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1.
J Ethnopharmacol ; 300: 115688, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36067838

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, a long term of improper diet causes the Dampness and disturbs Zang-Fu's functions including Kidney deficiency. Atractylodes lancea (Atr) and Magnolia officinalis (Mag) as a famous herb pair are commonly used to transform Dampness, with kidney protection. AIM OF THE STUDY: To explore how Atr and Mag protected against insulin signaling impairment in glomerular podocytes induced by high dietary fructose feeding, a major contributor for insulin resistance in glomerular podocyte dysfunction. MATERIALS AND METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyze constituents of Atr and Mag. Rat model was induced by 10% fructose drinking water in vivo, and heat-sensitive human podocyte cells (HPCs) were exposed to 5 mM fructose in vitro. Animal or cultured podocyte models were treated with different doses of Atr, Mag or Atr and Mag combination. Western blot, qRT-PCR and immunofluorescence assays as well as other experiments were performed to detect adiponectin receptor protein 1 (AdipoR1), protein kinase B (AKT), Sirt1, p53 and miR-221 levels in rat glomeruli or HPCs, respectively. RESULTS: Fifty-five components were identified in Atr and Mag combination. Network pharmacology analysis indicated that Atr and Mag combination might affect insulin signaling pathway. This combination significantly improved systemic insulin resistance and prevented glomerulus morphological damage in high fructose-fed rats. Of note, high fructose decreased IRS1, AKT and AdipoR1 in rat glomeruli and cultured podocytes. Further data from cultured podocytes with Sirt1 inhibitor/agonist, p53 agonist/inhibitor, or miR-221 mimic/inhibitor showed that high fructose downregulated Sirt1 to stimulate p53-driven miR-221, resulting in insulin signaling impairment. Atr and Mag combination effectively increased Sirt1, and decreased p53 and miR-221 in in vivo and in vitro models. CONCLUSIONS: Atr and Mag combination improved insulin signaling in high fructose-stimulated glomerular podocytes possibly through upregulating Sirt1 to inhibit p53-driven miR-221. Thus, the regulation of Sirt1/p53/miR-221 by this combination may be a potential therapeutic approach in podocyte insulin signaling impairment.


Assuntos
Atractylodes , Água Potável , Resistência à Insulina , Magnolia , MicroRNAs , Podócitos , Animais , Proteínas de Transporte/metabolismo , Cromatografia Líquida , Água Potável/metabolismo , Frutose/efeitos adversos , Humanos , Insulina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptores de Adiponectina/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Espectrometria de Massas em Tandem , Proteína Supressora de Tumor p53/metabolismo
2.
J Ethnopharmacol ; 300: 115720, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36113677

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The leaf tea of Hyptis crenata has its practical use in the Brazilian Amazon for treating gastrointestinal and liver disorders, sweating induction, and as an anti-inflammatory. AIM OF THE STUDY: Evaluation of the chemical composition, acute oral toxicity, and antinociceptive and anti-inflammatory activities of the H. crenata essential oil. MATERIAL AND METHODS: The essential oil was hydrodistilled and analyzed by GC and GC-MS. The antinociceptive action in mice was evaluated for the peripheral and central analgesic activity (abdominal contortion and hot plate tests), and the xylene-induced ear swelling was carried out for the nociception test. RESULTS: Oxygenated monoterpenes (53.0%) and monoterpene hydrocarbons (38.9%) predominated in the H. crenata oil, being 1,8-cineo1e (35.9%), α-pinene (20.8%), camphor (10.0%), and ß-pinene (7.3%) their primary constituents. The oral oil administration in the mice did not display changes in behavior patterns or animal mortality at 300 and 2000 mg/kg doses. The control group's biochemical parameters (ALP, AST, ALT) displayed a statistical difference from the treated group, unlike the renal parameters, which showed no variation between the groups. Oil reduced the abdominal contortions at doses of 100 (79.5%) and 300 mg/kg (44.4%), while with endodontacin, the dose was 5 mg/kg (75.2%). In addition, the oil could not decrease the paw licking/biting time at doses of 30, 100, and 300 mg/kg. However, it showed a significant antinociceptive effect on the second phase in the formalin test inhibiting licking time, with a reduction of 50.8% (30 mg/kg), 63.4% (100 mg/kg), 58.0% (300 mg/kg), and morphine (4 mg/kg, 78.3%). The oil administration produced significant inhibition of ear edema at all tested doses, with a better effect produced at 30 mg/kg (64.0% inhibition). CONCLUSION: The oil of Hyptis crenata, rich in 1,8-cineole, camphor, α-pinene, and ß-pinene, totaling 74%, displayed low acute toxicity and significant anti-inflammatory activity, with peripheral and no central antinociceptive action. Thus, these results show an actual perspective on using H. crenata oil in developing a phytotherapeutic product.


