Iron(III) and BF3·OEt2-Promoted O-Transfer Reaction of N-Aryl-α,ß-Unsaturated Nitrones to Prepare Difluoroboron ß-Ketoiminates.

We described an iron(III) and BF3·OEt2-promoted oxygen transfer reaction of N-aryl-α,ß-unsaturated nitrones to prepare various N,O-difluoroboron ß-ketoiminates in good yields ranging from 24% to 87%. Control experiments revealed that the enaminone was the vital intermediate for the formation of N,O-difluoroboron ß-ketoiminates, and iron(III) combined with BF3·OEt2 played as cocatalyst to promote the oxygen transfer reaction through intramolecular cyclization and N-O bond cleavage. More importantly, an estrone-derived N,O-difluoroboron ß-ketoiminate was easily prepared in 40% yield from estrone in four steps.

Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota.

Hyperlipidemia can directly cause metabolic diseases that seriously endanger disorder and metabolism and gut health. Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. Moreover, EGCG may protect liver function via reducing the glycerophospholipids increased by high-fat diet intervention. TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). The above results provided new insights into the hypolipidemic mechanism of TP and EGCG.

An updated systematic review and network meta-analysis comparing open, laparoscopic and robotic-assisted sacrocolpopexy for managing pelvic organ prolapse.

Abdominal sacrocolpopexy is considered as the gold standard treatment for pelvic organ prolapse. Sacrocolpopexy can be performed using open (OSC), laparoscopic (LSC), and robotic-assisted (RSC) approaches. The aim of this study is to compare the outcomes between these three approaches for managing pelvic organ prolapse by conducting a systematic review and network meta-analysis. A systematic search was performed in different databases from their earliest records to April 2021 with no restriction on languages. Only randomized controlled trials that compared the outcomes between OSC, LSC, and RSC were included in this study. A total of 6 studies with 486 participants were included in this study. Operative time was significantly shorter in OSC than in RSC and LSC. The probability rank showed less estimated blood loss in RSC and lowest overall postoperative complications in LSC. Probability scores also showed best anatomical outcomes for postoperative points C and Bp in RSC and for point Ba in LSC. Despite significantly longer operative time, RSC and LSC may provide better anatomical outcomes, less estimated blood loss, and less overall postoperative complications than OSC. However, this study did not find significant differences between RSC and LSC in efficacy and safety.

Comparing the outcomes and effectiveness of robotic-assisted sacrocolpopexy and laparoscopic sacrocolpopexy in the treatment of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Abdominal sacrocolpopexy is regarded as the gold standard for management of pelvic organ prolapse (POP). Nowadays, minimally invasive surgeries are preferred, and sacrocolpopexy can be performed using either a laparoscopic or robotic-assisted approach. The aim of the current study was to compare the efficacy and safety of robotic-assisted sacrocolpopexy (RASC) and laparoscopic sacrocolpopexy (LSC) through an updated systematic review and meta-analysis. METHODS: We performed a systematic literature review of different databases and related references from their inception until July 2020 without language restrictions. All randomized control trials and comparative studies that compared RASC and LSC for the management of POP were included. RESULTS: A total of 13 studies including 2115 participants were included for the pooled analysis. The pooled results revealed that RASC was associated with a significantly longer operative time (weighted mean difference, 29.53 min; 95% confidence interval [CI], 12.88 to 46.18 min, P = 0.0005), significantly less estimated blood loss (weighted mean difference, -86.52 ml; 95% CI -130.26 to -42.79 ml, P = 0.0001), significantly fewer overall intraoperative complications (odds ratio [OR] 0.6; 95% CI 0.40 to 0.91; P = 0.01) and significantly lower conversion rate (OR 0.39; 95% CI 0.19 to 0.82; P = 0.01) compared with LSC. There were no significant differences between the length of hospital stays, overall postoperative complications, postoperative stress incontinence, mesh erosion and effectiveness between the two groups. CONCLUSION: The current study showed comparable efficacy between RASC and LSC. Though RASC was associated with less blood loss and a lower conversion rate, the differences were not clinically significant. The choice of surgical procedure with either RASC or LSC is according to surgeon discretion and patient preferences.

