Short-term responses of soil enzyme activities and stoichiometry to litter input in Castanopsis carlesii and Cunninghamia lanceolata plantations.

Litter input triggers the secretion of soil extracellular enzymes and facilitates the release of carbon (C), nitrogen (N), and phosphorus (P) from decomposing litter. However, how soil extracellular enzyme activities were controlled by litter input with various substrates is not fully understood. We examined the activities and stoichiometry of five enzymes including ß-1,4-glucosidase, ß-D-cellobiosidase, ß-1,4-N-acetyl-glucosaminidase, leucine aminopeptidase and acidic phosphatase (AP) with and without litter input in 10-year-old Castanopsis carlesii and Cunninghamia lanceolata plantations monthly during April to August, in October, and in December 2021 by using an in situ microcosm experiment. The results showed that: 1) There was no significant effect of short-term litter input on soil enzyme activity, stoichiometry, and vector properties in C. carlesii plantation. In contrast, short-term litter input significantly increased the AP activity by 1.7% in May and decreased the enzymatic C/N ratio by 3.8% in August, and decreased enzymatic C/P and N/P ratios by 11.7% and 10.3%, respectively, in October in C. lanceolata plantation. Meanwhile, litter input increased the soil enzymatic vector angle to 53.8° in October in C. lanceolata plantations, suggesting a significant P limitation for soil microorganisms. 2) Results from partial least squares regression analyses showed that soil dissolved organic matter and microbial biomass C and N were the primary factors in explaining the responses of soil enzymatic activity to short-term litter input in both plantations. Overall, input of low-quality (high C/N) litter stimulates the secretion of soil extracellular enzymes and accelerates litter decomposition. There is a P limitation for soil microorganisms in the study area.

Bisphenol A Regulates the TNFR1 Pathway and Excessive ROS Mediated by miR-26a-5p/ADAM17 Axis to Aggravate Selenium Deficiency-Induced Necroptosis in Broiler Veins.

Selenium (Se) deficiency can affect the expression of microRNA (miRNA) and induce necroptosis, apoptosis, etc., resulting in damage to various tissues and organs. Bisphenol A (BPA) exposure can cause adverse consequences such as oxidative stress, endothelial dysfunction, and atherosclerosis. The toxic effects of combined treatment with Se-deficiency and BPA exposure may have a synergistic effect. We replicated the BPA exposure and Se-deficiency model in broiler to investigate whether the combined treatment of Se-deficiency and BPA exposure induced necroptosis and inflammation of chicken vascular tissue via the miR-26A-5p/ADAM17 axis. We found that Se deficiency and BPA exposure significantly inhibited the expression of miR-26a-5p and increased the expression of ADAM17, thereby increasing reactive oxygen species (ROS) production. Subsequently, we discovered that the tumor necrosis factor receptor (TNFR1), which was highly expressed, activated the necroptosis pathway through receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed-lineage kinase domain-like (MLKL), and regulated the heat shock proteins-related genes expressions and inflammation-related genes expressions after exposure to BPA and selenium deficiency. In vitro, we found that miR-26a-5p knockdown and increased ADAM17 can induce necroptosis by activating the TNFR1 pathway. Similarly, both N-Acetyl-L-cysteine (NAC), Necrostatin-1 (Nec-1), and miR-26a-5p mimic prevented necroptosis and inflammation caused by BPA exposure and Se deficiency. These results suggest that BPA exposure activates the miR-26a-5p/ADAM17 axis and exacerbates Se deficient-induced necroptosis and inflammation through the TNFR1 pathway and excess ROS. This study lays a data foundation for future ecological and health risk assessments of nutrient deficiencies and environmental toxic pollution.

Comparison of bleomycin polidocanol foam vs electrochemotherapy combined with polidocanol foam for treatment of venous malformations.