Assuntos
Hyptis , Óleos Voláteis , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Monoterpenos Bicíclicos , Brasil , Cânfora/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Eucaliptol/uso terapêutico , Hyptis/química , Camundongos , Monoterpenos/farmacologia , Monoterpenos/uso terapêutico , Derivados da Morfina/efeitos adversos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Chá , Xilenos
4.
Braz. j. biol ; 83: e242818, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285628

RESUMO

Abstract The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .


Resumo O estudo teve como objetivo avaliar o impacto da dieta rica em gordura (HFD) e da microbiota intestinal humana sintética (GM) combinada com HFD e dieta alimentar (CD) na indução de diabetes tipo 2 (T2D) usando modelo de camundongos. Para nosso conhecimento, este é o primeiro estudo usando transplante de GM humano selecionado através do método baseado em cultura acoplada à modulação dietética em camundongos para o estabelecimento in vivo de inflamação que leva a T2D e disbiose intestinal. Vinte bactérias (T2D1-T2D20) de amostras de fezes de indivíduos T2D confirmados verificaram ser morfologicamente diferentes e foram submetidas à purificação em meios diferentes aerobicamente e anaerobicamente, o que revelou sete bactérias mais comuns entre 20 isolados com base na caracterização bioquímica. Com base no sequenciamento do gene 16S rRNA, esses sete isolados foram identificados como Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenides (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). Esses sete isolados foram, posteriormente, usados ​​como microbioma intestinal sintético (GM) por seu papel na indução de T2D em camundongos. Linhagens consanguíneas de camundongos albinos foram divididas em quatro grupos e foram alimentadas com CD, HFD, GM + HFD e GM + CD. Camundongos que receberam a dieta modificada com HFD e GM + (CD / HFD) mostraram um aumento altamente significativo (P < 0,05) no peso e na concentração de glicose no sangue, bem como um nível elevado de citocinas inflamatórias (TNF-α, IL-6 e MCP-1) em comparação com os ratos que receberam apenas CD. O sequenciamento do gene 16S rRNA de 11 bactérias fecais obtidas de três animais selecionados aleatoriamente de cada grupo revelou disbiose intestinal em animais que receberam GM. Cepas bacterianas, incluindo Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) e Lactobacillus Gasseri (MT152635D), foram tratadas com dieta modificada / CD) em comparação com as linhagens Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629), que foram isoladas de camundongos recebendo CD / HFD. Em conclusão, esses resultados sugerem que a constituição de GM e dieta desempenham papel significativo na inflamação levando ao início ou/e possivelmente à progressão de T2D.


Assuntos
Humanos , Animais , Coelhos , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Bacteroides , RNA Ribossômico 16S/genética , Prevotella , Bacteroidetes , Ruminococcus , Dieta Hiperlipídica/efeitos adversos , Disbiose , Inflamação , Camundongos Endogâmicos C57BL
5.
Ann Pharmacother ; 57(1): 51-54, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35652701

RESUMO

BACKGROUND: There are more than 350 reports of hyperglycemia post-influenza vaccine according to the Vaccine Adverse Effect Reporting System. Only one case report has been published detailing unusual post-vaccination hyperglycemia. The mechanism as to why hyperglycemia may occur post-vaccination has not been fully elucidated. OBJECTIVE: Primary: To identify hyperglycemia within the first 24 hours of influenza vaccine. Secondary: To identify transient property of hyperglycemia within 4 days after vaccine. METHODS: Multicenter prospective cohort study. Recruitment conducted throughout San Antonio, Texas, during 2018-2020 influenza seasons. Patients were included if 18 years or older, had diabetes mellitus, and currently checking their blood glucose daily. Patients excluded if they had a recent medication change that would effect their blood glucose readings. Patients had hemoglobin A1c and blood glucose measured prior to vaccination with a single dose (0.5 mL) of the tri-valent influenza vaccine intramuscularly. Glucose readings were collected within 24 hours post-vaccination and subsequent mornings for 4 days. RESULTS: A total of 34 patients were included. Average patient age was 75 years with 60% white, 30% black, and 10% Hispanic. Median fasting glucose pre-vaccination was significantly lower than the median value 0 to 24 hours post-vaccination (140 vs 203 mg/dL, P < 0.0001). CONCLUSION AND RELEVANCE: Hyperglycemia was noted 0 to 24 hours post-vaccination and was transient in nature with a return to baseline by post-vaccination day 2. This trial was conducted to close a potential gap in counseling regarding the flu vaccine and decrease any potential concern surrounding the vaccine in patients with diabetes that could lead to reduced vaccination rates.


