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1.
Front Nutr ; 8: 714291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746202

RESUMO

Background: Evidence of an association between dairy product and main related dairy nutrient intake, and the asthenozoospermia risk have been limited and controversial. Methods: A hospital-based case-control study including 549 men with asthenozoospermia and 581 normozoospermic controls was carried out in the infertility clinics of Shengjing Hospital of China Medical University between June, 2020 and December, 2020. Dietary intake was assessed with a validated food frequency questionnaire. According to the World Health Organization guidelines, semen parameters were collected through masturbation and were measured with WLJY9000 instrument and flow cytometry. The daily intake of dairy products and related nutrients was categorized into three groups according to control distribution, and the lowest tertile was used as the reference category. An unconditional multiple logistic regression was used to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for asthenozoospermia risk. Results: After adjustment for potential confounders, we found no statistically significant associations between the intake of total dairy products and asthenozoospermia risk (ORT3vs.T1 = 1.19, 95%CI = 0.85-1.67). Additionally, we generated null findings regarding the main related nutrients from dairy, including protein (ORT3vs.T1 = 1.19, 95%CI = 0.85-1.68), fat (ORT3vs.T1 = 1.28, 95%CI = 0.91-1.80), calcium (ORT3vs.T1 = 1.20, 95%CI = 0.85-1.68), saturated fatty acids (ORT3vs.T1 = 1.30, 95%CI = 0.92-1.83), and phosphorous (ORT3vs.T1 = 1.18, 95%CI = 0.84-1.67), and the asthenozoospermia risk. Of note, after stratification by body mass index (BMI), and the saturated fatty acids consumption from dairy was significantly associated with a higher asthenozoospermia risk (ORT3vs.T1 = 1.76, 95%CI = 1.01-3.09) among participants with a BMI below 25 kg/m2. Conclusion: This study provided limited evidence of an association between the intake of total dairy products and the main related dairy nutrients including protein, fat, calcium, saturated fatty acids, and phosphorus, and the asthenozoospermia risk. Further studies are warranted to confirm our findings in the future.

2.
Perioper Med (Lond) ; 10(1): 37, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34743734

RESUMO

BACKGROUND: Homocysteine, folate, and vitamin B12 involved in 1-carbon metabolism are associated with cognitive disorders. We sought to investigate the relationships between these factors and delayed neurocognitive recovery (dNCR) after non-cardiac surgery. METHODS: This was a prospective observational study of patients (n = 175) who were ≥ 60 years of age undergoing non-cardiac surgery. Patients were evaluated preoperatively and for 1 week postoperatively by using neuropsychological tests and were divided into dNCR or non-dNCR groups according to a Z-score ≤ - 1.96 on at least two of the tests. The relationship between the occurrence of dNCR and preoperative levels of homocysteine, folate, and vitamin B12 was analyzed. Univariate and multivariable logistic regression analyses were conducted to identify factors associated with dNCR. RESULTS: Delayed neurocognitive recovery was observed in 36 of 175 patients (20.6%; 95% confidence interval [CI], 14.5-26.6%) 1 week postoperatively. Patients who developed dNCR had significantly higher median [interquartile range (IQR)] homocysteine concentrations (12.8 [10.9,14.4] µmol/L vs 10.6 [8.6,14.7] µmol/L; P = 0.02) and lower folate concentrations (5.3 [4.2,7.3] ng/mL vs 6.9 [5.3,9.5] ng/mL; P = 0.01) than those without dNCR. Compared to the lowest tertile, the highest homocysteine tertile predicted dNCR onset (odds ratio [OR], 3.9; 95% CI, 1. 3 to 11.6; P = 0.02), even after adjusting for age, sex, education, and baseline Mini Mental State Examination. CONCLUSIONS: Elderly patients with high homocysteine levels who underwent general anesthesia for non-cardiac surgery have an increased risk of dNCR. This knowledge could potentially assist in the development of preventative and/or therapeutic measures. TRIAL REGISTRATION: NCT03084393 ( https://www.clinicaltrials.gov ).

