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1.
Artigo em Inglês | MEDLINE | ID: mdl-39120498

RESUMO

Luminescent CuI complexes are an important class of coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The title Cu2I2P2S2-type binuclear complex, di-µ-iodido-bis[(thiourea-κS)(triphenylphosphine-κP)copper(I)], [Cu2I2(CH4N2S)2(C18H15P)2], conventionally abbreviated as Cu2I2TPP2TU2, where TPP and TU represent triphenylphosphine and thiourea, respectively, is described. In this complex, each CuI atom adopts a CuI2PS four-coordination mode and pairs of atoms are connected to each other by two µ2-I ligands to form a centrosymmetric binuclear cluster. It was also found that the paper-based film of this complex exhibited obvious luminescence light-up sensing for pyridine and 4-methylpyridine.

2.
World J Clin Cases ; 12(22): 5159-5167, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39109043

RESUMO

BACKGROUND: Lower extremity lymphedema is a common complication following treatment for gynecological malignancies. Its incidence rate can reach up to 70%, affecting ~20 million people worldwide. However, specialized treatment centers are scarce, and there is a lack of consensus on treatment approaches. Furthermore, there are even fewer reports on the systematic and effective treatment of severe lymphedema with malformations. Effective management of this condition remains a significant challenge for clinicians. CASE SUMMARY: A 40-year-old woman developed bilateral leg swelling 6 years after receiving treatment for endometrial cancer. Since August 2018, she experienced > 30 episodes of lymphangitis. Upon presentation, she exhibited bilateral leg swelling and deformation, with four large swellings in the posterior thigh that impeded movement, and pain in the limbs. Skin manifestations included lichenoid lesions and features of deep sclerosis. Radionuclide lymphoscintigraphy confirmed the diagnosis of lower limb lymphedema. After 6 mo of complex decongestive therapy (CDT) and three lymphaticovenous anastomosis (LVA) treatments, the patient lost 49 kg in weight. She also experienced a maximum circumference reduction of 35.2 cm in the left lower limb and 37.5 cm in the right lower limb. The leg pain disappeared, her swelling significantly decreased, and she regained the ability to walk, cycle, and run normally. CONCLUSION: The combined application of CDT and LVA therapy demonstrates significant positive effects in the treatment of severe, deformed stage III lymphedema.

3.
Neuroscience ; 555: 213-221, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39089569

RESUMO

Anxiety disorders are prevalent chronic psychological disease with complex pathogenic mechanisms. Current anxiolytics have limited efficacy and numerous side effects in many anxiety patients, highlighting the urgent need for new therapies. Recent research has been focusing on nutritional supplements, particularly amino acids, as potential therapies for anxiety disorders. Among these, L-Cysteine plays a crucial role in various biological processes. L-Cysteine exhibits antioxidant properties that can enhance the antioxidant functions of the central nervous system (CNS). Furthermore, metabolites of L-cysteine, such as glutathione and hydrogen sulfide have been shown to alleviate anxiety through distinct molecular mechanisms. Long-term administration of L-Cysteine has anxiolytic, antidepressant, and memory-improving effects. L-Cysteine depletion can lead to increased oxidative stress in the brain. This review delves into the potential mechanisms of L-Cysteine and its main products, glutathione (GSH) and hydrogen sulfide (H2S) in the management of anxiety and related diseases.

4.
Sci Rep ; 14(1): 17807, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090344

RESUMO

In recent years, a novel x-ray imaging modality has emerged that reveals unresolved sample microstructure via a "dark-field image", which provides complementary information to conventional "bright-field" images, such as attenuation and phase-contrast modalities. This x-ray dark-field signal is produced by unresolved microstructures scattering the x-ray beam resulting in localised image blur. Dark-field retrieval techniques extract this blur to reconstruct a dark-field image. Unfortunately, the presence of non-dark-field blur such as source-size blur or the detector point-spread-function can affect the dark-field retrieval as they also blur the experimental image. In addition, dark-field images can be degraded by the artefacts induced by large intensity gradients from attenuation and propagation-based phase contrast, particularly around sample edges. By measuring any non-dark-field blurring across the image plane and removing it from experimental images, as well as removing attenuation and propagation-based phase contrast, we show that a directional dark-field image can be retrieved with fewer artefacts and more consistent quantitative measures. We present the details of these corrections and provide "before and after" directional dark-field images of samples imaged at a synchrotron source. This paper utilises single-grid directional dark-field imaging, but these corrections have the potential to be broadly applied to other x-ray imaging techniques.