Assuntos
Diabetes Mellitus , Hiperglicemia , Vacinas contra Influenza , Idoso , Humanos , Glicemia , Diabetes Mellitus/epidemiologia , Hemoglobina A Glicada , Hiperglicemia/diagnóstico , Vacinas contra Influenza/efeitos adversos , Influenza Humana/prevenção & controle , Estudos Prospectivos , Vacinação/efeitos adversos
6.
Artigo em Inglês | MEDLINE | ID: mdl-35988848

RESUMO

BACKGROUND: Previous studies suggest that paliperidone might show a better profile for social functioning and cognitive abilities than risperidone. We aimed to study whether switching from risperidone to paliperidone palmitate (PP) is associated with improved cognitive abilities at 3 or 6 months after the switch. METHODS: Thirty-eight patients with a DSM-IV diagnosis of schizophrenia were studied. All patients were treated with oral risperidone or risperidone long-acting injection (RLAI) and had an indication to be switched to PP by their psychiatrists. Statistical analyses were conducted in a final sample of 27 patients who completed the follow-up visits. Three assessments were completed: 1) baseline (preswitch), 2) 3 months postswitch, and 3) 6 months postswitch. Social functioning at each visit was assessed with the Personal and Social Performance Scale. Cognitive assessment was conducted at each visit with the MATRICS Consensus Cognitive Battery. Statistical analyses were performed with R. Linear mixed models were used to explore longitudinal changes in social functioning and cognitive outcomes. RESULTS: PSP scores significantly improved over time after the switch from risperidone to PP. A sensitivity analysis found a significant negative interaction between time and PP maintenance doses (greater improvement in those patients receiving lower doses when compared to higher doses). Regarding longitudinal changes in cognitive functioning, patients improved in 6 out of 10 cognitive tasks involving processing speed, working memory, visual memory, reasoning and problem solving, and attention and vigilance. CONCLUSIONS: Our study suggests that switching from risperidone to PP in patients with schizophrenia is associated with an improvement in social functioning and cognitive performance.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Palmitato de Paliperidona/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/induzido quimicamente , Interação Social , Antipsicóticos/efeitos adversos , Cognição , Preparações de Ação Retardada/uso terapêutico
7.
Artigo em Inglês | MEDLINE | ID: mdl-36150422

RESUMO

Prenatal exposure to maternal immune activation (MIA) and chronic adolescent cannabis use are both risk factors for neuropsychiatric disorders. However, exposure to a single risk factor may not result in major mental illness, indicating that multiple exposures may be required for illness onset. Here, we examine whether combined exposure to prenatal MIA and adolescent delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, lead to enduring neuroanatomical and behavioural changes in adulthood. Mice were prenatally exposed to viral mimetic, poly I:C (5 mg/kg), or vehicle at gestational day (GD) 9, and postnatally exposed to chronic THC (5 mg/kg, intraperitoneal) or vehicle during adolescence (postnatal day [PND]28-45). Longitudinal magnetic resonance imaging (MRI) was performed pre-treatment, PND 25, post-treatment, PND 50, and in adulthood, PND85, followed by behavioural tests for anxiety-like, social, and sensorimotor gating. Post-mortem assessment of cannabinoid (CB)1 and 2 receptor expressing cells was performed in altered regions identified by MRI (anterior cingulate and somatosensory cortices, striatum, and hippocampus). Subtle deviations in neurodevelopmental trajectory and subthreshold anxiety-like behaviours were observed in mice exposed to both risk factors. Sex-dependent effects were observed in patterns of shared brain-behaviour covariation, indicative of potential sex differences in response to MIA and THC. Density of CB1 and CB2 receptor positive cells was significantly decreased in all mice exposed to MIA, THC, or both. These findings suggest that there may be a cumulative effect of risk factor exposure on gross neuroanatomical development, and that the endocannabinoid system may be sensitive to both prenatal MIA, adolescent THC, or the combination.


Assuntos
Cannabis , Alucinógenos , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Animais , Camundongos , Feminino , Masculino , Humanos , Cannabis/efeitos adversos , Dronabinol/efeitos adversos , Endocanabinoides , Receptor CB2 de Canabinoide , Agonistas de Receptores de Canabinoides , Poli I-C/toxicidade
8.
Crit Care Clin ; 39(1): 171-213, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36333031

RESUMO

Clinicians must individualize pharmacotherapy for patients with acute neurological injury based on multiple factors, including age, comorbidities, and chronic medication use. Many pharmacokinetic and pharmacodynamic properties are altered during acute illness, particularly absorption, distribution, metabolism, and elimination, which may result in loss of drug effect or toxicity. This article provides clinicians with general pharmacologic knowledge of the following drug regimens commonly prescribed to neurocritically ill adults: sedatives, analgesics, osmotherapy, antiseizure medications, antishivering agents, vasoactive agents, and antithrombotic reversal agents.


