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1.
Tree Physiol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617114

RESUMO

The circadian rhythm of plants is associated with stress responses; however, it is not clear whether increased host plant drought tolerance by arbuscular mycorrhizal fungi (AMF) is associated with changes in the circadian clock. The present study aimed to analyze the effect of Funneliformis mosseae (Nicol. & Gerd.) Schüßler & Walker on the circadian clock gene expression patterns in trifoliate orange (Poncirus trifoliata L. Raf.), along with gas exchange, abscisic acid (ABA) levels, and antioxidant enzyme gene expression under well-watered (WW) and drought stress (DS) conditions. Plant growth, net photosynthetic rate, stomatal conductance, and ABA levels were significantly higher in AMF- than in non-AMF-inoculated plants, regardless of soil water regimes. Six circadian clock genes, including PtPRR7, PtLHY, PtCCA1, PtGI, PtPIF3, and PtSRR1, were identified and showed rhythmic expression patterns over the course of the day. AMF inoculation reduced the expression of most circadian clock genes in different time periods. However, AMF treatment significantly increased PtPRR7 and PtGI expression at 17:00 p.m. under WW and DS conditions, PtLHY expression at 1:00 a.m., and PtSRR1 expression at 21:00 p.m. At 1:00 a.m., AMF inoculation up-regulated the expression of the circadian clock genes PtPRR7, PtCCA1, PtLHY, and PtPIF3 and the antioxidant enzyme genes PtFe-SOD, PtMn-SOD, PtCu/Zn-SOD, PtPOD, and PtCAT1. Correlation analysis revealed that these changes in circadian clock gene expression were associated with antioxidant enzyme gene expression, root ABA and gas exchange. We concluded that mycorrhizal fungi have the ability to regulate the daily rhythm of the circadian clock in trifoliate orange plants in response to drought.

2.
Australas J Ageing ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668629

RESUMO

OBJECTIVE: Myocardial injury leads to higher mortality in COVID-19, but the causes and risk factors are variable. We evaluated the potential risk factors for myocardial injury in COVID-19 patients to improve treatment strategies and reduce mortality. METHODS: This retrospective analysis enrolled 325 COVID-19 patients in Shanghai, China. RESULTS: The median age in our cohort was 51 [range 15-88] years, 26 (8%) were critically ill, and 177 patients (19.7%) had myocardial injury. The myocardial injury group comprised older, more critically ill patients with hypertension, other comorbidities, history of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, lower peripheral blood lymphocyte count and higher D-dimer levels. Binary logistic regression analysis identified only age was an independent risk factor for myocardial injury (odds ratio 1.019; 95% confidence interval 1.003-1.036; age increase by 1 year = myocardial injury risk increase by 1.9%). CONCLUSION: Older age was associated with a higher incidence of myocardial injury for COVID-19 patients.

3.
BMC Endocr Disord ; 21(1): 182, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488736

RESUMO

BACKGROUND: Obesity is associated with the development of polycystic ovary syndrome (PCOS) and contributes substantially to metabolic abnormalities in women with PCOS. The study aimed to describe and compare the practices of physicians in the diagnosis, evaluation, and treatment of obesity in patients with PCOS. METHODS: Reproductive endocrinologists (Repro-Endo) and obstetrician-gynecologists (non-reproductive medicine specialty, OB-Gyn) in China participated in a survey, and their responses were analyzed using χ2 tests, Fisher exact tests, and multivariable logistic regression analysis. RESULTS: The study analyzed 1318 survey responses (85.8% OB-Gyn; 97.3% women). Body mass index was the most common diagnostic criterion for obesity; only 1.3% of participants measured waist circumference to identify abdominal obesity. More Repro-Endo participants (25% of all participants) enquired about the psychological problems of patients with obesity than OB-Gyn participants, and 42.5% of participants reported ordering both a lipid profile and oral glucose tolerance test (OGTT) for patients with obesity and PCOS. Multivariable analysis, that included physician's specialty, age, hospital grade, and number of patients with PCOS seen annually, revealed that OB-Gyn participants were less likely to order OGTT (OR, 0.3; 95% CI, 0.2-0.4) and lipid profile (OR, 0.2; 95% CI, 0.1-0.3) than Repro-Endo participants. The most common treatments for patients with PCOS were lifestyle modification (> 95%) and metformin (> 80%). More Repro-Endo participants prescribed metformin at a dose of 1.5 g/day compared with OB-Gyn (47.6% vs. 26.3%), and more OB-Gyn participants reported being unclear about the appropriate dosage of metformin for patients with obesity and PCOS (8.9% vs. 1.6%). CONCLUSION: Our survey identified knowledge gaps in metabolic screening for patients with obesity and PCOS and a disparity in the evaluation and treatment of obesity in PCOS among different specialties. Similarly, it highlights the need to improve obesity management education for physicians caring for women with PCOS.

