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1.
Bioanalysis ; 14(5): 267-278, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35195037

RESUMO

Background: The degree of human hepatocyte replacement in chimeric mice with humanized liver has previously been shown to correlate with human plasma albumin measurements. However, there are no reports that directly compare the remaining endogenous mouse albumin with the newly expressed human albumin following engraftment. To better understand the disposition of serum albumin in PXB-mice, we developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to simultaneously quantitate both human and mouse albumin from plasma. Results: A robust correlation was observed between the serum human albumin levels measured by LC-MS/MS and the estimated replacement index of PXB-mice. Conclusion: All data were shown to be specific and suitable to accurately quantify both human and mouse albumin from plasma of chimeric mice with humanized livers.


Assuntos
Albumina Sérica Humana , Espectrometria de Massas em Tandem , Quimera , Cromatografia Líquida , Hepatócitos , Humanos , Fígado , Espectrometria de Massas em Tandem/métodos
2.
Aging (Albany NY) ; 14(undefined)2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35575836

RESUMO

To master the technology of reprogramming mouse somatic cells to induced pluripotent stem cells (iPSCs), which will lay a good foundation for setting up a technology platform on reprogramming human cancer cells into iPSCs. Mouse iPSCs (i.e., Oct4-GFP miPSCs) was successfully generated from mouse embryonic fibroblasts (MEFs) harboring Oct4-EGFP transgene by introducing four factors, Oct4, Sox2, c-Myc and Klf4, under mESC (Murine embryonic stem cells) culture conditions. Oct4-GFP miPSCs were similar to mESCs in morphology, proliferation, mESC-specific surface antigens and gene expression. Additionally, Oct4-GFP miPSCs could be cultured in suspension to form embryoid bodies (EBs) and differentiate into cell types of the three germ layers in vitro. Moreover, Oct4-GFP miPSCs could develop to teratoma and chimera in vivo. Unlike cell cycle distribution of MEFs, Oct4-GFP miPSCs are similar to mESCs in the cell cycle structure which consists of higher S phase and lower G1 phase. More importantly, our data demonstrated that MEFs harboring Oct4-EGFP transgene did not express GFP, until they were reprogrammed to the pluripotent stage (iPSCs), while the GFP expression was progressively lost when these pluripotent Oct4-GFP miPSCs exposed to EB-mediated differentiation conditions, suggesting the pluripotency of Oct4-GFP miPSCs can be real-time monitored over long periods of time via GFP assay. Altogether, our findings demonstrate that Oct4-GFP miPSC line is successfully established, which will lay a solid foundation for setting up a technology platform on reprogramming cancer cells into iPSCs. Furthermore, this pluripotency reporter system permits the long-term real-time monitoring of pluripotency changes in a live single-cell, and its progeny.

3.
Sci Adv ; 8(19): eabn1811, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35544556

RESUMO

New-generation infrared detectors call for higher operation temperature and polarization sensitivity. For traditional HgCdTe infrared detectors, the additional polarization optics and cryogenic cooling are necessary to achieve high-performance infrared polarization detection, while they can complicate this system and limit the integration. Here, a mixed-dimensional HgCdTe/black phosphorous van der Waals heterojunction photodiode is proposed for polarization-sensitive midwave infrared photodetection. Benefiting from van der Waals integration, type III broken-gap band alignment heterojunctions are achieved. Anisotropy optical properties of black phosphorous bring polarization sensitivity from visible light to midwave infrared without external optics. Our devices show an outstanding performance at room temperature without applied bias, with peak blackbody detectivity as high as 7.93 × 1010 cm Hz1/2 W-1 and average blackbody detectivity over 2.1 × 1010 cm Hz1/2 W-1 in midwave infrared region. This strategy offers a possible practical solution for next-generation infrared detector with high operation temperature, high performance, and multi-information acquisition.

