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1.
Minerva Anestesiol ; 90(4): 254-262, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38652448

RESUMO

BACKGROUND: We aimed to compare the analgesic effects and incidence of urinary retention between ultrasound-guided intersphincteric space block combined with low-dose ropivacaine spinal anesthesia and conventional-dose ropivacaine spinal anesthesia post-hemorrhoidectomy. METHODS: Fifty patients aged 20-65 years who underwent elective hemorrhoidectomy were stochastically assigned to one of two groups. Spinal anesthesia was induced with 8 mg ropivacaine, combined with ultrasound-guided intersphincteric space block in the treatment group. Spinal anesthesia was induced with 12 mg ropivacaine in the control group. The primary outcome was the postoperative pain score, measured using the Visual Analog Scale (VAS) at 4, 8, 12, 24, and 48 hours and at the first defecation postoperatively. Secondary outcomes included urinary retention, extent of anal sphincter relaxation, and the time required to lift the lower limbs out of bed postoperatively. RESULTS: The treatment group showed markedly lower VAS scores than those of the control group at 8, 12, 24, and 48 h, and at the first postoperative defecation time (P<0.05). The incidence of urinary retention was considerably lower in the treatment group than in the control group (24% vs. 52%, P=0.04). No remarkable difference in the degree of anal sphincter relaxation was observed between the two groups (P=0.556). The time taken by the treatment group patients to lift their lower limbs off the bed was much shorter than that in the control group (1.3±0.6 h vs. 3.2±1.2 h, P<0.001). CONCLUSIONS: Ultrasound-guided intersphincteric space block combined with low-dose ropivacaine spinal anesthesia provides good anesthesia and analgesia for hemorrhoidectomy.


Assuntos
Raquianestesia , Hemorroidectomia , Bloqueio Nervoso , Ultrassonografia de Intervenção , Humanos , Raquianestesia/métodos , Pessoa de Meia-Idade , Adulto , Masculino , Feminino , Hemorroidectomia/métodos , Bloqueio Nervoso/métodos , Idoso , Retenção Urinária/etiologia , Adulto Jovem , Ropivacaina/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Canal Anal , Hemorroidas/cirurgia , Anestésicos Locais/administração & dosagem
2.
Fish Shellfish Immunol ; 144: 109307, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38122953

RESUMO

Scavenger receptors (SRs) are pattern recognition receptors involved in the innate immune defense against pathogen infection in fish. However, there has not been much research done on teleosts. In this study, 18 members of the SR gene family were found in large yellow croaker. The identification of the SR gene family showed that the protein length of SR members in large yellow croaker were quite different, and most SR genes were distributed in nuclear and endoplasmic. The evolutionary relationship, exon/intron structure and motif analysis revealed that members of the SR gene family were highly conserved. The results of the expression profiles after Pseudomonas plecoglossicida infection and hypoxia-exposure demonstrated that SR members were involved in inflammatory reactions. Especially, COLEC12 and SCARF1 exhibited substantial changes in response to both P. plecoglossicida and hypoxia stress, indicating their possible immunological functions. The result of this study revealed that SR genes played a vital part in the innate immune response of large yellow croaker, and would give important details for a deeper comprehension of the SR gene family's regulation mechanism under various conditions in large yellow croaker.


Assuntos
Doenças dos Peixes , Perciformes , Infecções por Pseudomonas , Animais , Receptores Depuradores , Imunidade Inata/genética , Hipóxia/veterinária , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo
3.
Microorganisms ; 11(11)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38004752

RESUMO

Hfq is a global regulator and can be involved in multiple cellular processes by assisting small regulatory RNAs (sRNAs) to target mRNAs. To gain insight into the virulence regulation of Hfq in Vibrio harveyi, the hfq null mutant, ∆hfq, was constructed in V. harveyi strain 345. Compared with the wild-type strain, the mortality of pearl gentian sharply declined from 80% to 0% in ∆hfq when infected with a dose that was 7.5-fold the median lethal dose (LD50). Additionally, ∆hfq led to impairments of bacterial growth, motility, and biofilm formation and resistance to reactive oxygen species, chloramphenicol, and florfenicol. A transcriptome analysis indicated that the expression of 16.39% genes on V. harveyi 345 were significantly changed after the deletion of hfq. Without Hfq, the virulence-related pathways, including flagellar assembly and bacterial chemotaxis, were repressed. Moreover, eleven sRNAs, including sRNA0405, sRNA0078, sRNA0419, sRNA0145, and sRNA0097, which, respectively, are involved in chloramphenicol/florfenicol resistance, outer membrane protein synthesis, electron transport, amino acid metabolism, and biofilm formation, were significantly down-regulated. In general, Hfq contributes to the virulence of V. harveyi 345 probably via positively regulating bacterial motility and biofilm formation. It is involved in flagellar assembly and bacterial chemotaxis by binding sRNAs and regulating the target mRNAs.