OBJECTIVE: This study aims to investigate the difference in safety and efficacy between two treatments for venous malformations (VMs), electrochemotherapy combined with polidocanol foam (ECP) and bleomycin polidocanol foam (BPF), providing alternative therapies for VMs. METHODS: We conducted a retrospective review of 152 patients with VMs treated with ECP and BPF. Pre- and post-treatment magnetic resonance images (MRIs) were collected, and clinical follow-up assessments were performed. Imaging results were used to calculate lesion volume changes. Clinical outcomes included changes in pain and improvements in perceived swelling. Patients were followed up at 1 week and 6 months after surgery. All emerging complications were documented in detail. RESULTS: Of the 152 patients, 87 (57.2%) received BPF treatment, and 65 (42.8%) received ECP treatment. The most common location of VMs was the lower extremities (92/152; 60.2%), and the most common symptom was pain (108/152; 71.1%). Forty-three patients had previously undergone therapy in the BPF group (43/87; 49.4%), whereas 30 patients had received prior treatment in the ECP group (30/65; 46.2%). The study found that the percentage of lesion volume reduction in the BPF group was not significantly different from that in the ECP group (75.00% ± 17.85% vs 74.69% ± 8.48%; P = .899). ECP was more effective when the initial lesion volume was greater than 30 mL (67.66% ± 12.34% vs 73.47% ± 8.00%; P = .048). Patients treated with BPF had significantly less posttreatment pain than those treated with ECP, in different baseline lesion size. In the overall sample, pain relief was significantly higher in the BPF group than in the ECP group (4.21 ± 1.19 vs 3.57 ± 0.76; P = .002). However, there was no difference in pain relief between the two groups for the treatment of initially large VMs (4.20 ± 0.94 vs 3.70 ± 0.87; P = .113). The ECP group was significantly more likely to develop hyperpigmentation (5/87; 5.75% vs 11/65; 16.92%; P = .026) and swelling (9/87; 10.34% vs 16/65; 24.62%; P = .019) 1 week after surgery than the BPF group. CONCLUSIONS: Our study demonstrates that both BPF and ECP are effective treatments for VMs, with BPF being a safer option. ECP is a better choice for patients with the initial lesion volume greater than 30 mL, but it is more likely to lead to early swelling and hyperpigmentation.

TP induces hepatic intolerance to FasL-mediated hepatocyte apoptosis by inhibiting XIAP.

Triptolide (TP) is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook. F. (TWHF). Its severe toxic side effects, especially hepatotoxicity, have limited the clinical application of TP-related drugs. In this study, we investigated the mechanism of the hepatotoxic effects of TP from the perspective that TP inhibited the expression of the pro-survival protein X-linked inhibitor of apoptosis protein (XIAP) and enhanced FasL-mediated apoptosis of hepatocytes. TP and CD95/Fas antibody (Jo-2) were administered by gavage to C57BL/6 mice for 7 consecutive days. After co-administration of TP and Jo-2, mouse livers showed large areas of necrosis and apoptosis and significantly increased Caspase-3 activity. KEGG pathway enrichment analysis indicated that TP may cause the development of liver injury through the apoptotic signaling pathway. Proteinprotein interaction networks showed that XIAP played an essential role in this process. TP reduced the protein expression of XIAP after combination treatment with Jo-2/FasL in vivo/in vitro. TP and FasL co-stimulation significantly increased microRNA-137 (miR-137) levels in AML12 cells, while inhibition of miR-137 expression induced a rebound in XIAP protein expression. In conclusion, TP presensitizes hepatocytes and enhances the sensitivity of hepatocytes to the Fas/FasL pathway by inhibiting the protein expression of XIAP, leading to hepatocyte apoptosis.

Bisphenol A aggravate selenium deficiency-induced apoptosis via miR-215-3p/Dio1 to activate ROS/PI3K/AKT pathway in chicken arterial.