3.
Front Physiol ; 12: 739174, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764881

RESUMO

Non-alcoholic fatty liver diseases (NAFLDs) along with metabolic syndrome and Type-2 diabetes (T2D) are increasingly prevalent worldwide. Without an effective resolution, simple hepatic steatosis may lead to non-alcoholic steatohepatitis (NASH), characterized by hepatocyte damage, chronic inflammation, necrosis, fatty degeneration, and cirrhosis. The gut microbiome is vital for metabolic homeostasis. Conversely, dysbiosis contributes to metabolic diseases including NAFLD. Specifically, diet composition is critical for the enterotype of gut microbiota. We reasoned that green pigment rich in vegetables may modulate the gut microbiome for metabolic homeostasis. In this study, C57BL/6 mice under a high fat diet (HFD) were treated with sodium copper chlorophyllin (CHL), a water-soluble derivative of chlorophyll, in drinking water. After 28 weeks of HFD feeding, liver steatosis was established accompanied by gut microbiota dysbiosis, intestinal impairment, endotoxemia, systemic inflammation, and insulin resistance. Administration of CHL effectively alleviated systemic and intestinal inflammation and maintained tight junction in the intestinal barrier. CHL rebalanced gut microbiota in the mice under high fat feeding and attenuated hepatic steatosis, insulin resistance, dyslipidemia, and reduced body weight. Fecal flora transplants from the CHL-treated mice ameliorated steatosis as well. Thus, dietary green pigment or the administration of CHL may maintain gut eubiosis and intestinal integrity to attenuate systemic inflammation and relieve NASH.

4.
J Anesth ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757497

RESUMO

Low tidal volume ventilation strategy may lead to atelectasis without proper positive end-expiratory pressure (PEEP) and recruitment maneuver (RM) settings. RM followed by individualized PEEP was a new method to optimize the intraoperative pulmonary function. We conducted a systematic review and network meta-analysis of randomized clinical trials to compare the effects of individualized PEEP + RM on intraoperative pulmonary function and hemodynamic with other PEEP and RM settings. The primary outcomes were intraoperative oxygenation index and dynamic compliance, while the secondary outcomes were intraoperative heart rate and mean arterial pressure. In total, we identified 15 clinical trials containing 36 randomized groups with 3634 participants. Ventilation strategies were divided into eight groups by four PEEP (L: low, M: moderate, H: high, and I: individualized) and two RM (yes or no) settings. The main results showed that IPEEP + RM group was superior to all other groups regarding to both oxygenation index and dynamic compliance. LPEEP group was inferior to LPEEP + RM, MPEEP, MPEEP + RM, and IPEEP + RM in terms of oxygenation index and LPEEP + RM, MPEEP, MPEEP + RM, HPEEP + RM, IPEEP, and IPEEP + RM in terms of dynamic compliance. All comparisons were similar for secondary outcomes. Our analysis suggested that individualized PEEP and RM may be the optimal low tidal volume ventilation strategy at present, while low PEEP without RM is not suggested.

5.
Proc Natl Acad Sci U S A ; 118(47)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34789566

RESUMO

We report a molecular switching ensemble whose states may be regulated in synergistic fashion by both protonation and photoirradiation. This allows hierarchical control in both a kinetic and thermodynamic sense. These pseudorotaxane-based molecular devices exploit the so-called Texas-sized molecular box (cyclo[2]-(2,6-di(1H-imidazol-1-yl)pyridine)[2](1,4-dimethylenebenzene); 14+, studied as its tetrakis-PF6 - salt) as the wheel component. Anions of azobenzene-4,4'-dicarboxylic acid (2H+•2) or 4,4'-stilbenedicarboxylic acid (2H+•3) serve as the threading rod elements. The various forms of 2 and 3 (neutral, monoprotonated, and diprotonated) interact differently with 14+, as do the photoinduced cis or trans forms of these classic photoactive guests. The net result is a multimodal molecular switch that can be regulated in synergistic fashion through protonation/deprotonation and photoirradiation. The degree of guest protonation is the dominating control factor, with light acting as a secondary regulatory stimulus. The present dual input strategy provides a complement to more traditional orthogonal stimulus-based approaches to molecular switching and allows for the creation of nonbinary stimulus-responsive functional materials.

