Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 574
Filtrar
1.
J Org Chem ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726924

RESUMO

The simple, commercially available ZnBr2 has been successfully employed as a highly efficient and chemoselective catalyst for the dehydrogenative borylation of terminal alkynes with HBpin under mild conditions. It shows a good tolerance toward various functional groups such as aryl, alkyl, heteroaryl, etc. The plausible reaction mechanism has been investigated based on the corresponding stoichiometric experiments and DFT calculations.

2.
Int J Gen Med ; 14: 8383-8388, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819746

RESUMO

Objective: The present study evaluates the psychosocial care and the bronchoalveolar lavage (BAL)/fiberoptic bronchoscopy (FB) procedure in children with pediatric acute exogenous lipoid pneumonia (ELP) and summarizes the critical points of nursing. Methods: Data on the psychosocial factors of the patients and clinical information were collected. Participants comprised 41 children within three years of age. Results: All the children were cooperative with the BAL/FB procedure. The children's pain scores were between 4-6, and the psychological conditions of the children and caregivers were nervous/anxious upon admission. After the medical staff's psychological care and health education, the children's postoperative pain scores were reduced to 0-3, and the psychological state of the caregivers was positive. Conclusion: Psychological care can alleviate families' adverse emotions and promote treatment cooperation and recovery from the acute ELP.

3.
Opt Express ; 29(22): 35206-35215, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34808959

RESUMO

Holographic pancake optics have been designed and fabricated in eyewear display optics literature dating back to 1985, however, a see-through pancake optic solution has not been demonstrated to date. The key contribution here is the first full-color volume holographic pancake optic in an optical see-through configuration for applications in mobile augmented reality. Specifically, the full-color volume holographic pancake is combined with a flat lightguide in order to achieve the optical see-through property. The fabricated hardware optics has a measured field of view of 29 degrees (horizontal) by 12 degrees (vertical) and a measured large eyebox that allows a ±10 mm horizontal motion and ∼±3 mm vertical motion for a 4 mm diameter pupil. The measured modulation transfer function (average orientation) is 10% contrast at 10 lp/deg. Three holograms were characterized with respect to their diffraction efficiency, angular bandwidth, focal length, haze, and thickness parameters. The phase function in the reflection mode hologram implements a spherical mirror that has a relatively simple recording geometry.

4.
J Pharm Biomed Anal ; 208: 114403, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34798392

RESUMO

Morinda officinalis How (MO) possesses prominent tonifying kidney yang and strengthening bone and muscle effects in traditional Chinese medicine (TCM). Due to the complexity of MO components, the chemical mechanism leading to efficacy changes of MO caused by processing remain unclear. This study aimed to investigate and discover quality markers (Q-markers) related to the clinical efficacy of processed MO. The different processed products of MO have different clinical applications, although they originate from the same medicinal herb. The active chemical components from raw and processed MO that protect against reproductive oxidative stress damage were evaluated. The processed products of MO were prepared by different processing methods. The changes in oligosaccharides during processing were characterized by high-performance liquid chromatography with an evaporative light scattering detector (HPLC-ELSD), and the differential components in raw and processed MO were analyzed using SA, HCA, PCA, and OPLS-DA methods. The protective effects of raw and processed MO oligosaccharides (MOOs) against reproductive oxidative stress damage were evaluated based on the spermatic number, spermatic survival rate, abnormal sperm ratio and serum biochemical indicators in cyclophosphamide-induced (CTX-induced) male mice. The results revealed that processed MOOs had better pharmacological effects than raw MOOs. Therefore, gray correlation analysis (GRA) and the technique for order preference by similarity to ideal solution (TOPSIS) methods were used to investigate the spectrum-effect relationships of MOOs. Spectrum-effect relationship analysis revealed that all of the characteristic peaks contributed to the treatment of reproductive oxidative stress damage, and the relative correlation degrees were greater than 0.6. Among them, the peaks 1 F-fructofuranosylnystose, nystose, and 1-kestose and the peaks X2-X5, which were most closely correlated to the treatment of reproductive oxidative stress damage, were identified as inulin-oligosaccharides and inulo-oligosaccharides, respectively. It was proposed that these constituents could be considered Q-markers for processed products of MO. Thus, this study aimed to explore chemical markers that correlate with the clinical efficacy of processed MO.