4.
Org Biomol Chem ; 19(35): 7690-7694, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524340

RESUMO

A bifunctional cinchona squaramide catalyzed enantioselective aza-Friedel-Crafts reaction between 2-naphthols and benzothiazolimines has been developed, and a series of chiral 2'-aminobenzothiazolomethyl naphthols with potential antiproliferative and anthelmintic activities have been successfully and effectively prepared in good to excellent yields (up to 98%) with excellent enantioselectivities (up to >99% ee) even in a scale-up preparation under mild conditions.

5.
Am J Clin Pathol ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519764

RESUMO

OBJECTIVES: To demonstrate clinicopathologic features and evaluate the clonality of double PIK3CA alterations in colorectal cancers (CRCs). METHODS: Clonality was examined in 13 CRCs with double PIK3CA alterations (1.7% of CRCs or 9.6% of PIK3CA-mutated CRCs). Multiregional analyses were performed to confirm subclonal PIK3CA alterations. RESULTS: PIK3CA alterations were detected within exon 9 (51%), exon 20 (23%), exon 1 (15%), and exon 7 (6.0%). CRCs with exon 7 alterations showed a significantly higher incidence of double PIK3CA alterations. Most double PIK3CA alterations consisted of a hotpsot alteration and an uncommon alteration; they were often clonal and present within a single tumor population. Multiregional analyses of CRCs with predicted subclonal double-alterations revealed multiclonal CRCs with divergent PIK3CA variant status originating from a common APC- and KRAS-mutated founder lineage of adenoma. CONCLUSIONS: The findings supported multiclonal CRCs resulting from parallel evolution during the progression from adenoma to adenocarcinoma within the mitogen-activated protein kinase pathway, as previously demonstrated, or the mammalian target of rapamycin pathway. Further studies are warranted to elucidate clinical significance and potential targeted therapy for CRC patients with double PIK3CA alterations and impacts on clinical decision-making in patients with multiclonal CRCs harboring divergent PIK3CA mutational status.

6.
Radiology ; : 210201, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581624

RESUMO

Background Cerebral oxygenation is closely related to neural function in acute ischemic stroke (AIS) and can be measured noninvasively from asymmetrically prominent cortical veins (APCVs) using quantitative susceptibility mapping (QSM). Purpose To quantify venous oxygen saturation (SvO2) using brain MRI with QSM in patients with AIS, to analyze its change at 2-week follow-up, and to assess the influence of SvO2 in clinical prognosis. Materials and Methods Between 2016 and 2020, consecutive patients with AIS who underwent brain MRI within 24 hours from symptom onset and 2 weeks after treatment were retrospectively enrolled. The SvO2 of APCVs was quantified using QSM. The independent sample t test was used to compare the SvO2 between patients with and patients without APCVs. The paired sample t test was used to assess the dynamic change in SvO2. Pearson and Spearman correlation analysis was used to explore the relationship among dynamic change in SvO2 and hypoperfusion, National Institutes of Health Stroke Scale (NIHSS) score change, and 90-day modified Rankin Scale (mRS) score. The independent sample t test was used to compare the dynamic change in SvO2 between different clinical prognoses and outcome subgroups. Results APCVs were detected in 39 of 73 patients (mean age, 70 years ± 10 [standard deviation]; 49 men) at admission and disappeared in 35 patients at 2-week follow-up MRI. The mean SvO2 increased from 35.0% ± 5.8 to 64.5% ± 10.0 (P < .001) in 39 patients. For the 35 patients with APCVs that disappeared, the dynamic change in SvO2 negatively correlated with change in NIHSS score (r = -0.37, R2 = 0.19, P = .03) and 90-day mRS score (r = -0.54, R2 = 0.27, P = .001), and the dynamic change in SvO2 in the subgroup with good 90-day outcomes (n = 19) was greater than that in the subgroup with poor 90-day outcomes (n = 16) (mean, 34.5% ± 5.8 vs 29.7% ± 6.3; 95% CI: 0.6, 8.9; P = .03). Conclusion Improved oxygen saturation of asymmetric cortical veins detected using brain MRI with quantitative susceptibility mapping corresponded with better acute ischemic stroke outcomes for patients with asymmetrically prominent cortical veins that disappeared at 2-week follow-up MRI. © RSNA, 2021 Online supplemental material is available for this article.

