RENAL PROTECTIVE EFFECT AND CLINICAL ANALYSIS OF VITAMIN B 6 IN PATIENTS WITH SEPSIS.

ABSTRACT: Objective: To investigate the protective effect and possible mechanisms of vitamin B 6 against renal injury in patients with sepsis. Methods: A total of 128 patients with sepsis who met the entry criteria in multiple centers were randomly divided into experimental (intravenous vitamin B 6 therapy) and control (intravenous 0.9% sodium chloride therapy) groups based on usual care. Clinical data, the inflammatory response indicators interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor (TNF-α), and endothelin-1 (ET-1), the oxidative stress response indicators superoxide dismutase, glutathione and malondialdehyde, and renal function (assessed by blood urea nitrogen, serum creatinine, and renal resistance index monitored by ultrasound) were compared between the two groups. Results: After 7 d of treatment, the IL-6, IL-8, TNF-α, and ET-1 levels in the experimental group were significantly lower than those in the control group, the oxidative stress response indicators were significantly improved in the experimental group and the blood urea nitrogen, serum creatinine, and renal resistance index values in the experimental group were significantly lower than those in the control group ( P < 0.05). There was no statistical difference between the two groups in the rate of renal replacement therapy and 28 d mortality ( P > 0.05). However, the intensive care unit length of stay and the total hospitalization expenses in the experimental group were significantly lower than those in the control group ( P < 0.05). Conclusion: The administration of vitamin B 6 in the treatment of patients with sepsis attenuates renal injury, and the mechanism may be related to pyridoxine decreasing the levels of inflammatory mediators and their regulation by redox stress.

Worldwide trends in mortality for hypertensive heart disease from 1990 to 2019 with projection to 2034: data from the Global Burden of Disease 2019 study.

AIMS: This study aims to analyse the worldwide trends in hypertensive heart disease (HHD) mortality and associations with age, period, and birth cohort and predict the future burden of HHD deaths. METHODS AND RESULTS: Mortality estimates were obtained from Global Burden of Disease 2019 study. We used age-period-cohort (APC) model to examine the age, period, and cohort effects on HHD mortality between 1990 and 2019. Bayesian APC model was utilized to predict HHD deaths to 2034. The global HHD deaths were 1.16 million in 2019 and were projected to increase to 1.57 million in 2034, with the largest increment in low- and middle-income countries (LMICs). Between 1990 and 2019, middle/high-middle socio-demographic index (SDI) countries had the largest mortality reductions (annual percentage change = -2.06%), whereas low SDI countries saw a lagging performance (annual percentage change = -1.09%). There was a prominent transition in the age distribution of deaths towards old-age population in middle/high-middle SDI countries, while the proportion of premature deaths (aged under 60 years) remained at 24% in low SDI countries in 2019. Amongst LMICs, Brazil, China, and Ethiopia showed typically improving trends both over time and in recent birth cohorts, whereas 63 countries including Indonesia, the Philippines, and Pakistan had unfavourable or worsening risks for recent periods and birth cohorts. CONCLUSION: The HHD death burden in 2019 is vast and is expected to increase rapidly in the next decade, particularly for LMICs. Limited progress in HHD management together with high premature mortality would exact huge human and medical costs in low SDI countries. The examples from Brazil, China, and Ethiopia suggest that efficient health systems with action on improving hypertension care can reduce HHD mortality effectively in LMICs.

This study provides the first comprehensive analysis of the age, period, and cohort trends in mortality for hypertensive heart disease (HHD) across 204 countries and territories from 1990 to 2019, with projection to 2034. The death burden of HHD is substantial and growing rapidly in most of the world, particularly in low- and middle-income countries (LMICs). Wide disparities exist within LMICs in HHD management, with most low socio-demographic index countries showing little progress in reducing HHD mortality. The examples from Brazil, China, and Ethiopia suggest that prevention policies for HHD can reduce risks for younger birth cohorts and shift the risks for all age groups over time.

Hybrids of delavirdine and piperdin-4-yl-aminopyrimidines (DPAPYs) as potent HIV-1 NNRTIs: Design, synthesis and biological activities.