5.
Medicine (Baltimore) ; 100(46): e27474, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797274

RESUMO

ABSTRACT: The best time window of percutaneous coronary intervention (PCI) is within 12 hours for ST-segment elevation myocardial infarction (STEMI). However, there is limited evidence about the proper time of PCI for delayed STEMI patients.From June 2014 to June 2015, a total of 268 patients receiving PCI with second-generation drug-eluting stent in a Chinese hospital after 3 days of STEMI onset were enrolled in this retrospective study, who were divided into the early group (3-14 days) and the late group (>14 days). A propensity score match was conducted to reduce the baseline difference. The primary endpoint of all-cause death and secondary endpoints of major adverse cardiac and cerebrovascular event (myocardial infarction [MI], stroke, emergent revascularization, and rehospitalization due to heart failure) were compared using survival analysis.At last, 182 cases were matched after propensity score match, with no statistical difference in baseline characteristics and PCI data. Kaplan-Meier survival curve demonstrated no difference in all-cause death of the 2 groups (P = .512). However, the early group presented a higher incidence of MI than the late group (P = .036). The multivariate Cox regression analysis also demonstrated that the early PCI was an independent risk factor for MI compared with late PCI (hazard ratio = 3.83, 95%CI [1.91-8.82], P = .001). There was no statistical difference in other major adverse cardiac and cerebrovascular event, including stroke, emergent revascularization, and rehospitalization due to heart failure.Using the 2nd drug-eluting stent, early PCI (3-14 days) and late PCI (>14 days) have comparable efficacy and outcomes. However, patients receiving early PCI are subjected to a relatively higher risk of recurrent MI.

6.
Front Immunol ; 12: 764825, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733292

RESUMO

Eosinophils are a minor component of circulating granulocytes, which are classically viewed as end-stage effector cells in host defense against helminth infection and promoting allergic responses. However, a growing body of evidence has emerged showing that eosinophils are versatile leukocytes acting as an orchestrator in the resolution of inflammation. Rheumatoid arthritis (RA) is the most common chronic inflammatory disease characterized by persistent synovitis that hardly resolves spontaneously. Noteworthy, a specific population of eosinophils, that is, regulatory eosinophils (rEos), was identified in the synovium of RA patients, especially in disease remission. Mechanistically, the rEos in the synovium display a unique pro-resolving signature that is distinct from their counterpart in the lung. Herein, we summarize the latest understanding of eosinophils and their emerging role in promoting the resolution of arthritis. This knowledge is crucial to the design of new approaches to rebalancing immune homeostasis in RA, considering that current therapies are centered on inhibiting pro-inflammatory cytokines and mediators rather than fostering the resolution of inflammation.

7.
Front Microbiol ; 12: 770734, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745078

RESUMO

Resveratrol, a natural polyphenol compound with multiple bioactivities, is widely used in food and pharmaceutical industry. Endophytic fungus Alternaria sp. MG1, as a native producer of resveratrol, shows increasing potential application. However, strategies for improvement of the biosynthesis of resveratrol in this species are still scarce. In this study, different elicitors were used to investigate their effect on the biosynthesis of resveratrol in MG1 and the induction mechanism. Ultrasound and sodium butyrate had no effect and slight inhibition on the resveratrol production and related gene expression, respectively. UV radiation and co-culture with Phomopsis sp. XP-8 significantly promoted the biosynthesis of resveratrol with the highest production (240.57µg/l) coming from UV 20min. Co-culture altered the profiles of secondary metabolites in MG1 by promoting and inhibiting the synthesis of stilbene and lignin compounds, respectively, and generating new flavonoids ((+/-)-taxifolin, naringin, and (+)-catechin). Oligomeric proanthocyanidins (OPC) also showed an obviously positive influence, leading to an increase in resveratrol production by 10 to 60%. Two calcium-dependent protein kinases (CDPK) were identified, of which CDPK1 was found to be an important regulatory factor of OPC induction. Synergistic treatment of UV 20min and 100µm OPC increased the production of resveratrol by 70.37% compared to control and finally reached 276.31µg/l.