7.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445161

RESUMO

Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive clinical and histopathological phenotypes than extraocular cases, but the molecular drivers implicated in their oncogenesis remain poorly defined. A retrospective review of surgical and ocular pathology archives identified eleven primary resection specimens of OA sebaceous carcinomas with adequate tissue for molecular analysis; two extraocular cases were also examined. Next-generation sequencing was used to evaluate mutations and copy number changes in a large panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) confirmed MYC copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in TP53 (10/13) and RB1 (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the NF1 (3/12), PMS2 (4/12), ROS1 (3/12), KMT2C (4/12), MNX1 (6/12), NOTCH1 (4/12), PCLO (3/12), and PTPRT (3/12) loci. Low level copy number gain suggestive of amplification of the MYC locus was seen in two cases, and confirmed using FISH. MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.


Assuntos
Neoplasias Oculares/genética , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas de Ligação a Retinoblastoma/genética , Neoplasias das Glândulas Sebáceas/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Dosagem de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação
8.
J Mol Diagn ; 23(10): 1343-1358, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34358677

RESUMO

Somatic gene fusions are common in leukemias/lymphomas and solid tumors. The detection of gene fusions is crucial for diagnosis. NanoString fusion technology is a multiplexed hybridization method that interrogates hundreds of gene fusions in a single reaction. This study's objective was to determine the performance characteristics and diagnostic utility of NanoString fusion assays in a clinical diagnostics laboratory. Validation using 100 positive specimens and 15 negative specimens by a combined reference standard of fluorescence in situ hybridization (FISH)/RT-PCR/next-generation sequencing (NGS) assays achieved 100% sensitivity in leukemias/lymphomas and 95.0% sensitivity and 100% specificity in solid tumors. Subsequently, 214 consecutive clinical cases, including 73 leukemia/lymphoma specimens and 141 formalin-fixed, paraffin-embedded solid tumor specimens, were analyzed by gene fusion panels across 638 unique gene fusion transcripts. A variety of comparator tests, including FISH panels, conventional karyotyping, a DNA-based targeted NGS assay, and custom RT-PCR testing, were performed in parallel. The gene fusion assay detected 31 gene fusions, including 16 in leukemia/lymphoma specimens and 15 in solid tumor specimens. The overall sensitivity, specificity, and accuracy of gene fusions detected by the gene fusion panel in all 329 specimens (validation and consecutive clinical specimens) tested in this study were 94.8%, 100%, and 97.9%, respectively, compared with FISH/RT-PCR/NGS assays. The gene fusion panel is a reliable approach that maximizes molecular detection of fusions among both fresh and formalin-fixed, paraffin-embedded cancer specimens.