Both bisphenol A (BPA) and selenium (Se) deficiency can affect the expression of microRNAs (miRNAs), which can specifically regulate its target mRNA and induce apoptosis, and play a significant role in cardiovascular injury diseases. To explore the mechanism of apoptosis induced by BPA and Se deficiency in chicken arterial endothelial tissue and the role of miRNAs in this process, the model of BPA exposure/Se deficiency in chicken and PAEC cells have been employed. The targeting relationship between miR-215-3p and iodothyronine deiodinase 1 (Dio1) in PAEC was verified by double luciferase gene report. The level of miR-215-3p was detected by qRT-PCR. The oxidative stress level of arterial endothelial cells was detected by oxidative stress kit and DCFH-DA probe method. The PI3K/AKT pathway, mitochondrial dynamics, and apoptosis-related genes were detected by qRT-PCR and western blot. The mitochondrial ATP level and nitric oxide synthases (NOSs) level were detected with the kit. TUNEL, acridine orange/ethidium bromide, and flow cytometry were used to detect the level of apoptosis. The results showed that BPA exposure and Se deficiency led to overexpression of miR-215-3p, aggravated oxidative stress, inhibited activation of PI3K/AKT pathway, promoted mitochondrial division, increased expression of apoptosis related genes, and finally led to apoptosis of chicken arterial endothelial cells. We also established knockdown/overexpression models of miR-215-3p and Dio1 in vitro, and found that overexpression of miR-215-3p and knockout of Dio1 can induce apoptosis. Interestingly, miR-215-3p-Inhibitor and N-acetyl- l-cysteine (NAC) partially prevented apoptosis caused by BPA exposure and Se deficiency, and LY294002 aggravated apoptosis. These results suggest that BPA exposure aggravates the apoptosis of Se deficient arterial endothelial cells in chickens by regulating the ROS/PI3K/AKT pathway activated by miR-215-3p/Dio1. The miR-215-3p/Dio1 axis provides a new way to understand the toxic mechanism of BPA exposure and Se deficiency, and reveals a new regulatory model of apoptosis damage in vascular diseases.

Cinobufacini retards progression of pancreatic ductal adenocarcinoma through targeting YEATS2/TAK1/NF-κB axis.

BACKGROUND: Cinobufacini, a sterilized hot water extract of dried toad skin, had significant effect against several human cancers. However, there are few studies reporting the effect of cinobufacini on pancreatic cancer. PURPOSE: To investigate the effects of cinobufacini on the progress of pancreatic ductal adenocarcinoma and the underlying mechanisms. METHODS: Cell counting, EdU incorporation and flow Cytometry were performed to evaluate the effect of cinobufacini on cell cycle and growth. MIA-PaCa2 cells were implanted into the nude mice to determine whether cinobufacini represses PDAC progression in vivo. Luciferase reporter assay, western blotting and qPCR were carried out to measure the activity of NF-κB pathway and the alteration of YEATS2 and TAK1. Ectopic gene expression introduced by plasmids was used to verify the molecular mechanism. RESULTS: Our results showed that cinobufacini induced cell cycle arrest and inhibited the growth of PDAC cell in vitro, and repressed MIA-derived PDAC in vivo. Cinobufacini inhibited the phosphorylation of IKK, IκB and NF-κB p65 in PDAC cells. Furthermore, cinobufacini decreased the abundance of intracellular YEATS2 and total TAK1 protein in a time- and dose dependent manner. Ectopic expression of YEATS2 re-elevated the level of TAK1 and phosphorylated IKKα/ß, IκBα and p65 after cinobufacini treatment in PANC-1 cells. CONCLUSION: Cinobufacini retards the growth and progression of PDAC in vitro and in vivo through YEATS2/TAK1/NF-κB axis.

Selenium Deficiency Induces Inflammatory Response and Decreased Antimicrobial Peptide Expression in Chicken Jejunum Through Oxidative Stress.

Selenium deficiency can affect the level of selenoprotein in organs and tissues and cause inflammation. However, the mechanism of selenium deficiency on jejunal injury in chickens remains unclear. In this study, we established a selenium deficiency model in chickens by feeding a low selenium diet and observed ultrastructural and pathological changes in the jejunum. The expression levels of 25 selenoproteins, the levels of oxidative stress, tight junction (TJ) proteins, and antimicrobial peptides (AMP), as well as the expression levels of factors related to inflammatory signaling pathways, were examined in the intestine and analyzed using principal component analysis (PCA). The results of PCA and quantitative real-time PCR (qRT-PCR) showed that selenium deficiency mainly affected the expression of antioxidant selenoproteins in chicken jejunum, especially glutathione peroxidases, thioredoxin reductase, and iodothyronine deiodinase, thus weakening the antioxidant function in the intestine and inducing oxidative stress. We also found disruption of intestinal TJ structures, a significant reduction in TJ protein expression, and downregulation of antimicrobial peptide levels, suggesting that selenium deficiency led to damage of the intestinal barrier. In addition, a significant increase in inflammatory cell infiltration and expression of inflammatory factors was observed in the jejunum, indicating that selenium deficiency induces inflammatory injury. In conclusion, selenium deficiency downregulates antioxidant selenoproteins levels, induces oxidative stress, decreases intestinal AMP levels, and leads to inflammatory injury and disruption of the intestinal barrier in the jejunum. These results shed new light on the molecular mechanisms of intestinal damage caused by selenium deficiency.