8.
Oxid Med Cell Longev ; 2021: 8321400, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745424

RESUMO

Abnormal vascular smooth muscle cell (VSMC) proliferation has an important role in the pathogenesis of both atherosclerosis restenosis and hypertension. Vascular endothelial growth factor (VEGF) has been shown to stimulate VSMC proliferation. In addition, angiogenesis is one of the hallmarks of cancerous growth. VEGF is the key modulator for the initial stages of angiogenesis that acts through the endothelial-specific receptor tyrosine kinases (VEGFRs). VEGFR-2 blockage is a good approach for suppression of angiogenesis. In order to discover novel VEGFR-2 TK inhibitors, we have designed and synthesized three new series of pyridine-containing compounds. The new compounds were all screened against a panel of three cell lines (HepG-2, HCT-116, and MCF-7). Promising results encouraged us to additionally evaluate the most active members for their in vitro VEGFR-2 inhibitory effect. Compound 7a, which is the most potent candidate, revealed a significant increase in caspase-3 level by 7.80-fold when compared to the control. In addition, Bax and Bcl-2 concentration levels showed an increase in the proapoptotic protein Bax (261.4 Pg/ml) and a decrease of the antiapoptotic protein Bcl-2 (1.25 Pg/ml) compared to the untreated cells. Furthermore, compound 7a arrested the cell cycle in the G2/M phase with induction of apoptosis. The immunomodulatory effect of compound 7a, the most active member, showed a reduction in TNF-α by 87%. Also, compound 7a caused a potent inhibitory effect on smooth muscle proliferation. Docking studies were also performed to get better insights into the possible binding mode of the target compounds with VEGFR-2 active sites.

9.
World J Clin Cases ; 9(25): 7381-7390, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34616805

RESUMO

BACKGROUND: At present, there is controversy on the role of microvessel density (MVD) in tumors as a prognostic indicator of bladder transitional cell carcinoma (BTCC). However, the MVD in tumors is simply classified based on the expression of several different vascular markers, which has not been related to analytical research on the prognosis of patients with BTCC. AIM: To explore the classification of blood vessels in tumors and studied the relationship between MVD and the prognosis of patients with BTCC. METHODS: The tissue mass was detected by tissue microarray and immunohistochemical analysis with monoclonal antibodies against CD31, CD34, CD105, and vascular smooth muscle actin to investigate the MVD in BTCC. The measurement data are expressed as the mean ± SD. The difference between the groups was analyzed by the t-test, the counting data were analyzed by χ 2 test. The Kaplan-Meier survival curve was estimated by the product-limit method. The log-rank time-series test was employed to compare the tumor-free survival curves. RESULTS: The MVD was closely related to the pathological grade, invasive depth, and prognosis of BTCC. Significant differences were found between grade I and grade II, grade II and grade III, superficial and invasive type, and the tumor-free survival group and the recurrence or metastasis group (P < 0.01). Multivariate analysis showed that undifferentiated MVD was an independent prognostic factor for patient survival time. An inverse correlation between undifferentiated tumor MVD and differentiated tumor MVD in BTCC was also shown. CONCLUSION: The classification of blood vessels in BTCC could act as an important prognostic indicator and may also be of great significance in the treatment of cancer.

