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1.
J Plast Surg Hand Surg ; : 1-6, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35034565

RESUMO

Reverse homodigital dorsoradial flap (RHDF) of the thumb has become a qualified option for the reconstruction of thumb tissue defects. However, the sensory recovery of the flap in long term is still unknown. Therefore, this study focused on the sensory recovery of RHDFs for the coverage of thumb in hand after a long-term follow-up. From January 2010 to March 2011, 18 patients (14 men and four women) were treated consecutively with an RHDF. All the patients were followed up two times. The pain and cold intolerance of the flap were self-reported by the patients. The sensory recovery of the flap was evaluated using Semmes-Weinstein (SW) monofilament, moving two-point discrimination (M-2PD) and static two-point discrimination (S-2PD) tests. The average times of the first and second follow-up were 39 ± 4 and 88 ± 6 months, respectively. The mean value of SW monofilament sensitivity score and M-2PD at first follow-up was significantly higher than that of the second follow-up and contralateral thumb. The mean value of S-2PD at the second follow-up was significantly lower than that of the first follow-up and higher than that of the contralateral thumb. The cold intolerance severity score (CISS) at the first follow-up was higher than that at the second follow-up. No significant difference was found in terms of the pain between the two follow-ups. RHDFs without nerve coaptation for thumb coverage could obtain good sensory recovery after a long-term follow-up. Abbreviations: RHDF: reverse homodigital dorsoradial flap; CISS: cold intolerance severity score; SW: Semmes-Weinstein monofilament sensitivity score; M-2PD: moving two-point discrimination; S-2PD: static two-point discrimination; VAS: visual analog scale.

2.
Medicine (Baltimore) ; 100(50): e27970, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34918647

RESUMO

OBJECTIVE: Systematic evaluation of the efficacy and safety of unilateral biportal endoscopic decompression in the treatment of lumbar spinal stenosis. METHODS: We conducted a systematic literature search and compared the randomized controlled trials (RCTs) and retrospective studies of unilateral biportal endoscopy (UBE) and microscopic decompression (MD) in the treatment of lumbar spinal stenosis from several databases. RESULTS: Seven studies were included. The results of meta-analysis showed that the operation time of UBE was shorter than that of MD. [SMD = -0.443, 95% CI (-0.717, -0.169), P  = .002]. Compared with MD, the patients' back pain was slighter on the 1st day, 1-2 months and 6 months after UBE. During the long-term follow-up, there was no significant difference in back pain between MD and UBE [SMD = -0.519, 95% CI (-0.934, -0.104), P  = .014]. There was no significant difference in lower limb visual analogue score (VAS) score between UBE decompression and MD [SMD = -0.105, 95% CI (-0.356, 0.146), P  = .412]. The results of meta-analysis showed that the C-reactive protein (CRP) level of UBE was lower than that of MD [weighted mean difference = -1.437, 95% CI (-2.347, -0.527), P  = .002]. There was no significant difference in other clinical effects between the 2 groups. CONCLUSION: The operation time of UBE was shorter than that of MD, and it was superior to micro decompression in early back VAS score, lower limb VAS score and early postoperative CRP level. There was no statistical difference between UBE and MD in other outcomes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34964663

RESUMO

Objective: Dry eye disease (DED) is classified as aqueous deficient, evaporative, or mixed. We investigated the therapeutic effect of the novel anti-inflammatory drug phosphosulindac (PS) in rabbit models of DED encompassing its pathogenesis, and its transition to chronicity. Methods: We treated three rabbit models of DED with PS (hydrogel formulation) or vehicle topically applied 1 × /day. We induced aqueous-deficient DED (acute and chronic) by injecting Concanavalin A into lacrimal glands; evaporative DED by injecting into the upper eyelid inactivated Mycobacterium tuberculosis in complete Freund's adjuvant; and mixed DED through desiccative stress, induced by holding open the eye for 3 h. We determined corneal sensitivity, tear break-up time (TBUT), Schirmer's tear test (STT), tear osmolality, and fluorescein staining of the ocular surface. Results: PS reversed all abnormal DED parameters. In acute DED, PS dose dependently normalized corneal sensitivity and tear osmolality; and improved TBUT, STT, and fluorescein staining. PS normalized corneal sensitivity and improved all other parameters in chronic aqueous-deficient DED. In evaporative DED, PS normalized corneal sensitivity and improved TBUT and fluorescein staining (osmolality and STT were not significantly changed in this model). In the desiccative stress model, PS improved TBUT and fluorescein staining but had no effect on STT or tear osmolality. Conclusions: PS rapidly reversed almost all DED parameters in its three subtypes. The normalization of the suppressed corneal sensitivity suggests the possibility of marked symptomatic relief by PS. The hydrogel formulation allows once-daily dosing. PS merits further development as a potential treatment for DED.