5.
J Psychiatr Res ; 165: 64-69, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37463539

RESUMO

Depressed individuals are excessively sensitive to negative information but blunt to positive information, which has been considered as vulnerability to depression. Here, we focused on inhibitory control over attentional bias on social evaluation in individuals with depression. We engaged individuals with and without depressive symptoms (categorized by Beck Depression Inventory-II) in a novel attention control task using positive and negative evaluative adjectives as self-referential feedback given by social others. Participants were instructed to look at sudden onset feedback targets (pro-saccade) or the mirror location of the targets (anti-saccade) when correct saccade latencies and saccade errors were collected. The two indices showed that while both groups displayed longer latencies and more errors for anti-saccade relative to pro-saccade responses depressed individuals spent more time reacting correctly and made more errors than non-depressed individuals in the anti-saccade trials and such group differences were not observed in the pro-saccade trials. Although group differences in correct anti-saccade latencies were found for both positive and negative stimuli, depressed individuals spent more time making correct anti-saccade responses to negative social feedback than to positive ones whereas non-depressed individuals featured longer correct anti-saccade latencies for positive relative to negative evaluations. Our results suggest that depressed individuals feature an impaired ability in attention control for self-referential evaluations, notably those of negative valence, shedding new light on depression-distorted self-schema and corresponding social dysfunctions.

6.
J Hazard Mater ; 452: 131314, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37030222

RESUMO

The accumulation of volatile fatty acids (VFAs) caused by antibiotic inhibition significantly reduces the treatment efficiency of sulfamethoxazole (SMX) wastewater. Few studies have been conducted to study the VFAs gradient metabolism of extracellular respiratory bacteria (ERB) and hydrogenotrophic methanogen (HM) under high-concentration sulfonamide antibiotics (SAs). And the effects of iron-modified biochar on antibiotics are unknown. Here, the iron-modified biochar was added to an anaerobic baffled reactor (ABR) to intensify the anaerobic digestion of SMX pharmaceutical wastewater. The results demonstrated that ERB and HM were developed after adding iron-modified biochar, promoting the degradation of butyric, propionic and acetic acids. The content of VFAs reduced from 1166.0 mg L-1 to 291.5 mg L-1. Therefore, chemical oxygen demand (COD) and SMX removal efficiency were improved by 22.76% and 36.51%, and methane production was enhanced by 6.19 times. Furthermore, the antibiotic resistance genes (ARGs) such as sul1, sul2, intl1 in effluent were decreased by 39.31%, 43.33%, 44.11%. AUTHM297 (18.07%), Methanobacterium (16.05%), Geobacter (6.05%) were enriched after enhancement. The net energy after enhancement was 0.7122 kWh m-3. These results confirmed that ERB and HM were enriched via iron-modified biochar to achieve high efficiency of SMX wastewater treatment.


Assuntos
Sulfametoxazol , Águas Residuárias , Anaerobiose , Reatores Biológicos , Antibacterianos/farmacologia , Ácidos Graxos Voláteis , Bactérias , Preparações Farmacêuticas , Metano
7.
Curr Pharm Biotechnol ; 24(13): 1708-1714, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36959153