The hybrids of delavirdine and piperdin-4-yl-aminopyrimidine (DPAPYs) were designed from two excellent HIV-1 NNRTIs delavirdine and piperidin-4-yl-aminopyrimidine via molecular hybridization. The target compounds 4a-r were prepared and evaluated for their cellular anti-HIV activities and cytotoxicities as well as the inhibitory activities against HIV-1 reverse transcriptase (RT). All the newly synthesized compounds demonstrated moderate to excellent potency against wild-type (WT) HIV-1 with EC50 values in a range of 5.7 to 0.0086 µM and against RT with IC50 values ranging from 12.0 to 0.11 µM, indicating that the DPAPYs were specific RT inhibitors. Among all, 4d displayed the most potent activity against WT HIV-1 (EC50 = 8.6 nM, SI = 2151). Gratifyingly, it exhibited good to excellent potency against the single HIV-1 mutants L100I, K103N, Y181C, Y188L, E138K, as well as the double mutant F227L + V106A. Furthermore, the preliminary structure-activity relationships were summarized, molecular modeling was conducted to explore the binding mode of DPAPYs and HIV-1 RT, and their physicochemical properties were also predicted.

An aptamer-Fe3+ modified nanoparticle for lactate oxidation and tumor photodynamic therapy.

To develop a cancer targeting lactate attenuator in vivo for cancer phototherapy and inhibition of HIF-1, we report an aptamer modified photo-responsive nanoparticle (labeled as Mn-D@BPFe-A) for lactate oxidation and cancer phototherapy. Mn-D@BPFe-A was constructed by the assembly of functional complex with BSA, followed by surface metal coordination and the recognition of Fe3+ with GAG containing sequence. Upon irradiation, Mn-D@BPFe-A NPs can oxidize water with the generation of OH, which convert lactate into pyruvate both in vitro and in vivo. Obviously, the Mn-D@BPFe-A exhibits a significant tumor ablation owing to the light driven oxidation of lactic acid and dysfunction of mitochondria. Importantly, it can decrease both the level of lactate in cancer tissues and the expression of HIF-1α and Glut-1 in HepG-2 cells. These results demonstrated that oxidation of lactate with dysfunction of mitochondria by nucleic acid-Fe3+ modified nanoparticle is an effective strategy for the development of non-oxygen dependent photodynamic effect agents.

BODIPY-Mn nanoassemblies for accurate MRI and phototherapy of hypoxic cancer.

Hypoxia promotes not only the metastasis of tumors but also therapeutic resistance. Photosensitizer-mediated consumption of O2 during photodynamic therapy (PDT) reinforces tumor hypoxia. Herein, a light-dependent attenuator of a hypoxic environment is reported for accurate MRI and phototherapy of hypoxic cancer. First, a photoresponsive Mn(ii) nanoassembly was constructed, then it was assembled with bovine serum albumin (BSA) and modified with polyethylene glycol-folic acid (PEG-FA), forming cancer targeting Mn-DBA@BSA-FA nanoassemblies, which offer T1 signals and can catalyze the water oxidation reaction under irradiation of red light emitting diode (LED) light with the generation of O2 and heat. Moreover, they could selectively penetrate through and accumulate in the tumor tissues with clear T1 magnetic resonance imaging (MRI) signals, and have remarkably eliminated the tumors in vivo, while they are of low toxicity to the healthy organs. The release of the Mn(ii) complex from the nanoparticles in an acidic environment and the in vivo biodistribution results confirm the selective cancer targeting. Our work demonstrates the potential of nanoparticles as excellent theranostic agents for MR imaging combined with phototherapy triggered by near-infrared light.

A mitochondria targeting Mn nanoassembly of BODIPY for LDH-A, mitochondria modulated therapy and bimodal imaging of cancer.

HIF-1α and LDH-A are important targets for hypoxia-driven drug resistance. Mitochondria targeted fluorescent manganese(II)-complexes can be used as potential fluorescence imaging agents, MRI contrast agents and HIF-1α and LDH-A involved anticancer complexes. In this study, a fluorescent manganese(II) nanoparticle, labeled as (PEG-Mn-BDA), was synthesized and used as both fluorescent and MRI imaging agents in cancer cells. In vitro bioassay results indicate that PEG-Mn-BDA was able to inhibit LDH-A activity and depolarize mitochondrial membrane potential with the generation of intracellular ROS, which contributed to the induction of apoptosis. Moreover, the pro-apoptotic protein, caspase 3 was highly expressed. In vivo, PEG-Mn-BDA could also exert inhibition on a mouse hepatocellular carcinoma xenograft. These results suggest that mitochondria targeted PEG-Mn-BDA was able to simultaneously induce selective inhibition on cancer cells and a mouse carcinoma xenograft, label cancer cells with fluorescence and enhance MRI contrast. Therefore, PEG-Mn-BDA is a good candidate for cancer treatment and imaging.

