Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis.

OBJECTIVE: The specific breast milk-derived metabolites that mediate host-microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation. DESIGN: We enrolled 250 mother-infant pairs and collected 978 longitudinal faecal samples from infants from birth to 6 months of age, along with 243 maternal faecal samples for metagenomics. Concurrently, 239 corresponding breast milk samples were analysed for metabolomics. Animal and cellular experiments were conducted to validate the bioinformatics findings. RESULTS: The clinical findings suggested that a decrease in daily breastfeeding duration was associated with a reduced incidence of AD. This observation inspired us to investigate the effects of breast milk-derived fatty acids. We found that high concentrations of arachidonic acid (AA), but not eicosapentaenoic acid (EPA) or docosahexaenoic acid, induced gut dysbiosis in infants. Further investigation revealed that four specific bacteria degraded mannan into mannose, consequently enhancing the mannan-dependent biosynthesis of O-antigen and lipopolysaccharide. Correlation analysis confirmed that in infants with AD, the abundance of Escherichia coli under high AA concentrations was positively correlated with some microbial pathways (eg, 'GDP-mannose-derived O-antigen and lipopolysaccharide biosynthesis'). These findings are consistent with those of the animal studies. Additionally, AA, but not EPA, disrupted the ratio of CD4/CD8 cells, increased skin lesion area and enhanced the proportion of peripheral Th2 cells. It also promoted IgE secretion and the biosynthesis of prostaglandins and leukotrienes in BALB/c mice fed AA following ovalbumin immunostimulation. Moreover, AA significantly increased IL-4 secretion in HaCaT cells costimulated with TNF-α and INF-γ. CONCLUSIONS: This study demonstrates that AA is intimately linked to the onset of AD via gut dysbiosis.

Xuebijing injection combined with alprostadil in the treatment of diabetic nephropathy: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Diabetes nephropathy (DN), as one of the common complications of diabetes, is characterized by persistent albuminuria, decreased glomerular filtration rate, and elevated arterial blood pressure. At present, Xuebijing injection is widely used in the treatment of DN. However, few systematic reviews and meta-analysis related to Xuebijing injection intervention in DN were published. In order to more systematically and objectively evaluate the clinical efficacy of Xuebijing injection intervention in DN, we conducted systematic reviews and meta-analysis to verify it. OBJECTIVE: The purpose of the research was to systematically evaluate the clinical efficacy of Xuebijing injection combined with alprostadil in the treatment of diabetic nephropathy. METHODS: We searched the China National Knowledge Infrastructure (CNKI), China Biomedical Database (SinoMed), Weipu Database (VIP), Wanfang Database, PubMed, The Cochrane Library, Embase, Web of Science and other databases by computer, and searched the randomized controlled trials of Xuebijing injection combined with alprostadil in the treatment of DN at home and abroad from the establishment of the database to 2022. The main outcome indicators included blood glucose, and the secondary outcome indicators included blood lipid, renal function, urinary protein, and safety. Two evaluators independently screened the literature, extracted the data and evaluated the risk of bias in the included studies. RevMan 5.3 software was used to analyze the data. RESULTS: A total of 14 randomized controlled trials were included, including 1233 cases, 618 cases in the treatment group and 615 cases in the control group. The results of meta-analysis demonstrated that compared with the control group, the treatment group could effectively reduce fasting plasma glucose [mean difference [MD] = -1.90, 95% CI (-2.40, -1.40), P < .00001], glycosylated hemoglobin A1c [MD = -2.38, 95% CI (-2.51, -2.25), P < .00001], 2h postprandial blood glucose [MD = -2.92, 95% CI (-3.95, -1.89), P < .00001], triacylglycerol [MD = -1.08, 95% CI (-1.66, -0.50), P = .0003], total cholesterol [MD = -1.17, 95% CI (-1.39, -0.95), P < .00001], low-density lipoprotein cholesterol [MD = -1.19, 95% CI (-1.60, -0.78), P < .00001], high-density lipoprotein cholesterol [MD = 0.32, 95% CI (0.23, 0.42), P < .00001], serum creatinine [MD = -42.95, 95% CI (-57.46, -28.43), P < .00001], blood urea nitrogen [MD = -2.24, 95%CI (-2.62,-1.86), P < .00001], blood ß2 microglobulin [SMD = -1.49, 95% CI (-1.70, -1.28), P < .00001], urine ß2 microglobulin [SMD = -0.81, 95% CI (-1.04, -0.58), P < .00001], 24-hour urinary protein quantification [MD = -0.20, 95% CI (-0.26, -0.14), P < .00001], urinary albumin excretion rate [SMD = -1.15, 95% CI (-1.38, -0.93), P < .00001]. CONCLUSION: Xuebijing injection combined with alprostadil has more advantages in treating DN compared to routine Western medicine.

Antidepressant effects of dexmedetomidine compared with ECT in patients with treatment-resistant depression.