10.
Front Oncol ; 11: 680402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660263

RESUMO

Background: Microtubule-associated proteins (MAPs) have been considered to play significant roles in the tumor evolution of non-small cell lung cancer (NSCLC). Nevertheless, mRNA transcription levels and prognostic value of distinct MAPs in patients with NSCLC remain to be clarified. Methods: In this study, the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA) database, and Human Protein Atlas were utilized to analyze the relationship between mRNA/protein expression of different MAPs and clinical characteristics in NSCLC patients, including tumor type and pathological stage. The correlation between the transcription level of MAPs and overall survival (OS) of NSCLC patients was analyzed by Kaplan-Meier plotter. Besides, 50 frequently altered neighbor genes of the MAPs were screened out, and a network has been constructed via the cBioPortal and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) dataset. Meanwhile, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on the expression data of MAPs and their 50 frequently altered neighbor genes in NSCLC tissues. Furthermore, The Cancer Immunome Atlas (TCIA) was utilized to analyze the relationship between MAP expression and the response to immunotherapy. Finally, we used reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to verify the expression of MAPs in 20 patients with NSCLC. Results: The present study discovered that the mRNA transcription levels of MAP7/7D2 were enriched in NSCLC tissues, while those of the MAP2/4/6/7D3 were lower in NSCLC specimens than those in control specimens. The mRNA transcription level of MAP6 was significantly associated with the advanced stage of NSCLC. Besides, survival analysis indicated that higher mRNA expressions of MAP2/4/6/7/7D3 were correlated considerably with favorable OS of NSCLC patients, whereas increased mRNA expression levels of MAP1A/1S were associated with poor OS. Moreover, the expression of MAP1A/1B/1S/4/6/7D1/7D3 was significantly correlated with immunophenoscore (IPS) in NSCLC patients. Conclusions: Our analysis indicated that MAP1A/1S could serve as potential personalized therapeutic targets for patients with NSCLC, and the enriched MAP2/4/6/7/7D3 expression could serve as a biomarker for favorable prognosis in NSCLC. Besides, the expression of MAP1A/1B/1S/4/6/7D1/7D3 was closely related to the response to immunotherapy. Taken together, MAP expression has potential application value in the clinical treatment and prognosis assessment of NSCLC patients, and further verifiable experiments can be conducted to verify our results.

11.
Langmuir ; 37(42): 12271-12277, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34644074

RESUMO

Pinning of a three-phase contact line at the nanoscale cannot be explained by conventional macroscale theories and thus requires an experimental insight to understand this phenomenon. We performed in-situ transmission electron microscopy observation of the three-phase contact lines of bubbles inside graphene liquid cells to experimentally investigate the causes of nanoscale pinning. In our observations, the three-phase contact line was not affected by the 0.6 nm-thick inhomogeneity of the graphene surface, but thicker metal nanoparticles with diameters of 2-10 nm and nanoflakes caused pinning of the gas-liquid interface. Notably, we found that flake-like objects can cause pinning that prevents the bubble overcome the flake object in a noncontact state, with a 2 nm-thick liquid film between them and the bubble. This phenomenon can be explained by the repulsive force obtained using the Derjaguin, Landau, Verwey, and Overbeek theory. We also observed that the flake temporally prevented the gas-liquid interface moving away from the flake. We discussed the physical mechanism of the attractive force-like phenomenon by considering the nanoconfinement effect of the liquid sandwiched by two graphene sheets and the hydration layer formed near the solid surface.

12.
J Appl Toxicol ; 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34687223

RESUMO

Perfluorooctane sulfonate (PFOS) is a fluorinated organic pollutant with substantial accumulation in mammalian liver tissues. However, the impact of chronic PFOS exposure on liver disease progression and the underlying molecular mechanisms remain elusive. Herein, we for the first time revealed that micromolar range of PFOS exposure initiates the activation of NLR pyrin domain containing 3 (NLRP3) inflammasome to drive hepatocyte pyroptosis. We showed that 5 mg/kg/day PFOS exposure may exacerbated liver inflammation and steatosis in high-fat diet (HFD)-fed mice with concurrently elevated expression of NLRP3 and caspase-1. PFOS exposure resulted in viability impairment and LDH release in BRL-3A rat liver cells. 25-100 µM concentrations of PFOS exposure activated the NLRP3 inflammasome, leading to consequent GSDMD cleavage, IL-1ß release and the initiation of pyroptosis in a dose-dependent manner, whereas treatment with 10 µM NLRP3 inhibitor MCC950 abrogated this effect. Moreover, pretreatment of 5 mM ROS scavenger N-acetyl-L-cysteine (NAC) ameliorated PFOS-induced NLRP3 inflammasome activation and pyroptosis. Collectively, our data highlight a pivotal role of pyroptotic death in PFOS-mediated liver inflammation and metabolic disorder.