Highly transparent cerium doped gadolinium gallium aluminum garnet ceramic prepared with precursors fabricated by ultrasonic enhanced chemical co-precipitation.

Cerium doped gadolinium gallium aluminum garnet (GGAG:Ce) ceramic precursors have been synthesized with an ultrasonic chemical co-precipitation method (UCC) and for comparison with a traditional chemical co-precipitation method (TCC). The effect of ultra-sonication on the morphology of powders and the transmittance of GGAG:Ce ceramics are studied. The results indicate that the UCC method can effectively improve the homogenization and sinterability of GGAG:Ce powders, which contribute to obtain high transparent GGAG ceramic with the highest transmittance of 81%.

Neuroprotection by intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats in a model of ischemic stroke.

Our previous studies showed that bone marrow mononuclear cells (BMMNCs) from 5-fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to further explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in the same model. Rats were intravenously pre-treated with 5-FU, and BMRMNCs were collected 7 days later and subjected to flow cytometry for detection of CD34, CD45 and CD90. Middle cerebral artery occlusion (MCAO) was induced in rats, and BMMNCs and BMRMNCs were independently transplanted via the tail vein at 24 h after MCAO. NISSL staining was performed 14 days after cell transplantation and the viable cells in the hippocampus were counted. Stromal cell-derived factor 1 (SDF-1) mRNA expression was detected in the penumbra at 7 and 14 days after treatment. The contents of pro-inflammatory cytokines and growth factors as well as microvessel density (MVD) were determined at 14 days. Results showed more BMRMNCs were positive for CD34, CD45 and CD90. After transplantation, more viable cells were observed in the hippocampus of BMRMNCs treated rats. In addition, BMRMNCs transplantation significantly increased MVD, reduced pro-inflammatory cytokines and raised growth factors in the penumbra. However, the SDF-1 mRNA expression was comparable between BMRMNCs group and BMMNCs group. Our results indicate that BMRMNCs are likely to more effectively improve the local microenvironment to increase viable cells and elevate angiogenesis, exerting neuroprotective effects on cerebral ischemia in rats.

Effects of lactic acid bacteria on cardiac apoptosis are mediated by activation of the phosphatidylinositol-3 kinase/AKT survival-signalling pathway in rats fed a high-fat diet.

Through a high-fat diet, obesity leads to cardiomyocyte dysfunction and apoptosis. In addition, there is no evidence that probiotics have potential health effects associated with cardiac apoptosis in obese rats. The present study aimed to explore the effects of probiotics on obesity and cardiac apoptosis in rats fed a high-fat diet (HF). Eight­week­old male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (NC) and high-fat diet (HFC) groups, and high-fat diet supplemented with low (HFL), medium (HFM) or high (HFH) doses of multi­strain probiotics groups. The rats were subsequently studied for 8 weeks. Food intake and body weights were recorded following sacrifice, and food utilization rates, body fat and serum cholesterol levels were analysed. The myocardial architecture of the left ventricle was evaluated by hematoxylin­eosin staining, and key apoptotic­related pathway molecules were analysed by western blotting. Rat weights and triglyceride levels were decreased with oral administration of high doses of probiotics (HFH) compared to the HFC group. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HFC hearts, but were significantly decreased in groups that were provided multi­strain probiotics compared with NC hearts. Western blot analysis demonstrated that key components of the Fas receptor­ and mitochondrial­dependent apoptotic pathways were significantly suppressed in multi­strain probiotic treated groups compared to the HF group. Additionally, cardiac insulin, such as the insulin­like growth factor I receptor (IGFIR)­dependent survival signalling components, were highly induced in left ventricles from rats administered probiotics. Together, these findings strongly suggest that oral administration of probiotics may attenuate cardiomyocyte apoptosis by activation of the phosphatidylinositol­3 kinase/AKT survival­signalling pathway in obese rats.