4.
Technol Cancer Res Treat ; 21: 15330338211035270, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35538679

RESUMO

OBJECTIVE: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults. This study aimed to identify significant prognostic biomarkers related to GBM. METHODS: We collected 3 GBM and 3 healthy human brain samples for transcriptome and proteomic sequencing analysis. Differentially expressed genes (DEGs) between GBM and control samples were identified using the edge R package in R. Functional enrichment analyses, prediction of long noncoding RNA target genes, and protein-protein interaction network analyses were performed. Subsequently, transcriptomic and proteomic association analyses, validation using The Cancer Genome Atlas (TCGA) database, and survival and prognostic analyses were conducted. Then the hub genes directly related to GBM were screened. Finally, the expression of key genes was verified by quantitative polymerase chain reaction (qPCR). RESULTS: Totally, 1140 transcripts and 503 proteins were significantly up- or down-regulated. A total of 25 genes were upregulated and 62 were downregulated at both the transcriptome and proteome levels. Results from TCGA database showed that 84 of these 87 genes matched with transcriptome sequencing results. A Cox regression analysis suggested that Fibronectin 1(FN1) was a prognostic risk factor. The qPCR results showed that FN1 was significantly upregulated in GBM samples. CONCLUSIONS: FN1 may play a role in GBM progression through ECM-receptor interaction and PI3K-Akt signaling pathways. FN1 may be considered as a prognostic biomarkers related to GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteoma/genética , Proteômica , Transcriptoma
5.
Int Wound J ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524492

RESUMO

This retrospective study aimed to explore the clinical efficacy of chitosan-based hydrocolloid dressing in treating chronic refractory wounds. A total of 80 patients with chronic refractory wounds were randomly divided into the control group (n = 40) and the study group (n = 40). The control group was given inert saline gauze, while the study group was given chitosan-based hydrocolloid dressing. After 3 weeks of treatment, the wound healing efficiency, itching pain score, changes in the wound area, dressing change frequency, and cost were measured. There was a significant difference in the wound healing effect (t = 2.738), and degree of pain (t = 4.76) between the study and control groups, after 3 weeks of treatment. Similarly, a prominent reduction in the itching frequency (t = 8.62), and wound area (t = 6.379) was observed in the study group compared to the control group (P < .05). Moreover, the frequency and total cost of dressing change in the study group were also lower than the control group and the difference was statistically significant (P < .05). To summarise, the application of chitosan-based hydrocolloid dressing in treating chronic refractory can effectively alleviate pain, accelerate wound healing, relieve itching pain, and reduce the overall cost and frequency of dressing change.

6.
Clin Pharmacol Ther ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35561119

RESUMO

During its 4th transporter workshop in 2021, the International Transporter Consortium (ITC) provided updates on emerging clinically relevant transporters for drug development. Previously highlighted and new transporters were considered based on up-to-date clinical evidence of their importance in drug-drug interactions and potential for altered drug efficacy and safety, including drug-nutrient interactions leading to nutrient deficiencies. For the first time, folate transport pathways (PCFT, RFC, and FRα) were examined in-depth as a potential mechanism of drug-induced folate deficiency and related toxicities (e.g., neural tube defects, megaloblastic anemia). However, routine toxicology studies conducted in support of drug development appear sufficient to flag such folate deficiency toxicities, while prospective prediction from in vitro folate metabolism and transport inhibition is not well enough established to inform drug development. Previous suggestion of retrospective study of intestinal OATP2B1 inhibition to explain unexpected decreases in drug exposure were updated. Furthermore, when the absorption of a new molecular entity is more rapid and extensive than can be explained by passive permeability, evaluation of OATP2B1 transport may be considered. Emerging research on hepatic and renal OAT2 is summarized, but current understanding of the importance of OAT2 was deemed insufficient to justify specific consideration for drug development. Hepatic, renal, and intestinal MRPs (MRP2, MRP3, MRP4) were revisited. MRPs may be considered when they are suspected to be the major determinant of drug disposition (e.g., direct glucuronide conjugates); MRP2 inhibition as a mechanistic explanation for drug-induced hyperbilirubinemia remains justified. There were no major changes in recommendations from previous ITC whitepapers.

