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1.
Front Public Health ; 12: 1398948, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39145158

RESUMEN

Background: Rehabilitation therapists often perform physically demanding treatments that may result in work-related injuries, yet related studies are scarce. This study aimed to investigate the work-related injuries of rehabilitation therapists and provide feasible preventive measures. Methods: A cross-sectional study was carried out in 34 regions across China using an online questionnaire. The survey gathered responses primarily from 1,198 rehabilitative therapists working in 120 health institutes. Following data collection, descriptive analysis, chi-square tests, logistic regression, and receiver operating characteristic (ROC) curves were employed to analyze the data. Results: In this study, the incidence of work-related injuries was reported to be 87% (n = 1,041). The top three musculoskeletal issues reported were low back pain (12%), neck pain (10%), and shoulder pain (9%). Logistic regression and ROC curve analysis identified that working as a physiotherapist and years of work experience (OR [95% CI]: 1.03 [0.99-1.07]) were significant contributors to the incidence of work-related injuries. Specifically, neuro-physiotherapists (OR [95% CI]: 3.04 [1.56-5.92]), musculoskeletal physiotherapists (OR [95% CI]: 2.46 [1.16-5.18]), and intensive care physiotherapists (OR [95% CI]: 4.70 [1.24-17.88]) were at higher risk. Furthermore, five factors were proven to be associated with injury prevention as reported by therapists: patient engagement (OR [95% CI]: 0.38 [0.23-0.62]), improving techniques (OR [95% CI]: 0.59 [0.39-0.90]), maintaining exercise habits (OR [95% CI]: 0.59 [0.40-0.86]), utilizing instruments (OR [95% CI]: 0.80 [0.53-1.19]), and strengthening education (OR [95% CI]: 0.43 [0.21-0.90]). Conclusion: The present study investigated the factors contributing to work-related injuries among rehabilitation therapists, with a focus on identifying both risk and preventive measures. These findings offer new perspectives on decreasing injury risk.


Asunto(s)
Traumatismos Ocupacionales , Fisioterapeutas , Humanos , Estudios Transversales , Masculino , Femenino , Adulto , Encuestas y Cuestionarios , Traumatismos Ocupacionales/epidemiología , China/epidemiología , Fisioterapeutas/estadística & datos numéricos , Persona de Mediana Edad , Incidencia
2.
Aging Dis ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39133904

RESUMEN

Despite substantial evidence highlighting molecular communication within the components of neurovascular units (NVU), the interactions at the organelle level have been insufficiently explored in recent decades. Mitochondria, for instance, beyond their traditional role as energy supply for intracellular metabolism and survival, provide a novel perspective on intercellular connections through mitochondrial transfer. These transferred mitochondria not only carry bioactive molecules but also signal to mitigate risks in both healthy and pathological conditions. In this review, we summarized mitochondrial transfer events, relevant routes, and underlying molecular mechanisms originating from diverse cell populations within NVU. We particularly focus on the therapeutic potential of this mechanism in treating central nervous system disorders, notably neurodegenerative diseases marked by mitochondrial dysfunction and then highlight the promising prospects of exogenous mitochondrial supplementation as a treatment target.

3.
Materials (Basel) ; 17(15)2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39124388

RESUMEN

Ethylene-vinyl acetate copolymer (EVA), a crucial elastomeric resin, finds extensive application in the footwear industry. Conventional chemical foaming agents, including azodicarbonamide and 4,4'-oxybis(benzenesulfonyl hydrazide), have been identified as environmentally problematic. Hence, this study explores the potential of physical foaming of EVA using supercritical nitrogen as a sustainable alternative, garnering considerable interest in both academia and industry. The EVA formulations and processing parameters were optimized and EVA foams with densities between 0.15 and 0.25 g/cm3 were produced. Key findings demonstrate that physical foaming not only reduces environmental impact but also enhances product quality by a uniform cell structure with small cell size (50-100 µm), a wide foaming temperature window (120-180 °C), and lower energy consumption. The research further elucidates the mechanisms of cell nucleation and growth within the crosslinked EVA network, highlighting the critical role of blowing agent dispersion and localized crosslinking around nucleated cells in defining the foam's cellular morphology. These findings offer valuable insights for producing EVA foams with a more controllable cellular structure, utilizing physical foaming techniques.