Effect of calcium supplementation on severe hypocalcemia in patients with secondary hyperparathyroidism after total parathyroidectomy.

BACKGROUND: Severe hypocalcemia (SH) is a dreaded complication of total parathyroidectomy (TPTX) without auto-transplantation. AIM: To compare conventional and preventive calcium supplementation (CS) regimens in terms of SH occurrence after TPTX. METHODS: This retrospective study included patients who underwent TPTX between January 2015 and May 2018 at the China-Japan Friendship Hospital. From January 2015 to May 2016, conventional CS was performed in patients who underwent TPTX, with calcium amounts adjusted according to postoperative serum calcium levels. From October 2016 to May 2018, preventive CS was performed according to preoperative alkaline phosphatase (ALP) levels. The patients were defined as low-risk (ALP < 500 U/L) and high-risk (ALP > 500 U/L) for SH. All preoperative blood samples were collected in the fasting state on the day before surgery. Postoperative blood samples were obtained at 6-7 AM from the first postoperative day. RESULTS: A total of 271 patients were included. These patients were 47.7 ± 11.1 years old, and 57.6% were male. Their mean body mass index (BMI) was 22.9 ± 3.8 kg/m2. There were no significant differences in sex, age, BMI, preoperative ALP, serum calcium, serum phosphorus, calcium-phosphorus ratio, and intact parathyroid hormone (iPTH) between the two CS groups. Compared with conventional CS, preventive CS led to lower occurrence rates of hypocalcemia within 48 h (46.0% vs 74.5%, P < 0.001) and SH (31.7% vs 64.1%, P < 0.001). Multivariable analysis showed that preoperative iPTH levels [odds ratio (OR) = 1.001, 95% confidence interval (CI): 1.000-1.001, P = 0.009), preoperative ALP amounts (OR = 1.002, 95%CI: 1.001-1.003, P = 0.002), preoperative serum phosphorus levels (OR = 8.729, 95%CI: 1.518-50.216, P = 0.015) and preventive CS (OR = 0.132, 95%CI: 0.067-0.261, P < 0.001) were independently associated with SH. In patients with preoperative ALP ≥ 500 U/L, only preventive CS (OR = 0.147, 95%CI: 0.038-0.562. P = 0.005) was independently associated with SH. CONCLUSION: This study suggests that preventive CS could reduce the occurrence of SH, indicating its critical value for hypocalcemia after TPTX.

[Influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks: a Meta analysis]. / 脐带挤压与延迟断脐对胎龄<34周早产儿早期预后影响的Meta分析.

OBJECTIVES: To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis. RESULTS: A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05). CONCLUSIONS: Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.

[Outcome indicators in randomized controlled trials on traditional Chinese medicine intervention for tension-type headache in recent five years].

To evaluate the application of outcome indicators in randomized controlled trials(RCTs) concerning the treatment of tension-type headache(TTH) with traditional Chinese medicine(TCM) in recent five years, so as to provide a basis for the study of core outcome set(COS) for TCM intervention in TTH. The RCTs on TCM treatment of TTH in recent five years were systematically retrieved from CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov and China Clinical Trial Registry. After literature screening, data extraction and evaluation of the risk of bias, the outcome indicators in the included RCTs were subjected to qualitative analysis. The preliminary search yielded 19 042 articles, and 10 983 were left after the elimination of duplication. Finally, 52 RCTs(48 in Chinese and 4 in English) were included for qualitative analysis. The outcome indicators of RCTs included in this study were classified into seven domains: TCM syndrome, symptom and sign, physical and chemical detection, quality of life, long-term prognosis, economic evaluation, and safety event. The findings demonstrated that headache characteristic index in the symptom and sign domain was the index with the highest reporting frequency and reporting rate. Seventeen RCTs used TCM syndrome score as the outcome indicator. Further analysis revealed that there existed such problems in research design as non-distinction between primary and secondary outcome indicators, great difference in the adopted measurement tools for outcome indicators, and the neglect of measurement time of outcome indicators. Moreover, the syndrome indicators reflecting TCM advantages, objective evaluation indicators, safety and health-economic indicators were lacking. These limitations have affected the quality and reliability of RCTs on TTH treatment with TCM. It is suggested that the efficacy and characteristics of TCM should be combined into current clinical research, and the COS in RCTs regarding TCM treatment of TTH should be established according to internationally recognized standard procedures.