7.
Lab Invest ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562411

RESUMO

Nasopharyngeal carcinoma (NPC), which is marked by a distinct distribution, is a common subtype of epithelial carcinoma arising from the nasopharyngeal mucosal lining. SRGN acts as an important and poor prognostic factor of NPC through multiple different mechanisms. However, the biological role and mechanism of SRGN in NPC remain unknown. Expression levels of miR-148a-5p, CREB1, FoxO1, and SRGN in NPC tissues and cell lines were tested by qRT-PCR or/and Western blot. The impacts of miR-148a-5p, CREB1, FoxO1, and SRGN on NPC cell viability, proliferation, migration, and invasion were estimated in vitro by CCK-8, colony formation, wound healing and Transwell experiments, and in vivo by a xenograft tumor model. JASPAR analysis was used to predict the binding activity of Foxo1 (CREB1) with the miR-148a-5p (SRGN) promoter, and the interaction was validated by EMSA and ChIP assays. The miR-148a-5p-CREB1 interaction was validated by a dual-luciferase reporter and RIP assays. CREB1 and SRGN were increased while miR-148a-5p was decreased in NPC. Silencing of SRGN and CREB1, as well as miR-148a-5p overexpression, repressed NPC tumor progression in vitro and in vivo. CREB1 promoted SRGN expression in NPC by targeting the promoter area of SRGN. Silencing of FoxO1 facilitated NPC tumor progression, while silencing of STAT3 repressed NPC tumor progression. FoxO1 bound to and regulated miR-148a-5p in NPC, and miR-148a-5p targeted CREB1. Additionally, FoxO1 knockdown abolished the downregulation of CREB1 and SRGN induced by STAT3 silencing. Our results suggest that STAT3 regulates SRGN and promotes the growth and metastasis of NPC through the FoxO1-miR-148a-5p-CREB1 axis.

8.
J Ovarian Res ; 15(1): 55, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35513870

RESUMO

BACKGROUND: Increasing evidence has indicated that Maelstrom (MAEL) plays an oncogenic role in various human carcinomas. However, the exact function and mechanisms by which MAEL acts in epithelial ovarian cancer (EOC) remain unclear. RESULTS: This study demonstrated that MAEL was frequently overexpressed in EOC tissues and cell lines. Overexpression of MAEL was positively correlated with the histological grade of tumors, FIGO stage, and pT/pN/pM status (p < 0.05), and it also acted as an independent predictor of poor patient survival (p < 0.001). Ectopic overexpression of MAEL substantially promoted invasiveness/metastasis and induced epithelial-mesenchymal transition (EMT), whereas silencing MAEL by short hairpin RNA effectively inhibited its oncogenic function and attenuated EMT. Further study demonstrated that fibroblast growth factor receptor 4 (FGFR4) was a critical downstream target of MAEL in EOC, and the expression levels of FGFR4 were significantly associated with MAEL. (P < 0.05). CONCLUSION: Our findings suggest that overexpression of MAEL plays a crucial oncogenic role in the development and progression of EOC through the upregulation of FGFR4 and subsequent induction of EMT, and also provide new insights on its potential as a therapeutic target for EOC.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas de Ligação a DNA , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Ovarianas/patologia , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Fatores de Transcrição
9.
Microbiol Spectr ; : e0075922, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35481834

