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1.
Food Chem ; 339: 128106, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152886

RESUMO

It is practical to inhibit the allergenicity of ß-lactoglobulin (ß-LG) using natural products acting via noncovalent interactions; however, the mechanism of the effect has not been investigated in detail. Herein, the comprehensive noncovalent mechanism of inhibition of the antigenicity of ß-LG by six flavonoids (kaempferol, myricetin, phloretin, epigallocatechin-3-gallate (EGCG), naringenin, and quercetin) was investigated by spectroscopic and molecular docking methods. Our results indicate that six flavonoids reduced the antigenicity of ß-LG in the following order: EGCG > phloretin > naringenin > myricetin > kaempferol > quercetin, with antigenic inhibition rates of 72.6%, 68.4%, 59.7%, 52.3%, 51.4% and 40.8%, respectively. Six flavonoids induced distinct conformational changes in ß-LG, which were closely associated with a decline in antigenicity of ß-LG. The flavonoids bound to specific antigen epitopes in the ß-sheet and ß-turn of ß-LG to induce a decrease in the antigenicity of the protein.

2.
Food Chem ; 339: 128088, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979714

RESUMO

Flavonol glycosides are associated with astringency and bitterness of teas. To clarify the dominant enzymatic reaction of flavonol glycosides in tea leaves, the catalytic effects of polyphenol oxidase (PPO), peroxidase (POD) and ß-glucosidase were studied, with the maintaining rates of total flavonol glycosides (TFG) being 73.0%, 99.8% and 94.3%. PPO was selected for further investigations, including the effects of pH value (3.5 ~ 6.5), temperature (25 °C ~ 55 °C) and dosage (39 ~ 72 U/mL PPO and 36 U/mL PPO, 3 ~ 36 U/mL POD). The oxidation of flavonol glycosides were intensified at pH 6.5, with 51.8% and 15.4% of TFG maintained after PPO and PPO + POD treatments, suggesting an enhancement from POD. The sensitivity ranking to PPO was: myricetin glycosides > quercetin glycosides > kaempferol glycosides. The inhibitor treatment testified the leading role of PPO in catalyzing flavonol glycosides in tea leaves. Sugar moiety enhanced the docking affinity of flavonol glycosides for PPO. PPO shows the potential of modifying flavonol glycoside composition.

3.
J Ethnopharmacol ; : 113548, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33152427

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Huangkui capsule (HKC), extracted from Abelmoschus manihot (L.) medic (AM), as a patent proprietary Chinese medicine on the market for approximately 20 years, has been clinically used to treat chronic glomerulonephritis. Renal fibrosis has been implicated in the onset and development of diabetic nephropathy (DN). However, the potential application of HKC for preventing DN has not been evaluated. AIM OF THE STUDY: This study was designed to investigate the efficacy and underlying mechanisms of HKC combined with metformin (MET), the first-line medication for treating type 2 diabetes, in the treatment of renal interstitial fibrosis. MATERIALS AND METHODS: A rat model of diabetes-associated renal fibrosis was established by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) combined with a high-fat and high-glucose diet. The rats were randomly divided into five groups: normal control, DN, HKC (1.0 g/kg/day), MET (100 mg/kg/d), and HKC plus MET (1.0 g/kg/day + 100 mg/kg/d). Following drug administration for 8 weeks, we collected blood, urine, and kidney tissue for analysis. Biochemical markers and metabolic parameters were detected using commercial kits. Histopathological staining was performed to monitor morphological changes in the rat kidney. High-glucose-induced human kidney HK-2 cells were used to evaluate the renal protective effects of HKC combined with MET (100 µg/mL+10 mmol/L). MTT assay and acridine orange/ethidium bromide were used to examine cell proliferation inhibition rates and apoptosis. Immunofluorescence assay and western blot analysis were performed to detect renal fibrosis-related proteins including Klotho, TGF-ß1, and phosphorylated (p)-p38. RESULTS: Combination therapy (HKC plus MET) significantly improved the weight, reduced blood glucose (BG), blood urea nitrogen (BUN), total cholesterol (T-CHO), triglycerides (TG), low-density lipoprotein (LDL) and increased the level of high-density lipoprotein (HDL) of DN rats. Combination therapy also significantly reduced urine serum creatinine (SCR) and urine protein (UP) levels as well as reduced the degrees of renal tubule damage and glomerulopathy in DN rats. Combination therapy ameliorated renal fibrosis, as evidenced by reduced levels of alpha-smooth muscle actin and fibronectin and increased expression of E-cadherin in the kidneys. Moreover, HKC plus MET alleviated the degree of DN in part via the Klotho/TGF-ß1/p38MAPK signaling pathway. In vitro experiments showed that combination therapy significantly inhibited cell proliferation and apoptosis and regulated fibrosis-related proteins in high-glucose (HG)-induced HK-2 cells. Further studies revealed that combination therapy suppressed cell proliferation and fibrosis by inhibiting the Klotho-dependent TGF-ß1/p38MAPK pathway. CONCLUSIONS: HKC plus MET in combination suppressed abnormal renal cell proliferation and fibrosis by inhibiting the Klotho-dependent TGF-ß1/p38MAPK pathway. Collectively, HKC combined with MET effectively improved DN by inhibiting renal fibrosis-associated proteins and blocking the Klotho/TGF-ß1/p38MAPK signaling pathway. These findings improve the understanding of the pathogenesis of diabetes-associated complications and support that HKC plus MET combination therapy is a promising strategy for preventing DN.