4.
Pain Res Manag ; 2021: 6894001, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966473

RESUMO

Background: Robot-assisted pedicle screw placement is usually performed under general anesthesia to keep the body still. The aim of this study was to compare the accuracy of the robot-assisted technique under regional anesthesia with that of conventional fluoroscopy-guided percutaneous pedicle screw placement under general anesthesia in minimally invasive lumbar fusion surgery. Methods: This study recruited patients who underwent robot-assisted percutaneous endoscopic lumbar interbody fusion (PELIF) or fluoroscopy-guided minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) between December 2017 and February 2020 at a single center. Based on the method of percutaneous pedicle screw placement used, patients were divided into the robot-assisted under regional anesthesia (group RE-RO) and fluoroscopy-guided under general anesthesia (group GE-FLU) groups. The primary outcome measures were screw accuracy and the incidence of facet joint violation (FJV). Secondary outcome measures included X-ray and visual analogue scale (VAS) scores which were used to evaluate the degree of the postoperative pain at 4 hours and on postoperative days 1, 2, and 3. Intraoperative adverse events were also recorded. Results: Eighteen patients were included in group RE-RO, and 23 patients were included in group GE-FLU. The percentages of clinically acceptable screws (Gertzbein and Robbins grades A and B) were 94.4% and 91.5%, respectively. There was no significant difference in the percentages of clinically acceptable screws (p=0.44) or overall Gertzbein and Robbins screw accuracy grades (p=0.35). Only the top screws were included in the analysis of FJVs. The percentages of FJV (Babu grades 1, 2, and 3) were 5.6% and 28.3%, respectively. This difference was statistically significant (p=0.01). Overall, the FJV grades in group RE-RO were significantly better than those in group GE-FLU (p=0.009). The mean fluoroscopy time for each screw in group RE-RO was significantly shorter than that in group GE-FLU (group RE-RO: 5.4 ± 1.9 seconds and group GE-FLU: 6.8 ± 2.0 seconds; p=0.03). The postoperative pain between the RE-RO and GE-FLU groups was not statistically significant. The intraoperative adverse events included 1 case of registration failure and 1 case of guide-wire dislodgment in group RE-RO, as well as 2 cases of screw misplacement in group GE-FLU. No complications related to anesthesia were observed. Conclusion: Robot-assisted pedicle screw placement under regional anesthesia can be performed effectively and safely. The accuracy is comparable to the conventional technique. Moreover, this technique has the advantage of fewer FJVs and a lower radiation time.


Assuntos
Anestesia por Condução , Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Robótica , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos
5.
Exp Eye Res ; 213: 108827, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34742691

RESUMO

Drug development, resource- and time-intensive, extensively employs cell-based assays to assess the efficacy and safety of candidate drugs. The widely used immortalized cell lines, experimentally convenient, have limited predictive value. In contrast, ex-vivo models more faithfully reproduce diseases but are technically challenging to establish. To address this need, we developed a simplified process for ex-vivo cell culture, demonstrating its feasibility in ocular surface cells. Conjunctival cells were harvested by impression cytology and grown on mixed cellulose ester membrane filters (MCFs). Human and rabbit conjunctival cells cultured on MCFs are 100% viable at 24 h, and 43% viable at 72 h. A gene expression study evaluating 84 genes involved in ocular inflammation demonstrated that ex-vivo culturing maintains intact the expression of two thirds of these genes in human cells. That these cells are suitable for the assessment of ocular drugs was demonstrated by studying the effect of phosphosulindac (PS), a small molecule under development for the treatment of dry eye disease, in both human and rabbit conjunctival cells. PS, for example, suppressed the expression of CXCL10, a cytokine participating in the pathogenesis of dry eye disease, in human and in rabbit conjunctival cells cultured ex-vivo by 32% and 70%, respectively. Conjunctival cells cultured ex-vivo can be transfected to evaluate mechanistic questions. We successfully transfected such cells with a plasmid expressing luciferase under the control of an IFN-γ-responsive promoter or its control plasmid. IFN-γ stimulated luciferase expression by 85% in cells with the responsive plasmid but not in controls; PS significantly suppressed this induction by 37% without affecting the control plasmid. These findings demonstrate that human and rabbit conjunctival cells cultured ex-vivo with our method are viable and maintain their biological integrity; respond to biological and pharmacological agents; and are transfectable with informative plasmids. The unique advantage of this method is to potentially accelerate the development of novel drugs for the treatment of ocular surface diseases, and to advance our understanding of ocular surface pathophysiology.

