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1.
J Exp Bot ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490889

RESUMO

The formation of locule gel is an important process in tomato and a typical characteristic of berry fruit. In this study, we collected a tomato natural mutant that produces all-flesh fruits (AFF) in which the locule tissue remains in a solid state during fruit development. We built genetic populations to fine-map the causal gene of the AFF trait and identified the gene AFF (SlMBP3) as the locus conferring the locule gel formation. We determined the causal mutation as a 416-bp deletion that occurred in the promoter region of AFF and reduced its expression dosage. The 416-bp sequence is highly conserved among Solanaceae species, as well as within the tomato germplasm. Furthermore, with the BC6 NIL materials, we revealed that the reduced expression dosage of AFF did not impact the normal development of seeds but produced unique non-liquefied locule tissue, which was distinct from that of normal tomatoes in terms of metabolic components. We further revealed the importance of AFF gene in locule tissue liquefaction through combined analysis using mRNA-seq and metabolomics. Our findings provide clues to investigate fruit type differentiation in Solanaceae crops and also contribute to the application of the AFF gene in tomato breeding programs.

2.
J Org Chem ; 86(18): 13153-13159, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34476948

RESUMO

Herein we describe an efficient construction of HCF2Se and HCF2S groups by tandem substitutions between alkyl bromides and a reagent system consisting of MSeCN (or MSCN) and Ph3P+CF2H Br-. The tandem process occurs via the first nucleophilic substitution of alkyl bromides by -SeCN (or -SCN) and the subsequent nucleophilic difluoromethylation.

3.
Water Res ; 204: 117587, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34482096

RESUMO

Ecosystem degradation and biodiversity loss have been caused by economic booms in developing countries over recent decades. In response, ecosystem restoration projects have been advanced in some countries but the effectiveness of different approaches and indicators at large spatio-temporal scales (i.e., whole catchments) remains poorly understood. This study assessed the effectiveness of a diverse array of 440 aquatic restoration projects including wastewater treatment, constructed wetlands, plant/algae salvage and dredging of contaminated sediments implemented and maintained from 2007 to 2017 across more than 2000 km2 of the northwest Taihu basin (Yixing, China). Synchronized investigations of water quality and invertebrate communities were conducted before and after restoration. Our analysis showed that even though there was rapid urbanization at this time, nutrient concentrations (NH4+-N, TN, TP) and biological indices of benthic invertebrate (taxonomic richness, Shannon diversity, sensitive taxon density) improved significantly across most of the study area. Improvements were associated with the type of restoration project, with projects targeting pollution-sources leading to the clearest ecosystem responses compared with those remediating pollution sinks. However, in some locations, the recovery of biotic communities appears to lag behind nutrients (e.g., nitrogen and phosphorus), likely reflecting long-distance re-colonization routes for invertebrates given the level of pre-restoration degradation of the catchment. Overall, the study suggests that ecological damage caused by recent rapid economic development in China could potentially be mitigated by massive restoration investments synchronized across whole catchments, although these effects could be expected to be enhanced if urbanization rates were reduced at the same time.

4.
Ecotoxicol Environ Saf ; 225: 112767, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34507039

RESUMO

Serious hexavalent chromium [Cr(VI)] pollution has continuously threatened ecological security and public health. Microorganism-assisted remediation technology has strong potential in the treatment of environmental Cr(VI) pollution due to its advantages of high efficiency, low cost, and low secondary pollution. Sporosarcina saromensis M52, a strain with strong Cr(VI) removal ability, isolated from coastal intertidal zone was used in this study. Scanning electron microscopy coupled with energy dispersive X-ray analysis indicated M52 was relatively stable under Cr(VI) stress and trace amount of Cr deposited on the cell surface. X-ray photoelectron spectroscopy and X-ray diffraction analyses exhibited M52 could reduce Cr(VI) into Cr(III). Fourier transform infrared spectroscopy showed the bacterial surface was mainly consisted of polysaccharides, phosphate groups, carboxyl groups, amide II (NH/CN) groups, alkyl groups, and hydroxyl groups, while functional groups involving in Cr(VI) bio-reduction were not detected. According to these characterization analyses, the removal of Cr(VI) was primarily depended on bio-reduction, instead of bio-adsorption by M52. Genome analyses further indicated the probable mechanisms of bio-reduction, including the active efflux of Cr(VI) by chromate transporter ChrA, enzymatic redox reactions mediated by reductases, DNA-repaired proteases ability to minimize the ROS damage, and the formation of specific cell components to minimize the biofilm injuries caused by Cr(VI). These studies provided a theoretical basis which was useful for Cr(VI) remediation, especially in terms of increasing its effectiveness. THE MAIN FINDING OF THE WORK: M52 realized the bioremediation of Cr(VI) majorly through bio-reduction, including Cr(VI) efflux, chromate reduction, DNA repair, and the formation of specific cell components, instead of bio-adsorption.