4.
Infect Dis Ther ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146854

RESUMO

INTRODUCTION: Sepsis is a complication in acute-on-chronic liver failure (ACLF) patients associated with high rates of mortality and morbidity. Early diagnosis of sepsis in ACLF patients can improve prognosis. This study aimed to explore potential effective biomarkers for the early diagnosis of sepsis in ACLF patients. METHODS: Ninety-four ACLF patients with sepsis were enrolled from 10 hospitals across China from January 2015 to June 2016 as well as 49 ACLF patients without infection from Xiangya Hospital. The first-day admission data and SOFA score and CLIF-SOFA score were collected. The differences of indicators between groups were compared with Kruskal-Wallis test. The receiver-operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency of the selected factors. RESULTS: Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) and presepsin were significantly higher in ACLF-sepsis patients compared with ACLF patients with no infection (P < 0.001). sTREM-1 and presepsin presented higher diagnostic value in sepsis for ACLF patients compared with other biomarkers [white blood cells (WBC), procalcitonin (PCT) and C-reactive protein (CRP)]. Combining sTREM-1 or presepsin with the CLIF-SOFA score increased the diagnostic efficiency (AUC = 0.876 or AUC = 0.913, respectively). CONCLUSIONS: sTREM-1 and presepsin are potential biomarkers for the early diagnosis of sepsis in ACLF patients. The combination of presepsin and the CLIF-SOFA score is a promising method for diagnosing sepsis in ACLF patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02457637.