RESUMO

BACKGROUND: Hypertensive nephropathy (HN) is one kind of kidney disorders caused by long-term uncontrolled hypertension, usually resulting in severe kidney damage, including inflammation and oxidative stress, no matter in cells or tissues, from patients with nephropathy. In recent years, nephropathy accompanied by hypertension is becoming one of the main causes for kidney replacement therapy, but few effective treatments have been reported for HN treatment. Asystasia chelonoides (AC) is a kind of plant with the effects of anti-inflammation, lowering blood pressure, and anti-oxidative stress. Still, the therapeutic effect of AC in HN rats is not clear. METHODS: To establish HN model by feeding high sugar and high fat diet spontaneously hypertensive rats. Blood measurement, HE staining, PAS staining and biochemical analysis and were used to assess the therapeutic effects of AC extracts and western blotting analyzed the underlying mechanisms of AC extracts treatment in the HN rat model. RESULTS: AC extracts could significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in HN rats; and reduce the expression of total protein (TP), blood urea nitrogen (BUN), microalbuminuria (MALB), creatinine (Cr), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) concentrations, and also could down-regulate expression of IL-6, MDA and AGEs, up-regulate the expression of SOD in HN rats; HE staining and PAS staining demonstrated that AC extracts could alleviate the histopathological changes in HN rats; western blotting demonstrated that AC extracts could up-regulate the expression of PPARγ and down-regulate the expression of TGFß1 and NF-кB in HN rats. CONCLUSION: The finding of the article demonstrated that AC extracts had the better therapeutic effect for HN, and provided the pharmacological evidences for AC extracts treatment for HN.


Assuntos
Hipertensão Renal , Hipertensão , Ratos , Animais , Hipertensão Renal/complicações , Hipertensão Renal/patologia , Hipertensão/tratamento farmacológico , Ratos Endogâmicos SHR , Colesterol , Rim , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
8.
Sci Total Environ ; 859(Pt 1): 160305, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36410487

RESUMO

The transmission of antibiotic resistance genes (ARGs) affects the safety of aquaculture animals. Dissolved oxygen (DO) can affect the transmission of ARGs, but its mechanism of action in this process is unclear. We conducted laboratory breeding experiment with low and control DO groups. Combined quantitative PCR and 16S rRNA sequencing to study the effect of DO on the spread of ARGs. Hypoxia treatment significantly increased the accumulation of ammonium and nitrite in aquaculture water, and it increased the relative abundances of ARGs and mobile genetic elements (MGEs), especially the ARGs resistant to drugs in the categories of sulfonamide, (flor)/(chlor)/(am)phenicol, and MLSB (macrolide, lincosamide and streptogramin B) and the MGE intI-1(clinic), by 2.39-95.69 % in 28 days relative to the control DO treatment. Though the abundance of ARG carries, especially the Rhodocyclaceae, Caldilineaceae, Cyclobacteriaceae, Saprospiraceae, Enterobacteriaceae, Sphingomonadaceae families, showed higher abundance in low DO groups, relating to the vertical transmission of ARGs. Hypoxia treatment is more likely to promote the horizontal gene transfer (HGT)-related pathways, including ABC transporters, two component system, and quorum sensing, thus to induce the HGT of ARGs. The changed bacterial proliferation also altered the abundance of MGEs, especially intI-1(clinic), which induced HGT of ARGs as well. Additionally, pearson correlation results revealed that the succession of bacterial community function played the strongest role in ARG proliferation, followed by bacterial community structure and MGEs. Our results highlight the importance of suitable DO concentration in controlling the spread of ARGs especially the HGT of ARGs. In the context of global attention to food safety, our results provide important information for ensuring the safety of aquatic products and the sustainable development of aquaculture.


Assuntos
Antibacterianos , Genes Bacterianos , Animais , Antibacterianos/farmacologia , Antibacterianos/análise , RNA Ribossômico 16S , Resistência Microbiana a Medicamentos/genética , Aquicultura , Hipóxia , Proliferação de Células
9.
Cell Signal ; 100: 110470, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36122885

RESUMO

Trefoil factor 3 (TFF3, also known as intestinal trefoil factor) is a small-molecule peptide containing a typical trefoil structure. TFF3 has several biological effects, such as wound healing, immune regulation, neuroprotection, and cell migration and proliferation promotion. Although TFF3 binding sites were identified in rat kidneys more than a decade ago, the specific effects of this small-molecule peptide on kidneys remain unclear. Until recently, much of the research on TFF3 in the kidney field has focused exclusively on its role as a biomarker. Notably, a large prospective randomized study of patients with 29 common clinical diseases revealed that chronic kidney disease (CKD) was associated with the highest serum TFF3 levels, which were 3-fold higher than in acute gastroenteritis, which had the second-highest levels. Examination of each stage of CKD revealed that urine and serum TFF3 levels significantly increased with the progression of CKD. These results suggest that the role of TFF3 in CKD needs further research. The present review summarizes the renal physiological expression, biological functions, and downstream signaling of TFF3, as well as the upstream events that lead to high expression of TFF3 in CKD.