13.
Exp Ther Med ; 22(5): 1289, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630644

RESUMO

Chronic postsurgical pain (CPSP) has a high incidence, but the underlying mechanisms remain elusive. Previous studies have indicated that caveolin-1 (Cav-1) plays a notable role in pain modulation. To study the role of Cav-1 in CPSP in the present study, a rat model of skin/muscle incision and retraction (SMIR) was established. Under anesthesia, skin and superficial muscle of the medial thigh were incised and a small pair of retractors inserted. It was revealed that SMIR increased the expression of Cav-1 in the dorsal root ganglion (DRG) and the injured tissue around the incision. Furthermore, the infiltration of endothelial cells and macrophages in the injured tissue around the incision increased constantly, and the vascular permeability increased due to the destruction of the vascular endothelial barrier function around the injured tissue. Cav-1 was mainly expressed by CD68-positive macrophages and CD34-positive endothelial cells in the injured tissues around the incision, while it was also primarily localized in the medium and large neurofilament 200-positive neurons and a small number of calcitonin gene-related peptide- and isolectin B4-positive small and medium-sized neurons in the DRG. The results demonstrated that the sustained high expression levels of Cav-1 in the injured tissue around the incision could lead to the dysfunction of the vascular endothelial barrier and, thus, could induce the inflammatory response through the lipoprotein transport of endothelial cells, thereby resulting in peripheral sensitization. In addition, the sustained high expression levels of Cav-1 in the DRG could sensitize large-sized neurons and change the transmission mode of noxious stimuli. The findings of the present study indicated that a Cav-1-mediated process could participate in neuronal transmission pathways associated with pain modulation.

14.
J Crohns Colitis ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558619

RESUMO

Artificial intelligence (AI) techniques are quickly spreading across medicine as an analytical method to tackle challenging clinical questions. What were previously thought of as highly complex data sources, such as images or free text, are now becoming manageable. Novel analytical methods merge the latest developments in information technology infrastructure with advances in computer science. Once primarily associated with Silicon Valley, AI techniques are now making their way into medicine, including in the field of inflammatory bowel diseases (IBD). Understanding potential applications and limitations of these techniques can be difficult, in particular for busy clinicians. In this article, we explain the basic terminologies and provide particular focus on the foundations behind state-of-the-art AI methodologies in both imaging and text. We explore the growing applications of AI in medicine, with a specific focus on IBD to inform the practicing gastroenterologist and IBD specialist. Finally, we outline possible future uses of these technologies in daily clinical practice.

15.
Acta Pharm Sin B ; 11(9): 2924-2936, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34589405

RESUMO

Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and the confronting "Warburg effect" compromise the efficacy of hypoxia alleviation. Herein, we construct a cascade enzyme-powered nanomotor (NM-si), which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy. Catalase (Cat) and glucose oxidase (GOx) are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor (NM), with hexokinase-2 (HK-2) siRNA further condensed (NM-si). The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H2O2 gradient towards deep tumor, with hypoxia successfully alleviated in the meantime. The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis. In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel (PTX@HSA) after pre-treated with NM-si for TME reconstruction. This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.

16.
Cancer Cell Int ; 21(1): 514, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565365

RESUMO

BACKGROUND: ALDOA is a glycolytic enzyme found mainly in developing embryos, adult muscle and various malignant tumours, including pancreatic tumours. Our previous study revealed that ALDOA, an oncogene, can promote the proliferation and metastasis of pancreatic tumours. Furthermore, ALDOA could predict poor prognosis in patients with pancreatic tumours. METHODS: IHC analysis of PDAC tissues was conducted. Western blotting, PCR, cellular IF experiments and cell cycle assessment were conducted utilizing cell lines. GSEA and KEGG pathway analysis were used to identify potential downstream pathways. RESULTS: To explore the effects of ALDOA on the occurrence and development of pancreatic tumours, we analysed the RNA sequencing results and found that ALDOA could inhibit the DDR. Under normal circumstances, when DNA is damaged, initiation of the DDR causes cell cycle arrest, DNA repair or cell apoptosis. Further experiments showed that ALDOA could inhibit DNA repair and reverse cell cycle arrest induced by DNA damage so that DNA damage persisted to promote the occurrence and progression of cancer. CONCLUSIONS: Regarding the molecular mechanism, we found that ALDOA inhibited the DDR and improved activation of the cell cycle checkpoint PLK1 by suppressing ATM, which promotes tumour cell progression. Consequently, ALDOA has a profound effect on pancreatic cancer development.