Assuntos
Unidades de Terapia Intensiva , Neurofarmacologia , Adulto , Humanos , Hipnóticos e Sedativos/efeitos adversos , Analgésicos/farmacologia , Estado Terminal , Cuidados Críticos
9.
J Invest Surg ; 36(1): 1-10, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36341742

RESUMO

OBJECTIVE: To compare the recurrence rate and prognosis between minimally invasive surgical (MIS) approach and open surgical approach of endometrial carcinoma (EC) patients with different prognostic risk groups. METHODS: A retrospective analysis of all cases undergoing EC surgery between January 2011 and March 2018 was performed. The patients were grouped according to the management guidelines of EC patients jointly formulated by the ESGO/ESTRO/ESP 2020. Different surgical approaches were compared with regard to tumor characteristics, recurrence rate, disease-free survival (DFS), and overall survival (OS). RESULTS: A total of 665 patients met the inclusion criteria of which 196 patients underwent MIS (29.5%), and 469 patients underwent open surgery (70.5%). In the MIS group, there was a significant higher rate of recurrence (17.3% vs 6.6%, P = 0.000) compared to the open surgery group. The recurrence rate of MIS was 7.7% (P = 0.000) in the medium-high risk group and 8.2% (P = 0.014) in the high-risk group. Multivariate logistic regression analysis showed that the independent factors influencing recurrence included prognostic risk grouping, surgical approach and lymph vascular space invasion (LVSI) positivity (P < 0.05). K-M survival analysis revealed that in the intermediate and high-risk group of EC, MIS patients had a significantly lower DFS than those undergoing open surgery (P < 0.05), but no significant difference was found in OS. CONCLUSIONS: For patients with EC at moderate and high prognostic risk, MIS is associated with poorer DFS compared to open surgery, but OS was similar across prognostic risk groups. The application of MIS in patients with moderate and high-risk EC needs further research and analysis.


Assuntos
Neoplasias do Endométrio , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Intervalo Livre de Doença , Recidiva Local de Neoplasia/epidemiologia
10.
J Invest Surg ; 36(1): 1-7, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36350036

RESUMO

Background: Acute kidney injury (AKI) is a common complication in patients with severe acute pancreatitis (SAP). Caspase-11-mediated pyroptosis is essential for the progression of multiple diseases, but its role in SAP-induced AKI remains unknown.Aims: This research investigated whether caspase-11-mediated pyroptosis is involved in SAP-induced AKI and whether inhibiting caspase-11-mediated pyroptosis improves SAP-induced AKI.Methods: A rat model of SAP with AKI was established by slowly injecting 5% sodium taurocholate into the biliopancreatic duct, then wedelolactone (25 or 50 mg/kg), an inhibitor of caspase-11, was injected through the intra-peritoneum 1 and 6 h after SAP induction. Serum biochemical indexes, including serum amylase, lipase, interleukin (IL)-6, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-α, and creatinine (Cr) in rats, were evaluated using biochemical test kits. Caspase-11 and gasdermin D (GSDMD) expression in the kidney tissues was evaluated by western blotting and immunohistochemical staining. IL-1ß and IL-18 levels in kidney tissues were detected by ELISA kits. Furthermore, histopathological alterations of pancreas and kidney were assessed by H&E staining.Results: The serum biochemical indexes and pyroptosis-related proteins in kidney tissues were significantly increased after SAP induction. Furthermore, wedelolactone decreased the expression of pyroptosis-linked proteins in kidney tissues, reduced serum lipase, amylase, IL-6, TNF-α, BUN, and Cr, and ameliorated the renal and pancreatic histological damage in SAP rats.Conclusion: Caspase-11-mediated pyroptosis contributes to SAP-induced AKI, and targeting caspase-11-mediated pyroptosis might be a novel treatment strategy for SAP-induced AKI.