Detection of hepatitis B virus A1762T/G1764A mutant by amplification refractory mutation system

OBJECTIVE: To study the role of hepatitis B virus with A1762T/G1764A double mutation in liver cirrhosis and hepatocellular carcinoma, and create a sensitive, fast, accurate assay for detection of A1762T/G1764A double mutation. METHODS: We developed an accurate and fast real-time amplification refractory mutation system to detect A1762T/G1764A double mutation. Cloned hepatitis B virus genome was used as a control. Assay sensitivity was determined by serial dilution and mixed template experiments. Specificity was determined by cross experiments with wild and mutant hepatitis B virus. Fifty clinical samples were tested by the real-time amplification refractory mutation system and the results were compared with sequencing. RESULTS: The real-time amplification refractory mutation system had a sensitivity of 100 copies of virus with these mutations, and 0.1% weak population virus with double mutation could be found in mixtures. A total of 50 randomly collected clinical samples were detected by real-time amplification refractory mutation system, and the results were consistent with those by DNA sequencing. Hepatitis B virus genotype C was more prevalent in 39 of 50 samples than genotype B (11 samples), and about 75% of genotype C carried a double mutation compared to 45% of genotype B. However, the percentage of A1762T/G1764A double mutation in hepatitis B e antigen-negative (58.3%) samples was almost the same as in hepatitis B e antigen-positive (61%) samples. CONCLUSION: The real-time amplification refractory mutation system is sensitive and specific for detection of hepatitis B virus double mutation. .

Detection of hepatitis B virus A1762T/G1764A mutant by amplification refractory mutation system.

OBJECTIVE: To study the role of hepatitis B virus with A1762T/G1764A double mutation in liver cirrhosis and hepatocellular carcinoma, and create a sensitive, fast, accurate assay for detection of A1762T/G1764A double mutation. METHODS: We developed an accurate and fast real-time amplification refractory mutation system to detect A1762T/G1764A double mutation. Cloned hepatitis B virus genome was used as a control. Assay sensitivity was determined by serial dilution and mixed template experiments. Specificity was determined by cross experiments with wild and mutant hepatitis B virus. Fifty clinical samples were tested by the real-time amplification refractory mutation system and the results were compared with sequencing. RESULTS: The real-time amplification refractory mutation system had a sensitivity of 100 copies of virus with these mutations, and 0.1% weak population virus with double mutation could be found in mixtures. A total of 50 randomly collected clinical samples were detected by real-time amplification refractory mutation system, and the results were consistent with those by DNA sequencing. Hepatitis B virus genotype C was more prevalent in 39 of 50 samples than genotype B (11 samples), and about 75% of genotype C carried a double mutation compared to 45% of genotype B. However, the percentage of A1762T/G1764A double mutation in hepatitis B e antigen-negative (58.3%) samples was almost the same as in hepatitis B e antigen-positive (61%) samples. CONCLUSION: The real-time amplification refractory mutation system is sensitive and specific for detection of hepatitis B virus double mutation.

Advances in the study of the structures and bioactivities of metabolites isolated from mangrove-derived fungi in the South China Sea.

Many metabolites with novel structures and biological activities have been isolated from the mangrove fungi in the South China Sea, such as anthracenediones, xyloketals, sesquiterpenoids, chromones, lactones, coumarins and isocoumarin derivatives, xanthones, and peroxides. Some compounds have anticancer, antibacterial, antifungal and antiviral properties, but the biosynthesis of these compounds is still limited. This review summarizes the advances in the study of secondary metabolites from the mangrove-derived fungi in the South China Sea, and their biological activities reported between 2008 and mid-2013.

The involvement of programmed cell death 5 (PDCD5) in the regulation of apoptosis in cerebral ischemia/reperfusion injury.