6.
CNS Neurosci Ther ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792857

RESUMO

OBJECTIVE: Postoperative delirium (POD) is a common postoperative complication that is relevant to poor outcomes. Therefore, it is critical to find effective methods to identify patients with high risk of POD rapidly. Creating a fully automated score based on an automated machine-learning algorithm may be a method to predict the incidence of POD quickly. MATERIALS AND METHODS: This is the secondary analysis of an observational study, including 531 surgical patients who underwent general anesthesia. The least absolute shrinkage and selection operator (LASSO) was used to screen essential features associated with POD. Finally, eight features (age, intraoperative blood loss, anesthesia duration, extubation time, intensive care unit [ICU] admission, mini-mental state examination score [MMSE], Charlson comorbidity index [CCI], postoperative neutrophil-to-lymphocyte ratio [NLR]) were used to established models. Four models, logistic regression, random forest, extreme gradient boosted trees, and support vector machines, were built in a training set (70% of participants) and evaluated in the remaining testing sample (30% of participants). Multivariate logistic regression analysis was used to explore independent risk factors for POD further. RESULTS: Model 1 (logistic regression model) was found to outperform other classifier models in testing data (area under the curve [AUC] of 80.44%, 95% confidence interval [CI] 72.24%-88.64%) and achieve the lowest Brier Score as well. These variables including age (OR = 1.054, 95%CI: 1.017~1.093), extubation time (OR = 1.027, 95%CI: 1.012~1.044), ICU admission (OR = 2.238, 95%CI: 1.313~3.793), MMSE (OR = 0.929, 95%CI: 0.876~0.984), CCI (OR = 1.197, 95%CI: 1.038~1.384), and postoperative NLR (OR = 1.029, 95%CI: 1.002~1.057) were independent risk factors for POD in this study. CONCLUSIONS: We have built and validated a high-performing algorithm to demonstrate the extent to which patient risk changes of POD during the perioperative period, thus leading to a rational therapeutic choice.

7.
Int J Clin Pract ; : e15010, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807494

RESUMO

BACKGROUND: Low-dose ketamine has been proved to reduce opioid consumption, prevent depressant action and improve postoperative analgesia. Women undergoing mastectomy experience may not only have persistent postoperative pain syndromes but also emotional problems. However, the effect of intraoperative infusion of low-dose ketamine on postoperative quality of recovery among these patients has not yet been fully studied. METHODS: In this prospective, randomised, single-centre trial, 100 patients planned for modified radical mastectomy were randomly assigned to one of two groups: control group (group C) or ketamine group (group K) at a ratio of 1:1. Group K received the bolus dose of 0.5 mg/kg ketamine and followed by 0.25 mg·kg-1 ·h-1 after the compliment of anaesthesia induction until the end of the surgery, whilst group C received an equivalent dose and regiment of normal saline was group K. The primary outcome was to assess the effects of low-dose ketamine on postoperative quality of recovery using the 40-Item Quality of Recovery (QoR-40) scale on a postoperative day 1 (POD1). The secondary outcome was to assess the numeric rating scale (NRS) at 4, 24 and 48 h after the operation, identity-consequence fatigue scale (ICFS) scores at 3 and 7 days after the operation, hospital anxiety and depression scale (HADS) scores at 2 days and 3 months, as well as chronic pain at 3 months. In a post hoc analysis, the 5 subsections of the QoR-40 scores were also analysed. RESULTS: A total of 100 subjects were randomised. The primary outcome of QoR-40 scores on POD1 was available in 97 patients (49 in group C and 48 in group K). Global QoR-40 scores were not significantly different between group C and group K (169.8 ± 10.7 vs. 172.7 ± 7.5, 95% CI -1.35 (-5.50, 2.80), p = .519). In a post hoc analysis, pain scores were significantly higher in group K than in group C (29.8 ± 3.8 vs. 31.7 ± 2.1, 95% CI -1.81 (-3.00, -0.62), p = .003). The secondary outcomes, including NRS, ICFS scores, HADS scores and chronic pain had no difference between groups (p value for each >.15). CONCLUSION: Intraoperative low-dose ketamine infusion did not improve the overall quality of recovery on POD 1 in patients undergoing breast cancer surgery.

