16S rRNA sequencing, we observed substantial alterations in the composition of the gut microbiota induced by PA, notably, characterized by a significant reduction in Lactobacillus plantarum. Furthermore, PA significantly increased the levels of inflammatory factors Upd3 and Eiger in Drosophila intestines, and downregulated the expression of Gad and Tph, as well as 5-HT1A. Conversely, Gdh and Hdc were significantly upregulated in the PA group. Supplementation with L. plantarum or lactic acid significantly ameliorated PA-induced disruptions in both locomotor activity and sleep behavior. This supplementation also suppressed the expression of intestinal inflammatory factors, thus restoring impaired neurotransmitter-mediated sleep-wake regulation. Moreover, specific knockdown of intestinal epithelial Upd3 or Eiger similarly restored disrupted neurotransmitter expression, ultimately improving PA-induced disturbances in Drosophila locomotor activity and sleep behavior. These findings provide important insights into the intricate interplay between dietary components and essential behaviors, highlighting potential avenues for addressing health challenges associated with modern dietary habits.

[Clinical research of Pinggan Jiangya decoction combined with penetrating needling at Baihui (GV20) in a period of day from 7 am to 9 am in the treatment of grade 1 and 2 essential hypertension].

OBJECTIVE: To explore the clinical effect of Pinggan Jiangya decoction combined with penetrating needling at Baihui (GV20) in a period of day from 7 am to 9 am in the treatment of grade 1 and 2 essential hypertension (EH). METHODS: A total of 150 cases of grade 1 and 2 EH patients were randomized into an observation group and a control group, 75 cases in each group. In the control group, Pinggan Jiangya decoction was prescribed for oral administration one dose a day, while in the observation group, on the basis of the treatment as the control group, penetrating needling was exerted at GV20 once daily. The treatment duration was 8 weeks. Before and after treatment, the TCM syndrome score, 24 h average systolic blood pressure (24 h ASBP), 24 h average diastolic blood pressure (24 h ADBP), 24 h average pulse pressure difference (24 h PP), morning blood pressure surge (MBPS), 24 h SBP variability (24 h SBPV), 24 h DBP variability (24 h DBPV), serum levels of 5-hydroxytryptamine (5-HT) and melatonin (MT) were compared in the patients of the two groups. The clinical therapeutic effect was observed in the two groups. RESULTS: After the treatment, in the self-comparison of each group, the scores of headache, vertigo, backache, soft knees, tinnitus, 24 h ASBP， 24 h ADBP, 24 h PP, MBPS, 24 h SBPV and 24 h DBPV in the two groups were lower than those before treatment (P<0.01), and the above indexes in the observation group were lower than those in the control group (P<0.01). The level of serum 5-HT after the treatment was lower than that of before the treatment (P<0.01), while the level of MT was higher than that of before the treatment (P<0.01) in both two groups, and the level of 5-HT in the observation group was lower than that of the control group, while the level of MT was higher than that of the control group (P<0.01). The total effective rate of the observation group was 93.3% (70/75), better than 76.0% (57/75) of the control group (P<0.01). CONCLUSION: Pinggan Jiangya decoction combined with penetrating needling at GV20 in a period of day from 7 am to 9 am can regulate the levels of serum MT and 5-HT, effectively reduce blood pressure, improve blood pressure variability, control morning peak blood pressure, and has a remarkable effect in the treatment of grade 1 and 2 EH.

Effects of sodium butyrate supplementation on inflammation, gut microbiota, and short-chain fatty acids in Helicobacter pylori-infected mice.

BACKGROUND: Inflammation induced by Helicobacter pylori (H. pylori) infection is the basis for the pathogenesis of H. pylori. Butyric acid, a diet-related microbial-associated metabolite, is connected to inflammation, metabolic syndrome, and other diseases. Several studies have indicated the effects of sodium butyrate (SB) against bacteria; however, the effects of SB on the main virulence factors of H. pylori, H. pylori-induced inflammation, and gut microbiota composition remain unclear. MATERIALS AND METHODS: SB was supplemented in H. pylori coculture and administered to mice infected with H. pylori. The effects of SB intake on inflammation, gut microbiota composition, and short-chain fatty acids (SCFAs) in H. pylori-infected mice were assessed. RESULTS: The in vitro experiments demonstrated that SB not only inhibited the growth of H. pylori but also decreased the mRNA expression of CagA and VacA. SB intake reduced the production of virulence factors in H. pylori-infected mice, inhibited the IκBα/NF-κB pathway by reducing the expression of Toll-like receptors (TLRs), and reduced the production of TNF-α and IL-8. Further analysis demonstrated that H. pylori infection altered the relative abundance of the intestinal microbial community in mice. The level of SCFAs in the feces of H. pylori-infected mice was changed, although the intake of SB did not obviously change the level of SCFAs. CONCLUSIONS: Our study showed that SB may decrease H. pylori-induced inflammation by inhibiting the viability and virulence of H. pylori and may reduce inflammation in association with the gut microbiota in H. pylori-infected mice. This study may provide novel insights into the mechanisms by which SB, a diet-related microbial-associated metabolite, affects H. pylori-induced disease development.