4.
J Phys Chem Lett ; 15(28): 7327-7334, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38985131

RESUMEN

Methanesulfenic acid, CH3SOH, is a fleeting intermediate in the ·OH-initiated oxidation reactions of dimethyl sulfide (DMS) and dimethyl disulfide (DMDS) in the atmosphere. Herein, we report the characterization and photochemistry of CH3SOH in Ar- and N2-matrices at 10 K. The characterization of CH3SOH with matrix-isolation IR and UV-vis spectroscopy is supported by D and 13C isotope labeling experiments and quantum chemical calculations. In line with the observed absorption at 260 nm for CH3SOH, its photolysis at 254 nm leads to dissociation by yielding the novel water complex H2CS···H2O, which exhibits a five-membered ring structure with intermolecular S···HO and CH···O hydrogen bonding interactions. Upon further irradiation at 193 nm, the H2CS···H2O complex undergoes dehydrogenation to form CS···H2O, which can further convert to HC(O)SH under irradiation at 254 nm. When the photolysis of CH3SOH was performed in an O2-doped Ar-matrix, methanesulfonic acid (MSA, CH3SO3H) was obtained as the oxidation product.

5.
Eur J Pharmacol ; 979: 176806, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38986830

RESUMEN

Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-ß1) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.


Asunto(s)
Riñón , Cadenas Pesadas de Miosina , Insuficiencia Renal Crónica , Animales , Humanos , Masculino , Ratones , Línea Celular , Modelos Animales de Enfermedad , Fibrosis , Riñón/patología , Riñón/metabolismo , Ratones Endogámicos C57BL , Proteínas Motoras Moleculares/metabolismo , Proteínas Motoras Moleculares/genética , Cadenas Pesadas de Miosina/metabolismo , Cadenas Pesadas de Miosina/genética , Unión Proteica , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/genética , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/patología , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/complicaciones
6.
Clin Res Hepatol Gastroenterol ; 48(8): 102430, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39069260

RESUMEN

BACKGROUND: Cholangiocarcinoma (CCA) is a highly aggressive and invasive malignant tumor of the bile duct, with a poor prognosis and a high mortality rate. Currently, there is a lack of effective targeted treatment methods and reliable biomarkers for prognosis. METHODS: We downloaded RNA-seq and clinical data of CCA from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases as training and test sets. The apoptosis-related genes were obtained from the Molecular Signatures Database (MsigDB) database. We used univariate/multivariate Cox regression and Lasso regression analyses to construct a riskscore prognostic model. Based on the median riskscore, we clustered the patients into high-risk (HR) and low-risk (LR) groups. We carried out Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes (DEGs) in HR and LR groups. The single sample gene set enrichment analysis (ssGSEA) was employed to analyze the immune infiltration of the HR and LR groups. The CellMiner database was utilized to predict drugs and perform molecular docking on drugs and target proteins. RESULTS: We identified 8 genes with prognostic significance to construct a prognostic model. Results of GO and KEGG demonstrated that DEGs were mainly enriched in biological functions such as fatty acid metabolic processes and pathways such as the cAMP signaling pathway. Results of ssGSEA uncovered that immune cells such as DCs and Macrophages in the HR group, as well as immune functions such as Check-point and Parainflammation, were considerably higher than those in the LR group. Drug sensitivity prediction and results of molecular docking revealed that Rigosertib targeted the prognostic genes MAP3K1. HYPOTHEMYCIN and AMG900 effectively targeted JUN. CONCLUSION: Our project suggested that the prognostic model with apoptotic features can effectively predict prognosis in CCA patients, proffering prognostic biomarkers and potential therapeutic targets for CCA patients.

7.
J Am Chem Soc ; 146(29): 20494-20499, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39001838

RESUMEN

The photochemistry of nitrous acid (HONO), encompassing dissociation into OH and NO as well as the reverse association reaction, plays a pivotal role in atmospheric chemistry. Here, we report the direct observation of nitrosyl-O-hydroxide (HOON) in the photochemistry of HONO, employing matrix-isolation IR and UV-vis spectroscopy. Despite a barrier of approximately 30 kJ/mol, HOON undergoes spontaneous rearrangement to the more stable HONO isomer through quantum mechanical tunneling, with a half-life of 28 min at 4 K. Kinetic isotope effects and instanton theory calculations reveal that the tunneling process involves the concerted motion of the NO moiety (65.2%) and the hydrogen atom (32.3%). Our findings underscore the significance of HOON as a key intermediate in the photolytic dissociation-association cycle of HONO at low temperatures.