[Systematic review and Meta-analysis of efficacy and safety of gastrodin in treatment of tension-type headache].

The efficacy of gastrodin as a Chinese herbal medicine extract in the treatment of tension-type headache has been confirmed. This paper systematically reviewed the efficacy and safety of gastrodin in the treatment of tension-type headache, aiming to provide a new choice for the treatment of this disease. In this study, four Chinese databases, four English databases and two trial registries were searched from the date of establishment to September 2020. The related randomized controlled trials(RCTs) were screened out according to the predetermined criteria. The bias risk assessment tool developed by Cochrane collaboration was used to evaluate the quality of the reports. RevMan 5.4.1 was used for Meta-analysis, and GRADE system for the evidence-based evaluation on the quality of outcome indicators. A total of 177 articles were retrieved and 8 articles were finally included for analysis, with a total sample size of 1 091 cases, which included 565 cases in the treatment group and 526 cases in the control group. The overall quality of included stu-dies was not high. The results of Meta-analysis are as follows:(1)In terms of headache frequency, gastrodin group was better than wes-tern medicine group(MD=-2.90, 95%CI[-3.76,-2.03], P<0.000 01).(2)In terms of number of abnormal blood vessels in TCD, gastrodin group was better than western medicine group(MD=-88.96, 95%CI[-102.36,-75.55], P<0.000 01).(3)In terms of effective rate, gastrodin group was better than western medicine group(RR=1.47, 95%CI[1.29, 1.68], P<0.000 01). The results of subgroup analysis are as follows:(1)Effective rate based on age, for the patients upper age limit 40-46 years old, gastro-din group was better than western medicine group(RR=1.69, 95%CI[1.50, 1.90], P<0.000 01); for the patients upper age limit 55-60 years old, gastrodin group was better than western medicine group(RR=1.27, 95%CI[1.16, 1.38], P<0.000 01).(2)Effective rate based on dosage form, both the gastrodin capsules and injection groups were better than western medicine group(RR_(capsules)=1.42, 95%CI[1.08, 1.88], P=0.01; RR_(injection)=1.50, 95%CI[1.26, 1.77], P<0.000 01). GRADE evaluation showed that the above outcomes had low quality of evidence. Only one article detailed the occurrence of adverse reactions and thus the present study cannot make a positive conclusion on the safety of gastrodin in the treatment of tension-type headache. The small number and low quality of the included reports affected the reliability of the results. In the future, more high-quality randomized controlled trails are needed to improve the evaluation on the efficacy and safety of gastrodin in the treatment of tension-type headache.

[Systematic review and Meta-analysis of efficacy and safety of Toutongning Capsules in treatment of tension-type headache].