RESUMO

Our previous study found that Qiong-Yu-Gao (QYG), a traditional Chinese medicine formula derived from Rehmanniae Radix, Poria, and Ginseng Radix, has protective effects against cisplatin-induced acute kidney injury (AKI), but the underlying mechanisms remain unknown. In the present study, the potential role of gut microbiota in the nephroprotective effects of QYG was investigated. We found that QYG treatment significantly attenuated cisplatin-induced AKI and gut dysbiosis, altered the levels of bacterial metabolites, with short-chain fatty acids (SCFAs) such as acetic acid and butyric acid increasing and uremic toxins such as indoxyl sulfate and p-cresyl sulfate reducing, and suppressed histone deacetylase expression and activity. Spearman's correlation analysis found that QYG-enriched fecal bacterial genera Akkermansia, Faecalibaculum, Bifidobacterium, and Lachnospiraceae_NK4A136_group were correlated with the altered metabolites, and these metabolites were also correlated with the biomarkers of AKI, as well as the indicators of fibrosis and inflammation. The essential role of gut microbiota was further verified by both the diminished protective effects with antibiotics-induced gut microbiota depletion and the transferable renal protection with fecal microbiota transplantation. All these results suggested that gut microbiota mediates the nephroprotective effects of QYG against cisplatin-induced AKI, potentially via increasing the production of SCFAs, thus suppressing histone deacetylase expression and activity, and reducing the accumulation of uremic toxins, thereby alleviating fibrosis, inflammation, and apoptosis in renal tissue. IMPORTANCE Cisplatin-induced acute kidney injury is the main limiting factor restricting cisplatin's clinical application. Accumulating evidence indicated the important role of gut microbiota in pathogenesis of acute kidney injury. In the present study, we have demonstrated that gut microbiota mediates the protective effects of traditional Chinese medicine formula Qiong-Yu-Gao against cisplatin-induced acute kidney injury. The outputs of this study would provide scientific basis for future clinical applications of QYG as prebiotics to treat cisplatin-induced acute kidney injury, and gut microbiota may be a promising therapeutic target for chemotherapy-induced nephrotoxicity.

10.
Eur J Obstet Gynecol Reprod Biol ; 272: 213-216, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35381543

RESUMO

OBJECTIVE: To determine efficacy and safety of salvage autologous pubovaginal sling (PVS) placement after a two or more failed synthetic midurethral sling. METHODS: Women undergoing autologous PVS placement for two or more failed synthetic MUS between 2008 and 2019 were identified. Those patients were conducted a follow-up examination. Outcomes of surgery were assessed using the cough stress test with a full bladder and symptom questionnaire, including Incontinence Visual Analogue Scale (I-VAS) and Incontinence Quality of Life (I-QOL) questionnaire. Surgical results were categorized into three classes: cured, improved, and failed. Secondary measures included patients' recommendation of autologous fascial sling (AFS). RESULTS: A total of 18 eligible patients met the criteria, of whom median age at surgery was 67 (52-74) years with a median follow-up of 80 (12-144) months. Preoperatively, all patients were identified by urodynamic test with Valsalva leak point pressure (VLPP) < 60 cmH2O. All patients had concomitant part sling excision combined with urethrolysis at the salvage operation. At the follow-up examination, sixteen in eighteen (88.89%) patients were cured and improved. The postoperative total score and each individual domain in I-QOL improved significantly compared with the baseline (p < 0.001). Postoperative I-VAS was significantly lower than preoperative (1.3 ± 0.6 vs. 7.8 ± 2.2, p < 0.001). A total of 16 patients (88.89%) recommended the AFS to others. Neither perioperative blood transfusions nor other complications above Clavien level 3 were observed. CONCLUSIONS: Our study indicates that autologous PVS is effective and safe in women with recurrent stress urinary incontinence after two or more failed synthetic MUS.

11.
RSC Adv ; 12(6): 3755-3762, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35425359

RESUMO

Binary Cu x O1-x compounds have some advantages as optoelectronic functional materials, but their further development has encountered some bottlenecks, such as inaccurate bandgap values and slow improvement of photoelectric conversion efficiency. In this work, all possible stoichiometric ratios and crystal structures of binary Cu x O1-x compounds were comprehensively analyzed based on a high-throughput computing database. Stable and metastable phases with different stoichiometric ratios were obtained. Their stability in different chemical environments was further analyzed according to the component phase diagram and chemical potential phase diagram. The calculation results show that Cu, Cu2O and CuO have obvious advantages in thermodynamics. The comparison and analysis of crystal microstructure show that the stable phase of Cu x O1-x compounds contains the following two motifs: planar square with Cu atoms as the center and four O atoms as the vertices; regular tetrahedron with O atoms as the center and four Cu atoms as the vertices. In different stoichiometric ratio regions, the electron transfer and interaction modes between Cu and O atoms are different. This effect causes energy differences between bonding and antibonding states, resulting in the different conductivity of binary Cu x O1-x compounds: semi-metallic ferromagnetic, semiconducting, and metallicity. This is the root of the inconsistent and inaccurate bandgap values of Cu x O1-x compounds. These compositional, structural, and property variations provide greater freedom and scope for the development of binary Cu x O1-x compounds as optoelectronic functional materials.