6.
J Med Chem ; 64(23): 17448-17454, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34797669

RESUMO

The growing epidemic of diabetes means that there is a need for therapies that are more efficacious, safe, and convenient. Here, we report the efficient synthesis of a novel disulfide dimer of human insulin tethered at the N-terminus of its B-chain through placement of a cysteine residue. The resulting peptide was shown to bind to both the insulin receptor isoform B and insulin-like growth factor-1 receptor with comparable affinity to native insulin. In in vivo insulin tolerance tests, the dimer was equipotent to Actrapid insulin and possessed a sustained duration of action greater than that of Actrapid and Glargine. While the secondary structure of our dimeric insulin was similar to that of insulin, it was more resistant to proteolysis. More importantly, our analogue was produced in quantitative yield from a monomeric thiol insulin scaffold. Our results suggest that this dimer has significant potential to address the clinical needs in the treatment of diabetes.

7.
Brain Behav ; : e2402, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758196

RESUMO

BACKGROUND: Recreational N2 O abuse is an important etiology of neurological impairment in young patients, which may easily be ignored clinically. Few current studies have investigated the characteristics or the effects experienced by its users. We aimed to explore any correlation between the clinical severity and biomarkers and spinal magnetic resonance imaging (MRI) abnormalities, identify independent factors associated with spinal MRI abnormalities, and ascertain factors affecting depression/anxiety in patients with N2 O-related neurological disorders. METHODS: Patients with N2 O-related neurological disorders were enrolled retrospectively between February 2017 and July 2020. Their demographic, clinical, laboratory, neuroimaging, electrophysiological, and neuropsychological findings were analyzed. Correlation analyses were conducted using Spearman's or Pearson's correlation and linear regression analysis. Independent factors associated with spinal MRI abnormalities were identified using univariate and multivariate analyses. RESULTS: The principal clinical manifestations of N2 O-related neurological disorders (n = 63; 38 men, 25 women; mean age ± SD: 22.60 ± 4.46 years) were sensory disturbance, followed by gait disturbance and pyramidal tract damage. A significant negative correlation existed between serum vitamin B12 levels and clinical severity (r = -0.309, p = .014), which disappeared after linear regression. An interval of less than 6 months between initial N2 O abuse and hospitalization was independently associated with spinal MRI abnormalities (39.47% vs. 72.00%, respectively; χ2  = 6.40, p = .01). Thirty-eight (60.32%) and 40 (63.49%) patients experienced anxiety and depression, respectively. Moreover, the higher the clinical scores/serum homocysteine levels, the greater the severity of anxiety/depression (r = 0.442, p < .01; r = 0.346, p < .01; r = 0.477, p < .01; r = 0.324, p < .01). CONCLUSIONS: The significant inverse correlation between initial vitamin B12 levels and clinical severity could aid prognosis prediction in patients with N2 O-related neurological disorders. Spinal MRI abnormalities were not related to clinical severity but depended on the time interval between initial N2 O abuse and hospitalization. Anxiety and depression were common comorbidity in these patients, and their severity increased with the intensity of clinical impairment and/or serum homocysteine levels.