This study aims to systematically evaluate the clinical efficacy and safety of Toutongning Capsules in the treatment of tension-type headache(TTH), so as to provide a corresponding basis for clinical treatment. Eight commonly used medical research databases and two clinical trial registration systems were retrieved with the time interval from the establishment of the database or system to November 2020. The randomized controlled trials of Toutongning Capsules in the treatment of TTH were screened out according to the pre-set criteria. The quality of the included papers was evaluated by the bias risk assessment tool in Cochrane Reviewers Handbook 6.1 and the data were statistically analyzed by RevMan v5.4 provided by Cochrane collaboration. A total of 13 studies were included and the quality of methodology was generally low. Meta-analysis showed that Toutongning Capsules assisted with western medicine therapy can effectively reduce the pain intensity(MD_(VAS)=-1.94,95%CI[-2.50,-1.38],P<0.000 01;MD_(NRS)=-0.83,95%CI[-0.86,-0.80],P<0.000 01), headache duration(SMD=-0.98,95%CI[-1.17,-0.79],P<0.000 01), headache frequency(MD=-1.01,95%CI[-1.16,-0.85],P<0.000 01), headache index(MD=-11.13,95%CI[-12.10,-10.16],P<0.000 01), anxiety and depression scale score(MD_(HAMA)=-4.02,95%CI[-6.58,-1.46],P=0.002;MD_(HAMD)=-2.67,95%CI[-4.04,-1.29],P=0.000 1), while Toutongning Capsules as monotherapy only reduced the headache score(MD=-2.24,95%CI[-2.97,-1.51],P<0.000 01). The available clinical studies demonstrate that Toutongning Capsules combined with western medicine in the treatment of TTH can improve the related outcome indicators, but the clinical safety and efficacy of Toutongning Capsules alone remain unclear. Due to the small number and low quality of the included studies, large-sample, multi-center, high-quality and strictly designed randomized controlled trials are still needed to verify the clinical efficacy in the future.

Potential protective effects of thiamine supplementation on the ruminal epithelium damage during subacute ruminal acidosis.

In ruminants, the ruminal epithelium not only has the function of absorbing nutrients but also is an important tissue to prevent harmful substances in the rumen from entering the blood circulation. Thus, the normal function of ruminal epithelium is critical for ruminants. However, subacute ruminal acidosis induced by high-concentrate diets often damages the barrier function of ruminal epithelium in ruminants. Recently, many studies have shown that dietary supplementation with thiamine is an effective method to alleviate subacute ruminal acidosis. In order to provide theoretical reference for the in-depth study of subacute ruminal acidosis and the application of thiamine in the future, this review introduces the effects of subacute ruminal acidosis on morphological structure, inflammatory response, and tight junction of ruminal epithelium. In addition, this paper summarizes the role of thiamine in maintaining ruminal epithelial function of ruminants during subacute ruminal acidosis challenge.

Inhibition of histone acetyltransferase by naringenin and hesperetin suppresses Txnip expression and protects pancreatic ß cells in diabetic mice.

BACKGROUND: The damage of pancreatic ß cells is a major pathogenesis of the development and progression of type 2 diabetes and there is still no effective therapy to protect pancreatic ß cells clinically. In our previous study, we found that Quzhou Fructus Aurantii (QFA), which is rich in flavanones, had the protective effect of pancreatic ß cells in diabetic mice. However, the underlying mechanism is still unclear. PURPOSE: In the current study, we administered naringenin and hesperetin, two major active components of QFA, to protect pancreatic ß cells and to investigate the underlying molecular mechanism focusing on the epigenetic modifications. METHODS: We used diabetic db/db mouse and INS-1 pancreatic ß cell line as in vivo and in vitro models to investigate the protective effect of naringenin and hesperetin on pancreatic ß cells under high glucose environment and the related mechanism. The phenotypic changes were evaluatedby immunostaining and the measurement of biochemical indexes. The molecular mechanism was explored by biological techniques such as western blotting, qPCR, ChIP-seq and ChIP-qPCR, flow cytometry and lentivirus infection. RESULTS: We found that naringenin and hesperetin had an inhibitory effect on histone acetylation. We showed that naringenin and hesperetin protected pancreatic ß cells in vivo and in vitro, and this effect was independent of their direct antioxidant capacity. The further study found that the inhibition of thioredoxin-interacting protein (Txnip) expression regulated by histone acetylation was critical for the protective role of naringenin and hesperetin. Mechanistically, the histone acetylation inhibition by naringenin and hesperetin was achieved through regulating AMPK-mediated p300 inactivation. CONCLUSION: These findings highlight flavanones and the phytomedicine rich in flavanones as important dietary supplements in protecting pancreatic ß cells in advanced diabetes. In addition, targeting histone acetylation by phytomedicine is a potential strategy to delay the development and progression of diabetes.