12.
RSC Adv ; 12(8): 4939-4945, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35425495

RESUMO

Flexible optoelectronic devices have numerous applications in personal wearable devices, bionic detectors, and other systems. There is an urgent need for functional materials with appealing electrical and optoelectronic properties, stretchable electrodes with outstanding mechanical flexibility, and gate medium with flexibility and low power consumption. Two-dimensional transition metal dichalcogenides (TMDCs), a novel kind of widely studied optoelectrical material, have good flexibility for their ultrathin nature. P(VDF-TrFE) is a kind of organic material with good flexibility which has been proved to be a well-performing ferroelectric gate material for photodetectors. Herein, we directly fabricated a well-performing photodetector based on ReS2 and P(VDF-TrFE) on a flexible substrate. The device achieved a high responsivity of 11.3 A W-1 and a high detectivity of 1.7 × 1010 Jones from visible to near-infrared. Moreover, with strain modulation, the device's responsivity improved 2.6 times, while the detectivity improved 1.8 times. This research provides a prospect of flexible photodetectors in the near-infrared wavelength.

13.
Dis Markers ; 2022: 2005616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419118

RESUMO

Objective: To investigate the optimal temperature of hypothermia treatment in rats with cardiac arrest caused by ventricular fibrillation (VF) after the return of spontaneous circulation (ROSC). Methods: A total of forty-eight male Sprague-Dawley rats were induced by VF through the guidewire with a maximum of 5 mA current and untreated for 8 min. Cardiopulmonary resuscitation (CPR) was performed for 8 min followed by defibrillation (DF). Resuscitated rats were then randomized into the normothermia (37°C) group, milder (35°C) group, mild (33°C) group, or moderate (28°C) group. Hypothermia was immediately induced with surface cooling. The target temperature was maintained for 4 h before rewarming to 37 ± 0.5°C. Moreover, at the end of the 4 h, a rat in each group was randomly selected to be sacrificed for the cerebral cortex electron microscopy observation (n = 1). The other resuscitated animals were observed for up to 72 h after ROSC (n = 7). Left ventricular ejection fraction (LVEF) and left ventricular end diastolic volume (LVEDV) were measured. Survival time, survival rate, and neurological deficit score (NDS) were recorded for 72 h. Results: During hypothermia, higher LVEF was observed in the hypothermia groups when compared with normothermia group (35°C vs. 37°C, p < 0.05, 33°C and 28°C vs. 37°C, p < 0.01). Among the hypothermia groups, LVEF was higher in the 28°C group than that of 35°C (p < 0.05). However, both the heart rate (HR) (p < 0.01) and LVEDV (28°C vs. 35°C, p < 0.01, 28°C vs. 37°C and 33°C, p < 0.05) were lowest in the 28°C group when compared with the other groups. There were no significant differences of LVEF and LVEDV between the group 35°C and 33°C (p > 0.05). After rewarming, the LVEF of 35°C group was higher than that of group 37°C, 33°C, and 28°C (35°C vs. 37°C and 28°C, p < 0.01, 35°C vs. 33°C, p < 0.05). Group 35°C and 33°C resulted in longer survival (p < 0.01), higher survival rate (p < 0.01), and lower NDS (35°C vs. 37°C and 28°C, p < 0.01, 33°C vs. 37°C and 28°C, p < 0.05) compared with the group 37°C and 28°C. The extent of damage to cerebral cortex cells in group of 35°C and 33°C was lighter than that in group of 37°C and 28°C. The 35°C group spent less time in the process of cooling and rewarming than the group 33°C and 28°C (p < 0.01). Conclusions: An almost equal protective effect of milder hypothermia (35°C) and mild hypothermia (33°C) in cardiac arrest (CA) rats was achieved with more predominant effect than moderate hypothermia (28°C) and normothermia (37°C). More importantly, shorter time spent in cooling and rewarming was required in the 35°C group, indicating its potential clinical application. These findings support the possible use of milder hypothermia (35°C) as a therapeutic agent for postresuscitation.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Hipotermia Induzida , Hipotermia , Animais , Reanimação Cardiopulmonar/métodos , Modelos Animais de Doenças , Parada Cardíaca/terapia , Humanos , Hipotermia/terapia , Hipotermia Induzida/métodos , Masculino , Ratos , Ratos Sprague-Dawley , Volume Sistólico , Fibrilação Ventricular/terapia , Função Ventricular Esquerda
14.
Macromol Biosci ; : e2100529, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35362658