5.
J Food Biochem ; : e13544, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33147650

RESUMO

Inflammation is a protective response of the immune defense system and inflammatory response could be regulated by autophagy. ß-Carotene has shown anti-inflammatory potential. However, whether ß-carotene could alleviate rat intestinal inflammation by modulating autophagy and its anti-inflammation underlying mechanisms remain unknown. In this study, we found that ß-carotene significantly reduced (p < .05) the production of nitric oxide (NO), prostaglandin (PG)E2, tumor necrosis factor (TNF)-α, and interleukin-1ß (IL-1ß) levels by the Griess reaction and enzyme-linked immunosorbent assay (ELISA), and we found that ß-carotene significantly suppressed (p < .05) the mRNA expression levels of IL-1ß and TNF-α by RT-PCR. In addition, H&E staining revealed that ß-carotene could improve intestinal morphology and cell morphology. Furthermore, the levels of signaling proteins of microtubule-associated protein light chain 3 (LC3), AKT, Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3), nuclear factor-kappa B (NF-κB), and c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) were detected by Western blot analysis. We found that ß-carotene significantly attenuated (p < .05) the related signaling proteins activated by lipopolysaccharide (LPS) stimulation in rats. Moreover, this conclusion was also verified in intestinal epithelial cell (IEC)-6. 3-Methyladenine (3-MA) is widely used as inhibitor of autophagy via its inhibitory effect on class III PI3K. Simultaneously, pretreatment of 3-MA suppressed the inhibiting effects of ß-carotene on the related signaling proteins. This study demonstrates that ß-carotene could attenuate the LPS-induced intestinal inflammation in rats via modulating autophagy and regulating the JAK2/STAT3 and JNK/p38 MAPK signaling pathways. We also found the same phenomenon when we verified the results with the IEC-6 cells. These findings provide new insights into improving the nutritional value of basic diets and enhancing immune performance. PRACTICAL APPLICATIONS: ß-Carotene is a generally acknowledged natural carotenoid nutrient that exhibits provitamin A activity, and it is widely found in fruits or vegetables. Our study provide a new insight into the anti-inflammatory mechanism of ß-carotene. Treatment with ß-carotene can be used for the beneficial effect against LPS-induced inflammation damage. This study not only lays the foundation for the related research on the anti-inflammatory properties of ß-carotene in vitro and in rat models, but also holds important significance in the field of food.

6.
J Orthop Surg Res ; 15(1): 546, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213494

RESUMO

BACKGROUND: Anemia is one of severe complications in the perioperative period of total hip arthroplasty (THA). Erythropoietin (EPO) has been considered to improve patients' anemia state, but its efficiency and safety remains controversial. METHODS: A total of 152 patients who underwent total hip arthroplasty from January 2017 to March 2019 were randomized to 2 groups. Recombinant human erythropoietin (rHu-EPO) group was treated with rHu-EPO subcutaneous injection 10000 IU after operation and once daily in the next week, while control group was treated with none extra treatment. Routine hematologic examination and thrombelastography (TEG) performed at different time point respectively. Doppler ultrasound for bilateral lower limbs was performed 1 day before surgery and 7 days after surgery. Auxiliary examination outcomes, blood transfusions outcomes, and postoperative complications were recorded as assessment indicators. RESULTS: The difference in the relevant indexes of traditional coagulation and TEG values between two groups were not significantly. No significant difference was observed in the incidence of thromboembolism events and other complications between two groups during postoperative period. The amount of intraoperative blood loss was similar between the two groups. However, the postoperative use and dosage of allogeneic blood in the rHu-EPO group were lower than those in the control group. The hemoglobin and hematocrit level in the rHu-EPO group were higher than that in the control group after surgery. CONCLUSION: Postoperative subcutaneous injection of rHu-EPO can improve hematological anemia-related parameters, reduce the use and dosage of allogeneic blood transfusions (ABTs), and has no significant influence on the formation of thrombosis and other complications in patients undergoing total hip arthroplasty in short term.

7.
BMC Infect Dis ; 20(1): 820, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172401

RESUMO

BACKGROUND: Respiratory infections are a serious threat to human health. So, rapid detection of all respiratory pathogens can facilitate prompt treatment and prevent the deterioration of respiratory disease. Previously published primers and probes of the TaqMan array card (TAC) for respiratory pathogens are not sensitive to Chinese clinical specimens. This study aimed to develop and improve the TAC assay to detect 28 respiratory viral and bacterial pathogens in a Chinese population. METHODS: To improve the sensitivity, we redesigned the primers and probes, and labeled the probes with minor groove binders. The amplification efficiency, sensitivity, and specificity of the primers and probes were determined using target-gene containing standard plasmids. The detection performance of the TAC was evaluated on 754 clinical specimens and the results were compared with those from conventional methods. RESULTS: The performance of the TAC assay was evaluated using 754 clinical throat swab samples and the results were compared with those from gold-standard methods. The sensitivity and specificity were 95.4 and 96.6%, respectively. The lowest detection limit of the TAC was 10 to 100 copies/µL. CONCLUSIONS: TAC is an efficient, accurate, and high-throughput approach to detecting multiple respiratory pathogens simultaneously and is a promising tool for the identification of pathogen outbreaks.