5.
Medicine (Baltimore) ; 103(32): e39221, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39121318

RESUMO

BACKGROUND: This study aimed to examine the effect of gaze stability exercises on balance, gait ability, and fall efficacy in patients with chronic stroke, as well as to investigate whether any observed effects were maintained 2 weeks later. METHODS: In this experiment, 30 chronic stroke patients were selected. The patients were randomly divided into 3 groups (10 patients in each group). All patients in the 3 groups performed basic neurodevelopmental treatment. Group 1 performed balance exercises accompanied by gaze stability exercises. Group 2 performed gaze stability exercises, and group 3 performed balance exercises. Each exercise program for 40 minutes 3 times a week for 4 weeks. After the intervention period, the patient's balance, gait ability, and fall efficacy were measured again. In order to know whether the training effect is maintained, a 2-week follow-up test was conducted after the training. RESULTS: The results of this study showed that there was a significant improve in balance (overall stability index, limit of stability test, and Berg Balance Scale), gait ability (gait velocity, cadence, step time and step length, Timed Up and Go [TUG] test), and fall efficacy over the different time within the 3 groups. The effect was observed to be maintained in follow-up tests after 2 weeks. In the comparison among 3 groups, the overall stability index, limit of stability test in the balance test and the gait velocity, cadence, step time, step length and Timed Up and Go test in the gait test all showed statistically significant differences, and the other items did not have significant differences. In most of the assessments, group 1 that used balance exercise combined with gaze stability exercise showed a better improvement than the other 2 groups. CONCLUSION: As a result, for stroke patients, gaze stability exercise is an effective arbitration method to improve balance and gait ability and fall efficacy. With balance exercise combined with gaze stability exercise, a greater effect can be seen than with gaze stability exercise or balance exercise alone. Thus, this combination exercise program can be recommended as effective.


Assuntos
Acidentes por Quedas , Terapia por Exercício , Marcha , Equilíbrio Postural , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Equilíbrio Postural/fisiologia , Masculino , Feminino , Reabilitação do Acidente Vascular Cerebral/métodos , Terapia por Exercício/métodos , Pessoa de Meia-Idade , Acidentes por Quedas/prevenção & controle , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Marcha/fisiologia , Idoso , Seguimentos , Doença Crônica , Resultado do Tratamento
6.
Eur J Pharmacol ; 980: 176871, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39117263

RESUMO

Non-small cell lung cancer (NSCLC) poses a global health threat, and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, afatinib, and osimertinib have achieved significant success in clinical treatment. However, the emergence of resistance limits the long-term efficacy of these treatments, necessitating urgent exploration of novel EGFR-TKIs. This review provides an in-depth summary and exploration of the resistance mechanisms associated with EGFR-TKIs, with a specific focus on representative drugs like gefitinib, afatinib, and osimertinib. Additionally, the review introduces a therapeutic strategy involving the combination of Chinese herbal medicines (CHMs) and chemotherapy drugs, highlighting the potential role of CHMs in overcoming NSCLC resistance. Through systematic analysis, we elucidate the primary resistance mechanisms of EGFR-TKIs in NSCLC treatment, emphasizing CHMs as potential treatment medicines and providing a fresh perspective for the development of next-generation EGFR-TKIs. This comprehensive review aims to guide the application of CHMs in combination therapy for NSCLC management, fostering the development of more effective and comprehensive treatment modalities to ultimately enhance patient outcomes.