10.
J Ethnopharmacol ; 292: 115165, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35247475

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown. AIM OF THE STUDY: To clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms. MATERIALS AND METHODS: We used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined. RESULTS: FTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80+ macrophage cell infiltration and Ly-6G+ neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ. CONCLUSION: FTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Animais , LDL-Colesterol , Colágeno , Diabetes Mellitus/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Inflamação/tratamento farmacológico , Interleucina-17 , Rim , Masculino , Medicina Tradicional Chinesa , Camundongos , NF-kappa B , Proteinúria/tratamento farmacológico
11.
Sci Rep ; 12(1): 2828, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35181731

RESUMO

This study aimed to evaluate the effects of the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) on cartilage injury in an osteoarthritis (OA) rat model. Sodium iodoacetate (3 mg/50 µL) was used to induce OA in the left knee joint of rats. On day 14 after OA induction, 50 µL of SVF (5 × 106cells), ADSCs (1 × 106 cells), or 0.9% normal saline (NS) was injected into the left knee-joint cavity of each group. The macroscopic view and histological sections revealed that the articular cartilage in the NS group was damaged, inflamed, uneven and thin, and had hyperchromatic cell infiltration. Notably, the cartilage surface had recovered to nearly normal and appeared smooth and bright on day 14 in the SVF and ADSC groups. Additionally, the white blood cell counts in the SVF and ADSC groups were higher than those in the NS group on day 14. Plasma IL-1ß levels on days 7 and 14 were reduced in the SVF and ADSC groups. These results indicated that both SVF and ADSC treatments may assist in articular cartilage regeneration after cartilage injury. Cell therapy may benefit patients with OA. However, clinical trials with humans are required before the application of SVF and ADSC treatments in patients with OA.


Assuntos
Cartilagem Articular/crescimento & desenvolvimento , Terapia Baseada em Transplante de Células e Tecidos , Osteoartrite/terapia , Fração Vascular Estromal/transplante , Adipócitos/transplante , Animais , Cartilagem Articular/patologia , Modelos Animais de Doenças , Humanos , Células-Tronco Mesenquimais , Osteoartrite/patologia , Ratos , Regeneração/genética
12.
Sci Total Environ ; 820: 153312, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35065128

RESUMO

Constructed wetlands have been widely used for organic wastewater treatment owing to low operating costs and simple maintenance. However, there are some disadvantages such as unstable efficiency in winter. In this study, a microalgal electroactive biofilm-constructed wetland was coupled with anaerobic digestion for full-scale treatment of swine wastewater. In a 12-month outdoor trial, the overall removal efficiencies of chemical oxygen demand, ammonium, nitrate, total nitrogen, total phosphorus, and nitrite reached 98.26%/95.14%, 97.96%/92.07%, 85.45%/66.04%, 95.07%/91.48%, 91.44%/91.52%, and 85.45%/84.67% in summer/winter, respectively. Hydrolytic bacteria were dominant in the anaerobic digestion part, and Cyanobium, Shewanella, and Azoarcus were enriched in the microalgal electroactive biofilm. The operating cost of the entire system was approximately 0.118 $/m3 of wastewater. These results confirm that the microalgal electroactive biofilm significantly enhances the efficiency and stability of constructed wetlands. In conclusion, the anaerobic digestion-microalgal electroactive biofilm-constructed wetland is technically and economically feasible for the treatment of swine wastewater.