Assuntos
Bactérias/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções Respiratórias/diagnóstico , Vírus/genética , China/epidemiologia , Primers do DNA , Confiabilidade dos Dados , Humanos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Sensibilidade e Especificidade
8.
Artigo em Inglês | MEDLINE | ID: mdl-33185947

RESUMO

Streptococcus mutans (S. mutans) effectively utilizes dietary sucrose for the exopolysaccharide productions, which are mostly synthesized by the effects of glucosyltransferases (Gtfs). In the present study, the acetylome of S. mutans was identified and quantitative acetylome analysis of the bacterial biofilm growth (SMB) was compared with that of planktonic growth (SMP). The dynamic changes of protein acetylation were quantified using the integrated approach involving TMT labeling and Kac affinity enrichment followed by high-resolution mass spectrometry-based quantitative proteomics. In total, 973 acetylation sites in 445 proteins were identified, among which 617 acetylation sites in 302 proteins were quantitated. The overall analysis indicated that 22.7% of proteins were acetylated. Among the quantified proteins in SMB, the acetylation degree of lysine in 56 sites increased, while that of lysine decreased in 52 sites. In the acetylome of S. mutans, six significantly enriched motifs were identified and obtained including Kac****K, KacF, Kac****R, KacY, KacH, F*Kac. In addition, KEGG pathway-based enrichment analysis indicated significant enrichments in glycolysis/gluconeogenesis, and RNA degradation. Particularly, most downregulated acetylated lysine proteins were glucosyltransferase-SI, glucosyltransferase-I, and glucosyltransferase-S in S. mutans biofilm, which probably reveals a switch-off mechanism for the regulation of glucosyltransferases function during the biofilm development.

9.
Respir Physiol Neurobiol ; : 103587, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212243

RESUMO

The present study numerically investigated the transportation time of the inhaled chemicals in three realistic human airway models by adopting a methodology from the field of the building ventilation. Two indexes including "scale of ventilation efficiency 3 (SVE3)" and "local purging flow rate (L-PFR)" were used to evaluate the respective arrival time and staying time under different inhalation flow rates. The general trend of the SVE3 was predicted as expected and the exceptions of the nasal cavities were attributed to the uneven allocation of the inhaled flow between the internal channels and the formation of the vortex circulation there. The complicated situation of the L-PFR was also explained by the structure constrains. Moreover, the variation of the two indexes with the flow rate was sensitive to the inter-subjective differences but the distribution pattern was not changed significantly. By combining the SVE3 and L-PFR, it could help with assessing the potential effect of the inhaled chemicals on the human health for engineering applications to which the relative impacts are more interested than the absolute value. But for the precise evaluation regarding a specific chemical, comprehensive simulation is still necessary with the surface adsorption included under realistic respiration cycles.

10.
Ann Med ; : 1-24, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33183091

RESUMO

OBJECTIVE: To illustrate the effect of corticosteroids and heparin, respectively, on Coronavirus Disease 2019 (COVID-19) patients' CD8+ T cells and D-Dimer. METHODS: In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-Dimer, respectively. RESULTS: There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-Dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (ß = 0.154%, 95% CI=(0, 0.302), p = 0.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (ß = 0.163%, 95% CI=(0.027, 0.295), p = 0.020) significantly increased the rising rate of CD8+ T cell in 14 to 56 DFS. CONCLUSION: The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.

11.
BMC Urol ; 20(1): 182, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172469

RESUMO

BACKGROUND: Aggressive angiomyxoma (AA) is a rare tumor that typically occurs in the pelvis and perineum, most commonly in women of reproductive age. However, no para-ureteral AA has been reported according to the literature. Case presentation We herein describe the first case of para-ureteral AA. A 62-year-old male presented to our institute in March 2017 with a para-ureteral mass that was 15 mm in diameter incidentally. No symptom was observed and laboratory analysis was unremarkable. Magnetic resonance and computed tomography imaging showed a non-enhancing mass abutting the left ureter without causing obstruction. Laparoscopic resection of the mass was performed without injury to the ureter. Pathologic and immunohistochemical results were consistent with AA. Till now, no recurrence was noticed. CONCLUSIONS: We reported a rare case of para-ureteral AA, along with a literature review. Early diagnosis, proper surgical plan and long-term close follow-up is recommended for its high risk of recurrence and malignant potential.