8.
Pain Res Manag ; 2021: 6454760, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777672

RESUMO

Background: Symptomatic thoracic disc herniation is a challenge in spinal surgery, especially for cases with calcification. Traditional open operation has a high complication rate. The authors introduced a modified full-endoscopic transforaminal ventral decompression technique in this study and evaluated its imaging and clinical outcomes. Materials and Methods: Eleven patients with symptomatic thoracic disc herniation who underwent full-endoscopic transforaminal ventral decompression in a single medical center were enrolled. The surgical technique was performed as described in detail. Dilator sliding punching, endoscope-monitored foraminoplasty, and base cutting through the "safe triangle zone" are the key points of the technique. Clinical outcomes were assessed by the modified Japanese Orthopedic Association (mJOA) score for neurological improvement and the visual analogy score (VAS) for thoracic and leg pain. The operation time, hospital stay, and complications were also analyzed. Results: Postoperative magnetic resonance imaging (MRI) revealed good decompression of the spinal cord. The mJOA improved from 7.4 (range: 5-10) to 10.2 (range: 9-11). Axial thoracic pain improved in 8 of 9 patients. Leg pain and thoracic radicular pain improved in all patients. No complications were observed. The average operation time was 136 minutes (range: 70-180 minutes). The average length of hospital stay was 5.3 days (range: 2-8 days). Conclusion: Minimally invasive full-endoscopic transforaminal ventral decompression for the treatment of symptomatic thoracic disc herniation with or without calcification is feasible and may be another option for this challenging spine disease.

9.
J Exp Clin Cancer Res ; 40(1): 359, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781982

RESUMO

BACKGROUND: Highly expressed STOML2 has been reported in a variety of cancers, yet few have detailed its function and regulatory mechanism. This research aims to reveal regulatory mechanism of STOML2 and to provide evidence for clinical therapeutics, via exploration of its role in colorectal cancer, and identification of its interacting protein. METHODS: Expression level of STOML2 in normal colon and CRC tissue from biobank in Nanfang Hospital was detected by pathologic methods. The malignant proliferation of CRC induced by STOML2 was validated via gain-of-function and loss-of-function experiments, with novel techniques applied, such as organoid culture, orthotopic model and endoscopy monitoring. Yeast two-hybrid assay screened interacting proteins of STOML2, followed by bioinformatics analysis to predict biological function and signaling pathway of candidate proteins. Target protein with most functional similarity to STOML2 was validated with co-immunoprecipitation, and immunofluorescence were conducted to co-localize STOML2 and PHB. Pathway regulated by STOML2 was detected with immunoblotting, and subsequent experimental therapy was conducted with RAF inhibitor Sorafenib. RESULTS: STOML2 was significantly overexpressed in colorectal cancer and its elevation was associated with unfavorable prognosis. Knockdown of STOML2 suppressed proliferation of colorectal cancer, thus attenuated subcutaneous and orthotopic tumor growth, while overexpressed STOML2 promoted proliferation in cell lines and organoids. A list of 13 interacting proteins was screened out by yeast two-hybrid assay. DTYMK and PHB were identified to be most similar to STOML2 according to bioinformatics in terms of biological process and signaling pathways; however, co-immunoprecipitation confirmed interaction between STOML2 and PHB, rather than DTYMK, despite its highest rank in previous analysis. Co-localization between STOML2 and PHB was confirmed in cell lines and tissue level. Furthermore, knockdown of STOML2 downregulated phosphorylation of RAF1, MEK1/2, and ERK1/2 on the MAPK signaling pathway, indicating common pathway activated by STOML2 and PHB in colorectal cancer proliferation. CONCLUSIONS: This study demonstrated that in colorectal cancer, STOML2 expression is elevated and interacts with PHB through activating MAPK signaling pathway, to promote proliferation both in vitro and in vivo. In addition, combination of screening assay and bioinformatics marks great significance in methodology to explore regulatory mechanism of protein of interest.

10.
Org Biomol Chem ; 19(37): 8014-8017, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34596198

RESUMO

In this report, we introduce a novel building block for Fmoc/tBu solid phase peptide synthesis (SPPS) of ß-linked O-GlcNAcylated peptides. This building block carries acid labile silyl ether protecting groups, which are fully removed under TFA-mediated peptide cleavage conditions from the resin, thus requiring fewer synthetic steps and no intermediate purification as compared to other acid or base labile protecting group strategies.