Assuntos
Microalgas , Purificação da Água , Anaerobiose , Animais , Nitrogênio/análise , Suínos , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias , Purificação da Água/métodos , Áreas Alagadas
13.
Cell Death Dis ; 13(1): 62, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039476

RESUMO

Trefoil factor 3 (TFF3) is the last small-molecule peptide found in the trefoil factor family, which is mainly secreted by intestinal goblet cells and exerts mucosal repair effect in the gastrointestinal tract. Emerging evidence indicated that the TFF3 expression profile and biological effects changed significantly in pathological states such as cancer, colitis, gastric ulcer, diabetes mellitus, non-alcoholic fatty liver disease, and nervous system disease. More importantly, mucosal protection would no longer be the only effect of TFF3, it gradually exhibits carcinogenic activity and potential regulatory effect of nervous and endocrine systems, but the inner mechanisms remain unclear. Understanding the molecular function of TFF3 in specific diseases might provide a new insight for the clinical development of novel therapeutic strategies. This review provides an up-to-date overview of the pathological effects of TFF3 in different disease and discusses the binding proteins, signaling pathways, and clinical application.


Assuntos
Fator Trefoil-3 , Doença , Humanos , Transdução de Sinais , Fator Trefoil-3/genética
14.
Sci Total Environ ; 819: 153120, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35041966

RESUMO

Antibiotic resistance genes (ARGs) have drawn increasing attention as novel environmental pollutants because of the threat they impose on human and animal health. The sea bass (Lateolabrax maculatus) is the third most cultured marine fish in China. Therefore, a study of ARG pollution in the sea bass culture environment is of great significance for the healthy and sustainable development of the sea bass industry. Here, we systematic investigated the contents of 23 antibiotic resistance-related genes (ARRGs), including 19 ARGs and four mobile genetic elements, and analyzed bacterial community composition and environmental parameters in sea bass ponds. The relative abundance (ARRG copies/16S ribosomal RNA gene copies) of ARRGs was up to 3.83 × 10-2. Sul1 was the most abundant ARRG, followed by ereA, intI-1, sul2, dfrA1, and aadA. Both the ARRG changes and aquatic microbiota succession were mainly driven by water temperature (WT), dissolved oxygen (DO), and NO3-. WT is positively correlated with the most ARGs and some of the top 38 Operational Taxonomic Units (OTUs) belonging to the orders of Frankiales, Micrococcales, Chitinophagales, and Sphingomonadales. Furthermore, WT is negatively related with some other OTUs of the orders Frankiales, Xanthomonadales, Micrococcales, and Rhizobiales. However, DO and NO3- have the opposite function with WT on specific taxa and ARGs. These results indicate that sea bass ponds are reservoirs of ARGs, and are driven mainly by the nutrient, temperature, and oxygen with inducing specific microbial taxa. The regulation of environmental factors (increasing DO and NO3-) can be conducted to reduce drug resistance risk in aquaculture ponds. Therefore, environmental factors and specific taxa could be the indicators of ARG contamination and can be used to establish an antibiotic elimination system and consequently realize a sustainable aquaculture industry.


Assuntos
Bass , Lagoas , Animais , Antibacterianos/farmacologia , China , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Nutrientes , Oxigênio , Temperatura
15.
Microb Pathog ; 157: 104965, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34015493

RESUMO

Vibrio harveyi is a Gram-negative bacterium that occurs widely in the ocean and a kind of pathogenic bacteria associated with vibriosis in grouper. We investigated whether the VscCD protein of the type Ⅲ secretion system (T3SS) was important for pathogenicity of V. harveyi. Mutations to the vscC and vscD genes (ΔvscCD) and complementation of the ΔvscCD mutant (C-ΔvscCD) were created. Moreover, the biological characteristics of the wild-type (WT) and mutant strains of V. harveyi 345 were compared. The results showed that deletion of the vscCD genes had no effect on bacterial growth, swimming/swarming ability, secretion of extracellular protease, or biofilm formation. However, as compared with the V. harveyi 345: pMMB207 (WT+) and complementary (C-ΔvscCD) strains, the ΔvscCD: pMMB207 (ΔvscCD+) mutant displayed decreased resistance to acid stress, H2O2, and antibiotics. In addition, infection of the pearl gentian grouper (♀Epinephelus fuscoguttatus × â™‚Epinephelus lanceolatu) showed that as compared with the WT+ and C-ΔvscCD strains, the ΔvscCD+ strain significantly reduced cumulative mortality of the host. The colonization ability of the ΔvscCD+ mutant in the spleen and liver tissues of the pearl gentian grouper was significantly lower than that of the WT+ and C-ΔvscCD strains. In the early stage of infection with the ΔvscCD+ strain, the expression levels of IL-1ß, IL-16, TLR3, TNF-α, MHC-Iα, and CD8α were up-regulated to varying degrees. As compared with the WT+ and C-ΔvscCD strains, luxR expression was significantly up-regulated in the ΔvscCD+ strain, while the expression of vcrH and vp1668 was significantly down-regulated. As an important component of the T3SS, VscCD seemed to play a significant role in the pathogenesis of V. harveyi.