5.
Behav Res Ther ; 146: 103950, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34509130

RESUMO

Child neglect robustly predicts many behavioral problems and adulthood mental disorders, but little is known about its association with daily lifestyles and psychological development during childhood, particularly in the longitudinal study. We aimed to examine the association of child neglect with physical activity (PA), screen time (ST), eating habits (EHs), and depression/self-esteem using a two-wave follow-up study of primary schoolchildren in Wuhan, China. Data of 1085 schoolchildren aged 8-10 years (boys: 53.5%) were analyzed. Child neglect, lifestyles, and depression/self-esteem were collected in 2018 (T1) and 2019 (T2). Autoregressive cross-lagged models (ARCLMs) were fitted to explore the interrelationships among these variables. In ARCLM including child neglect and lifestyles, higher child neglect at T1 was significantly associated with higher ST and more risky EHs at T2, while insignificantly associated with PA. In ARCLM including child neglect and depression/self-esteem, lower T1 child neglect significantly predicted a higher T2 depression, but insignificantly for T2 self-esteem. In ARCLM including all variables, child neglect still significantly predicted later ST and depression, but insignificantly predicted EHs. Our study underscores that child neglect is strongly intertwined with ST, EHs, and depression during childhood. The prevention of child neglect may promote some healthy lifestyles and depression in children.

6.
Fish Shellfish Immunol ; 118: 197-204, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509628

RESUMO

Tongue sole tissue factor pathway inhibitor 2 (TFPI-2) C-terminus derived peptide, TC38, has previously been shown to kill Vibrio vulnificus cells without lysing the cell membrane; thus, the remaining bacterial shell has potential application as an inactivated vaccine. Therefore, this study aimed to evaluate the immune response induced by the novel V. vulnificus vaccine. The protective potential of TC38-killed V. vulnificus cells (TKC) was examined in a turbot model. Fish were intramuscularly vaccinated with TKC or FKC (formalin-killed V. vulnificus cells) and challenged with a lethal-dose of V. vulnificus. The results showed that compared with FKC, TKC was effective in protecting fish against V. vulnificus infection, with relative percent of survival (RPS) rates of 53.29% and 63.64%, respectively. The immunological analysis revealed that compared with the FKC and control groups, the TKC group exhibited: 1) significantly higher respiratory burst ability and bactericidal activity of macrophages at 7 d post-vaccination; 2) increased alkaline phosphatase, acid phosphatase, lysozyme, and total superoxide dismutase levels post-vaccination; 3) higher serum agglutinating antibody titer with corresponding higher serum bactericidal ability, and a more potent serum agglutination effect, as well as an increased IgM expression level; 4) higher expression of immune relevant genes, which were involved in both innate and adaptive immunity. Taken together, this is the first study to develop a novel V. vulnificus inactivated vaccine based on AMP inactivation, and TKC is an effective vaccine against V. vulnificus infection for aquaculture.