13.
J Agric Food Chem ; 68(47): 14071-14080, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33196171

RESUMO

Amino acids are very important for oolong tea brisk-smooth mouthfeel which is mainly associated with bruising and withering treatment (BWT). In this study, metabolome and transcriptome analyses were performed to comprehensively investigate the changes in abundance of amino acids and the expression pattern of relevant genes during BWT of oolong tea manufacturing. Levels of most amino acids increased during BWT in the leaves harvested from 4 cultivars, while expression of the relevant function genes responsible for synthesis and transformation of amino acids up-regulated accordingly. Upstream hub genes including receptor-like protein kinase IKU2, serine/threonine-protein kinase PBL11, MYB transcription factor MYB2, ethylene-responsive transcription factor ERF114, WRKY transcription factor WRKY71, aspartate aminotransferase AATC, UDP-glycosyltransferase U91D1, and 4-hydroxy-4-methyl-2-oxoglutarate aldolase 2 RRAA2, were predicted to be involved in regulation of the function genes expression and the amino acids metabolism through weighted gene coexpression network analysis. A modulation mechanism for accumulation of amino acids during BWT was also proposed. These findings give a deep insight into the metabolic reprogramming mechanism of amino acids during BWT of oolong tea.

14.
Parasite ; 27: 65, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33231548

RESUMO

Enterocytozoon bieneusi is an intestinal pathogen that infects a wide range of species, including humans. Cattle constitute an important host for E. bieneusi; however, there is a scarcity of information on the prevalence and genotyping of E. bieneusi in cattle in the Hainan Province of China. In this study, PCR analysis of 314 fecal samples from cattle in six cities of Hainan was performed for genotype identification. The average prevalence of E. bieneusi in these animals was 9.9% (31/314), and ranged from 0.0% (0/12) to 20.5% (8/39). Five known genotypes - EbpC (n = 14), BEB4 (n = 12), J (n = 2), I (n = 1), and CHG5 (n = 1) - and a novel genotype: HNC-I (n = 1) - were identified. Genotypes EbpC and HNC-I were placed in zoonotic Group 1, and the remaining four genotypes (BEB4, J, I, and CHG5) were placed in Group 2. Since 93.5% of the genotypes found in the cattle (29/31) (EbpC, BEB4, J, and I) have previously been found in humans, these genotypes are probably involved in the transmission of microsporidiosis to humans.

15.
Bioorg Med Chem ; 29: 115876, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33246255

RESUMO

DDR1 is a receptor tyrosine kinase that is activated by triple-helical collagens and has become an attractive target for anticancer therapy given its involvement in tumor growth, metastasis development, and tumor dormancy. Several drugs on the market, such as dasatinib and nilotinib, were reported to potently suppress the function of DDR1 and show significant therapeutic benefits in a variety of preclinical tumor models. Whereas only a few selective DDR1 inhibitors were disclosed in recent years. A series of 4-amino-1H-pyrazolo[3,4-d]pyrimidin derivatives were designed and synthesized. All compounds were evaluated via DDR1 kinase inhibition assay and cell anti-proliferative assay. One of the representative compounds, 6c, suppressed DDR1 kinase activity with an IC50 value of 44 nM and potently inhibited cell proliferation in DDR1-overexpressing cell lines HCT-116 and MDA-MB-231 with IC50 value of 4.00 and 3.36 µM respectively. Further molecular docking study revealed that 6c fitted ideally into DDR1 binding pocket and maintained the crucial hydrogen bonds with DDR1 kinase domain. Overall, these results suggest that the compound 6c is a potential DDR1 inhibitor deserving further investigation for cancer treatment.