OBJECTIVE: This pilot study was designed to investigate the antidepressant effects of dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, in patients with treatment-resistant depression (TRD). The antidepressant effects of dexmedetomidine was compared with ECT, which is widely used in clinical practice for treatment of patients with TRD. METHODS: Seventy six patients with TRD were randomly assigned to receive 10 sessions of DEX infusions or electroconvulsive therapy (ECT) treatment. The primary outcome was the changes of depression severity determined by the improvement of 24-item Hamilton Depression Rating Scale (HDRS-24). The second outcomes were the rates of therapeutic response (reduction in HDRS-24 ≥ 50 %) and remission (HDRS-24 ≤ 10 and reduction in HDRS-24 ≥ 60 %) at posttreatment and after 3 months of follow-up visits. RESULTS: We found that 10 sessions of DEX infusions or ECT treatments significantly improved HDRS-24 scores at posttreatment and after 3 months of follow-up visits compared with the baseline. In addition, there was no significant difference between DEX infusions and ECT treatments regarding HDRS-24 at these evaluating points. Furthermore, the depression severity dropped to mild after 2 sessions of DEX infusion. In contrast, at least 6 sessions of ECT treatment were needed to achieve a same level. Finally, the rates of therapeutic response and remission were comparable between the two groups. No serious adverse events were observed. CONCLUSIONS: Based on current published evidence, we conclude that DEX exhibits rapid and durable antidepressant properties similar to ECT but with fewer side effects.

A conserved Toll-like receptor-to-NF-κB signaling pathway in the endangered coral Orbicella faveolata.

Herein, we characterize the Toll-like receptor (TLR)-to-NF-κB innate immune pathway of Orbicella faveolata (Of), which is an ecologically important, disease-susceptible, reef-building coral. As compared to human TLRs, the intracellular TIR domain of Of-TLR is most similar to TLR4, and it can interact in vitro with the human TLR4 adapter MYD88. Treatment of O. faveolata tissue with lipopolysaccharide, a ligand for mammalian TLR4, resulted in gene expression changes consistent with NF-κB pathway mobilization. Biochemical and cell-based assays revealed that Of-NF-κB resembles the mammalian non-canonical NF-κB protein p100 in that C-terminal truncation results in translocation of Of-NF-κB to the nucleus and increases its DNA-binding and transcriptional activation activities. Moreover, human IκB kinase (IKK) and Of-IKK can both phosphorylate conserved residues in Of-NF-κB in vitro and induce C-terminal processing of Of-NF-κB in vivo. These results are the first characterization of TLR-to-NF-κB signaling proteins in an endangered coral, and suggest that these corals have conserved innate immune pathways.

Synthesis and luminescence of novel near-infrared emitting BaZrSi3 O9 :Cr3+ phosphors.

The BaZrSi3 O9 :Cr3+ phosphors were prepared by a high temperature solid state method. Their structures were confirmed with XRD and their luminescence properties were investigated. Under excitation at 455 nm, BaZrSi3 O9 :Cr3+ phosphors exhibited a broad near infrared emission band peaked at 800 nm, which was assigned to the 4 T2 →4 A2 transition of Cr3+ . The near infrared emission intensity reached a maximum at Cr3+ concentration of 0.7%. There was a concentration quenching phenomenon of Cr3+ in BaZrSi3 O9 matrix and the corresponding concentration quenching mechanism was investigated. With efficient near infrared emission in the range of 700-1000 nm, BaZrSi3 O9 :Cr3+ phosphors may find applications in solar energy conversion.

Self-nanoemulsifying drug delivery system of persimmon leaf extract: Optimization and bioavailability studies.

In current study, a self-nanoemulsifying drug delivery system (SNEDDS) of persimmon (Diospyros kaki) leaf extract (PLE) was developed and characterized to compare its in vitro dissolution and relative bioavailability with commercially available tablets (Naoxinqing tablets). Pseudo-ternary phase diagrams were constructed by phase diagram by micro plate dilution (PDMPD) method, of which the evaluation method was improved to use Multiskan Ascent for identifying turbidity. The formulation of PLE-loaded SNEDDS was optimized by an extreme vertices experimental design. The optimized nanoemulsion formulation, loading with 44.48 mg/g PLE total flavonoids, consisted of Cremophor EL, Transcutol P, Labrafil M 1944 CS (56:34:10, w/w), and it remained stable after storing at 40°C, 25°C, 4°C for at least 6 months. When diluted with water, the SNEDDS droplet size was 34.85 nm and the zeta potential was -6.18 mV. Compared with the commercial tablets, the AUC of both quercetin and kaempferol, which are representative active flavonoids of PLE, was increased by 1.5-fold and 1.6-fold respectively following oral administration of PLE-loaded SNEDDS in fasting beagle dogs. These results indicate that SNEDDS is a promising drug delivery system for increasing the oral bioavailability of PLE.