8.
Int J Biol Macromol ; 277(Pt 2): 134231, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39074699

RESUMEN

To investigate the impact of chlorantraniliprole on Procambarus clarkii, acute toxicity tests were performed. Results indicated that 96 h post-exposure to chlorantraniliprole (60 mg/L) led to the separation of the hepatopancreas basement membrane, causing cell swelling, rupture, and vacuolation. Moreover, acid phosphatase (ACP) and alkaline phosphatase (AKP) activities exhibited divergent trends across four concentrations of chlorantraniliprole (0, 30, 60, and 90 mg/L). Hydrogen peroxide (H2O2) and catalase (CAT) levels significantly increased, while total superoxide dismutase (T-SOD) and malonaldehyde (MDA) activities decreased, indicating oxidative stress in the hepatopancreas. A total of 276 differentially expressed genes (DEGs) were identified, with 204 up-regulated and 72 down-regulated. Out of these, 114 DEGs were successfully annotated and classified into 99 pathways, with a primary focus on the cytochrome P450-mediated xenobiotic metabolism pathway. The DEGs enriched in this pathway, along with transcriptome data, were validated using quantitative-polymerase chain reaction. This study enhances the transcriptome database of P. clarkii and provides fundamental insights into its immune defense and antioxidant mechanisms. Additionally, it lays a theoretical foundation for future research on disease prevention in P. clarkii within rice-shrimp culture systems.

9.
Adv Mater ; : e2404734, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39081101

RESUMEN

The van der Waals (vdW) interface provides two important degrees of freedom-twist and slip-to tune interlayer structures and inspire unique physics. However, constructing diversified high-quality slip stackings (i.e., lattice orientations between layers are parallel with only interlayer sliding) is more challenging than twisted stackings due to angstrom-scale structural discrepancies between different slip stackings, sparsity of thermodynamically stable candidates and insufficient mechanism understanding. Here, using transition metal dichalcogenide (TMD) homobilayers as a model system, this work theoretically elucidates that vdW materials with low lattice symmetry and weak interlayer coupling allow the creation of multifarious thermodynamically advantageous slip stackings, and experimentally achieves 13 and 9 slip stackings in 1T″-ReS2 and 1T″-ReSe2 bilayers via direct growth, which are systematically revealed by atomic-resolution scanning transmission electron microscopy (STEM), angle-resolved polarization Raman spectroscopy, and second harmonic generation (SHG) measurements. This work also develops modulation strategies to switch the stacking via grain boundaries (GBs) and to expand the slip stacking library from thermodynamic to kinetically favored structures via in situ thermal treatment. Finally, density functional theory (DFT) calculations suggest a prominent dependence of the pressure-induced electronic band structure transition on stacking configurations. These studies unveil a unique vdW epitaxy and offer a viable means for manipulating interlayer atomic registries.

10.
bioRxiv ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38826355

RESUMEN

An "induced PARP inhibitor (PARPi) sensitivity by epigenetic modulation" strategy is being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARPi treatments. To expand its clinical applications and identify more efficient combinations, we performed a drug screen by combining PARPi with 74 well-characterized epigenetic modulators that target five major classes of epigenetic enzymes. Both type I PRMT inhibitor and PRMT5 inhibitor exhibit high combination and clinical priority scores in our screen. PRMT inhibition significantly enhances PARPi treatment-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMTs maintain the expression of genes associated with DNA damage repair and BRCAness and regulate intrinsic innate immune pathways in cancer cells. Analyzing large-scale genomic and functional profiles from TCGA and DepMap further confirms that PRMT1, PRMT4, and PRMT5 are potential therapeutic targets in oncology. Finally, PRMT1 and PRMT5 inhibition act synergistically to enhance PARPi sensitivity. Our studies provide a strong rationale for the clinical application of a combination of PRMT and PARP inhibitors in patients with HR-proficient ovarian or breast cancer.