7.
Cell Transplant ; 30: 9636897211041585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34470528

RESUMO

Global cerebral ischemia induced by cardiac arrest usually leads to poor neurological outcomes. Numerous studies have focused on ways to prevent ischemic damage in the brain, however clinical therapies are still limited. Our previous studies revealed that delta opioid receptor (DOR) activation with [d-Ala2, d-Leu5] enkephalin (DADLE), a DOR agonist, not only significantly promotes neuronal survival on day 3, but also improves spatial memory deficits on days 5-9 after ischemia. However, the neurological mechanism underlying DADLE-induced cognitive recovery remains unclear. This study first examined the changes in neuronal survival in the CA1 region at the advanced time point (day 7) after ischemia/reperfusion (I/R) injury and found a significant amelioration of damaged CA1 neurons in the rats treated with DADLE (2.5 nmol) when administered at the onset of reperfusion. The structure and function of CA1 neurons on days 3 and 7 post-ischemia showed significant improvements in both the density of the injured dendritic spines and the basic transmission of the impaired CA3-CA1 synapses following DADLE treatment. The molecular changes involved in DADLE-mediated synaptic modulation on days 3 and 7 post-ischemia implied the time-related differential regulation of PKCα-MARCKS on the dendritic spine structure and of BDNF- ERK1/2-synapsin I on synaptic function, in response to ischemic/reperfusion injury as well as to DADLE treatment. Importantly, all the beneficial effects of DADLE on ischemia-induced cellular, synaptic, and molecular deficits were eliminated by the DOR inhibitor naltrindole (2.5 nmol). Taken together, this study suggested that DOR activation-induced protective signaling pathways of PKCα-MARCKS involved in the synaptic morphology and BDNF-ERK-synapsin I in synaptic transmission may be engaged in the cognitive recovery in rats suffering from advanced cerebral ischemia.

8.
Can J Physiol Pharmacol ; : 1-12, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34492212

RESUMO

G (1-5)-NH2, G (1-7)-NH2, and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood-brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. The antinociceptive effects of these fragments (2, 6, 20, and 60 nmol/mouse) were tested at 5, 10, 20, 30, 40, 50, and 60 min after intravenous (i.v.) injection. These fragments induced dose- and time-related antinociceptive effects relative to saline. Using the near infrared fluorescence imaging experiments, our results showed that these fragments could cross the brain-blood barrier and enter the brain. The antinociceptive effects of these fragments were completely antagonized by naloxone (intracerebroventricular, i.c.v.); however, naloxone methiodide (intraperitoneal, i.p.), which is the peripheral restricted opioid receptor antagonist, did not antagonize these antinociceptive effects. Furthermore, the GHS-R1α antagonist [D-Lys3]-GHRP-6 (i.c.v.) completely antagonized these antinociceptive effects, too. These results suggested that these fragments induced antinociceptive effects through central opioid receptors and GHS-R1α. In conclusion, our studies indicated that these active fragments of ghrelin could cross the brain-blood barrier and enter the brain and induce antinociceptive effects through central opioid receptors and GHS-R1α after intravenous injection.

9.
Neurotoxicology ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508789

RESUMO

Carbon black (CB) has been demonstrated to have adverse effects on the lung tissue. Few studies explored the effects of CB on the cerebellum, widely recognized to contribute to gait and balance coordination and timing in the motor domain. Some studies have reported that inflammatory response and damaged autophagy are important mechanisms of CB toxicity and can be repaired after the recovery. The present study aimed to determine whether long-term CB exposure could induce the inflammation and damaged autophagy of the cerebellum. The rats were randomly divided into four groups. The control group received the filtered air for 90 days; the carbon black (CB) group received CB particles for 90 days; the recovery (R) group received CB for 90 days and recovered for another 14 days; the recovery control (RC) group received filtered air for 104 days. The purpose of the R group was to test whether neuroinflammation and autophagy could be repaired after short-term recovery. The western blot and immunohistochemistry revealed that long-term CB exposure induced augmented level of pro-inflammatory cytokines (Interleukin-1ß, IL-1ß; Interleukin-6, IL-6; and Tumor Necrosis Factor-α, TNF-α) and anti-inflammatory cytokine (Interleukin-10, IL-10). The autophagic markers (Beclin1 and LC3) were increased in both CB group and R group. These findings clearly demonstrated that long-term CB exposure induced inflammation and autophagy in the cerebellum, which were not obviously changed after short-term recovery.