16.
Sci Rep ; 10(1): 20763, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247161

RESUMO

Hepatitis B virus (HBV) is the major causative factor of chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. We previously demonstrated that a proinflammatory cytokine IL-1ß reduced the level of HBV RNA. However, the mechanism underlying IL-1ß-mediated viral RNA reduction remains incompletely understood. In this study, we report that immune regulator Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) can reduce HBV RNA in hepatocytes. MCPIP1 expression level was higher in the liver tissue of HBV-infected patients and mice. Overexpression of MCPIP1 decreased HBV RNA, whereas ablating MCPIP1 in vitro enhanced HBV production. The domains responsible for RNase activity or oligomerization, were required for MCPIP1-mediated viral RNA reduction. The epsilon structure of HBV RNA was important for its antiviral activity and cleaved by MCPIP1 in the cell-free system. Lastly, knocking out MCPIP1 attenuated the anti-HBV effect of IL-1ß, suggesting that MCPIP1 is required for IL-1ß-mediated HBV RNA reduction. Overall, these results suggest that MCPIP1 may be involved in the antiviral effect downstream of IL-1ß.

17.
Virol Sin ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068260

RESUMO

The recent emergence and rapid global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose an unprecedented medical and socioeconomic crisis, and the disease caused by it, Coronavirus disease 2019 (COVID-19), was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Chinese scientists and physicians rapidly identified the causative pathogen, which turned out to be a novel betacoronavirus with high sequence similarities to bat and pangolin coronaviruses. The scientific community has ignited tremendous efforts to unravel the biological underpinning of SARS-CoV-2, which constitutes the foundation for therapy and vaccine development strategies. Here, we summarize the current state of knowledge on the genome, structure, receptor, and origin of SARS-CoV-2.

18.
Mol Brain ; 13(1): 143, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081841

RESUMO

Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1-/-) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1-/- mice was associated with decreased interleukin-1ß, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1-/- mice compared to WT mice at 7 d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.

19.
Sci Total Environ ; : 142959, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33121791

RESUMO

With the development of industry and human society, more attention was paid for the toxic effects of organic pollutants that are closely related to human daily life. Previous studies mainly focused on the dose-response relationship and cytotoxic effects of pollutants to organisms,while little research focused on pollutant-protein interactions at molecular level. However, the binding of organic pollutants to biomolecules, especially proteins like transporters, membrane receptor and nuclear receptors, is often the first step of toxic effects. It can make a series of endocrine disrupting and genotoxic effects through cell signaling pathway by binding specific target proteins including serum albumin, thyroid transporter, estrogen receptor, androgen receptor, and aryl hydrocarbon receptor. Thus, the research of interactions between organic pollutants and proteins is helpful and necessary to understand the distribution, metabolism and toxicity mechanism of compounds in organisms at the molecular level. This paper reviewed the latest research progress of the interaction types of persistent organic pollutants (POPs), emerging pollutants and some other pollutants with targeted proteins. In addition, we summarized several main experimental techniques for studying pollutant-protein interactions including ultraviolet/visible absorption spectrometry (UV-vis), fluorescence, infrared spectrometry, circular dichroic spectra (CD), molecular docking and X-ray crystallography. This review contributes to the molecular mechanism of the interaction between organic pollutants and biomolecules.

20.
Inhal Toxicol ; : 1-12, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33124512

RESUMO

OBJECTIVE: The exposure to airborne particles are of great concern in public health. The present study was aimed to clarify the effects of the breathing mode (nasal and oral inhalation) and exposure conditions on particle inhalation and deposition in human airway. METHODS: A scanned upper airway embedded body model in an extended computational domain was constructed to perform numerical investigation into the inhalation and deposition of airborne particles. RESULTS: It was clarified that the inhalation of sub-micro and micro particles was of high efficiency and insensitive to the breathing mode, while super microparticles were much less inhalable, in particular under the nasal intake. Moreover, the relative variation of environmental wind speed and direction could significantly reshape the breathing zone as well as modify the critical inhalable area at far upstream. In addition, the breathing mode was found to be affective on the regional deposition of the microparticles, and increasing the proportion of nasal inhalation flowrate slightly enhanced the total deposition in the upper airway model. CONCLUSION: The breathing mode and exposure conditions significantly influence the particle inhalability and deposition pattern in human airway, which should be considered in the evaluation of health risk associated with airborne particle exposure.

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