11.
J Am Chem Soc ; 146(27): 18699-18705, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38943601

RESUMEN

Carbonyl nitrenes are versatile intermediates that have been extensively characterized; however, their phosphorus analogues remain largely unknown. Herein, we report the observation of a rare example of carbonyl phosphinidene NH2C(O)P, which was generated through the photolytic (193 nm) dehydrogenation of phosphinecarboxamide (NH2C(O)PH2) in a solid N2-matrix at 12 K. The characterization of NH2C(O)P in the triplet ground state with matrix-isolation IR and ultraviolet-visible (UV-vis) spectroscopy is supported by comprehensive isotope labeling experiments (D and 15N) and quantum chemical calculations. Upon visible-light irradiation at 680 nm, NH2C(O)P inserts into dihydrogen by the reformation of NH2C(O)PH2 with concomitant isomerization to the more stable aminophosphaketene (NH2PCO). Additionally, the photoisomerization of NH2C(O)PH2 to NH2C(OH) = PH along with decomposition by yielding hydrogen-bonded complexes HNCO···PH3 and HPCO···NH3 has been observed in the matrix.

12.
J Colloid Interface Sci ; 672: 446-454, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38850869

RESUMEN

The design of pre-catalysts and the rational manipulation of corresponding electrochemical reconstruction are vitally important to construct the highly durable and active catalysts for seawater oxidation, but rather challenging. Herein, a novel core-shell catalyst of Co2(PS3)@Co2P (labeled as CoPS) by epitaxial growth of amorphous cobalt phosphide (Co2P) on crystalline cobalt phosphorous trichalcogenide (Co2(PS3)) is firstly designed as a pre-catalyst for alkaline seawater oxidation. Various characterization techniques are employed to demonstrate that the unique amorphous-crystalline nanowire structure (CoPS) achieves the rapid surface reconstruction into active CoOOH and diversiform oxyanions species (labeled as CoPS-R). Theoretical simulations uncover that the in situ derived oxyanions (PO42-, SO32- and SO42-) on the surface of CoOOH can tune the electron distribution of Co site, thereby optimizing the chemisorption of oxygen evolution reaction (OER) intermediates on CoOOH and reducing the energy barrier of determining step. Consequently, in an alkaline natural seawater solution, the reconstructed CoPS-R catalyst exhibits small overpotentials of 357 and 402 mV for OER at 200 and 500 mA cm-2, respectively, together with an impressive durability over 500 h at a large current density of 500 mA cm-2 benefiting from the strong repulsive effect of the derived PO42-, SO32- and SO42- oxyanions. This work offers a new insight for comprehending the relationship of structure-composition-activity and develops a new approach toward the construction of efficient and robust OER catalysts for seawater electrolysis.

13.
Biomed Pharmacother ; 175: 116704, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38749181

RESUMEN

Long non-coding RNAs (lncRNAs) are pivotal controllers of gene expression through epigenetic mechanisms, Methylation, a prominent area of study in epigenetics, significantly impacts cellular processes. Various RNA base methylations, including m6A, m5C, m1A, and 2'-O-methylation, profoundly influence lncRNA folding, interactions, and stability, thereby shaping their functionality. LncRNAs and methylation significantly contribute to tumor development, especially in lung cancer. Their roles encompass cell differentiation, proliferation, the generation of cancer stem cells, and modulation of immune responses. Recent studies have suggested that dysregulation of lncRNA methylation can contribute to lung cancer development. Furthermore, methylation modifications of lncRNAs hold potential for clinical application in lung cancer. Dysregulated lncRNA methylation can promote lung cancer progression and may offer insights into potential biomarker or therapeutic target. This review summarizes the current knowledge of lncRNA methylation in lung cancer and its implications for RNA epigenetics and pulmonary diseases.