9.
Exp Neurol ; 345: 113818, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34324860

RESUMO

Transcranial direct-current stimulation (tDCS) is proved safe and shows therapeutic effect in cerebral ischemic stroke in clinical trials. But the underlying molecular mechanisms remain unclear. Here we show that tDCS treatment reduces the infarct volume after rat cerebral ischemia-reperfusion (I/R) injury and results in functional improvement of stroke animals. At the cellular and molecular level, tDCS suppresses I/R-induced upregulation of Cezanne in the ischemic neurons. Cezanne inhibition confers neuroprotection after rat I/R and oxygen glucose deprivation (OGD) in the cortical neuronal cultures. Inhibiting Cezanne increases the level of SIRT6 that is downregulated in the ischemic neurons. Suppressing SIRT6 blocks Cezanne inhibition-induced neuroprotective effect and overexpressing SIRT6 attenuates OGD-induced neuronal death. We further show that downregulating Cezanne reduces DNA double-strand break (DSB) through upregulation of SIRT6 in OGD-insulted neurons. Together, this study suggests that Cezanne-dependent SIRT6-DNA DSB signaling pathway may mediate the neuroprotective effect of tDCS in ischemic neurons.

10.
J Cosmet Dermatol ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34240515

RESUMO

BACKGROUND: Patch test, as a helpful tool in clinic diagnosis and safety assessment of cosmetics, is affected by many factors. OBJECTIVES: To investigate the influencing factors of patch test reactions in a highly standardized large-scale dataset of Chinese. METHODS: Patch test data (n = 151,280) from safety assessments of cosmetic products were obtained following internationally standardized patch testing protocols during 2004-2017 in China. RESULTS: The frequency of patch test reactions was 1.45% (2,191/151,280), with majority of the reactions being "score 1" reactions (also known as doubtful reactions, n = 2,075) and a small number being "score 2" reactions (weak reactions, n = 116). Patch test reactions were 67% more frequent in winter (p < 0.001), associated with temperatures (p < 0.001), rather than relative humidity (P:0.29). The frequency of reactions was higher in men than in women (p:0.001), especially in winter. The risk to develop reactions clearly increased with age in women (p < 0.001), but not in men (p:0.14). In women, the frequency of reactions in the old group (≥50 years old) was 30% more than the young group (<30 years old). CONCLUSIONS: The frequency of patch test reactions to cosmetic products was 1.45% in our large-scale study. The influencing factors of patch test include season, sex, and age, which should be considered when conducting and interpreting patch testing.

11.
Sci Rep ; 11(1): 13660, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34211003

RESUMO

Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative tranquilizing effects. However, the component of G. lucidum that promotes sleep has not been clearly identified. Here, the effect and mechanism of the acidic part of the alcohol extract of G. lucidum mycelia (GLAA) on sleep were studied in mice. Administration of 25, 50 and 100 mg/kg GLAA for 28 days promoted sleep in pentobarbital-treated mice by shortening sleep latency and prolonging sleeping time. GLAA administration increased the levels of the sleep-promoting neurotransmitter 5-hydroxytryptamine and the Tph2, Iptr3 and Gng13 transcripts in the sleep-regulating serotonergic synapse pathway in the hypothalamus during this process. Moreover, GLAA administration reduced lipopolysaccharide and raised peptidoglycan levels in serum. GLAA-enriched gut bacteria and metabolites, including Bifidobacterium, Bifidobacterium animalis, indole-3-carboxylic acid and acetylphosphate were negatively correlated with sleep latency and positively correlated with sleeping time and the hypothalamus 5-hydroxytryptamine concentration. Both the GLAA sleep promotion effect and the altered faecal metabolites correlated with sleep behaviours disappeared after gut microbiota depletion with antibiotics. Our results showed that GLAA promotes sleep through a gut microbiota-dependent and serotonin-associated pathway in mice.