Assuntos
Injúria Renal Aguda , Pancreatite , Ratos , Animais , Pancreatite/complicações , Pancreatite/tratamento farmacológico , Piroptose , Caspases/efeitos adversos , Doença Aguda , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Creatinina , Fator de Necrose Tumoral alfa , Amilases , Interleucina-6 , Lipase
11.
J Invest Surg ; 36(1): 1-7, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36345736

RESUMO

AIM: To compare the short- and long-term treatment outcomes of open radiofrequency ablation combined with splenectomy and pericardial devascularization versus liver transplantation for hepatocellular carcinoma patients with portal hypertension and hypersplenism. METHODS: During the study period, the treatment outcomes of consecutive HCC patients with portal hypertension and hypersplenism who underwent open radiofrequency ablation, splenectomy and pericardial devascularization (the study group) were compared with the treatment outcomes of a case-matched control group of HCC patients who underwent liver transplantation. RESULTS: The study group consisted of 32 patients, and the control group comprised 32 patients selected from 155 patients who were case-matched by tumor size, age, gender, MELD sore, tumor location, TNM classification, degree of splenomegaly and Child-Pugh staging. Baseline data on preoperative laboratory tests and tumor characteristics were comparable between the two groups. The mean follow-up was 43.2 ± 5.3 months and 44.9 ± 5.8 months for the study and control groups, respectively. Although the disease-free survival rates of the control group were better than those of the study group (P < 0.001), there was no significant difference in the cumulative overall survival time or the incidence of portal vein thrombosis between the two groups (P = 0.670, 0.083). Compared with the control group, the study group had significantly less intraoperative blood loss, and lower incidences of postoperative pleural effusion and pneumonia (all P < 0.05). CONCLUSION: Open radiofrequency ablation, splenectomy and pericardial devascularization for small HCCs with portal hypertension and hypersplenism can be an alternative therapy for a subset of carefully selected patients under the shortage of liver donors.


Assuntos
Carcinoma Hepatocelular , Hiperesplenismo , Hipertensão Portal , Neoplasias Hepáticas , Transplante de Fígado , Ablação por Radiofrequência , Humanos , Hiperesplenismo/etiologia , Hiperesplenismo/cirurgia , Esplenectomia/efeitos adversos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Transplante de Fígado/efeitos adversos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Hipertensão Portal/complicações , Hipertensão Portal/cirurgia , Ablação por Radiofrequência/efeitos adversos , Resultado do Tratamento , Cirrose Hepática
12.
J Invest Surg ; 36(1): 1-9, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36345760

RESUMO

BACKGROUND/AIMS: Sepsis is one of the major problems encountered in intensive care units, causing organ damage and increasing mortality. Suberosin (SBR) is a type of coumarin with antioxidant and anti-inflammatory activities. The goal of this study is to explore the protective effects of SBR on the lungs in a rat model of sepsis. METHODS: Male Wistar rats were utilized in this study. A cecal ligation and puncture (CLP) model was applied to induce sepsis. Rats were separated into six groups with nine animals in each group, including healthy control, SBR, CLP, and CLP + SBR (5, 10, and 20 mg/kg) groups. Superoxide dismutase (SOD), glutathione (GSH) enzyme activities, and malondialdehyde (MDA) level were measured via enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were evaluated by real-time polymerase chain reaction (RT-PCR). Histopathological changes in the lungs were investigated with hematoxylin and eosin (H&E). RESULTS: MDA levels and GSH and SOD enzyme activities were negatively affected in the CLP group, but SBR treatment ameliorated these oxidative stress parameters in the SBR1-3 groups (p< 0.05). The mRNA expressions of TNF-α and IL-1ß were increased in the CLP group, and SBR treatment decreased those expression levels in a dose-dependent manner (p < 0.05). Organ damage and necrosis were seen in the CLP group and were alleviated in the SBR3 group. Immunohistochemical (IHC) analysis of lung tissues demonstrated decreased TNF-α and IL-1ß immunopositivity in the SBR1-3 groups (p< 0.05). CONCLUSIONS: SBR ameliorated sepsis-related lung injury in a dose-dependent manner. This compound has significant potential as a future agent in the treatment of sepsis.


Assuntos
Lesão Pulmonar , Sepse , Ratos , Masculino , Animais , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo , Ratos Wistar , Sepse/complicações , Sepse/tratamento farmacológico , Cumarínicos/farmacologia , Ligadura/efeitos adversos , Pulmão/patologia , Punções , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , RNA Mensageiro , Modelos Animais de Doenças
13.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1868(1): 159246, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36202338