7.
Front Cardiovasc Med ; 11: 1401586, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39131705

RESUMO

Background: This study aimed to investigate alterations in serum markers [creatine kinase-MB (CKMB), cardiac troponin T (cTnT), myoglobin (Myo), B-type natriuretic peptide (BNP), D-dimer (DD), procalcitonin (PCT) and interleukin-6 (IL6)] in early Omicron variant infection and analyzed their correlation with clinical parameters. Methods: Retrospective analysis of 1,138 mild/asymptomatic cases at Tianjin First Central Hospital, including age, gender, serum markers and nucleic acid test results. Statistical analysis used SPSS software, version 24.0. Results: Elevated cTnT, BNP (125-400), and DD (0.55-1.10) levels were prevalent at 12.92%, 15.64%, and 14.50%, respectively. Females had significantly higher proportions with slightly elevated BNP (19.34%) and DD (19.69%) levels. Patients over 35 had a higher proportion of slight elevation in BNP (20.00%). Abnormal levels of serum markers were significantly associated with older age, increased PCT and IL6 levels, as well as delayed nucleic acid clearance. Additionally, levels of immunoglobulin G (IgG) were notably reduced in these cases. Patients with prolonged nucleic acid clearance (>14 days) had higher BNP and DD levels upon admission. Logistic regression identified PCT (OR = 237.95) as the most significant risk factor for abnormal serum markers for cardiovascular system injury. Conclusion: Early Omicron infection might do subclinical damage to the cardiovascular system. Elevated cTnT, BNP and DD levels were correlated with age, gender, inflammatory factors, and IgG. Notably, high PCT level emerged as the most robust predictor of abnormal serum biomarkers.

8.
Nat Commun ; 15(1): 6843, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39122671

RESUMO

Despite the potential of small molecules and recombinant proteins to enhance the efficiency of homology-directed repair (HDR), single-stranded DNA (ssDNA) donors, as currently designed and chemically modified, remain suboptimal for precise gene editing. Here, we screen the biased ssDNA binding sequences of DNA repair-related proteins and engineer RAD51-preferred sequences into HDR-boosting modules for ssDNA donors. Donors with these modules exhibit an augmented affinity for RAD51, thereby enhancing HDR efficiency across various genomic loci and cell types when cooperated with Cas9, nCas9, and Cas12a. By combining with an inhibitor of non-homologous end joining (NHEJ) or the HDRobust strategy, these modular ssDNA donors achieve up to 90.03% (median 74.81%) HDR efficiency. The HDR-boosting modules targeting an endogenous protein enable a chemical modification-free strategy to improve the efficacy of ssDNA donors for precise gene editing.


Assuntos
DNA de Cadeia Simples , Edição de Genes , Rad51 Recombinase , Reparo de DNA por Recombinação , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/genética , Humanos , Edição de Genes/métodos , Rad51 Recombinase/metabolismo , Rad51 Recombinase/genética , Sistemas CRISPR-Cas , Células HEK293 , Proteínas Associadas a CRISPR/metabolismo , Proteínas Associadas a CRISPR/genética , Proteína 9 Associada à CRISPR/metabolismo , Proteína 9 Associada à CRISPR/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Endodesoxirribonucleases/metabolismo , Endodesoxirribonucleases/genética , Reparo do DNA por Junção de Extremidades
9.
J Phys Chem B ; 128(32): 7722-7735, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39091133