10.
Int J Mol Sci ; 22(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34502551

RESUMO

The evolutionarily conserved c-Jun N-terminal kinase (JNK) signaling pathway is a critical genetic determinant in the control of longevity. In response to extrinsic and intrinsic stresses, JNK signaling is activated to protect cells from stress damage and promote survival. In Drosophila, global JNK upregulation can delay aging and extend lifespan, whereas tissue/organ-specific manipulation of JNK signaling impacts lifespan in a context-dependent manner. In this review, focusing on several tissues/organs that are highly associated with age-related diseases-including metabolic organs (intestine and fat body), neurons, and muscles-we summarize the distinct effects of tissue/organ-specific JNK signaling on aging and lifespan. We also highlight recent progress in elucidating the molecular mechanisms underlying the tissue-specific effects of JNK activity. Together, these studies highlight an important and comprehensive role for JNK signaling in the regulation of longevity in Drosophila.

11.
Food Res Int ; 148: 110630, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34507774

RESUMO

The feasibility was investigated of 4D printing of lotus root gel compounded with a pigment that responds to pH change and alters colour. The pigment comprised of a combination of anthocyanins and lemon yellow; it was used in gel preparation for printing. The flowability and self-support properties of the lotus root-pigment gel were studied to evaluate its 3D printing performance. The gel viscosity decreased with the increase of printing temperature over the range 40, 50, and 60 °C. The gel with a ratio (lotus root powder/compound pigment) of 0.35 extruded smoothly and maintained high formability at temperatures below 60 °C. The pH response of compound pigment enabled the printed sample to change colour from reddish/yellowish to green after spraying with NaHCO3. The a* and b* values decreased significantly (p < 0.05) after spraying for 1 min. The gel with ratios of 0.30 and 0.35 achieved rapid colour change both superficially and internally. Through several different model designs (apple, Christmas tree, letters, and Chinese characters), high-quality 4D printing could be realized without problem. Thus, lotus root gel can be mixed with suitable pigments in correct proportion for 4D printing at appropriate temperature to ensure good flowability.

12.
Biotechnol J ; : e2100277, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34472222

RESUMO

Meta-l-lactic acid fermentation from non-treated kitchen refuse was reconstructed using a combination of isolated bacterial strains under several pH control strategies. The meta-fermentation system was successfully reconstructed using a combination of Weizmannia coagulans MN-07, Caldibacillus thermoamylovorans OM55-6, and Caldibacillus hisashii N-11 strains. Additionally, a simplified constant pH control strategy was employed, which decreased fermentation time and increased production. The optimum pH (6.5) for the reconstructed meta-fermentation was favorable for the respective pure cultures of the three selected strains. The l-lactic acid production performance of the reconstructed meta-fermentation system was as follows: concentration, 24.5 g L-1 ; optical purity, 100%; productivity, 0.341 g L-1 h-1 ; yield, 1.06 g g-1 . These results indicated that constant pH control was effective in the reconstructed meta-fermentation with the best performance of l-lactic acid production at pH optimal for the selected bacterial growth, while the switching from swing pH control would suppress the activities of unfavorable bacterial species in un-isolated meta-fermentation. GRAPHICAL ABSTRACT AND LAY SUMMARY: The meta-fermentation system was successfully reconstructed using a combination of three strains isolated from the compost. Additionally, a simplified constant pH control strategy was effective in the reconstructed system with decreased fermentation time and increased production of l-lactic acid at the optimum pH (6.5) value, which was favorable for the respective pure cultures of the three selected strains. The reconstructed meta-LA fermentation system proposed in this study increases organic biomass recycling efficiency.

13.
Bioorg Med Chem Lett ; 51: 128354, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34506932

RESUMO

A monocarboxylic inhibitor was designed and synthesized to disrupt the protein-protein interaction (PPI) between GRB2 and phosphotyrosine-containing proteins. Biochemical characterizations show compound 7 binds with the Src homology 2 (SH2) domain of GRB2 and is more potent than EGFR1068 phosphopeptide 14-mer. X-ray crystallographic studies demonstrate compound 7 occupies the GRB2 binding site for phosphotyrosine-containing sequences and reveal key structural features for GRB2-inhibitor binding. This compound with a -1 formal charge offers a new direction for structural optimization to generate cell-permeable inhibitors for this key protein target of the aberrant Ras-MAPK signaling cascade.