AIMS: Programmed Cell Death 5 (PDCD5) is a protein that accelerates apoptosis in different types of cells in response to various stimuli and is down-regulated in many cancer tissues. We hypothesized in this study that down-regulating PDCD5 can protect the brain from ischemic damage by inhibiting PDCD5-induced apoptotic pathway. METHODS: One hundred and sixty male Sprague-Dawley rats were randomly assigned to five groups: Sham surgery (n = 25), MCAO (n = 45), MCAO+rhPDCD5 (RhPDCD5) (n = 30), MCAO+control siRNA (n = 30), and MCAO+PDCD5 siRNA (n = 30). At 24 h following MCAO, immunohistochemistry and Western blot were performed. RESULTS: PDCD5 siRNA reduced the infarct volume, improved neurological deficits, improved cerebral blood flow (CBF), and reduced Evans blue extravasation. Meanwhile, over-expression of PDCD5 protein with recombinant human PDCD5 (rhPDCD5) had an opposite effect. Immunohistochemistry and Western blot demonstrated PDCD5 siRNA decreased the expressions of key proapoptotic proteins such as p53, Bax/Bcl-2, and cleaved caspase-3 in the penumbra areas, whereas rhPDCD5 increased cell apoptosis. Double fluorescence labeling showed the positive immunoreactive materials of PDCD5 were partly colocalized with MAP2, GFAP, CD34, p53, and caspase-3 in the penumbra areas in brain. CONCLUSIONS: PDCD5-induced apoptosis and over-expression of PDCD5 are harmful to the ischemic neurons in vivo. Meanwhile, the inhibition of PDCD5 may be protective via reducing the apoptotic-related protein such as p53, Bax, and caspase-3. This observation may have potential for the treatment of ischemic cerebral stroke.

p53-induced uncoupling expression of aquaporin-4 and inwardly rectifying K+ 4.1 channels in cytotoxic edema after subarachnoid hemorrhage.

AIMS: To investigate the mechanism behind cytotoxic edema formation following subarachnoid hemorrhage (SAH). METHODS: We explored the role of aquaporin-4 (AQP4), inwardly rectifying K(+) 4.1 (Kir4.1) channels and their upstream orchestrators p53 and p38MAPK in this process. A p53 inhibitor, pifithrin-α (PFT-α) was administered intraperitoneally to rats undergoing SAH by endovascular perforation. Totally, 98 male SD rats were categorized into sham, SAH, SAH+ dimethyl sulfoxide (DMSO), SAH+ 0.2 or 2.0 mg/kg PFT-α groups. At 24 h after SAH, MRI (diffusion-weighted imaging [DWI]), immunohistochemistry, and Western blot were used. RESULTS: MRI (DWI) showed a significant cytotoxic edema in the brain following SAH with PFT-α therapy reducing it. Immunohistochemistry and Western blot showed an increased level of p53, phosphorylated-p38MAPK and AQP4 and a reduced level of Kir4.1; all of which could be reversed following PFT-α treatment. Treble labeling staining revealed colocalization of p53 with phosphorylated-p38MAPK and unmatched expression of AQP4 and Kir4.1 within astrocyte cells. CONCLUSION: These results indicated p53 mediates the formation of cytotoxic edema in the brain following SAH; an uncoupling expression of AQP4 and Kir4.1 on astrocytic end feet orchestrated by p38MAPK was partly responsible.

Differential expression of microRNAs in GH-secreting pituitary adenomas.

BACKGROUND: The purpose of this study was to (1) identify specific miRNAs in growth hormones (GH)-secreting pituitary adenomas; (2) determine the relationship between the expression of these miRNAs and tumor size, somatostatin analogs treatment, and responsiveness to somatostatin analogs (SSA). METHODS: Fifteen GH-secreting adenomas patients were treated with lanreotide for 4 months before surgery. Patients with 50% reduction of GH secretion by lanreotide were considered as SSA responders, while patients with less than 50% of GH reduction were considered as SSA nonresponders. We analyzed the miRNAs in 21 GH-secreting pituitary adenomas and 6 normal pituitaries by miRCURY™ LNA array and some differentially expressed miRNAs were validated by quantitative real-time PCR. RESULTS: Fifty-two miRNAs were differentially expressed between GH-secreting pituitary adenomas and normal pituitaries. Differential expression of 9 miRNAs was observed between micro- and macro-adenomas. Thirteen miRNAs were differentially expressed between tumor samples from lanreotide-treated patients and those from lanreotide-untreated patients. Seven miRNAs were differentially expressed between SSA responders or GH nonresponders. Several identified miRNAs may be involved in cell proliferation, apoptosis, cancer development and progression. CONCLUSIONS: Our results indicate that altered miRNAs expression is involved in GH-secreting pituitary adenomas transformation, which will shed light on the mechanisms for the treatment of acromegaly by SSA. Identification and characterization of the targets of altered miRNAs genes may elucidate molecular mechanisms involved in the pathogenesis of pituitary adenoma.