8.
ACS Nano ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723467

RESUMO

Cytokine immunotherapy represents an attractive strategy to stimulate robust immune responses for renal injury repair in ischemic acute kidney injury (AKI). However, its clinical application is hindered by its nonspecificity to kidney, short circulation half-life, and severe side effects. An ideal cytokine immunotherapy for AKI requires preferential delivery of cytokines with accurate dosage to the kidney and sustained-release of cytokines to stimulate the immune responses. Herein, we developed a DNA nanoraft cytokine by precisely arranging interleukin-33 (IL-33) nanoarray on rectangle DNA origami, through which IL-33 can be preferentially delivered to the kidney for alleviation of AKI. A nanoraft carrying precisely quantified IL-33 predominantly accumulated in the kidney for up to 48 h. Long-term sustained-release of IL-33 from nanoraft induced rapid expansion of type 2 innate lymphoid cells (ILC 2s) and regulatory T cells (Tregs) and achieved better treatment efficiency compared to free IL-33 treatment. Thus, our study demonstrates that a nanoraft can serve as a structurally well-defined delivery platform for cytokine immunotherapy in ischemic AKI and other renal diseases.

9.
Zootaxa ; 5061(1): 115-133, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34810638

RESUMO

Five new species of the genus Sinophorus Frster, 1869 (Ichneumonidae, Campopleginae) are described and illustrated from China: S. dioryctriae sp. nov., S. latistrigis sp. nov., S. neimengensis sp. nov., S. petilidentis sp. nov. and S. spissus sp. nov. A key to the Chinese species of Sinophorus is provided.


Assuntos
Himenópteros , Animais , China
10.
Zootaxa ; 5066(1): 1-121, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34810764

RESUMO

The genus Campoplex Gravenhorst, 1829 (Hymenoptera, Ichneumonidae, Campopleginae) from China is revised. Thirty-nine new species are proposed (C. absitus sp. nov., C. acarus sp. nov., C. adustantennalis sp. nov., C. angustaulacis sp. nov., C. apacicarinatus sp. nov., C. artivultus sp. nov., C. atricrus sp. nov., C. collucatus sp. nov., C. concretus sp. nov., C. confluentus sp. nov., C. cyclus sp. nov., C. densipunctatus sp. nov., C. exareola sp. nov., C. granalvus sp. nov., C. grandialphus sp. nov., C. grandicella sp. nov., C. granulosus sp. nov., C. galbipedis sp. nov., C. hei sp. nov., C. liuae sp. nov., C. lobatus sp. nov., C. longiclypeus sp. nov., C. maurotrochanter sp. nov., C. medicarinatus sp. nov., C. monochroma sp. nov., C. obtusoclypeus sp. nov., C. parassosae sp. nov., C. perpendicularis sp. nov., C. proportionis sp. nov., C. protenus sp. nov., C. plicopunctatus sp. nov., C. pseudocyclus sp. nov., C. pseudostrigatus sp. nov., C. shanxiensis sp. nov., C. strigatus sp. nov., C. taenius sp. nov., C. tanae sp. nov., C. xizangensis sp. nov., and C. xuthomelonus sp. nov.) and one species is recorded as new to Nepal (C. oriens Gupta Maheshwary). A key to Chinese species of Campoplex is provided.


Assuntos
Himenópteros , Lepidópteros , Animais , China
11.
ACS Nano ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34694775

RESUMO

Emerging viruses will continue to be a threat to human health and wellbeing into the foreseeable future. The COVID-19 pandemic revealed the necessity for rapid viral sensing and inhibitor screening in mitigating viral spread and impact. Here, we present a platform that uses a label-free electronic readout as well as a dual capability of optical (fluorescence) readout to sense the ability of a virus to bind and fuse with a host cell membrane, thereby sensing viral entry. This approach introduces a hitherto unseen level of specificity by distinguishing fusion-competent viruses from fusion-incompetent viruses. The ability to discern between competent and incompetent viruses means that this device could also be used for applications beyond detection, such as screening antiviral compounds for their ability to block virus entry mechanisms. Using optical means, we first demonstrate the ability to recapitulate the entry processes of influenza virus using a biomembrane containing the viral receptor that has been functionalized on a transparent organic bioelectronic device. Next, we detect virus membrane fusion, using the same, label-free devices. Using both reconstituted and native cell membranes as materials to functionalize organic bioelectronic devices, configured as electrodes and transistors, we measure changes in membrane properties when virus fusion is triggered by a pH drop, inducing hemagglutinin to undergo a conformational change that leads to membrane fusion.