RESUMO

Current treatments for chronic neuropathic pain often fall short. A small-molecular compound ZL006 can suppress N-Methyl-d-aspartate receptor (NMDAR)-mediated neuropathic pain behaviors without blocking essential NMDAR function and brings new hope for neuropathic pain therapy. The persistent nature of neuropathic pain mandates the long-term treatment. However, similar to existing analgesics, ZL006 has only a short duration of action. To unleash the therapeutic potential of ZL006, the stability of ZL006 in aqueous solutions is investigated, and a ZL006-incorporated P407-based thermoresponsive injectable hydrogel is developed. The computational analysis is performed to help achieve the desired ZL006-loaded hydrogel system and elucidate the gelation mechanism. The hydrogel matrix can be loaded with ZL006 in an aqueous phase at room temperature without costly specialized equipment and no organic solvent, where the sol is formed and injectable. On subcutaneous administration and subsequent rapid warming to physiological temperature, the sol is converted to a gel. The thermoresponsive hydrogel at body temperature enables the extended release of encapsulated ZL006, and therefore a single subcutaneous injection of ZL006-hydrogel produces a prolonged and stable analgesic action in mice with spinal nerve ligation. The study provides a practical chronic neuropathic pain therapy and a new perspective on future applications of ZL006.

15.
J Oncol ; 2022: 2800488, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422863

RESUMO

Purpose: Poly(ADP-ribose) polymerase 1 (PARP1) is necessary for single-strand break (SSB) repair by sensing DNA breaks and facilitating DNA repair through poly ADP-ribosylation of several DNA-binding and repair proteins. Inhibition of PARP1 results in collapsed DNA replication fork and double-strand breaks (DSBs). Accumulation of DSBs goes beyond the capacity of DNA repair response, ultimately resulting in cell death. This work is aimed at assessing the synergistic effects of the DNA-damaging agent temozolomide (TMZ) and the PARP inhibitor niraparib (Nira) in human multiple myeloma (MM) cells. Materials and Methods: MM RPMI8226 and NCI-H929 cells were administered TMZ and/or Nira for 48 hours. CCK-8 was utilized for cell viability assessment. Cell proliferation and apoptosis were detected flow-cytometrically. Immunofluorescence was performed for detecting γH2A.X expression. Soft-agar colony formation assay was applied to evaluate the antiproliferative effect. The amounts of related proteins were obtained by immunoblot. The combination index was calculated with the CompuSyn software. A human plasmacytoma xenograft model was established to assess the anti-MM effects in vivo. The anti-MM activities of TMZ and/or Nira were evaluated by H&E staining, IHC, and the TUNEL assay. Results: The results demonstrated that cotreatment with TMZ and Nira promoted DNA damage, cell cycle arrest, and apoptotic death in cultured cells but also reduced MM xenograft growth in nude mice, yielding highly synergistic effects. Immunoblot revealed that TMZ and Nira cotreatment markedly increased the expression of p-ATM, p-CHK2, RAD51, and γH2A.X, indicating the suppression of DNA damage response (DDR) and elevated DSB accumulation. Conclusion: Inhibition of PARP1 sensitizes genotoxic agents and represents an important therapeutic approach for MM. These findings provide preliminary evidence for combining PARP1 inhibitors with TMZ for MM treatment.