17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(8): 933-937, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34590559

RESUMO

OBJECTIVE: To investigate the role and regulatory mechanism of triggering receptor expressed on myeloid cell 2 (TREM2) in mice lung ischemia/reperfusion injury (LIRI). METHODS: Thirty-six healthy male C57BL/6 mice were divided into six groups according to the random number method (n = 6): normal control group, and LIRI 2, 6, 12, 24, 48 hours group. Mice LIRI models were established by clamping the left hilum. The wet/dry weight ratio (W/D) of left lung tissue was measured. Lung injury was observed and evaluated by hematoxylin-eosin (HE) staining and electron microscopy. The levels of interleukins (IL-1ß, IL-18) in lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of TREM2 and caspase-1 were determined by polymerase chain reaction (PCR). The protein expressions of TREM2, caspase-1, Gasdermin-D (GSDMD) were determined by Western blotting. RESULTS: At 2 hours after LIRI, lung injury began to appear, the lung ultrastructure changed, and the lung injury score increased; at 6 hours, the degree of lung injury was the most serious; after 12 hours, the lung injury gradually reduced and the lung injury score gradually decreased. Compared with the normal control group, lung W/D ratio and lung injury score of LIRI 2, 6, 12, 24, 48 hours groups were significantly higher, the differences were statistically significant (lung W/D ratio: 7.06±0.52, 8.34±0.17, 6.42±0.35, 5.34±0.25, 5.59±0.45 vs. 4.69±0.23; lung injury score: 5.50±0.54, 9.75±0.89, 5.88±0.84, 3.63±0.74, 4.13±0.64 vs. 1.13±0.35, all P < 0.05). Compared with the normal control group, the levels of IL-1ß and IL-18 in lung tissue were significantly increased at 2 hours after LIRI, reached a peak at 6 hours [IL-1ß (ng/L): 502.76±12.25 vs. 56.50±8.07, IL-18 (ng/L): 414.02±10.75 vs. 81.63±5.29, both P < 0.05], then decreased gradually, and were still significantly higher than the normal control group at 48 hours. The PCR and Western blotting showed that the expression of TREM2 was significantly lower than that in the normal control group at 2 hours after LIRI, and reached a valley at 6 hours [TREM2 mRNA (2-ΔΔCt): 0.47±0.05 vs. 1.02±0.05, TREM2/GAPDH: 0.23±0.13 vs. 0.48±0.17, both P < 0.05], then gradually increased, and reached the peak at 24 hours [TREM2 mRNA (2-ΔΔCt): 3.98±0.15 vs. 1.02±0.05, TREM2/GAPDH: 0.71±0.17 vs. 0.48±0.17, both P < 0.05]. The trend of expression of caspase-1 and GSDMD were opposite to that of TREM2, which increased at first and then decreased, and reached a peak at 6 hours after reperfusion [caspase-1 mRNA (2-ΔΔCt): 2.20±0.13 vs. 1.01±0.02, caspase-1/GAPDH: 0.64±0.02 vs. 0.20±0.06, GSDMD/GAPDH: 1.23±0.01 vs. 0.87±0.02, all P < 0.05]. CONCLUSIONS: TREM2 might be involved in LIRI in mice. The mechanism may be related to the effect of TREM2 on caspase-1-mediated pyroptosis.


Assuntos
Lesão Pulmonar , Traumatismo por Reperfusão , Animais , Pulmão , Masculino , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides , Receptores Imunológicos , Fator de Necrose Tumoral alfa
18.
Transl Oncol ; 14(12): 101214, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34500231