12.
Cancer Genet ; 258-259: 18-22, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34233240

RESUMO

The anaplastic lymphoma kinase (ALK) fusions/rearrangements in non-small cell lung cancer (NSCLC) act as oncogenic driver mutations. ALK tyrosine kinase inhibitors have anti-tumor activities in ALK-positive NSCLC. Although the EML4-ALK fusion is common in NSCLC, concomitance of an additional ALK fusion together with an EML4-ALK fusion is not common. Here, we present a lung adenocarcinoma with two ALK fusions, a novel RMDN2-ALK fusion accompanied by an EML4-ALK fusion, detected by a targeted next generation sequencing assay. The genomic translocation breakpoints of the RMDN2-ALK fusion were mapped to intron 2 for RMDN2 and exon 15 for ALK, and EML4-ALK breakpoints were mapped to intron 13 for EML4 and intron 19 for ALK. ALK break-apart FISH detected multiple ALK rearrangements, a gene fusion panel (NanoString) test confirmed the EML4-ALK fusion, and RNA-sequencing revealed two ALK fusions. The RMDN2 gene locates at the short arm of chromosome 2 between ALK and EML4 genes. The intact ALK kinase domain fused to RMDN2. Genome-wide copy number variants were found in multiple chromosome arms and the short arm of chromosome 2, suggestive of complex rearrangements. Further detailed analyses of breakpoints and copy number variants may shed light on mechanisms of their formation and pathogenesis in lung malignancies.

13.
Exp Cell Res ; 406(1): 112722, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34242623

RESUMO

Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in women. MIER3 (Mesoderm induction early response 1, family member3) is considered as a potential oncogene for breast cancer. However, the role of MIER3 in breast cancer remain largely unknown. The expression of MIER3 was detected and the relationship between its expression and clinicopathological characteristics was also analyzed. The effect of MIER3 on proliferation and migration of breast cancer cells was detected in vitro and in vivo. Western blot, IF, and Co-IP were employed to detect the relationship between MIER3, HDAC1, HDAC2, and Snail. ChIP assay was performed to determine the binding of MIER3/HDAC1/HDAC2/Snail complex to the promoter of E-cadherin. In this study, we found that MIER3 was upregulated in breast cancer tissue and closely associated with poor prognosis of patients. MIER3 could promote the proliferation, migration, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Further studies showed that MIER3 interacted with HDAC1/HDAC2 and Snail to form a repressive complex which could bind to E-cadherin promoter and was related to its deacetylation. Our study concluded that MIER3 was involved in forming a co-repressor complex with HDAC1/HDAC2/Snail to promote EMT by silencing E-cadherin.


Assuntos
Neoplasias da Mama/genética , Histona Desacetilase 1/genética , Histona Desacetilase 2/genética , Proteínas Nucleares/genética , Fatores de Transcrição da Família Snail/genética , Idoso , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/metabolismo , Humanos , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição da Família Snail/metabolismo , Análise de Sobrevida , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Phys Med Biol ; 66(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34181583

RESUMO

Whole slide histopathology images (WSIs) play a crucial role in diagnosing lymph node metastasis of breast cancer, which usually lack fine-grade annotations of tumor regions and have large resolutions (typically 105 × 105pixels). Multi-instance learning has gradually become a dominant weakly supervised learning framework for WSI classification when only slide-level labels are available. In this paper, we develop a novel second-order multiple instances learning method (SoMIL) with an adaptive aggregator stacked by the attention mechanism and recurrent neural network (RNN) for histopathological image classification. To be specific, the proposed method applies a second-order pooling module (matrix power normalization covariance) for instance-level feature extraction of weakly supervised learning framework, attempting to explore second-order statistics of deep features for histopathological images. Additionally, we utilize an efficient channel attention mechanism to adaptively highlight the most discriminative instance features, followed by an RNN to update the final bag-level representation for the slide classification. Experimental results on the lymph node metastasis dataset of 2016 Camelyon grand challenge demonstrate the significant improvement of our proposed SoMIL framework compared with other state-of-the-art multi-instance learning methods. Moreover, in the external validation on 130 WSIs, SoMIL also achieves an impressive area under the curve performance that competitive to the fully-supervised framework.