Study on the interaction of Fe(III) complex of BODIPY appended di(picolyl)amine with water and HeLa cells.

The iron complex [(m-BDA)FeCl3] (Fe1) (m-BDA=8-[di(2-picolyl)amine-3-benzyl]-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene) was characterized by spectroscopic methods. The emission intensity of Fe1 is weaker than that of m-BDA due to the electrostatic interaction between the Fe(III) ion and m-BDA. However, the coordination of water with the central Fe(III) ion in Fe1 changed metal-ligand charge transfer, thus the quenched emission at 509 nm was recovered. Furthermore, Fe1 can catalyze water oxidation to generate dioxygen when irradiated by green LED light (10W). In particular, the Fe1 can enter into HepG-2 cells and show different inhibition rates in black and under irradiation. The anticancer activity of Fe1 was greatly enhanced under irradiation. Our results demonstrate that Fe(III) complexes of BODIPY can be developed as new kinds of photodynamic agents.

[Effects of land use type on spatiotemporal distribution of soil nutrients in Dianchi watershed, Yunnan Province of Southwest China].

Surface soil samples were monthly collected from six land use types (abandoned greenhouse field, forest land, sloped farmland, table land, flat vegetable land and greenhouse field) in Dianchi watershed of Yunnan to determine the soil pH and the contents of soil organic matter (OM), total nitrogen (TN), and total phosphorus (TP), aimed to understand the effects of different land use types on the spatiotemporal distribution of the soil nutrients. The soil pH, SOM, TN and TP, contents, and soil C/N differed significantly with soil land use types. The soil pH was in the order of abandoned greenhouse field > flat vegetable land > greenhouse field > table land > sloped farmland > forest land; the OM content was in the sequence of abandoned greenhouse field > flat vegetable land > greenhouse field > sloped farmland > forest land > table land; the TN content was in the order of greenhouse field > flat vegetable land > abandoned greenhouse field > sloped farmland > table land > forest land; the TP content was in the order of flat vegetable field > greenhouse field > abandoned greenhouse field > sloped farmland > table land > forest land; and the C/N ratio was in the sequence of forest land > sloped farmland > flat vegetable plot > table land > abandoned greenhouse field > greenhouse field. The OM, TN and TP contents were affected by fertilization, irrigation, field cultivation and season. All the test parameters had the highest values in rainy season, which could be related to the local top-dressing habits. There were significant positive correlations among the TN, TP and OM under all the land use types. In greenhouse field and abandoned greenhouse field, due to the severe human disturbances, the soil pH and OM, TN and TP contents were obviously higher than those in forestland and table land.

[Determination of effective components in different positions of Panax notoginseng by HPLC].

OBJECTIVE: A quantitative method was developed by gradient elution for the determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in different positions of Panax Notoginseng by HPLC. The content of 4 kinds saponins in different positions of Panax Notoginseng were compared. METHODS: The different positions of Panax notoginseng (including root, rhizome, branch root, leaf, flower) were extracted with methanol. The HPLC condition was as following: Kromasil C18 column (250 mm x 4.6 mm, 5 microm), acetonitrile and water linearity gradient elution, flow rate at 1.0 mL/min, column temperature at 25 degrees C, wavelength 203 nm. RESULTS: The linear ranges of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 were 4.4-440 microg/mL, 4.32-1080 microg/mL, 4.24-212 microg/mL and 4.48-1120 microg/mL, respectively. The RSD (n=5) of average contents of intra-day and inter-day of 4 kinds saponins were 0.46%, 0.24%, 0.77%, 0.68% and 1.64%, 0.69%, 0.52%, 0.65%, respectively. The average recoveries were (102.93 +/- 1.22)%, (103.18 +/- 0.49)%, (103.20 +/- 1.58)%, (103.86 +/- 0.39)%, respectively. The content of 4 kinds saponins in different position of Panax notoginseng was: rhizome > root > branch root > flower > leaf; the content of 4 kinds saponin in the root of Panax notoginseng was: 80 pieces in 500 g >60 pieces in 500 g >20 pieces in 500 g >40 pieces in 500 g >100 pieces in 500 g. CONCLUSION: This method is simple, sensitive, accurate and repeat, and is suitable in determination of the content of 4 kinds saponins in different positions of Panax notoginseng.