14.
Toxicology ; 462: 152931, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508823

RESUMO

A new focus in toxicology research is the impact of parental exposure to environmental toxic substances on the characteristics of offspring. In the present study, newly produced eggs of Drosophila melanogaster were treated with different concentrations of cadmium (0, 1, 2, 4, 8 mg/kg) to study the effects of development. The results showed that cadmium changed the larval body length and weight, prolonged the pupation and eclosion time, and changed the relative expression levels of development-related genes (baz, ß-Tub60D, tj). Furthermore, the parental Drosophila (F0) were treated with cadmium (4.5 mg/kg) from egg stage, and when grows to adults, they mated in standard medium to produce the de-stressed offspring (F1-F4) to assess the transgenerational effects of developmental delay. The results showed that the delayed effects of the pupation and eclosion time could be maintained for two generations, and the inhibiting effects of juvenile hormone (JH) and ecdysone (20-hydroxyecdysone, 20E) could be maintained for two or three generations. More importantly, cadmium increased the expression of DNA methylation-related genes (dDnmt2, dMBD2/3) in the ovaries (F0-F2) and testicles (F0 and F1). In addition, cadmium accumulated in parental Drosophila (F0) was not transmitted to offspring through reproductive pathway. These results demonstrate that the developmental toxicity caused by cadmium could be transmitted to the de-stressed offspring, and the observed transgenerational inheritance effects may be associated with epigenetic regulation, underscoring the need to consider fitness of future generations in evaluating the toxicity and environmental risks of cadmium.

15.
BMC Med Res Methodol ; 21(1): 186, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544374

RESUMO

BACKGROUND: The emergence of antimicrobial resistance across populations is a global threat to public health. Surveillance programs often monitor human and animal populations to evaluate trends of emergence in these populations. Many national level antibiotic resistance surveillance programs quantify the proportion of resistant bacteria as a means of monitoring emergence and control measures. The reason for monitoring these different populations are many, including interest in similar changes in resistance which might provide insight into emergence and control options. METHODS: In this research, we developed a method to quantify the correlation in antimicrobial resistance across populations, for the conventionally unnoticed mean shift of the susceptible bacteria. With the proposed Bayesian latent class mixture model with censoring and multivariate normal hierarchy, we address several challenges associated with analyzing the minimum inhibitory concentration data. RESULTS: Application of this approach to the surveillance data from National Antimicrobial Resistance Monitoring System led to a detection of positive correlation in the central tendency of azithromycin resistance of the susceptible populations from Salmonella serotype Typhimurium across food animal and human populations. CONCLUSIONS: Our proposed approach has been shown to be accurate and superior to the commonly used naïve estimation by simulation studies. Further implementation of this Bayesian model could serve as a useful tool to indicate the co-existence of antimicrobial resistance, and potentially a need of clinical intervention.

16.
BMC Neurol ; 21(1): 364, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536997

RESUMO

BACKGROUND: Few studies have investigated the influence of white matter lesions (WMLs) on the prognosis of acute cardioembolic stroke (CES). We aimed to explore the role of WMLs in predicting 3-month prognosis of CES without reperfusion therapy. METHODS: A number of 251 acute CES patients without reperfusion therapy at a single center were retrospectively recruited. The severity of WMLs was evaluated by Fazekas scale and patients were divided into mild WMLs group (188 cases, Fazekas ≤ 2 points) and moderate to severe WMLs group (63 cases, Fazekas ≥ 3 points) accordingly. General data and clinical features of the two groups were compared. Functional outcomes of patients were followed up for 3 months using the modified Rankin scale (mRS) and patients were divided into poor outcome group (mRS ≥ 3) and favorable outcome group (mRS ≤ 2). The effect of WMLs on the prognosis was identified by binary logistic regression. RESULTS: Patients in moderate to severe WMLs group were older (P < 0.001). Also, they had higher baseline National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001) and elevated incidence of asymptomatic cerebral hemorrhage (P = 0.040) and stroke associated pneumonia (P = 0.001) than those in mild WMLs group. At 3 months, there were 100 cases in the poor outcome group. Patients in poor outcome group had higher baseline NIHSS score, increased proportion of moderate to severe WMLs, and elevated incidence of stroke associated pneumonia than those in favorable outcome group (P < 0.001). Binary logistic regression analysis showed that moderate to severe WMLs (odds ratio [OR] = 4.105, 95 % confidence interval [CI] = 1.447-11.646), baseline NIHSS score (OR = 1.368, 95 % CI = 1.240-1.511), and stroke-associated pneumonia (OR = 4.840, 95 %CI = 1.889-12.400) were independent risk factors for poor outcome. CONCLUSIONS: Moderate to severe WMLs is an independent risk factor for prognosis of CES patients without reperfusion therapy.