15.
Endocr Pract ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34174413

RESUMO

OBJECTIVE: To develop and validate an individualized risk prediction model for the need for central cervical lymph node dissection in patients with clinical N0 papillary thyroid carcinoma (PTC) diagnosed using ultrasound. METHODS: Upon retrospective review, derivation and internal validation cohorts comprised 1585 consecutive patients with PTC treated from January 2017 to December 2019 at hospital A. The external validation cohort consisted of 406 consecutive patients treated at hospital B from January 2016 to June 2020. Independent risk factors for central cervical lymph node metastasis (CLNM) were determined through univariable and multivariable logistic regression analysis. An individualized risk prediction model was constructed and illustrated as a nomogram, which was internally and externally validated. RESULTS: The following risk factors of CLNM were established: a solitary primary thyroid nodule's diameter, shape, calcification, and capsular abutment-to-lesion perimeter ratio. The areas under the receiver operating characteristic curves of the risk prediction model for the internal and external validation cohorts were 0.921 and 0.923, respectively. The calibration curve showed good agreement between the nomogram-estimated probability of CLNM and the actual CLNM rates in the 3 cohorts. The decision curve analysis confirmed the clinical usefulness of the nomogram. CONCLUSION: This study developed and validated a model for predicting the risk of CLNM in individual patients with clinical N0 PTC, which should be an efficient tool for guiding clinical treatment.

16.
Skin Res Technol ; 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33999461

RESUMO

OBJECTIVE: To investigate effect of scratching and friction on human skin function and functional differences between scratching and friction. METHOD: Forty healthy volunteers were enrolled. Scratching and friction behavior was modeled by scalpel and sandpaper simulation to forearm for 80 times, respectively. Noninvasive bioengineering devices were used to measure basic skin physiological parameters and exfoliated stratum corneum collected and protein quantified. Parameters were recorded at baseline (BL) and after every 20 times interventions (20, 40, 60, and 80 times). RESULTS: Compared to BL, transepidermal water loss (TEWL) value increased significantly at both scratched and friction sites (P < .001) with a significant higher value for friction (P < .001). There was no significant difference in stratum corneum hydration (SCH) value postscratching (P > .05), while it decreased first and then increased significantly at friction site (P < .001). Roughness values (contract (CONT), variety (VAR), and scaliness (SEsc)) were raised significantly at both sites (P < .001). Net change in CONT and SEsc values of friction was higher than scratched sites (P > .05). There was no significant difference in blood flow after both scratching and friction (P > .05). Quantity of keratinocyte protein from friction sites was statistically higher than scratching after 80 times interventions (P < .05). CONCLUSION: Both noninvasive detections and protein quantification indicated more damage from friction, which may have significance for behavior guidance of patients with pruritus and implication for further investigation.

17.
J Food Biochem ; 45(7): e13757, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34032295

RESUMO

Although astragaloside IV protects from acute myocardial infarction (AMI)-induced chronic heart failure (CHF), the underlying mechanism of action is unclear. We determined the potential therapeutic effect of astragaloside IV using molecular docking approaches and validated the findings by the ligation of the left anterior descending (LAD) coronary artery-induced AMI rat model. The interaction between astragaloside IV and myeloid differentiation factor 88 (MyD88) was evaluated by SwissDock. To explore the mechanisms underlying the beneficial effects of astragaloside IV in the LAD coronary artery ligation-induced AMI model, we administered the rats with astragaloside IV for 4 weeks. Hemodynamic indexes were used to evaluate the degree of myocardial injury in model rats. The histopathological changes in myocardium were detected by hematoxylin & eosin (H&E) staining and Masson's staining. Myocardium homogenate contents of collagen I and collagen III were evaluated by ELISA. The level of myocardial hydroxyproline (HYP) was determined by alkaline hydrolysis. Immunohistochemistry was used to examine collagen I. Western blotting was used to examine relevant proteins. As per the molecular docking study results, astragaloside IV may act on MyD88. Furthermore, astragaloside IV improved hemodynamic disorders, alleviated pathological changes, and reduced abnormal collagen deposition and myocardial HYP in vivo. Astragaloside IV significantly reduced the overexpression of TLR4, MyD88, NF-Κb, and TGF-ß, which further validated the molecular docking findings. Hence, astragaloside IV ameliorates AMI by reducing inflammation and blocking TLR4/MyD88/NF-κB signaling. These results indicate that astragaloside IV may alleviate AMI. PRACTICAL APPLICATIONS: Astragaloside IV, a small active substance extracted from Astragalus membranaceus, has demonstrated potent protective effects against cardiovascular ischemia/reperfusion, diabetic nephropathy, and other diseases. Molecular docking experiments showed that astragaloside IV might act on the myeloid differentiation factor 88 (MyD88). Astragaloside IV can effectively reduce the overexpression of TLR4, MyD88, and NF-κB p65, indicating that astragaloside IV inhibits inflammation via TLR4/MyD88/NF-κB signaling pathway. These results indicate that astragaloside IV may alleviate acute myocardial infarction.