RESUMO

Non-alcoholic Fatty Liver Disease (NAFLD) or pathological hepatic lipid overload, is considered to affect obese individuals. However, NAFLD in lean individuals is prevalent, especially in South Asian population. The pathophysiology of lean NAFLD is not well understood and most animal models of NAFLD use the high-fat diet paradigm. To bridge this gap, we have developed a diet-independent model of NAFLD in zebrafish. We have previously shown that chronic systemic inflammation causes metabolic changes in the liver leading to hepatic fat accumulation in an IL6 overexpressing (IL6-OE) zebrafish model. In the present study, we compared the hepatic lipid composition of adult IL6-OE zebrafish to the controls and found an accumulation of saturated triacylglycerols and a reduction in the unsaturated triacylglycerol species reminiscent of NAFLD patients. Zebrafish is an ideal system for chemical genetic screens. We tested whether the hepatic lipid accumulation in the IL6-OE is responsive to chemical treatment. We found that PPAR-gamma agonist Rosiglitazone, known to reduce lipid overload in the high-fat diet models of NAFLD, could ameliorate the fatty liver phenotype of the IL6-OE fish. Rosiglitazone treatment reduced the accumulation of saturated lipids and showed a concomitant increase in unsaturated TAG species in our inflammation-induced NAFLD model. Our observations suggest that the IL6-OE model can be effective for small molecule screening to identify compounds that can reverse hepatic lipid accumulation, especially relevant to lean NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Peixe-Zebra/metabolismo , Rosiglitazona , Interleucina-6/genética , Dieta Hiperlipídica/efeitos adversos , Triglicerídeos/metabolismo , Inflamação/complicações
14.
J Ethnopharmacol ; 301: 115801, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36216199

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The processed lateral root of Aconitum carmichaelii Debx. is known as Fuzi, an extensively used Traditional Chinese Medicine to treat cardiovascular diseases, rheumatism arthritis, bronchitis, pains, and hypothyroidism, etc. Although Chinese Pharmacopeia regulates the safe clinical dosage of Fuzi at 3-15 g/person/day, such recommendation not only lacks bench evidence but also does not differentiate Fuzi with different processing types, such as Heishunpian and Paofupian. AIM OF THE STUDY: The current study aimed to 1) determine No-Observed-Adverse-Effect-Levels of Heishunpian and Paofupian in rats and 2) investigate the related toxicity mechanisms for their safe clinical use. MATERIALS AND METHODS: After giving clinically relevant dosing regimen of Heishunpian/Paofupian to rats, we conducted toxicity assessments including ECG monitoring, histopathological changes and serum biomarkers to detect organ injury. Metabolomic study in the liver revealed changes in endogenous metabolite levels after two-week treatment of Fuzi preparations or its corresponding six toxic alkaloids mixtures. RESULTS: The NOAEL for both bolus and two-week treatments of Heishunpian and Paofupian in rats was designated to be 7.5 g/kg and 15 g/kg, respectively. Corresponding recommended doses in humans were 7.5-25 g/person/day for Heishunpian and 15-50 g/person/day for Paofupian. Metabolic profiles revealed more significant alterations in endogenous substances from rats receiving the two Fuzi preparations than their corresponding toxic alkaloids mixtures. Upregulation of bile acid pathway could be responsible for Fuzi induced liver injury. CONCLUSIONS: Compared to the current maximum recommended dose, our suggested upper limit of guided dose for Heishunpian was comparable, whereas that for Paofupian could be further elevated. Both C19-diterpenoid alkaloids and co-occurring components in Fuzi preparations contributed to their hepatotoxicity via upregulation of bile acid pathway.


Assuntos
Aconitum , Alcaloides , Doença Hepática Induzida por Substâncias e Drogas , Diterpenos , Medicamentos de Ervas Chinesas , Humanos , Ratos , Animais , Aconitum/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Alcaloides/metabolismo , Diterpenos/metabolismo , Medicina Tradicional Chinesa/efeitos adversos , Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Raízes de Plantas/toxicidade
15.
J Ethnopharmacol ; 301: 115828, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36240979

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal properties of Gaultheria have been used in traditional medicine to treat pain and inflammation. AIM OF THE STUDY: Hence, the purpose of this study was to evaluate the analgesic, antipyretic, and anti-inflammatory properties of Gaultheria trichophylla Royle extract and salicylate-rich fraction in vivo, in vitro, and in silico. MATERIALS AND METHODS: In vivo analgesic, antipyretic, and anti-inflammatory of extract and a salicylate-rich fraction (at doses of 100, 200, 300, and 150 mg/kg) were assessed using healthy albino mice employing acetic acid-induced writhing, tail immersion test, carrageenan-induced inflammation, and croton oil-induced edema. For in vitro testing of extracts COX and LOX enzyme inhibition assays were used. Molecular docking studies were conducted for in silico testing of the inhibitory activity of the dominant compound Gaultherin against COX and LOX. RESULTS: G-EXT 200 and 300 and G-SAL 150 mg/kg reduced pyrexia significantly (P < 0.05 and P < 0.01). G-EXT-200, 300, and G-SAL 150 reduce the writing to a significant level (p > 0.05, p < 0.01). G-EXT 200 and 300 and G-SAL 150 mg/kg doses the analgesic effect was significant (p > 0.05, p > 0.01) and was comparable to tramadol. G-EXT 100 200, 300 mg/kg showed 43.8%, 47.94% and 56% respectively. G-SAL 150 mg, rich in salicylates, showed maximum inhibition of 65.75% next to standard drug diclofenac with 76.7% inhibition. G-EXT 100 and 200 mg/kg dose showed significant (p < 0.05) reduction in ear edema. With 300 mg/kg dose the effect was more (61.89%, p < 0.01). The salicylate-rich fraction G-SAL and Celecoxib showed an almost similar effect (p < 0.01). Significance inhibition was shown in the COX-2 test (G-EXT 39.70 and G-SAL 77.20 IC50 µg/ml) and in the 5-LOX test (G-EXT 28.3 and G-SAL 39.70 IC50 µg/ml). The preliminary in silico results suggest that the investigated compound showed excellent inhibitory activity against COX and LOX enzymes as evident from the free binding energy. Molecular docking revealed that Gaultherin binds well in the COX and LOX enzyme catalytic region. CONCLUSION: The extract and salicylate-rich fraction obtained from G. trichophylla showed significant analgesic, anti-inflammatory, and antipyretic effects in vivo, in vitro, and in silico assays that support its use in traditional medicine.