The JAK2/STAT3 pathway is involved in the anti-melanoma effects of brevilin A.

AIMS: Melanoma is lethal. Constitutively active signal transducer and activator of transcription 3 (STAT3) has been proposed as a pathogenic factor and a therapeutic target of melanoma. Brevilin A, a sesquiterpene lactone isolated from Centipeda minima (L.) A. Br. et Aschers., has been shown to exert antineoplastic effects and inhibit the STAT3 pathway in nasopharyngeal, lung, prostate and breast cancer cells. This study aimed to determine whether brevilin A has anti-melanoma effects, and whether STAT3 signaling is involved in the effects. MAIN METHODS: A mouse A375 xenograft model, as well as A375 and A2058 cell models were employed to assess the in vivo and in vitro anti-melanoma effects of brevilin A. A375 cells stably expressing STAT3C, a constitutively active STAT3 mutant, were used to determine the role of STAT3 signaling in brevilin A's anti-melanoma effects. KEY FINDINGS: Intraperitoneal injection of brevilin A dose-dependently inhibited melanoma growth in mice and suppressed STAT3 phosphorylation in the tumors. In cultured cells, brevilin A reduced cell viability, induced apoptosis, suppressed migration and invasion, decreased protein levels of phospho-JAK2 (Y1007/1008) and phospho-STAT3 (Tyr705), and restrained STAT3 nuclear localization. STAT3 over-activation diminished brevilin A's effects on cell viability and migration. Collectively, brevilin A exerts anti-melanoma effects and these effects are at least in part attributed to the inhibition of the JAK2/STAT3 pathway. SIGNIFICANCE: Our findings provide a pharmacological basis for developing brevilin A as a new phytotherapeutic agent against melanoma.

A newborn with seizures born to a mother diagnosed with primary carnitine deficiency.

BACKGROUND: Maternofetal carnitine transport through the placenta is the main route of fetal carnitine uptake. Decreased free carnitine levels discovered by newborn screening has identified many asymptomatic adult women with systemic primary carnitine deficiency (PCD). Here, we presented amplitude integrated electroencephalogram (aEEG) and magnetic resonance imaging (MRI) findings from a neonate with epilepsy whose mother was carnitine deficient. CASE PRESENTATION: A one-day-old female newborn was admitted after experiencing seizures for half a day; status epilepticus was found on the continuous normal voltage background pattern with immature sleep-wake cycling during aEEG monitoring. On T1-weighted, T2-weighted, FLAIR, and DWI head MRI, there were various degrees of hyperintense signals and diffusion restrictions in the deep white matter of the right hemisphere. Tandem mass spectrometry discovered carnitine deficiency on the second day, which elevated to normal by the 9th day before L-carnitine supplementation was started. The patient was treated with phenobarbital after admission. No further seizures were noted by day 5. It was confirmed that the patient's mother had a low level of serum-free carnitine. Gene analyses revealed that the newborn had heterozygote mutations on c.1400C > G of the SLC22A5 gene, and her mother had homozygous mutations on c.1400C > G. The patient had a good outcome at the 8-month follow up. CONCLUSIONS: Maternal carnitine deficiency that occurs during the perinatal period may manifest as secondary epilepsy with cerebral injury in neonates. The short-term neurodevelopmental outcomes were good. Early diagnosis of asymptomatic PCD in female patients can provide guidance for future pregnancies.

[Triterpenes constituents from male flowers of Eucommia ulmoides].

Nine triterpenes compounds were isolated from the male flowers of Eucommia ulmoides by recrystallization and chromatographic techniques over silica gel, Sephadex LH-20, and RP-18 gel. Their chemical structures were identified on the basis of spectral analysis and as 3-oxo-12-en-ursane-28-O-α-L-arabinofuranosyl (1 --> 6) -ß-D-glucopyranoside (1), 2α, 3ß-dihydroxyurs-12-en-28-oic acid(28 --> 1) -ß-D-glucopyranosyl ester (2), ursolic acid (3), α-amyrin (4), uvaol (5), ursolic acid acetate (6), 3-O-acetate oleanoic acid (7), betulinic acid (8), and betulinol (9). Compound 1 was a new compound, and compounds 2, 4-7 were isolated from the Eucommiu genus for the first time. Cytotoxic activity was tested for all the compounds against K562 and HepG2 cells. The results showed that only compound 3, exhibited cytotoxic activity.