Cerebralcare Granule, a Chinese herb compound preparation, improves cerebral microcirculatory disorder and hippocampal CA1 neuron injury in gerbils after ischemia-reperfusion.

AIM OF THE STUDY: Cerebralcare Granule (CG) is a Chinese herb compound preparation that has been used for treatment of cerebrovascular related diseases. However, the effect of post-treatment with CG on ischemia and reperfusion (I/R) induced cerebral injury is so far unclear. MATERIALS AND METHODS: In present study, cerebral global I/R was induced in Mongolian gerbils by clamping bilateral carotid arteries for 30 min followed by reperfusion for 5 days, and CG (0.4 g/kg or 0.8 g/kg) was administrated 3h after the initiation of reperfusion. RESULTS: Post-treatment with CG for 5 days attenuated the I/R-induced production of hydrogen peroxide in, leukocyte adhesion to, and albumin leakage from cerebral microvessels, and, meanwhile, protected neuron from death, reduced the number of caspase-3- and Bax-positive cells, and increased Bcl-2-positive cells in hippocampal CA1 region. CONCLUSION: The results suggest that CG given after initiation of reperfusion is able to ameliorate cerebral microvascular dysfunction and hippocampal CA1 neuron damage caused by I/R.

Pifithrin-alpha reduces cerebral vasospasm by attenuating apoptosis of endothelial cells in a subarachnoid haemorrhage model of rat.

BACKGROUND: The mechanism of cerebral vasospasm following subarachnoid haemorrhage (SAH) is not understood. Here, we hypothesized that apoptosis of endothelial cells induced by p53 and its target gene em dash p53 upregulated modulator of apoptosis (PUMA) played an important role in development of cerebral vasospasm. We also observed the effects of a p53 inhibitor, pifithrin-alpha (PFT-alpha), on reducing the expression of p53 and PUMA, consequently decreasing the apoptosis of endothelial cells and alleviating cerebral vasospasm. METHODS: Male Sprague-Dawley rats weighing 300-350 g were randomly divided into five groups: a control group (sham surgery), a SAH group, a SAH+dimethyl sulfoxide (DMSO) group, a SAH + PFT-alpha (0.2 mg/kg) group and a SAH + PFT-alpha (2.0 mg/kg) group. PFT-alpha was injected intraperitoneally immediately after SAH. Rats were sacrificed 24 hours after SAH. Western blot and immunohistochemical staining were used to detect the levels of p53, PUMA and caspase-3 protein. In addition, mortality and neurological scores were assessed for each group. Statistical significance was assured by analysis of variance performed in one way ANOVA followed by the Tukey test. The neurological and mortality scores were analyzed by Dunn's method and Fisher exact test, respectively. RESULTS: After SAH, Western blot and immunohistochemical staining showed the levels of p53, PUMA and caspase-3 in the endothelial cells and the numbers of TdT mediated dUTP nick end labelling (TUNEL) positive endothelial cells were all significantly increased in the basilar arteries (P<0.05), but significantly reduced by PFT-alpha (P<0.05). These changes were accompanied by increasing diameters and declining wall thickness of basilar arteries (P<0.05), as well as reduced mortality and neurological deficits of the rats (P<0.05). CONCLUSIONS: PFT-alpha could protect cerebral vessels from development of vasospasm and improve neurological outcome as well as reduce the mortality via suppressing apoptosis induced by p53 in the endothelial cells of cerebral vessels.

Apolipoprotein C-II promoter T-->A substitution at position -190 affects on the transcription of the gene and its relationship to hyperlipemia.

A Chinese patient with severe hypertriglyceridemia was found to have similar clinical features to that of malignant hyperlipemia in infancy. DNA sequence analysis of the apoC-II gene from the patient's parents revealed a novel heterozygous mutation of T-->A substitution at position -190 base in the apoC-II promoter. We speculated that the patient was a homozygote of the same mutation that resulted in the deficiency of apoC-II. In vitro expression studies showed T-->A substitution in the apoC-II promoter leads to a decrease by approximately 20% in transcriptional activity compared with its counterpart that inserted the normal promoter. These results suggested that T-->A substitution at position -190 in the apoC-II gene promoter only partly affected transcriptional activity of the apoC-II promoter, leading to decrease of apoC-II expression in quantity.