Assuntos
Doenças dos Peixes , Vibrioses , Vibrio , Animais , Peróxido de Hidrogênio , Sistemas de Secreção Tipo III/genética , Vibrio/genética , Vibrioses/veterinária
16.
J Ethnopharmacol ; 274: 114056, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33771638

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi formula (FTZ) of which a patented preparation of Chinese herbal medicine has been well documented with significant clinical curative effect for hyperglycemia and hyperlipidemia. Because of the complexity of the chemical constituents of Chinese herbal formulas, the holistic pharmacological mechanism of FTZ acting on type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) remains unclear. AIM OF THE STUDY: To investigate the pharmacological efficacy and mechanism of FTZ in the treatment of T2DM accompanied by NAFLD. MATERIALS AND METHODS: Network pharmacology and validation in minipigs were used in this study. First, potential bioactive compounds of FTZ were identified by the traditional Chinese medicine system pharmacology technology platform (TCMSP). Then, targets of compounds were gathered using DrugBank, SwissTargetPrediction and TCMSP, while targets for T2DM and NAFLD were collected from CTD (compounds-targets-diseases network) and GeneCards. Common targets were defined as direct therapeutic targets acting on T2DM with NAFLD. In addition, crucial targets were chosen by the protein-protein interaction (PPI) network and contribution to compound-therapeutic targets in T2DM with the NAFLD network. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the metabolism-related signaling pathways affected by FTZ. Candidate patterns selected by network pharmacology were tested in the minipigs model of T2DM with NAFLD. Measurements of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS) and fasting blood glucose (FBG) in the blood and the expression levels of proteins, including PI3K-AKT and HIF-1α, in the livers of the minipigs were followed by the administration of FTZ. RESULTS: A total of 116 active compounds and 82 potential targets related to T2DM and NAFLD were found. Pathway and functional enrichment analysis showed that FTZ mainly regulates metabolism-related pathways, including PI3K-AKT, HIF-1α, TNFα and MAPK. Animal experiments showed that FTZ treatment significantly reduced the serum levels of TG, TC, LDL-C and FBG, increased serum levels of HDL-C, ameliorated systemic insulin resistance (IR), and attenuated liver damage in minipigs with T2DM and NAFLD. FTZ treatment has an obviously favorable influence on hepatic steatosis and liver lipid accumulation in the histopathologic features of HE, Oil red O staining, and electron microscopy. Mechanistically, FTZ improved liver metabolism by increasing the phosphorylation of PI3K-AKT and decreasing the expression of HIF-1α. CONCLUSION: Network pharmacology was supported by experimental studies, which indicated that FTZ has demonstrated therapeutic benefits in T2DM and NAFLD by regulating the PI3K-AKT and HIF-1α signaling pathways.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Glicemia/efeitos dos fármacos , Cápsulas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Insulina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Farmacologia/métodos , Fosfatidilinositol 3-Quinases/metabolismo , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reprodutibilidade dos Testes , Suínos , Porco Miniatura
17.
PLoS Genet ; 16(5): e1008763, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32384077

RESUMO

The ACK family tyrosine kinase SID-3 is involved in the endocytic uptake of double-stranded RNA. Here we identified SID-3 as a previously unappreciated recycling regulator in the Caenorhabditis elegans intestine. The RAB-10 effector EHBP-1 is required for the endosomal localization of SID-3. Accordingly, animals with loss of SID-3 phenocopied the recycling defects observed in ehbp-1 and rab-10 single mutants. Moreover, we detected sequential protein interactions between EHBP-1, SID-3, NCK-1, and DYN-1. In the absence of SID-3, DYN-1 failed to localize at tubular recycling endosomes, and membrane tubules breaking away from endosomes were mostly absent, suggesting that SID-3 acts synergistically with the downstream DYN-1 to promote endosomal tubule fission. In agreement with these observations, overexpression of DYN-1 significantly increased recycling transport in SID-3-deficient cells. Finally, we noticed that loss of RAB-10 or EHBP-1 compromised feeding RNAi efficiency in multiple tissues, implicating basolateral recycling in the transport of RNA silencing signals. Taken together, our study demonstrated that in C. elegans intestinal epithelia, SID-3 acts downstream of EHBP-1 to direct fission of recycling endosomal tubules in concert with NCK-1 and DYN-1.