11.
Pain Physician ; 24(7): E1147-E1153, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34704724

RESUMO

BACKGROUND: Refractory intercostal neuralgia is a troublesome disease with long treatment cycle and short-term therapeutic effects. No treatment modality has given effective pain relief. The authors present here a safe and effective endoscopic surgical option for refractory intercostal neuralgia. OBJECTIVES: To introduce the surgical techniques of percutaneous endoscopic intercostal neurectomy used for refractory intercostal neuralgia and to evaluate its safety and efficacy. STUDY DESIGN: A retrospective study. SETTING: The Department of Orthopedics at the Hebei General Hospital in China. METHODS: Thirteen patients with refractory intercostal neuralgia were treated with percutaneous endoscopic intercostal neurectomy. Patients were followed up to 12 months postoperatively. The pain was measured by the Visual Analog Scale (VAS) score. Complications, such as aspiration, dysfunction, infection, and local hematoma were analyzed. RESULTS: Pain was relieved in all 13 patients, with only 1 patient reporting burning sensation along the intercostal nerve distribution area after operation. No other complications were found. All patients had significant improvement, with significantly lower VAS scores recorded postoperatively. No recurrence was reported during the follow-up period. LIMITATIONS: The retrospective nature of this study is a limitation, as well as the small sample size and short observation time. CONCLUSIONS: Endoscopic intercostal neurotomy is an effective and safe minimally invasive surgical treatment for refractory intercostal neuralgia.

12.
J Appl Lab Med ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499739

RESUMO

BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) is a promising biomarker for the early prediction of acute kidney injury (AKI). However, the clinical utility of L-FABP in different populations or settings remains unclear. We present a meta-analysis of studies evaluating the performance of L-FABP in AKI prediction. METHODS: We performed a literature search in MEDLINE, EMBASE, and Cochrane library, using search terms "acute kidney injury" and "L-FABP." Studies investigating the performance characteristics of L-FABP for the early diagnosis of AKI were included. Data about patient characteristics, diagnostic criteria of AKI, quantitative data required for construction of a 2 × 2 table (number of participants, sensitivity, specificity, and case number), study settings, and outcomes were extracted. The bivariable model was applied to calculate the estimated sensitivity and specificity of L-FABP. A summary ROC curve was created by plotting the true-positive rate against the false-positive rate at various cutoff values from different studies. RESULTS: We found 27 studies reporting measurement of urine (n = 25 studies) or plasma (n = 2 studies) L-FABP. Overall, the estimated sensitivity was 0.74 (95% CI: 0.69-0.80) and specificity was 0.78 (95% CI: 0.71-0.83). L-FABP demonstrated a stable area under the ROC of 0.82 (95% CI: 0.79-0.85) in variable clinical settings including intensive care unit, surgery, and contrast-induced AKI. In subgroup analysis excluding pediatric and post radiocontrast exposure cohorts, L-FABP had comparative diagnostic performance with neutrophil gelatinase associated lipocalin (NGAL). CONCLUSIONS: Despite broad prevalence, L-FABP is a clinically useful marker with moderate accuracy in variable clinical settings as demonstrated in our subgroup analysis. Except for pediatric patients and those post-radiocontrast exposure, L-FABP has comparable discriminative capability as NGAL.

13.
Bioconjug Chem ; 32(10): 2148-2153, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34494823

RESUMO

The current commercially available glucagon formulations for the treatment of severe hypoglycemia must be reconstituted immediately prior to use, owing to the susceptibility of glucagon to fibrillation and aggregation in an aqueous solution. This results in the inconvenience of handling, misuse, and wastage of this drug. To address these issues, we synthesized a glycosylated glucagon analogue in which the 25th residue (Trp) was replaced with a cysteine (Cys) and a Br-disialyloligosaccharide was conjugated at the Cys thiol moiety. The resulting analogue, glycoglucagon, is a highly potent full agonist at the glucagon receptor. Importantly, glycoglucagon exhibits markedly reduced propensity for fibrillation and enhanced thermal and metabolic stability. This novel analogue is thus a valuable lead for producing stable liquid glucagon formulations that will improve patient compliance and minimize wastage.