17.
J Dairy Sci ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34538494

RESUMO

Ketotic dairy cows exhibit a state of negative energy balance (NEB) characterized by elevated circulating levels of ß-hydroxybutyrate (BHB) and fatty acids. Impaired hepatic insulin signaling in dairy cows occurs frequently during the transition into lactation, but its role on liver function during this period is not well known. In nonruminants, endoplasmic reticulum (ER) stress is a causal factor contributing to impaired insulin signaling in the liver. Thus, the aim of this study was to investigate the status of hepatic insulin and ER stress signaling and whether ER stress contributes to impaired insulin signaling in dairy cows with ketosis. Healthy (control cows, n = 10, BHB ≤0.6 mM) and ketotic (ketotic cows, n = 10, BHB ≥1.2 mM) cows at 3 to 10 d in milk were selected for liver biopsy and blood sampling before feeding. In vitro experiments were conducted with isolated hepatocytes from 5 healthy calves (1 d old, fasted female, 30-40 kg of body weight). Treatments included BHB (0, 0.9, 1.8, 3.6 mM), tauroursodeoxycholic acid (TUDCA, a canonical inhibitor of ER stress), and different incubation times (0.5, 1, 2, 3, 5, 7, 9, or 12 h). Ketotic cows had lower daily milk yield (median: 29.50 vs. 23.00 kg), higher plasma nonesterified fatty acid (NEFA) (median: 0.33 vs. 1.17 mM), BHB (median: 0.43 vs. 3.22 mM), aspartate aminotransferase (median: 70.58 vs. 155.70 U/L), alanine aminotransferase (median: 18.31 vs. 37.90 U/L), lower plasma glucose (median: 4.32 vs. 2.37 mg/dL), and revised quantitative insulin sensitivity check index (median: 0.39 vs. 0.37) compared with healthy cows. Increased abundance of phosphorylated insulin receptor substrate-1 (IRS1) and decreased abundance of phosphorylated protein kinase B (AKT) and glycogen synthase kinase-3ß (GSK3ß) in ketotic cows indicated a state of insulin resistance. In addition, abundance of phosphorylated protein kinase RNA-like ER kinase (PERK) and inositol requiring protein-1α (IRE1α), and cleavage of activating transcription factor-6 (ATF6) were greater in the liver of ketotic cows. In vitro, at the early stages of incubation, treatment with BHB upregulated abundance of phosphorylated of IRE1α, PERK, and the cleavage of ATF6, as well as several unfolded protein response genes [X-box-binding protein-1 (XBP1), 78 kDa glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP)]. Furthermore, in response to increasing doses of BHB, the phosphorylation level of PERK, IRE1α, and the cleavage of ATF6, and the abundance of XBP1, GRP78, and CHOP increased. In addition, BHB treatment increased phosphorylation of IRS1 and decreased phosphorylation of AKT and GSK3ß, and upregulated abundance of gluconeogenic genes (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase). Importantly, these changes were reversed by inhibiting ER stress with TUDCA treatment. Overall, the present study indicated that reversing ER stress during ketosis might help alleviate hepatic insulin resistance. Targeting ER stress may represent a potential therapeutic target for controlling the negative aspects of ketosis on liver function.