RESUMO

The protein-induced fluorescence change technique was employed to investigate the interactions between proteins and their DNA substrates modified with the Cy3 fluorophore. It has been reported that the human hepatoma-derived growth factor (HDGF), containing the chromatin-associated N-terminal proline-tryptophan-tryptophan-proline (PWWP) domain (the N-terminal 100 amino acids of HDGF) capable of binding the SMYD1 promoter, participates in various cellular processes and is involved in human cancer. This project investigated the specific binding behavior of HDGF, the PWWP domain, and the C140 domain (the C-terminal 140 amino acids of HDGF) sequentially using protein-induced fluorescence change. We found that the binding of HDGF and its related proteins on Cy3-labeled 15 bp SMYD1 dsDNA will cause a significant decrease in the recorded Cy3 fluorophore intensity, indicating the occurrence of protein-induced fluorescence quenching. The dissociation equilibrium constant was determined by fitting the bound fraction curve to a binding model. An approximate 10-time weaker SMYD1 binding affinity of the PWWP domain was found in comparison to HDGF. Moreover, the PWWP domain is required for DNA binding, and the C140 domain can enhance the DNA binding affinity. Furthermore, we found that the C140 domain can regulate the sequence-specific binding capability of HDGF on SMYD1.


Assuntos
Proteínas de Ligação a DNA , DNA , Peptídeos e Proteínas de Sinalização Intercelular , Ligação Proteica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , DNA/química , DNA/metabolismo , Domínios Proteicos , Sítios de Ligação , Carbocianinas/química , Proteínas Musculares , Fatores de Transcrição
10.
Commun Biol ; 7(1): 1003, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152196

RESUMO

Rhein, a component derived from rhubarb, has been proven to possess anti-inflammatory properties. Here, we show that rhein mitigates obesity by promoting adipose tissue thermogenesis in diet-induced obese mice. We construct a macrophage-adipocyte co-culture system and demonstrate that rhein promotes adipocyte thermogenesis through inhibiting NLRP3 inflammasome activation in macrophages. Moreover, clues from acetylome analysis identify SIRT2 as a potential drug target of rhein. We further verify that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of SIRT2 abrogates adipose tissue thermogenesis and metabolic benefits in obese mice induced by rhein. Together, our findings elucidate that rhein inhibits NLRP3 inflammasome activation in macrophages by regulating SIRT2, and thus promotes white adipose tissue thermogenesis during obesity. These findings uncover the molecular mechanism underlying the anti-inflammatory and anti-obesity effects of rhein, and suggest that rhein may become a potential drug for treating obesity.


Assuntos
Antraquinonas , Macrófagos , Camundongos Endogâmicos C57BL , Obesidade , Sirtuína 2 , Termogênese , Animais , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Antraquinonas/farmacologia , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Termogênese/efeitos dos fármacos , Sirtuína 2/metabolismo , Sirtuína 2/genética , Masculino , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética
11.
J Med Chem ; 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39129245

RESUMO

COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, CFP-1, that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5. By using this platform, we identified 2-aminothiazole-4-carboxylic acids as new CSN5 inhibitors, which inhibited CSN5 but slightly downregulated PD-L1 in cancer cells. Furthermore, through the integration of deep learning-enabled virtual screening, we discovered that shikonins are nanomolar CSN5 inhibitors, which can upregulate PD-L1 in HCT116 cells. The binding modes of these structurally distinct inhibitors with CSN5 were explored by using microsecond-scale molecular dynamics simulations and tryptophan quenching assays.

12.
J Nanobiotechnology ; 22(1): 485, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138462

RESUMO

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.


Assuntos
Fosfatase Alcalina , Antibacterianos , Cobre , Desinfecção , Escherichia coli , Pró-Fármacos , Espécies Reativas de Oxigênio , Cobre/química , Cobre/farmacologia , Animais , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Fosfatase Alcalina/metabolismo , Ratos , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Desinfecção/métodos , Ácido Ascórbico/farmacologia , Ácido Ascórbico/química , Ácido Ascórbico/análogos & derivados , Nanopartículas Metálicas/química , Ratos Sprague-Dawley , Masculino
13.
JAMA Ophthalmol ; 142(8): e241225, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39145830

RESUMO

This case report describes a diagnosis of streaky multifocal choroiditis in a boy who presented with distorted vision in his left eye for 3 years.