16.
Urology ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35469808

RESUMO

OBJECTIVE: To compare the effectiveness and safety of sacrospinous ligament fixation (SSLF) and uterosacral ligaments suspension (ULS) for surgical correction of pelvic organ prolapse (POP). METHODS: Comparative studies were identified in PubMed, EMBASE, MEDLINE, Cochrane library, Medicine and clinicaltrials.gov databases. Randomized controlled trials, prospective and retrospective cohort studies were included. Primary outcomes were collected including anatomical success rate (Defined as anterior or posterior vaginal wall beyond the hymen), surgical success rate, recurrence and total complication rate, while secondary outcomes were specific complications rates. Data were analyzed using Revman (Version 5.4). RESULTS: After searching databases and removing the duplicate studies, a total of 57 articles had entered the screening stage. Finally, nine moderate and high quality studies (4 randomized controlled trials and 5 retrospective studies) with 4516 participants were included. For primary outcomes, there was no statistical difference between the two groups regarding surgical success rate (RR=1.00; 95% CI: 0.91-1.01; I2= 0%; P=0.98), anatomical success (RR=0.90; 95% CI: 0.78-1.05; I2= 61%; P=0.19), recurrence rate (RR=1.26; 95% CI: 0.85-1.87; I2= 75%; P=0.24) and total complication rate (RR=1.07; 95% CI: 0.89-1.28; I2= 33%; P=0.47). Subgroup analysis regarding different follow-up times (1,2 and 5 years) and stages (Stage 2 and stage 3-4) found similar results in primary outcomes. CONCLUSIONS: In conclusion, SSLF and ULS have the same efficacy and safety for patients. However, SSLF seems to have lower complication rates of vaginal granulation tissue and urethral injury and is gradually favored by surgeons because of its short operation time and simple operation. We still need more high-quality research, especially in terms of the incidence of complications.

17.
Mycopathologia ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35445313

RESUMO

Deep cutaneous fungal infections including deep dermatophytosis are responsible for significant morbidity and mortality, especially in immunocompromised patients. Variable and longer turnaround time on tissue culture results delay diagnosis. We sought to seek the fast bedside diagnosis for disseminated deep dermatophytosis by direct microscopy using a blunt scalpel or needle aspiration before biopsy. This is a 6-year retrospective review of patients with a diagnosis of disseminated deep dermatophytosis seen at a single tertiary care institution. Trichophyton rubrum was isolated in four patients, and T. mentagrophyte complex in one patient. All the dermatophyte isolates can grow at 37 °C. Microscopy of purulence sampling from intact nodules demonstrated abundant septate hyphae, and also isolation from purulence was concordance with skin tissue culture. Ultrasound-guided sampling from non-eroded can yield purulence, and direct microscopy of purulence may facilitate rapid diagnosis of deep dermatophytosis and serve to prevent disease progression and dissemination.

18.
Org Lett ; 24(16): 3069-3074, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35442692

RESUMO

Fungal cytochrome P450 enzymes have been shown to catalyze regio- and stereoselective oxidative intermolecular phenol coupling. However, an enzyme capable of catalyzing undirected para-para (C4-4') coupling has not been reported. Here, we revealed the biosynthetic gene cluster (BGC) of phomoxanthone A from the marine fungus Diaporthe sp. SYSU-MS4722. We heterologously expressed 14 biosynthetic genes in Aspergillus oryzae NSAR1 and found that PhoCDEFGHK is involved in the early stage of phomoxanthone A biosynthesis to give chrysophanol and that chrysophanol is then processed by PhoBJKLMNP to yield penexanthone B. A feeding experiment suggested that PhoO, a cytochrome P450 enzyme, catalyzed the regioselective oxidative para-para coupling of penexanthone B to give phomoxanthone A. The mechanism of PhoO represents a novel enzymatic 4,4'-linkage dimerization method for tetrahydroxanthone formations, which would facilitate biosynthetic engineering of structurally diverse 4,4'-linked dimeric tetrahydroxanthones.