Assuntos
Proteínas de Caenorhabditis elegans/fisiologia , Citocinese/genética , Dinaminas/fisiologia , Endocitose/fisiologia , Endossomos/metabolismo , Proteínas Tirosina Quinases/fisiologia , Proteínas de Transporte Vesicular/fisiologia , Animais , Animais Geneticamente Modificados , Transporte Biológico/genética , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Endocitose/genética , Estudo de Associação Genômica Ampla , Transdução de Sinais/genética , Proteínas rab de Ligação ao GTP/metabolismo
18.
J Ethnopharmacol ; 253: 112616, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32007631

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Renshen Shouwu extract (RSSW) is a patented Traditional Chinese Medicine included in Chinese Pharmacopoeia for neurasthenia, forgetfulness, insomnia, inappetence and excessive fatigue. Our previous study had demonstrated the neuroprotective effect of RSSW against ischemic stroke in rats with middle cerebral artery occlusion (MCAO). However, its underlying mechanism remains unknown. AIM OF THE STUDY: In this study, we investigated the neurogenesis and angiogenesis effects of RSSW in ischemic stroke rats, and further revealed its underlying mechanism focused on TLR4/NF-κB/NLRP3 signaling pathway. MATERIALS AND METHODS: Firstly, active compounds of RSSW were determined by High Performance Liquid Chromatography (HPLC). Secondly, Middle cerebral artery occlusion (MCAO) was performed to induce ischemic stroke in rats and 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was employed to evaluate whether MCAO surgery was successfully established. Neurological deficit evaluation was conducted according to the Zea Longa' method. Then, we explored the neurogenesis and angiogenesis effects after oral administration of RSSW (50 mg/kg, 100 mg/kg) in MCAO-induced rats by Immunofluorescence Staining. Moreover, the proteins involved in TLR4/NF-κB/NLRP3 signaling pathway (TLR4, p-NF-κB p65, NF-κB p65, NLRP3, pro-IL-1ß, IL-1ß, pro-Caspase-1, Caspase-1) were determined by western blotting. RESULTS: It was observed that RSSW treatment significantly increased the number of newborn neurons and brain microvessel density (MVD) after ischemic stroke. What's more, RSSW treatment significantly downregulated TLR4, p-NF-κB p65/p65, NLRP3, pro-IL-1ß, IL-1ß, pro-Caspase-1, Caspase-1 proteins involved in TLR4/NF-κB/NLRP3 signaling pathway. CONCLUSIONS: RSSW enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 inflammatory signaling pathway following ischemic stroke in rats. Hence, RSSW may be a promising Chinese Medicine for the treatment of ischemic stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Panax/química , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Masculino , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Acidente Vascular Cerebral/fisiopatologia , Receptor 4 Toll-Like/metabolismo
19.
ACS Sens ; 4(10): 2588-2592, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31613098

RESUMO

This letter reports on a novel cost-efficient and multifunctional barcode-like sensors array (BLSA) printed with a conductive bioinspired smart ink. The conductive  ink (P@G ink), which can be further chemically engineered with different organic ligands, was generated via facile one-pot hydrothermal reduction of graphene oxide (GO) in dopamine (DA) as coreductan Usingvarious  chemical derivatives of the P@G inks on a flexible substrate (e.g., Kapton), a highly integrated BLSA as well as smart nose/tongue mimic array were generated for simultaneous sensing and distinguishing of complex physical and chemical stimuli, including temperature, light, air pressure, relative humidity, and volatile organic compounds (VOCs). Due to these very attractive features, the reported P@G ink-based BLSA would have the potential for unique opportunities regarding "all-in-one"-yet cost-effective-disposable electronics and sensors.


Assuntos
Equipamentos e Provisões Elétricas , Tinta , Pressão do Ar , Biomimética , Dopamina , Grafite , Umidade , Luz , Temperatura , Compostos Orgânicos Voláteis
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