Asunto(s)
Epigénesis Genética , Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Animales , Regulación Neoplásica de la Expresión Génica , Metilación , Enfermedades Pulmonares/genética , Metilación de ADN/genética
14.
Sleep Breath ; 28(4): 1679-1690, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38739211

RESUMEN

OBJECTIVE: This investigation seeks to examine the association between serum vitamin D concentrations and the prevalence of sleep disorders, additionally elucidating the causal relationship via Mendelian Randomization (MR) analysis. MATERIALS AND METHODS: This research employed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016, focusing on adults aged 20-50 years reporting sleep disorders. The research encompassed 4913 American adults. Weighted multivariable logistic regression models and cubic spline analyses were utilized to evaluate the association between serum vitamin D concentrations and the incidence of sleep disorders. Additionally, a two-sample Mendelian Randomization analysis was performed to evaluate the potential causal link between serum vitamin D concentrations and the risk of sleep disorders. RESULTS: Within the 2011-2016 NHANES cohort of the U.S. population, a notable inverse association was detected between serum vitamin D concentrations and sleep disorders (ß = - 3.81, 95% CI: - 6.10 to - 1.52, p = 0.003). After multivariate adjustments, a higher incidence of sleep disorders was associated with lower vitamin D Concentrations (OR 1.52, 95% CI 1.10-2.10, trend p = 0.014). Restricted cubic spline regression analysis indicated a linear association between serum vitamin D concentrations and sleep disorders(non-linearity p > 0.05). Lastly, the two-sample MR analysis yielded evidence supporting a potential causal connection between serum vitamin D concentrations and sleep disorders, with each unit increase in genetically predicted serum vitamin D reducing the odds ratio to 0.78 (95% CI 0.61-0.99, p = 0.044). CONCLUSIONS: These results imply that lower vitamin D concentrations in the population might correlate with a heightened risk of sleep disorders, suggesting the importance of considering vitamin D supplementation when treating sleep disorders.


Asunto(s)
Análisis de la Aleatorización Mendeliana , Encuestas Nutricionales , Trastornos del Sueño-Vigilia , Vitamina D , Humanos , Adulto , Persona de Mediana Edad , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/sangre , Trastornos del Sueño-Vigilia/genética , Vitamina D/sangre , Masculino , Femenino , Estados Unidos/epidemiología , Adulto Joven , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/genética
15.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1102-1112, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621917

RESUMEN

This study systematically combed the randomized controlled trial(RCT) of Chinese patent medicines in treatment of type 2 diabetes mellitus(T2DM) in recent five years by using the method of evidence map. It understood the distribution and quality of evidence in this field and found the existing Chinese patent medicines in treatment of T2DM and the problems in its research. The study collected the commonly used Chinese patent medicines for the treatment of T2DM from three drug catalogs, retrieved Chinese and English databases to obtain RCT literature related to Chinese patent medicines in recent five years, and extracted information such as sample size, study drug, combination medication, course of treatment, and outcome indicators from the literature. It also conducted quality evaluation based on the Cochrane collaborative network bias risk assessment tool and used charts to display the analysis results. A total of 19 kinds of Chinese patent medicines are collected, of which 13 kinds of Chinese patent medicines are mentioned in 131 articles related to RCT. The literature concerning Shenqi Jiangtang Capsules/Granules, Jinlida Granules, and Xiaoke Pills accounts for a large proportion. Outcome indicators include blood glucose, blood lipids, pancreatic islet cell function, and clinical symptoms. In terms of literature quality, 75 articles have correct random methods, and 1 article performs allocation hiding and blind methods. Therefore, the clinical orientation of Chinese patent medicines for the treatment of T2DM is broad, failing to reflect their own characteristics and lacking safety information. Insufficient attention has been paid to TCM syndrome scores, quality of life, and blood lipid outcome indicators that reflect the characteristics of traditional Chinese medicine(TCM). The number of studies on the treatment of T2DM by Chinese patent medicines varies greatly among varieties, and the quality of the studies is low. It is suggested that the holders of the marketing license of T2DM Chinese patent medicines should carry out a post-marketing re-evaluation of the varieties of traditional Chinese patent medicines for treating T2DM according to the relevant requirements of the State Food and Drug Administration, standardize the clinical positioning, and revise and improve the safety information in the instructions. It is recommended that researchers construct a core indicator dataset for Chinese patent medicine treatment of T2DM, improve the efficacy evaluation system, and develop an experimental plan based on CONSORT before conducting RCT.