Assuntos
Antipiréticos , Ericaceae , Gaultheria , Animais , Camundongos , Gaultheria/química , Antipiréticos/farmacologia , Simulação de Acoplamento Molecular , Anti-Inflamatórios/efeitos adversos , Analgésicos/efeitos adversos , Salicilatos/química , Salicilatos/farmacologia , Salicilatos/uso terapêutico , Febre/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Carragenina , Inflamação/tratamento farmacológico
16.
J Ethnopharmacol ; 301: 115835, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36252878

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Er-Xian decoction (EXD) is a traditional Chinese medicine (TCM) formula used to treat osteoporosis (OP). However, the anti-OP mechanism of EXD has not yet been fully elucidated. AIM OF THE STUDY: The study aimed to verify the anti-OP effect of EXD and to explore its underlying mechanism. METHODS: The anti-OP targets and mechanisms of EXD were predicted by network pharmacological analysis. Then, an ovariectomized (OVX) rat model was established to validate the key anti-OP mechanism of EXD. Firstly, the therapeutic effect of EXD on OP was confirmed using micro-CT bone analysis, pathological observation, and ELISA detection. Secondly, serum metabolites related to key biological processes were detected using an automatic biochemical analyzer and GC-MS. Finally, ELISA, qRT-PCR, and western blot were utilized to further explore the potential key anti-OP pathway of EXD. RESULTS: A total of 159 anti-OP targets of EXD were identified. Functional annotation revealed that OP treatment using EXD was associated with lipid metabolism, fatty acid (FA) metabolism, and PI3K/AKT signaling pathway. Experimental studies confirmed that EXD ameliorated ovariectomy-induced bone loss and bone microstructure deterioration. EXD treatment also upregulated the level of serum estrogen and downregulated the level of OC, PⅠNP, CTX-1, TC, and LDL-C. Besides, principal component analysis (PCA) and heat map of serum FAs distinguished OVX rats from the SHAM and EXD groups. Serum concentrations of important n-3 FAs, including C20:3N3, C20:5N3, and C22:5N3, were significantly increased in the EXD group. The increased stearoyl-CoA desaturase 1 (SCD1) index 1 and index 2 in the OVX group were reversed by EXD administration. Additionally, EXD reversed the decreased serum IGF1 level and tibia IGF1R, PI3K, and AKT expression in OVX rats. CONCLUSION: EXD ameliorated ovariectomy-induced bone loss by modulating lipid metabolism, FA metabolism, and IGF1/PI3K/AKT pathway.


Assuntos
Medicamentos de Ervas Chinesas , Osteoporose , Humanos , Feminino , Ratos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Ovariectomia/efeitos adversos , Transdução de Sinais , Metabolismo dos Lipídeos , Ácidos Graxos/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo
17.
Food Chem ; 403: 134322, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36166922

RESUMO

Acerola (Malpighia emarginata) by-product (ABP) has various bioactive compounds with hypoglycaemic, antioxidant and anti-inflammatory activity. The ABP effects on the biochemical changes in the enterohepatic axis caused by a high-fat diet (HFD) remains unclear. This study assessed whether the ABP or fenofibrate administration for 28 days interferes in lipid, glucose, or inflammatory changes in the enterohepatic axis of rats fed HFD. ABP induced in the rats fed HFD a reduction in body weight, serum lipids, blood glucose, and liver fat accumulation; increased insulin tolerance, and faecal bile acid excretion; regulated organic acid synthesis, faecal and colonic microbial growth; reduced M1 macrophage and increased M2 macrophage infiltration in the colon and liver, respectively. The fenofibrate did not improve the lipid or glucose alterations in enterohepatic axis of rats fed HFD. ABP has functional/nutraceutical potential in treating HFD-induced metabolic disorders with beneficial effects on lipid and glucose metabolism, and reduction of inflammation.