12.
Theranostics ; 11(19): 9397-9414, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646377

RESUMO

Rationale: Most current cardiac regeneration approaches result in very limited cell division and little new cardiomyocyte (CM) mass. Positive feedback loops are vital for cell division, but their role in CM regeneration remains unclear. We aimed to determine whether the lncRNA small nucleolar RNA host gene 1 Snhg1 (Snhg1) could form a positive feedback loop with c-Myc to induce cardiac regeneration. Methods: Quantitative PCR and in situ hybridization experiments were performed to determine the Snhg1 expression patterns in fetal and myocardial infarction (MI) hearts. Gain- and Loss-of-function assays were conducted to explore the effect of Snhg1 on cardiomyocyte (CM) proliferation and cardiac repair following MI. We further constructed CM-specific Snhg1 knockout mice to confirm the proliferative effect exerted by Snhg1 using CRISPR/Cas9 technology. RNA sequencing and RNA pulldown were performed to explore how Snhg1 mediated cardiac regeneration. Chromatin immunoprecipitation and luciferase reporter assays were used to demonstrate the positive feedback loop between Snhg1 and c-Myc. Results: Snhg1 expression was increased in human and mouse fetal and myocardial infarction (MI) hearts, particularly in CMs. Overexpression of Snhg1 promoted CM proliferation, angiogenesis, and inhibited CM apoptosis after myocardial infarction, which further improved post-MI cardiac function. Antagonism of Snhg1 in early postnatal mice inhibited CM proliferation and impaired cardiac repair after MI. Mechanistically, Snhg1 directly bound to phosphatase and tensin homolog (PTEN) and induced PTEN degradation, activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway to promote CM proliferation. The c-Myc protein, one of downstream targets of PI3K/AKT signaling, functioned as a transcription factor by binding to the promoter regions of Snhg1. Perturbation of the positive feedback between Snhg1 and c-Myc by mutation of the binding sequence significantly affected Snhg1-induced CM proliferation. Conclusions: Snhg1 effectively elicited CM proliferation and improved cardiac function post-MI by forming a positive feedback loop with c-Myc to sustain PI3K/Akt signaling activation, and thus may be a promising cardiac regeneration strategy in treating heart failure post-MI.

13.
J Clin Sleep Med ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473048

RESUMO

STUDY OBJECTIVES: Shift work is commonly increasing, and some physiological changes occur as workers sleep less and their circadian rhythms are disrupted. This umbrella review not only summarizes the evidence but also evaluates the validity of the associations of shift work with different health outcomes. METHODS: We searched the MEDLINE, Web of Science, and Embase databases from their inception to April 25, 2020. This study has been registered at PROSPERO; the registration number is CRD42020188537. For each systematic review and/or meta-analysis, we estimated the summary effect size, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. RESULTS: Eight eligible systematic reviews and meta-analyses were identified, providing data on 16 associations. We observed highly suggestive evidence for associations between shift work and myocardial infarction (having ever versus having never done shift work) and diabetes mellitus incidence (per five-year increment in shift work). Furthermore, we observed suggestive evidence for an association between shift work and diabetes mellitus incidence (having ever versus having never done shift work). Two health outcomes, including prostate cancer incidence (having ever versus having never done shift work and rotating night shift work versus daytime work), and colorectal cancer incidence (longest versus shortest shift work time) were only supported by weak evidence. CONCLUSIONS: This umbrella review found that shift work was associated with several health outcomes with different levels of evidence. Associations for myocardial infarction and diabetes mellitus incidence were supported by highly suggestive evidence.