14.
ACS Infect Dis ; 7(11): 2959-2970, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34587737

RESUMO

Oral dental infections are one of the most common diseases affecting humans, with caries and periodontal disease having the highest incidence. Caries and periodontal disease arise from infections caused by oral bacterial pathogens. Current misuse and overuse of antibiotic treatments have led to the development of antimicrobial resistance. However, recent studies have shown that cationic antimicrobial peptides are a promising family of antibacterial agents that are active against oral pathogenic bacteria and also possess less propensity for development of antimicrobial resistance. This timely Review has a focus on two primary subjects: (i) the oral bacterial pathogens associated with dental infections and (ii) the current development of antimicrobial peptides targeting oral pathogens.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Microbiota , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias , Humanos
15.
Medicine (Baltimore) ; 100(38): e27282, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559135

RESUMO

OBJECTIVE: The purpose of this systematic review and meta-analysis is to explore the screw positioning accuracy, complications related to pedicle screw implantation, revision rate and radiation exposure between robot screw placement and traditional fluoroscopic screw placement. METHODS: We searched several databases, including CNKI, Wanfang database, cqvip datebase, PubMed, Cochrane library and EMBASE, to identify articles that might meet the criteria. Meta-analysis was performed using Revman 5.3 software. RESULTS: A total of 13 randomized controlled trial were included. The results showed that the pedicle screw accuracy of the robot assisted group was significantly better than that of the conventional freehand (FH) group (OR = 3.5, 95% confidence interval [CI] [2.75,4.45], P < .0001). There was no significant difference in the complications caused by pedicle screw implantation between the robot-assisted group and the conventional FH group [OR = 0.39, 95%CI (0.10,1.48), P = .17]. The rate of facet joint invasion in the robot-assisted group was significantly lower than that in the conventional FH group (OR = 0.06, 95%CI [0.01,0.29], P = .0006). The revision rate in the robot-assisted group was significantly lower than that in the conventional FH group (OR = 0.19, 95%CI [0.05,0.71], P = 0.0.01). There was no significant difference in the average radiation of pedicle screws implantation between the robot-assisted group and the conventional FH (mean difference = -7.94, 95%CI [-20.18,4.30], P = .20). CONCLUSION: The robot-assisted group was significantly better than the conventional FH in the accuracy of pedicle screw placement and facet joint invasion rate and revision rate. There was no significant difference in the complication and fluoroscopy time between the two groups.


Assuntos
Vértebras Lombares/cirurgia , Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Vértebras Torácicas/cirurgia , Fluoroscopia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação
16.
Anal Chem ; 93(36): 12204-12212, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34461717

RESUMO

Diels-Alder chemistry is a well-explored avenue for the synthesis of bioactive materials; however, its potential applications have recently expanded following the development of reactions that can be performed in buffered aqueous environments at low temperatures, including fulvene-maleimide [4 + 2] cycloadditions. In this study, we synthesized two novel amine-reactive fulvene linkers to demonstrate the application of this chemistry for generating mass spectrometry-cleavable labels ("mass tags"), which can be used for the labeling and detection of proteins. Successful conjugation of these linkers to maleimide-labeled peptides was observed at low temperatures in phosphate-buffered saline, allowing the non-destructive modification of proteins with such mass tags. The labile nature of fulvene-maleimide adducts in the gas phase also makes them suitable for both matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) mass spectrometric analysis. Unlike previous examples of MALDI mass tags, we show that fulvene-maleimide cycloaddition adducts fragment predictably upon gas-phase activation without the need for bulky photocleavable groups. Further exploration of this chemistry could therefore lead to new approaches for mass spectrometry-based bioassays.


Assuntos
Peptídeos , Espectrometria de Massas por Ionização por Electrospray , Ciclopentanos , Maleimidas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
17.
Front Psychiatry ; 12: 687739, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305683

RESUMO

Background: Depression is common in Alzheimer's disease (AD) with an unclear neural mechanism. This study aimed to investigate the underlying cerebral perfusion associated with depression in AD and evaluate its clinical significance. Method: Twenty-one AD patients and 21 healthy controls (HCs) were enrolled in this study. The depressive symptom was defined according to the Hamilton Depression Rating Scale (HAMD). Nine patients were diagnosed as AD with depression symptoms (HAMD >7). Three-dimensional pseudocontinuous arterial spin labeling MR imaging was conducted to measure regional cerebral blood flow (CBF). Neuropsychological tests covered cognition and depressive scores. Between-group comparisons on clinical variables and regional CBFs, relationship between regional CBF and depressive score, and identification of AD patients with depression were performed using covariance analysis, linear regression, and receiver operating characteristic (ROC) analysis, respectively. Results: Compared with HCs, AD patients without depression exhibited lower gray matter CBF (p = 0.016); compared with AD patients without depression, AD patients with depression had higher CBF in the right supplementary motor area (39.23 vs. 47.91 ml/100 g/min, p = 0.017) and right supramarginal gyrus (35.54 vs. 43.85 ml/100 g/min, p = 0.034). CBF in the right supplementary motor area was correlated with depressive score (ß = 0.46, p = 0.025). The combination of CBF in the right supplementary motor area and supramarginal gyrus and age could identify AD patients with depression from those without depression with a specificity of 100%, sensitivity of 66.67%, accuracy of 85.71%, and area under the curve of 0.87. Conclusions: Our findings suggested that hyperperfusion of the right supplementary motor area and right supramarginal gyrus were associated with depression syndrome in AD, which could provide a potential neuroimaging marker to evaluate the depression state in AD.