Assuntos
Vias Biossintéticas , Fenol , Sistema Enzimático do Citocromo P-450/metabolismo , Fenóis/metabolismo , Xantonas
19.
Front Surg ; 9: 861406, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35388360

RESUMO

Objective: It is well known that accurate location of the leak in the operation is crucial for repairing cerebrospinal fluid leakage. The study aims to investigate the application of intraoperative injection of normal saline through lumbar drainage in repairing complex leaks. Methods: The fistulas of all patients with CSF leak were located by computed tomography cisternography (CTC) or heavy T2 magnetic resonance imaging (MRI) before surgery. Before anesthesia, the patient underwent lumbar drainage implantation, and then 20 ml of normal saline was slowly injected through the lumbar drainage to observe the patient's response. The surgical approach was designed based on the preoperative imaging data. When the operation was near to the suspected fistula, normal saline was injected through lumbar drainage (20 ml each time) to confirm the leak location. After CSF leak repair, saline was injected again to confirm whether the repair was successfully. Result: Of the 5 patients with complex leaks, 4 cases were repaired by transnasal endoscopy method, and 1 case was repaired by transnasal endoscopy method and epidural method. A total of 7 leaks were found during the operation. During the operation, 40-120 ml of normal saline was injected through lumbar drainage. Cauda equina neuralgia was developed in patients who received 120 ml normal saline, which was relieved by intrathecal injection of dexamethasone. During the follow-up of 3 months, 1 case suffered from brain abscess, which was controlled by vancomycin. There was no recurrence of rhinorrhea. Conclusion: Intraoperative injection of normal saline through lumbar drainage can not only better expose the complex leak but also check the repair effect of the leak during transnasal endoscopic repair, which is effective and avoids side effects.

20.
Int Immunopharmacol ; 107: 108706, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35313270

RESUMO

Periodontitis is a chronic periodontal inflammatory disease and its etiology remains not fully understood. Chlorogenic acid (CA) is an ingredient isolated from nature product and exerts anti-inflammatory property. The purpose of the present study was to estimate the effect of CA on LPS-induced Human gingival fibroblasts (HGFs) and explore its mechanism. The CysLT1R inhibitor montelukast, Nrf2 inhibitor ML385, NLRP3 inhibitor MCC950 were employed to investigate the mechanism. As a result, the bioinformatic analysis indicated that CysLT1R, Nrf2, NLRP3 in the affected site of periodontitis patients gingival tissues were notably altered compared with those in unaffected site of healthy donors gingival tissues. The treatment with CA inhibited the contents of IL-1ß, IL-18 both in LPS-induced HGFs. CA ameliorated the expressions of CysLT1R, Nrf2, HO-1, NLRP3, ASC, pro-caspase-1, active caspase-1 in vitro. CA treatment promoted the nuclear translocation of Nrf2, suppressed oxidative stress and elevated mitochondrial membrane potential. The co-treatment with montelukast, ML385, MCC950 proved that CysLT1R, Nrf2, NLRP3 participated in the CA-mediated anti-inflammatory reaction. Molecular docking showed that CA might combine with CysLT1R. In conclusion, our data suggested that CA could attenuate inflammation in HGFs, which was possibly through CysLT1R/Nrf2/NLRP3 signaling.


Assuntos
Fator 2 Relacionado a NF-E2 , Periodontite , Anti-Inflamatórios/farmacologia , Caspase 1/metabolismo , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Fibroblastos , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Periodontite/metabolismo , Receptores de Leucotrienos
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