Assuntos
Corioidite , Angiofluoresceinografia , Coroidite Multifocal , Humanos , Masculino , Criança , Corioidite/diagnóstico , Corioidite/tratamento farmacológico , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Acuidade Visual
14.
Rev Cardiovasc Med ; 25(4): 111, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39076545

RESUMO

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 10 4 ). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 ( ≤ 0.69, n = 950), Q2 (0.69-2.44, n = 950), Q3 (2.44-9.52, n = 950), and Q4 ( > 9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan-Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147-0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150-0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422-0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401-0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).

15.
Rev Cardiovasc Med ; 25(1): 17, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39077643

RESUMO

Background: The correlation between 5 ' -Nucleotidase ( 5 ' -NT) and the clinical outcomes in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) is not clear. This study aims to clarify this relationship. Methods: The PRACTICE study enrolled 15,250 patients between December 2016 and October 2021. After filtering out those without 5 ' -NT data, a total of 6555 patients were analyzed with a median follow-up of 24 months. Based on the receiver operating characteristic (ROC) curve analysis, a 5 ' -NT level of 5.57 U/L was selected as the optimal cutoff value. All research samples were divided into high-value ( ≥ 5.57 U/L, n = 2346) and low-value groups ( < 5.57 U/L, n = 4209). Key clinical outcomes included all-cause death (ACD), cardiovascular death (CD), major adverse cardiovascular events (MACE), and major adverse cardiovascular and cerebrovascular events (MACCE). After separating patients into high and low value groups, multivariate Cox regression analysis was used to correct for potential confounding variables. Finally, risk ratios and their 95% confidence intervals (CIs) were calculated. Results: During the follow-up period, 129 instances of ACD were recorded-49 cases (1.2%) in the low-value group and 80 cases (3.4%) in the high-value group. Similarly, 102 CDs occurred, including 42 low-value group cases (1.0%) and 60 high-value group cases (2.6%). A total of 363 MACE occurred, including 198 low-value group cases (4.7%) and 165 high-value group cases (7%). A total of 397 cases of MACCE occurred, including 227 low-value group cases (5.4%) and 170 high-value group cases (7.2%). As serum 5 ' -NT increased, the incidence of ACD, CD, MACE and MACCE increased. After multivariate Cox regression, high 5 ' -NT levels were linked with a 1.63-fold increase in ACD risk (hazard ratio [HR] = 2.630, 95% CI: [1.770-3.908], p < 0.001) when compared to low 5 ' -NT patients. Similarly, the risk of CD, MACE, and MACCE increased by 1.298-fold (HR = 2.298, 95% CI: [1.477-3.573], p < 0.001), 41% (HR = 1.410, 95% CI: [1.124-1.768], p = 0.003) and 30.5% (HR = 1.305, 95% CI: [1.049-1.623], p = 0.017), respectively. Conclusions: high serum 5 ' -NT levels were independently correlated with adverse clinical outcomes in CAD patients following PCI, affirming its potential as a prognostic indicator.

16.
Biomed Environ Sci ; 37(6): 594-606, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38988110

RESUMO

Objective: The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats ( C6orf120 -/- ) and THP-1 cells. Method: Six-eight-week-old C6orf120 -/- and wild-type (WT) SD rats were injected with Con A (16 mg/kg), and euthanized after 24 h. The sera, livers, and spleens were collected. THP-1 cells and the recombinant protein (rC6ORF120) were used to explore the mechanism in vitro. The frequency of M1 and M2 macrophages was analyzed using flow cytometry. Western blotting and PCR were used to detect macrophage polarization-associated factors. Results: C6orf120 knockout attenuated Con A-induced autoimmune hepatitis. Flow cytometry indicated that the proportion of CD68 +CD86 +M1 macrophages from the liver and spleen in the C6orf120 -/- rats decreased. C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α, IL-1ß, and IL-6 in the liver. C6orf120 knockout did not affect the polarization of THP-1 cells. However, rC6ORF120 promoted the THP-1 cells toward CD68 +CD80 +M1 macrophages and inhibited the CD68 +CD206 +M2 phenotype. Conclusion: C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120 -/- rats.