14.
Front Nutr ; 8: 706869, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395499

RESUMO

Background: Evidence of associations between a pro-inflammatory diet and asthenozoospermia risk is limited. We therefore performed a case-controlled study to investigate associations between pro-inflammatory diet using dietary inflammatory index (DII) scores and asthenozoospermia risk in China. Methods: Our hospital-based case-controlled study comprised 549 incident asthenozoospermia men and 581 healthy controls. All were interviewed at the infertility clinic in Shengjing Hospital of China Medical University from June 2020 to December 2020. DII scores were calculated based on dietary intake which were assessed using a validated food frequency questionnaire. Semen parameters were analyzed according to World Health Organization guidelines. An unconditional logistic regression model was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for asthenozoospermia risk. The lowest tertile served as the reference category for regression analyses. Results: After adjustment for age in the primary multivariable model, we failed to determine a significant negative association between DII and asthenozoospermia risk (for the highest tertile of DII scores compared to the lowest tertile) (OR = 0.77, 95% CI: 0.57-1.03). Similarly, non-significant associations were also identified in the multivariable model after adjusting for more potential confounders (OR = 0.86; 95% CI: 0.58-1.27). Additionally, in subgroup analyses stratified by age, body mass index, and smoking status, non-significant results were consistent with the main findings. Conclusions: To our knowledge, this is the first study exploring this particular topic. Our research does not support an association between DII scores and asthenozoospermia risk. Further prospective studies with more DII relevant foods and nutrients are warranted to confirm our findings.

15.
CNS Neurosci Ther ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34415671

RESUMO

INTRODUCTION: The blood-brain barrier (BBB) disruption contributes to postoperative delirium, but cost-effective and non-invasive assessment of its permeability is not practicable in the clinical settings. Urine albumin to creatinine ratio (UACR), reflecting systemic vascular endothelial dysfunction, may be a prognostic and predictive factor associated with postoperative delirium. The aim was to analyze the relationship between UACR and postoperative delirium in elderly patients undergoing elective non-cardiac surgery. MATERIALS AND METHODS: Through stratified random sampling, a cohort of 408 individuals aged 60 years and older scheduled for elective non-cardiac surgery were included between February and August 2019 in the single-center, prospective, observational study. The presence of delirium was assessed using the Confusion Assessment Method (CAM) or Confusion Assessment Method for the ICU (CAM-ICU) on the day of surgery, at 2 h after the surgery ending time and on the first 3 consecutive days with repeated twice-daily, with at least 6-h intervals between assessments. Urine samples were collected on one day before surgery, and 1st day and 3rd day after surgery. The primary outcome was the presence of postoperative delirium, and association of the level of UACR with postoperative delirium was evaluated with unadjusted/adjusted analyses and multivariable logistic regression. RESULTS: Postoperative delirium was observed in 26.75% (107 of 400) of patients within 3 days post-surgery. UACR-Pre (OR, 1.30; 95% CI, 1.14-1.49, p < 0.001), UACR-POD1 (OR, 1.20; 95% CI, 1.13-1.27, p < 0.001), and UACR-POD3 (OR, 1.14; 95% CI, 1.08-1.20, p < 0.001) between the delirium and non-delirium groups show a significant difference, even after adjusting for age, education levels, and other factors. CONCLUSION: As the marker of endothelial dysfunction, the high perioperative UACR value may be linked to the postoperative delirium in elderly patients undergoing elective non-cardiac surgery.

16.
J Cell Mol Med ; 25(18): 8947-8956, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34405526

RESUMO

Amyloid-ß (Aß) deposition in the brain has been implicated in the development of Alzheimer's disease (AD), and neuroinflammation generates AD progression. Therapeutic effects of anti-inflammatory approaches in AD are still under investigation. Curcumin, a potent anti-inflammatory and antioxidant, has demonstrated therapeutic potential in AD models. However, curcumin's anti-inflammatory molecular mechanisms and its associated cognitive impairment mechanisms in AD remain unclear. The high-mobility group box-1 protein (HMGB1) participates in the regulation of neuroinflammation. Herein, we attempted to evaluate the anti-inflammatory effects of chronic oral administration of curcumin and HMGB1 expression in APP/PS1 transgenic mice AD model. We found that transgenic mice treated with a curcumin diet had shorter escape latencies and showed a significant increase in percent alternation, when compared with transgenic mice, in the Morris water maze and Y-maze tests. Additionally, curcumin treatment could effectively decrease HMGB1 protein expression, advanced glycosylation end product-specific receptor (RAGE), Toll-like receptors-4 (TLR4) and nuclear factor kappa B (NF-κB) in transgenic mice hippocampus. However, amyloid plaques detected with thioflavin-S staining in transgenic mice hippocampus were not affected by curcumin treatment. In contrast, curcumin significantly decreased GFAP-positive cells, as assessed by immunofluorescence staining. Taken together, these data indicate that oral administration of curcumin may be a promising agent to attenuate memory deterioration in AD mice, probably inhibiting the HMGB1-RAGE/TLR4-NF-κB inflammatory signalling pathway.