Herb pair of Ephedrae Herba-Armeniacae Semen Amarum alleviates airway injury in asthmatic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ephedrae Herba (EH, Ephedra sinica Stapf.) and Armeniacae Semen Amarum (ASA, Prunus armeniaca L. var. ansu Maxim.) have been used to treat asthma, cold, fever, and cough in China for thousands of years. AIM OF THE STUDY: In this study, we aimed to investigate the optimal ratio of EH and ASA compatibility (EAC) to reduce airway injury in asthmatic rats and its possible mechanism. METHODS: Rats were sensitized with a mixture of acetylcholine chloride and histamine bisphosphate 1 h before sensitization by intragastric administration of EAC or dexamethasone or saline for 7 days. Subsequently, the ultrastructure of rat airway epithelial tissue changes, apoptosis of the airway epithelial cells, and the expression of mRNA and protein of EGRF and Bcl-2 were detected. RESULTS: Transmission electron microscope: EAC (groups C and E) had the most prominent effect on repairing airway epithelial cells' ultrastructural changes in asthmatic rats. TUNEL: dexamethasone and EAC (groups B、C、E and F) inhibited the apoptosis of airway epithelial cells in asthmatic rats (P < 0.05). In situ hybridization: EAC (group E) inhibited the overexpression of EGFR and Bcl-2 mRNA (P < 0.05).Western Blotting: EAC (groups A、B、C、E and F) inhibited the upregulation of airway epithelial EGFR and Bcl-2 protein expression (P < 0.01). CONCLUSIONS: Our findings indicate that EAC can inhibit abnormal changes in airway epithelial structure and apoptosis of airway epithelial cells, thereby alleviating airway injury. In this study, the best combination of EH and ASA to alleviate airway epithelial injury in asthmatic rats was group E (EH: ASA = 8: 4.5).

Effect of different parts of Pinelliae Rhizoma Decoction against airway inflammation and analysis of effective components / 中国中药杂志

This study investigated the material basis and mechanism of Pinelliae Rhizoma Decoction in the treatment of airway inflammation. The cigarette smoke combined with lipopolysaccharide(LPS) was used to induce an airway inflammation model in mice. The expression levels of IL-6 and IL-8 in the bronchoalveolar lavage fluid(BALF) and the phosphorylation levels of p38 and IκB in the lungs of mice were taken as indexes to screen the effective extracts by system solvent extraction from Pinelliae Rhizoma Decoction(dichloromethane extract, ethyl acetate extract, n-butanol extract, etc.). Meanwhile, the human bronchial epithelial(16-HBE) cell model of cigarette smoke extract(CSE)-induced injury was established, and the mRNA expression levels of IL-6 and IL-8 and the phosphorylation levels of p38 and IκB proteins were also taken as indexes to evaluate the anti-inflammatory effect of different extracts of Pinelliae Rhizoma Decoction. The results showed that Pinelliae Rhizoma Decoction significantly antagonized airway inflammation in mice by down-regulating the expression levels of IL-6 and IL-8 in mice with airway inflammation and 16-HBE cells with CSE-induced injury and inhibiting the phosphorylation levels of p38 and IκB. The dichloromethane and ethyl acetate extracts of Pinelliae Rhizoma Decoction showed significant anti-inflammatory effects, while such effects of other extracts were not prominent. Furthermore, the database of Pinelliae Rhizoma composition was constructed, and the components in effective extracts were analyzed by HPLC-TOF-MS and Nano-LC-MS/MS. As revealed by the results, the compositions of the two effective extracts were similar with 36 common components. They were combined and then divided into Pinelliae Rhizoma alkaloids(PTAs) and Pinelliae Rhizoma non-alkaloids(PTNAs) by 732 cation-exchange resin. Further in vitro investigation confirmed the significant anti-inflammatory effect of PTNAs, while such effect of PTAs was not manifest. The MS analysis showed 172 peptides and 7 organic acids in PTNAs. The peptide content in PTNAs was 63.5% measured by quantitative analysis of BCA assay, and the organic acid content was 9.92% by potentiometric titration method. The findings of this study suggested that Pinelliae Rhizoma Decoction could antagonize airway inflammation in mice by inhibiting phosphorylation of p38 and IκB and blocking the activation of MAPK and NF-κB signaling pathways, and the effective components were related to the peptides and organic acids in PTNAs. The above results lay a foundation for the research on the mechanism and material basis of Pinelliae Rhizoma in antagonizing airway inflammation.