Assuntos
Concanavalina A , Hepatite Autoimune , Macrófagos , Ratos Sprague-Dawley , Animais , Macrófagos/efeitos dos fármacos , Hepatite Autoimune/imunologia , Hepatite Autoimune/genética , Ratos , Concanavalina A/toxicidade , Humanos , Masculino , Técnicas de Inativação de Genes , Células THP-1
17.
Org Lett ; 26(30): 6407-6412, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39029092

RESUMO

Chiral coumarins and their derivatives are ubiquitous structural motifs found in an array of biologically and therapeutically active natural products and drugs. Herein, a highly enantioselective dual remote copper-catalyzed vinylogous alkynylallylic substitution of yne-allylic esters with coumarins has been developed. The practicality of this method is exemplified by the use of readily available starting materials; mild reaction conditions; excellent regio-, enantio-, and stereoselectivities; and the very broad substrate scope (67 examples), while the scalability and further applications of this method are illustrated by the gram-scale reaction and the series of derivations of the products.

18.
Heliyon ; 10(13): e33437, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39040373

RESUMO

Background: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. Methods: Pregnant women (n = 282,911) participating in a free NIPT (April 2018-December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. Results: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. Conclusion: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

19.
J Rheumatol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009401

RESUMO

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) psoriatic arthritis (PsA) working group provided updates at the GRAPPA 2023 annual meeting on its work to evaluate composite outcome measures for PsA. An ongoing systematic literature review is in progress to evaluate psychometric measurement properties using the OMERACT filter 2.2 for a list of candidate composite outcome measures, which include minimal disease activity (MDA), Disease Activity for Psoriatic Arthritis (DAPSA), American College of Rheumatology (ACR) response criteria, Psoriatic Arthritis Disease Activity Score (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), 3 visual analog scale (3VAS), and 4VAS. The performance of the 3VAS and 4VAS in clinical practice and a synthesis of new data were presented, including estimates for minimal clinically important differences and thresholds of meaning, discrimination and construct validity, and longitudinal construct validity. Numeric rating scale (NRS) versions of the VAS have also been tested. Performance characteristics and psychometric properties are similar to the ASSESS study, a UK multicenter study, indicating that the VAS scales may be feasible tools for routine clinical care with a preference for the 4VAS because of superior face validity and clinical utility.

20.
Saf Health Work ; 15(2): 129-138, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39035803

RESUMO

The COVID-19 pandemic has led to a significant surge in glove usage, as recommended by the World Health Organization. Despite efforts to ensure the quality and safety of gloves, glove-associated skin diseases such as hand dermatitis have become ubiquitous, particularly among health care workers. This review discusses the prevalence, causes, and risk factors of hand dermatitis, as well as research efforts in medical gloves in the past decade to overcome glove-related hand dermatitis. Research papers from 2013 to 2022 were reviewed, selecting only 49 relevant papers from the Ovid, PubMed, and Scopus databases. The average prevalence of hand dermatitis among health care workers increased from 21.08% to 37.24% upon the impact of the COVID-19 pandemic. The cases are likely due to allergies to latex proteins, rubber additives, and accelerators commonly found in gloves. Using alternatives to latex gloves, such as accelerator-free and latex-free glove options, can help reduce allergy-induced hand dermatitis. Strict hand hygiene practices, such as frequent hand washing and the use of sanitizers, are also contributing factors in contracting hand dermatitis. Over the past decade, glove research advancements have focused mainly on reducing or immobilizing latex proteins. These include the use of biodegradable dialdehyde, sodium alginate, arctigenin, bromelain, papain, UV-LED, prototype photoreactors, and structure-modified nanosilica with silane A174. Two effective hand dermatitis preventive measures, i.e. an additional layer of glove liners and the use of gentle alcohol-based hand sanitizer, were recommended. These advancements represent promising steps towards mitigating hand dermatitis risks associated with glove usage.

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