RESUMO

P-glycoprotein (P-gp) acts as a pump to transport cytotoxic drugs out of cells and is upregulated in cancer cells. Suppressing the expression of P-gp is an effective strategy to overcome multidrug resistance in cancer chemotherapy. Temozolomide (TMZ) is the recommended drug for the standard treatment of patients with glioblastoma, but its clinical application is restricted due to drug resistance. Transient receptor potential channel-5 (TRPC5), a Ca2+-permeable channel, has been attributed to a different drug resistance mechanism except DNA repair system; therefore, we aimed to elucidate the mechanism regarding the role of TRPC5 in TMZ resistance. TRPC5 and P-glycoprotein (P-gp) are upregulated in TMZ-resistant glioblastoma cell lines. The downregulation of TRPC5 inhibited P-gp expression and led to a significant reversal of TMZ resistance in TMZ-resistant cell lines. TRPC5-siRNA restricted the growth of tumour xenografts in an athymic nude mouse model of TMZ-resistant cells. In specimens from patients with recurrent glioblastoma, TRPC5 was found to be highly expressed, accompanied by the upregulation of P-gp expression. The nuclear factor of activated T cell isoform c3 (NFATc3), which acts as a transcriptional factor, bridges TRPC5 activity to P-gp induction. In conclusion, these results demonstrate the functional role of the TRPC5-NFATc3-P-gp signalling pathway in TMZ resistance in glioblastoma cells.

19.
BMC Endocr Disord ; 21(1): 170, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416890

RESUMO

BACKGROUND: The occurrence of hypomagnesemia in patients with primary hyperparathyroidism (PHPT) has been noted previously; however, the association of hypomagnesemia and severity of primary hyperparathyroidism remains unknown. The present study aimed to evaluate the association of hypomagnesemia with biochemical and clinical manifestations in patients with PHPT. METHODS: This was a retrospective study conducted at a tertiary hospital. We obtained data from 307 patients with PHPT from January 2010 through August 2020. Data on demographics, history, laboratory findings, bone densitometry findings, and clinical presentation and complications were collected and were compared in normal magnesium group vs hypomagnesemia group. RESULTS: Among the 307 patients with PHPT included in our study, 77 patients (33/102 [32.4%] males and 44/205 [21.5%] females) had hypomagnesemia. Mean hemoglobin levels in the hypomagnesemia group were significantly lower than those in the normal magnesium group in both males and females. In contrast, patients with hypomagnesemia had a higher mean serum calcium and parathyroid hormone than individuals with normal magnesium. The typical symptoms of PHPT, such as nephrolithiasis, bone pain/fractures, polyuria, or polydipsia, were more common in the hypomagnesemia group. In addition, patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis. Even after adjusting for potential confounders, including age, sex, body mass index, estimated glomerular filtration rate, and parathyroid hormone levels, these associations remained essentially unchanged. CONCLUSION: Biochemical and clinical evidence indicates that patients with PHPT with hypomagnesemia have more severe hyperparathyroidism than those without hypomagnesemia. In addition, PHPT patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis.

20.
J Immunol Res ; 2021: 1891519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34423050

RESUMO

The presence of anti-citrullinated protein antibodies (ACPAs) in the serum is one of the immunological features of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide (CCP) assay has been widely used in clinic for the diagnosis of RA. However, up to 40% of RA patients are anti-CCP negative and the diagnostic sensitivity in this population needs to be improved for better clinical management. In this study, peptides with Multiple Citrulline Similar Motif (MCSM) were synthesized and a new ELISA system, which we called RA_CP, was developed to detect citrullinated antigens with MCSM present in the serum. 106 RA,48 other arthritis patients and 41 sex- and age-matched healthy controls (HCs) were included in this study. Patients with RA have a significantly higher amount of citrullinated antigens with MCSM than other arthritis patients and HCs. RA patients with positive anti-CCP are also MCSM positive, whereas 75% anti-CCP negative patients are positive for MCSM. The diagnostic sensitivity for anti-CCP and MCSM was 81.1% and 95.3%, while the specificity was 100% and 94.4%, respectively. ROC curve analyses showed that the area under the curve (AUC) values were 0.906 (95% CI: 0.860-0.951) for anti-CCP and 0.948 (95% CI: 0.912-0.985) for MCSM while the combination of MCSM and anti-CCP test has the highest AUC (0.971, 95% CI: 0.946-0.996). Our results suggest that detection of citrullinated antigens with MCSM has improved sensitivity compared with anti-CCP assay and could serve as a biomarker in diagnosis of RA patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...