17.
Molecules ; 26(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299516

RESUMO

The metal-organic rotaxane framework (MORF) structures with the advantage of mechanically interlocking molecules (MIMs) have attracted intense interest from the chemical community. In this study, a set of MORFs (i.e., MORF-Pb-1 and MORF-Pb-2) are constructed using Pb2+, a tetraimidazolium macrocycle (Texas-sized molecular box; 14+), and aromatic dicarboxylate (p-phthalate dianions (PTADAs; 2) or 2,6-naphthalene dicarboxylate dianions (3)) via a one-pot three-layer diffusion protocol. In particular, an unusual Pb…Pb weak interaction was shown in MORF-Pb-1 (charactered with distance of 3.656 Å).

18.
J Cell Mol Med ; 25(15): 7342-7353, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34213839

RESUMO

Diabetes-related depression (DD) is a major complication of diabetes mellitus. Our previous studies indicated that glutamate (Glu) and hippocampal neuron apoptosis are key signal and direct factor leading to diabetes-related depression, respectively. However, the accurate pathogenesis remains to be unclear. We hypothesized that diabetes-related depression might be associated with the mitophagy-mediated hippocampal neuron apoptosis, triggered by aberrant Glu-glutamate receptor2 (GluR2)-Parkin pathway. To testify this hypothesis, here the rat model of DD in vivo and in vitro were both established so as to uncover the potential mechanism of DD based on mitophagy and apoptosis. We found that DD rats exhibit an elevated glutamate levels followed by monoamine neurotransmitter deficiency and depressive-like behaviour, and DD modelling promoted autophagosome formation and caused mitochondrial impairment, eventually leading to hippocampal neuron apoptosis via aberrant Glu-GluR2-Parkin pathway. Further, in vitro study demonstrated that the simulated DD conditions resulted in an abnormal glutamate and monoamine neurotransmitter levels followed by autophagic flux increment, mitochondrial membrane potential reduction and mitochondrial reactive oxygen species and lactic dehydrogenase elevation. Interestingly, both GluR2 and mammalian target of rapamycin (mTOR) receptor blocker aggravated mitophagy-induced hippocampal neuron apoptosis and abnormal expression of apoptotic protein. In contrast, both GluR2 and mTOR receptor agonist ameliorated those apoptosis in simulated DD conditions. Our findings revealed that mitophagy-mediated hippocampal neuron apoptosis, triggered by aberrant Glu-GluR2-Parkin pathway, is responsible for depressive-like behaviour and monoamine neurotransmitter deficiency in DD rats. This work provides promising molecular targets and strategy for the treatment of DD.

19.
Annu Rev Virol ; 8(1): 459-489, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34197186

RESUMO

Viral fusion glycoproteins catalyze membrane fusion during viral entry. Unlike most enzymes, however, they lack a conventional active site in which formation or scission of a specific covalent bond is catalyzed. Instead, they drive the membrane fusion reaction by cojoining highly regulated changes in conformation to membrane deformation. Despite the challenges in applying inhibitor design approaches to these proteins, recent advances in knowledge of the structures and mechanisms of viral fusogens have enabled the development of small-molecule inhibitors of both class I and class II viral fusion proteins. Here, we review well-validated inhibitors, including their discovery, targets, and mechanism(s) of action, while highlighting mechanistic similarities and differences. Together, these examples make a compelling case for small-molecule inhibitors as tools for probing the mechanisms of viral glycoprotein-mediated fusion and for viral glycoproteins as druggable targets.

20.
Zootaxa ; 4974(3): 504536, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34186584

RESUMO

The genus Casinaria Holmgren, 1859 (Hymenoptera, Ichneumonidae, Campopleginae) from China is revised. Nine new species are proposed (C. albifunda sp. nov., C. artivultis sp. nov., C. exilis sp. nov., C. exiloides sp. nov., C. hei sp. nov., C. melasoma sp. nov., C. partolstoyi sp. nov., C. remota sp. nov., and C. xui sp. nov.) and two species are recorded as new to China (C. ajanta Maheshwary Gupta and C. varuni Maheshwary Gupta). A key to the Chinese species of Casinaria is provided.


Assuntos
Himenópteros/classificação , Animais , China
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