Assuntos
Fator 88 de Diferenciação Mieloide , Infarto do Miocárdio , Animais , Simulação de Acoplamento Molecular , Fator 88 de Diferenciação Mieloide/metabolismo , Infarto do Miocárdio/tratamento farmacológico , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Saponinas , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Triterpenos
18.
J Cosmet Dermatol ; 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34056830

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that erupts periodically. Although the negative impact of the disorder on overall quality of life has been well established, new treatments for AD are still needed. Various studies have reported on cannabidiol's effectiveness in relieving pain and easing inflammation while not presenting major health risks. AIMS: In this communication, we aim to demonstrate the effectiveness of a novel cannabidiol (CBD) and aspartame formulation, JW-100, in relieving signs and symptoms of AD. PATIENTS/METHODS: We conducted a double-blinded placebo-controlled interventional study randomizing patients to one of three treatment groups: JW-100 (CBD plus aspartame), CBD only, or placebo topical formulations. The Investigator's Static Global Assessment (ISGA) score was used to document any changes in AD resulting from the applied interventions at 14 days. RESULTS: Fifty-seven patients completed the trial and were included in the final analysis. The ISGA score of the patients at baseline was 2.56, 2.24, and 2.24, for the JW-100, CBD, and placebo groups, respectively. After two weeks of treatment, the ISGA score reduced by 1.28, 0.81, and 0.71, for the JW-100, CBD, and placebo groups, respectively. The JW-100 cohorts demonstrated statistically significant ISGA score reduction (p = 0.042). 50% of patients in the JW-100 group achieved ISGA score of clear or almost clear (0 or 1) with at least a 2-grade improvement from baseline after treatment (p = 0.028). Only 20% and 15% of patients in the CBD only and placebo groups reported ISGA score of clear or almost clear (0 or 1). CONCLUSIONS: JW-100, a novel topical formulation containing CBD and aspartame, was demonstrated to produce statistically significant improvements in AD following 14 days of topical application.

19.
Food Chem Toxicol ; 153: 112278, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34019943

RESUMO

Bergamottin (BGM) is a major furanocoumarin constituent of grapefruit and is reported to have inhibitory effects on cytochrome P450 enzymes. This study investigated the chemical interactions between BGM and the enzyme CYP2C9. BGM exhibited time-, concentration-, and NADPH-dependent inhibition of CYP2C9. Co-incubation with diclofenac, a reversible inhibitor of CYP2C9, attenuated the time-dependent enzyme inhibition. Exhaustive dialysis did not restore enzyme activity post-inhibition. Glutathione (GSH) and catalase/superoxide dismutase failed to reverse BGM-induced CYP2C9 inactivation. A GSH trapping study suggested that BGM was metabolized to an epoxide and/or γ-ketoenal that may have been responsible for the enzyme inactivation. In conclusion, BGM can be characterized as a mechanism-based inactivator of CYP2C9 acting via the formation of an epoxide and/or γ-ketoenal.


Assuntos
Inibidores do Citocromo P-450 CYP2C9/farmacologia , Citocromo P-450 CYP2C9/metabolismo , Furocumarinas/farmacologia , Inibidores do Citocromo P-450 CYP2C9/metabolismo , Diclofenaco/farmacologia , Furocumarinas/metabolismo , Humanos , Microssomos Hepáticos/metabolismo
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