Assuntos
Fenofibrato , Malpighiaceae , Ratos , Animais , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Fenofibrato/análise , Fenofibrato/metabolismo , Fenofibrato/farmacologia , Frutas/química , Fígado/metabolismo , Malpighiaceae/química , Lipídeos/análise , Metabolismo dos Lipídeos
18.
Food Chem ; 403: 134336, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36191423

RESUMO

Konjac glucomannan's influence on the regulation of diabetes mellitus, hyperlipidemia, and gut microbial flora was evaluated in this study. In addition, a high-fat diet and streptozotocin were used to induce type 2 diabetes mellitus in rats. At the end of the study, we analyzed various parameters such as body weight, plasma lipid profile, insulin levels by immunohistochemistry, degree of fibrosis in the liver, protein expression of PPAR-γ and p-SREBP-1C and gut microbial changes using 16S rRNA sequencing. The results of our study suggest that KGM supplementation significantly reduced the plasma lipid profile (TC, TG, VLDL, LDL, etc.). In addition, KGM has improved insulin levels, which were visualized using immunohistochemistry. Furthermore, KGM also regulated the protein expression of key regulatory proteins of lipid metabolism PPAR-γ and p-SREBP-1C (Group 3). Similar results were seen in the groups treated with the standard drug rosiglitazone (group 4). Finally, the 16S rRNA sequencing shows that KGM contributes to gut microbiota composition alterations, and it was observed using the Simpson, Shannon, Chao-1, and actual otus indices (group 3). KGM further alters the production of beneficial SCFAs and helps host good health. Furthermore, several metabolic pathways have been activated in T2DM rats. As a result, it becomes apparent that the digestive system's microbiome will play a role in T2DM. KGM has various health advantages but is particularly useful in treating hyperlipidemia and diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hiperlipidemias , Insulinas , Ratos , Animais , PPAR gama/genética , RNA Ribossômico 16S/genética , Hipoglicemiantes/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Fibras na Dieta/farmacologia , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Insulinas/farmacologia , Insulinas/uso terapêutico , Lipídeos/farmacologia
19.
J Environ Sci (China) ; 125: 823-830, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375964

RESUMO

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is a commonly used organophosphate-based flame retardant and can bio-accumulate in human tissues and organs. As its structure is similar to that of neurotoxic organophosphate pesticides, the neurotoxicity of TDCIPP has raised widespread concerns. TDCIPP can increase neuronal apoptosis and induce autophagy. However, its regulatory mechanism remains unclear. In this study, we found that the expression upregulation of the DNA Damage-Inducible Transcript 4 (DDIT4) protein, which might play essential roles in TDCIPP-induced neuronal autophagy and apoptosis, was observed in TDCIPP-treated differentiated rat PC12 cells. Furthermore, we determined the protective effect of the DDIT4 suppression on the autophagy and apoptosis induced by TDCIPP using Western blot (WB) and Flow cytometry (FACS) analysis. We observed that TDCIPP treatment increased the DDIT4, the autophagy marker Beclin-1, and the microtubule-associated protein light chain 3-II (LC3II) expressions and decreased the mTOR phosphorylation levels. Conversely, the suppression of DDIT4 expression increased the p-mTOR expression and decreased cell autophagy and apoptosis. Collectively, our results revealed the function of DDIT4 in cell death mechanisms triggered by TDCIPP through the mTOR signaling axis in differentiated PC12 cells. Thus, this study provided vital evidence necessary to explain the mechanism of TDCIPP-induced neurotoxicity in differentiated PC12 cells.


Assuntos
Apoptose , Autofagia , Organofosfatos , Fatores de Transcrição , Animais , Ratos , Organofosfatos/efeitos adversos , Compostos Organofosforados , Células PC12 , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo
20.
Immunol Allergy Clin North Am ; 43(1): 43-52, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36411007

RESUMO

Disease programming reflects interactions between genes and the environment. Unlike the genome, environmental exposures and our response to exposures change over time. Starting in utero, the respiratory system and related processes develop sequentially in a carefully timed cascade, thus effects depend on both exposure dose and timing. A multitude of environmental and microbial exposures influence respiratory disease programming. Effects result from toxin-induced shifts in a host of molecular, cellular, and physiologic states and their interacting systems. Moreover, pregnant women and the developing child are not exposed to a single toxin, but to complex mixtures.


Assuntos
Transtornos Respiratórios , Feminino , Humanos , Gravidez , Exposição Ambiental/efeitos adversos , Sistema Respiratório
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