18.
Clin J Pain ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34483232

RESUMO

OBJECTIVE: We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine for the treatment of knee Osteoarthritis (OA) pain. METHODS: A comprehensive literature search used three English and four Chinese biomedical databases from inception through July 10, 2020. We included randomized controlled trials of duloxetine with intervention duration of two weeks or longer for knee OA. The primary outcome was pain intensity measured by Brief Pain Inventory and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcome measurements included 36-Item Short Form Health Survey, Patient's Global Impression of Improvement (PGI-I), Clinical Global Impressions of Severity (CGI-S), and adverse events. The quality of all included studies was evaluated using the Cochrane risk-of-bias criteria. The review was registered in the PROSPERO (CRD 42020194072). RESULTS: Six studies totaling 2,059 subjects met the eligibility criteria. Duloxetine had significant reductions in Brief Pain Inventory 24-h average pain (Mean Difference [MD]=-0.74; 95% confidence interval [CI], -0.92 to -0.57; P<0.00001; I2=13%; 5 trials; 1695 patients), patient general activity (MD=-0.76; 95% CI, -0.96 to -0.56; P<0.00001; I2=0%; 5 trials; 1694 patients), WOMAC physical function subscale (MD=-4.22; 95% CI, -5.14 to -3.30; P<0.00001; I2=26%; 5 trials; 1986 patients), PGI-I (MD=-0.48; 95% CI, -0.58 to -0.37; P<0.00001; I2=29%; 5 trials; 1741 patients), and CGI-S (MD=-0.34; 95% CI, -0.44 to -0.24; P<0.00001; I2=0%; 4 trials; 1178 patients) compared with placebo control. However, no difference on WOMAC pain subscale (SMD=-1.68; 95% CI, -3.45 to 0.08; P=0.06; I2=100%; 3 trials; 1104 patients) and in serious adverse events (RR=0.92; 95% CI, 0.40 to 2.11; P=0.84; I2=0%; 5 trials; 1762 patients) between duloxetine and placebo. Furthermore, duloxetine failed to show superior effects for improving the life quality and demonstrated more treatment-emergent adverse events. CONCLUSIONS: Duloxetine may be an effective treatment option for knee OA patients but further rigorously designed and well-controlled randomized trials are warranted.

19.
BMC Pregnancy Childbirth ; 21(1): 592, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465292

RESUMO

BACKGROUND: Treatment of tuberculosis (TB) during pregnancy can reduce maternal and foetal complications. However, it may also induce fatal liver injury. CASE PRESENTATION: We present a case of a 26-year-old pregnant woman who underwent orthotopic liver transplantation for anti-TB drug-induced fulminant hepatic failure (FHF). Her tuberculous pleurisy was treated with rifampin, isoniazid and pyrazinamide. An artificial liver support system (ALSS) was unable to reverse the liver injury while serving as a bridge to liver transplantation. She had a successful liver transplantation operation at 17 3/7 weeks of gestation. The foetal ultrasound scan showed mild foetal bilateral ventriculomegaly at 21 5/7 weeks of gestation, and labour was induced via double-balloon catheter as soon as the allograft function was stable. Despite immunosuppression, the TB was well controlled with linezolid, levofloxacin and pyridoxine at the 8 months follow-up. CONCLUSIONS: Anti-TB drug-induced liver failure during pregnancy is rare. We present a case of successful treatment of FHF in which an artificial liver support system combined with liver transplantation. The FHF was caused by anti-TB drugs with difficulties due to pregnancy status and post-transplant anti-TB treatment. Mild foetal ventriculomegaly was found in our case. Further research is still needed to identify the risks of TB treatment and liver transplantation in pregnant women. A multidisciplinary team coordinated properly to optimize patient outcomes.

20.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3877-3885, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472263

RESUMO

Twenty-six compounds, including sixteen meroterpenoids(1-16), a triterpenoid(17), four terpenoid derivatives(18-21), and five aromatic compounds(22-26), were isolated from the leaves of Psidium guajava. Their structures were identified by spectroscopic analyses including NMR and MS. Compounds 21-26 were obtained from plants of Psidium for the first time. Based on the structure,(R)-2-ethylhexyl 2H-1,2,3-triazole-4-carboxylate(24 a), an α-glucosidase inhibitor recently isolated from Paramignya trimera, should be revised as compound 24. Meroterpenoids 1-16 were evaluated for their antitumor and antifungal activities. Meroterpenoids psiguajadial D(4), guapsidial A(5), 4,5-diepipsidial A(7), guadial A(14), and guadial B(15) showed cytotoxicities against five human tumor cell lines(HL-60, A-549, SMMC-7721, MCF-7, and SW-480), among which 5 was the most effective with an IC_(50) of 3.21-9.94 µmol·L~(-1).


Assuntos
Psidium , Antifúngicos/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Extratos Vegetais , Folhas de Planta , Terpenos
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