New-generation intravenous fat emulsions and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.

BACKGROUND: Fat emulsion is an important component of parenteral nutrition in premature infants. However, intravenous fat emulsions (IVFE) was reported to be associated with some serious complications, such as bronchopulmonary dysplasia (BPD). Compared to conventional soybean oil-based IVFE, new-generation IVFE may protect against BPD but the results are conflicting. METHODS: Relevant literatures search was conducted and the summary effect estimates of odds ratio (OR) and 95% confidence interval (CI) were calculated with fixed-effects models. RESULTS: Of 22 studies involving 3781 infants were selected in this study and BPD was reported as part of the included studies. The pooled estimate for 13 studies, comparing administration of new-generation IVFE with conventional IVFE, indicated that new-generation IVFE was not associated with a reduced risk of BPD in preterm infants, compared with conventional IVFE (OR 0.96; 95% CI 0.80-1.14); the pooled estimate for 18 studies, comparing administration of fish oil-containing IVFE with non-fish oil IVFE, indicated that fish oil-containing IVFE has no protective effect against the occurrence of BPD in preterm infants (OR 0.88; 95% CI 0.71-1.08). CONCLUSIONS: There is no evidence to support that the new-generation IVFEs could prevent the incidence of BPD or fish oil-containing IVFEs could show a beneficial effect to BPD in premature infants.

The flavonoid-rich Quzhou Fructus Aurantii extract modulates gut microbiota and prevents obesity in high-fat diet-fed mice.

BACKGROUND: Flavonoids are reported to modulate the composition of gut microbiota, which play an important role in preventing obesity and associated metabolic diseases. In this study, we investigated the effect of Total Flavonoids of Quzhou Fructus Aurantii Extract (TFQ) on gut microbial community in mice fed with a high-fat diet (HFD). METHODS: C57BL/6J mice were fed with either a chow diet or HFD with or without oral gavage of TFQ (300 mg/kg/day) for 12 weeks. RESULTS: Our data indicate TFQ significantly reduced obesity, inflammatio,n and liver steatosis. TFQ elevates the expression of tight junction proteins and reduces metabolic endotoxemia. In addition, TFQ treatment reverses HFD-induced gut dysbiosis, as indicated by the reduction of Firmicutes to Bacteroidetes ratio, the increase of genera Akkermansia and Alistipes, and the decrease of genera Dubosiella, Faecalibaculum, and Lactobacillus. CONCLUSION: These findings support a prebiotic role of TFQ as a dietary supplement for the intervention of gut dysbiosis and obesity-related metabolic disorders.

Trichosporon fermentans biomass flocculation from soybean oil refinery wastewater using bioflocculant produced from Paecilomyces sp. M2-1.

The soybean oil refinery (SOR) wastewater contains a high concentration of chemical oxygen demand (COD) and lipid, so the direct emissions of SOR wastewater will result in environmental pollution and waste of resources. Oleaginous yeast Trichosporon fermentans can consume organic materials in SOR wastewater to synthesize microbial oil, which achieves the purpose of SOR wastewater resource utilization. The effective harvesting technology of oleaginous yeasts can improve the utilization efficiency. In this study, Paecilomyces sp. M2-1 with high flocculating activity was isolated. The flocculants produced by M2-1 (MBF2-1) include 75% (w/w) polysaccharides, rely on cations, and display the flocculation percentage of above 77% in the range of pH 2-11. Especially under alkaline conditions, the flocculation percentage can be kept above 97%. The results of scanning electron microscope observation and zeta potential measurements suggested that the bridging, net trapping, and sweeping were the main flocculation mechanism of MBF2-1. MBF2-1 could flocculate T. fermentans that was used to reduce the organic matter in SOR wastewater and to produce microbial oil. Under the optimum conditions, the flocculation percentage of MBF2-1 against T. fermentans from SOR wastewater can reach 95%. Fatty acid content percent in microbial oil from T. fermentans was not almost affected by flocculation of MBF2-1. Moreover, MBF2-1 can further remove 55% and 53% of COD and oil content in the fermented SOR wastewater, respectively. The properties and high flocculating percentage displayed by MBF2-1 indicated its potential application prospect in oleaginous yeast harvest and food industry wastewater treatment.