Asunto(s)
Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/efectos adversos , Medicina Tradicional China , Medicamentos sin Prescripción/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
J Invest Dermatol ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38580106

RESUMEN

Systemic sclerosis (SSc) is a challenging autoimmune disease characterized by progressive fibrosis affecting the skin and internal organs. Despite the known infiltration of macrophages and neutrophils, their precise contributions to SSc pathogenesis remain elusive. In this study, we elucidated that CD206hiMHCIIlo M2-like macrophages constitute the predominant pathogenic immune cell population in the fibrotic skin of a bleomycin-induced SSc mouse model. These cells emerged as pivotal contributors to the profibrotic response by orchestrating the production of TGF-ß1 through a MerTK signaling-dependent manner. Notably, we observed that neutrophil infiltration was a prerequisite for accumulation of M2-like macrophages. Strategies such as neutrophil depletion or inhibition of CXCR1/2 were proven effective in reducing M2-like macrophages, subsequently mitigating SSc progression. Detailed investigations revealed that in fibrotic skin, neutrophil-released neutrophil extracellular traps were responsible for the differentiation of M2-like macrophages. Our findings illuminate the significant involvement of the neutrophil-macrophage-fibrosis axis in SSc pathogenesis, offering critical information for the development of potential therapeutic strategies.

17.
Phys Chem Chem Phys ; 26(12): 9295-9308, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38469695

RESUMEN

Understanding selectivity mechanisms of inhibitors towards highly homologous proteins is of paramount importance in the design of selective candidates. Human aldo-keto reductases (AKRs) pertain to a superfamily of monomeric oxidoreductases, which serve as NADPH-dependent cytosolic enzymes to catalyze the reduction of carbonyl groups to primary and secondary alcohols using electrons from NADPH. Among AKRs, AKR1B1 is emerging as a promising target for cancer treatment and diabetes, despite its high structural similarity with AKR1B10, which leads to severe adverse events. Therefore, it is crucial to understand the selectivity mechanisms of AKR1B1 and AKR1B10 to discover safe anticancer candidates with optimal therapeutic efficacy. In this study, multiple computational strategies, including sequence alignment, structural comparison, Protein Contacts Atlas analysis, molecular docking, molecular dynamics simulation, MM-GBSA calculation, alanine scanning mutagenesis and pharmacophore modeling analysis were employed to comprehensively understand the selectivity mechanisms of AKR1B1/10 inhibition based on selective inhibitor lidorestat and HAHE. This study would provide substantial evidence in the design of potent and highly selective AKR1B1/10 inhibitors in future.


Asunto(s)
Inhibidores Enzimáticos , Simulación de Dinámica Molecular , Humanos , Simulación del Acoplamiento Molecular , NADP/metabolismo , Aldo-Ceto Reductasas/metabolismo , Inhibidores Enzimáticos/farmacología , Aldehído Reductasa/metabolismo
18.
Front Public Health ; 12: 1360824, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550325

RESUMEN

Background: Home-based exercise (HBE) represents an alternative to increase the accessibility of rehabilitation programs and relieve the burden on the health care system for people with knee osteoarthritis. Objectives: To summarize for the first time the effectiveness of HBE as compared to center-based exercise (CBE), both with and without HBE, on patient-reported and performance-based outcomes in people with KOA. Methods: Searches were conducted on PubMed, Cochrane, Embase, Web of Science, and Scopus until March 10, 2023, without date or language restrictions. Randomized controlled trials investigating HBE versus CBE or HBE combined with CBE for people with KOA were eligible. The primary outcomes were patient-reported: pain, physical disability, and quality of life. The secondary outcomes were performance-based: walking ability, lower limb muscle strength, and balance function. Risk of bias was assessed with the Cochrane Risk of Bias tool and quality of evidence according to the GRADE. Results: Eleven trials involving 956 participants were included. There was no difference in short-term pain (SMD, 0.22 [95% CI, -0.04 to 0.47], p = 0.09; I2 = 0%), physical disability (SMD, 0.17 [95% CI, -0.19 to 0.54], p = 0.35; I2 = 0%), walking ability (SMD, -0.21 [95% CI, -0.64 to 0.22], p = 0.33; I2 = 35%) and lower limb muscle strength (SMD, -0.24 [95% CI, -0.88 to 0.41], p = 0.47; I2 = 69%) between HBE and CBE. HBE combined with CBE has better benefits compared with HBE alone in short-term pain (SMD, 0.89 [95% CI, 0.60 to 1.17], p < 0.001; I2 = 11%) and physical disability (SMD, 0.25 [95% CI, 0.00 to 0.50], p = 0.05; I2 = 0%). Conclusion: Based on limited evidence, HBE is as effective as CBE on short-term pain, physical disability, walking ability, and lower limb muscle strength in people with knee osteoarthritis. Furthermore, combining HBE with CBE may enhance the overall efficacy of the intervention. Systematic review registration: PROSPERO, CRD42023416548.