18.
Clin Exp Immunol ; 206(2): 141-152, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34309827

RESUMO

Primary anti-phospholipid antibody syndrome (pAPS) is a multi-organ autoimmune disease, and autoantibodies are involved in its pathogenesis. Follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) are critical for B cell maturation and antibody production, but their roles in pAPS remain unknown. We enrolled 32 pAPS patients and 23 healthy controls (HCs) and comprehensively analyzed circulating Tfh and Tfr, as well as their subsets, using flow cytometry. Clinical data including autoantibody levels were collected and their correlations with Tfh and Tfr subsets were analyzed. In addition, correlation analyses between B cell functional subsets and Tfh and Tfr were performed. Changes and potential effects of serum cytokines on Tfr and Tfh were further explored. We found the circulating Tfr was significantly decreased while Tfh and Tfh/Tfr ratios were increased in pAPS patients. Tfh2, inducible T cell co-stimulator (ICOS)+  programmed cell death 1 (PD-1)+  Tfh and Ki-67+  Tfh percentages were elevated, while CD45RA- forkhead box protein 3 (FoxP3)hi , Helios+ , T cell immunoglobulin and ITIM (TIGIT)+  and Ki-67+  Tfr percentages were decreased in pAPS patients. New memory B cells and plasmablasts were increased and altered B cell subsets and serum autoantibodies were positively correlated with Tfh, Tfh2, ICOS+ PD-1+  Tfh cells and negatively associated with Tfr, CD45RA- FoxP3hi Tfr and Helios+  Tfr cells. In addition, pAPS with LA/aCL/ß2GPI autoantibodies showed lower functional Tfr subsets and higher activated Tfh subsets. Serum interleukin (IL)-4, IL-21, IL-12 and transforming growth factor (TGF)-ß1 were up-regulated and associated with Tfh and Tfr subset changes. Our study demonstrates that imbalance of circulating Tfr and Tfh, as well as their functional subsets, is associated with abnormal autoantibody levels in pAPS, which may contribute to the pathogenesis of pAPS.

19.
Bioconjug Chem ; 32(8): 1845-1851, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34254789

RESUMO

The applications of bioconjugation chemistry are rapidly expanding, and the addition of new strategies to the bioconjugation and ligation toolbox will further advance progress in this field. Herein, we present a detailed study of the Diels-Alder cycloaddition (DAC) reaction between pentafulvenes and maleimides in aqueous solutions and investigate the reaction as an emerging bioconjugation strategy. The DAC reactions were found to proceed efficiently, quantitatively yielding cycloadducts with reaction rates ranging up to ∼0.7 M-1 s-1 for a series of maleimides, including maleimide-derivatized peptides and proteins. The absence of cross-reactivity of the pentafulvene with a large panel of functional (bio)molecules and biological media further demonstrated the bioorthogonality of this approach. The utility of the DAC reaction for bioorthogonal bioconjugation applications was further demonstrated in the presence of biological media and proteins, as well as through protein derivatization and labeling, which was comparable to the widely employed sulfhydryl-maleimide coupling chemistry.

20.
Opt Lett ; 46(11): 2770-2773, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061109

RESUMO

Freeform illumination design for extended sources is a very challenging but rewarding issue that can benefit a wide range of illumination systems. Here, we propose a method that can achieve compact and highly efficient illumination lenses by deconvolving the blur caused by the extent from light sources. We combine the illumination calculation with the mathematical model of spatially variant convolution and develop a direct computational scheme to calculate the blur kernel without approximations. Two design examples with high optical performances are presented to demonstrate the effectiveness of the proposed method.

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