Asunto(s)
Terapia por Ejercicio , Osteoartritis de la Rodilla , Medición de Resultados Informados por el Paciente , Humanos , Osteoartritis de la Rodilla/rehabilitación , Terapia por Ejercicio/métodos , Calidad de Vida , Servicios de Atención de Salud a Domicilio , Fuerza Muscular/fisiología , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Adv Mater ; 36(18): e2311429, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38298173

RESUMEN

Relieving inflammation via scavenging toxic reactive oxygen species (ROS) during the acute phase of spinal cord injury (SCI) proves to be an effective strategy to mitigate secondary spinal cord injury and improve recovery of motor function. However, commonly used corticosteroid anti-inflammatory drugs show adverse side effects which may induce increased risk of wound infection. Fortunately, hydrogen (H2), featuring selective antioxidant performance, easy penetrability, and excellent biosafety, is being extensively investigated as a potential anti-inflammatory therapeutic gas for the treatment of SCI. In this work, by a facile in situ growth approach of gold nanoparticles (AuNPs) on the piezoelectric BaTiO3, a particulate nanocomposite with Schottky heterojunction (Au@BT) is synthesized, which can generate H2 continuously by catalyzing H+ reduction through piezoelectric catalysis. Further, theoretical calculations are employed to reveal the piezoelectric catalytic mechanism of Au@BT. Transcriptomics analysis and nontargeted large-scale metabolomic analysis reveal the deeper mechanism of the neuroprotective effect of H2 therapy. The as-prepared Au@BT nanoparticle is first explored as a flexible hydrogen gas generator for efficient SCI therapy. This study highlights a promising prospect of nanocatalytic medicine for disease treatments by catalyzing H2 generation; thus, offering a significant alternative to conventional approaches against refractory spinal cord injury.


Asunto(s)
Oro , Hidrógeno , Nanopartículas del Metal , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/metabolismo , Hidrógeno/química , Catálisis , Animales , Oro/química , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Titanio/química , Ratones , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Nanocompuestos/química
20.
Chemosphere ; 352: 141380, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38368958

RESUMEN

Polybrominated diphenyl ethers (PBDEs) have been detected in various environmental media and human tissues. PBDEs concentrations in dust from college buildings and homes and in paired hair and urine samples from students were determined. This is of great significance to explore the accumulation and excretion patterns of PBDEs in the human body. The median PBDEs concentrations in the dust (College: 84.59 ng/g; Home: 170.32 ng/g) and hair (undergraduate: 6.16 ng/g; Home: 3.25 ng/g) samples were generally lower than were found in the majority of previous studies. The PBDEs concentrations in the hair and urine samples were subjected to principal component analysis, and the results combined with the PBDEs detection rates confirmed that hair is a useful non-invasive sampling medium for assessing PBDEs exposure and the risks posed. Body mass indices (BMIs) were used to divide students who had not been exposed to large amounts of PBDEs into groups. Body fat percentage is an important factor affecting the accumulation of PBDE in the human body. Environmental factors were found to affect the PBDEs concentrations in the hair and urine samples less for normal-weight students (BMI≤24) than overweight students (BMI>24). Short-term environmental changes to more readily affect the PBDEs concentrations in the tissues of the normal-weight than overweight students. PBDEs with seven or more bromine substituents were found not to be readily excreted in urine. Performing molecular docking simulations of the binding of isomers BDE-99 and BDE-100 to megalin. The binding energy was higher for BDE-100 and megalin than for BDE-99 and megalin, meaning BDE-99 would be more readily excreted than BDE-100.


Asunto(s)
Monitoreo del Ambiente , Éteres Difenilos Halogenados , Bifenilos Polibrominados , Humanos , Monitoreo del Ambiente/métodos , Éteres Difenilos Halogenados/análisis , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/análisis , Polvo/análisis , Simulación del Acoplamiento Molecular , Sobrepeso , Cabello/química , Exposición a Riesgos Ambientales/análisis
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