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1.
Huan Jing Ke Xue ; 45(5): 2640-2650, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629528

RESUMO

DOM is the largest reservoir of organic carbon in the world, and it plays a crucial role in the biogeochemical cycles of natural water bodies. A river is a transition area connecting source water and receiving water that controls the DOM exchange between them. Therefore, in this study, ultraviolet visible spectroscopy (UV-vis) and three-dimensional fluorescence spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC) were used to analyze the spectral characteristics and sources of dissolved organic matter in the Fuhe River, Xiaobai River, Baigouyin River, and Puhe River of Baiyangdian. The results showed that a245 and a355 in the Fuhe River and Xiaobai River were significantly higher than those in the Baigouyin River and Puhe River. E2/E3 showed that the DOM relative molecular mass of the inflow river water body was Puhe River > Baigouyin River > Fuhe River > Xiaobai River. Three components, tyrosine-like (C1), terrigenous humus (C2), and tryptophan-like (C3), were determined using three-dimensional fluorescence through PARAFAC. There was no difference among the fluorescence components (P>0.05), but there were differences among the C2 and C3 components (P<0.05). The proportion of easily degradable protein-like components (C1+C3) was higher than that of humus-like components (C2). The autogeny index BIX was greater than 1, and the humification index HIX was less than 4, indicating that the autogeny characteristics of the river bodies were obvious, and the humification degree was weak. The FI index was the highest (1.96±0.25), and the HIX index was the lowest (0.46±0.08), and the self-generated source characteristics gradually strengthened along the direction of the river entering the lake, indicating that the water body of the Fuhe River showed higher endogenous and autogenic characteristics. Based on the correlation analysis of fluorescence components and characteristic parameters of DOM, the correlations between the Fuhe River and Xiaobaihe River and between the Baigouyin River and Puhe River bodies were similar. The correlation between fluorescence components of DOM and water quality parameters of each lake was significantly different, and it was strongly correlated with nitrogen and phosphorus in water. According to multiple linear regression analysis, there was no significant difference among C1 components, but there was a significant difference between C2 and C3 components. In summary, the carbon cycle process of Baiyangdian Lake was further understood through the study on the DOM spectral characteristics and sources of the inflow river waters in the summer flood season.

2.
ChemSusChem ; : e202400481, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38571332

RESUMO

All-solid-state sodium metal batteries face the challenges of low ionic conductivity of solid electrolytes and poor wettability towards metallic Na anode. Herein, Na3Zr2Si2PO12 solid electrolyte is doped with Ca2+, obtaining a high ionic conductivity of 2.09 × 10-3 S cm-1 with low electronic conductivity of 1.43 × 10-8 S cm-1 at room temperature, which could accelerate Na+ transportation and suppress sodium dendrite growth. Meanwhile, a graphite-based interface layer is coated on Na3.4Zr1.8Ca0.2Si2PO12 (Na3.4Zr1.8Ca0.2Si2PO12-G) in order to improve the solid-solid contact between solid electrolyte and Na anode, realizing a uniform current distribution and smooth Na metal plating/stripping, and thus achieving a triple higher critical current density of 3.5 mA cm-2 compared with that of Na3.4Zr1.8Ca0.2Si2PO12. In addition, the assembled Na3V2(PO4)3/Na3.4Zr1.8Ca0.2Si2PO12-G/Na all-solid-state battery exhibits excellent electrochemical performances with a reversible capacity of 79.64 mAh g-1 at 1 C and capacity retention of 97.75% after 500 cycles.

3.
Subst Abuse Treat Prev Policy ; 19(1): 23, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627809

RESUMO

BACKGROUND: In Singapore, where drug use is a highly stigmatized and criminalized issue, there is limited understanding of the challenges faced by individuals, particularly sexual minority men, in their journey towards recovery from substance dependence or addiction. This qualitative study aimed to investigate the driving forces behind drug use, the factors contributing to drug cessation, and the elements influencing the recovery process. METHODS: Data were extracted from clinical records provided by  The Greenhouse Community Services Limited between January 2020 to May 2022. These records encompassed information from four distinct forms: the intake assessment, progress notes, case closing summary, and the care plan review. Thematic analysis was employed to identify and categorize recurring themes within the data. RESULTS: Data from beneficiaries (n = 125) were analyzed and yielded a series of themes related to facilitators of drug use, motivations to cease drug use, and managing one's ongoing recovery. Within the facilitators of drug use, two sub-themes were identified: (a) addressing trauma and triggers and (b) managing emotions. Additionally, managing one's recovery was marked by four significant sub-themes: (a) uncovering personal identities, (b) losing motivation and drive, (c) overcoming obstacles, and (d) preparing for aftercare. CONCLUSIONS: The study contributes valuable insights into the dynamics of ongoing recovery management, offering potential avenues for interventions that could enhance support for individuals in their journey to overcome substance dependence. Enhancing psychoeducation and fostering peer support have the potential to facilitate the recovery process. Clearly, a holistic approach is needed to address these complex issues that cuts across our societies.


Assuntos
Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Singapura , Estudos Retrospectivos , Serviços de Saúde Comunitária , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Seguridade Social
4.
Appl Microbiol Biotechnol ; 108(1): 292, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592514

RESUMO

Pulchinenoside B4, a natural saponin monomer from the Pulsatilla plant, plays an important role as an immunomodulator in the treatment of acute inflammation. Oral ulcer (OU) is a common ulcerative injury disease that occurs in the oral mucosa, including mucosal ulceration and abnormalities of lips and tongue. A close correlation exists between gut microbiota and circulating metabolites in patients with OU. However, the correlation between gut microbiota and serum metabolomics is not clear. Therefore, this study aimed to explore the changes in gut microbiota and metabolites in OU. The 16S ribosomal RNA (16S rRNA) gene sequencing was used to detect the changes in the composition of gut microbiota in OU rat model. Moreover, the endogenous small metabolites were explored by collecting the non-targeted serum metabolomics data. A total of 34 OU-related biomarkers were identified, mainly related to fatty acid metabolism and inflammatory pathways. The administration of B4 effectively reduced the occurrence of OU and restored the levels of multiple endogenous biomarkers and key gut microbial species to the normal level. This study demonstrated that the gut microbiota and metabolites were altered in the OU rat model, which were significantly restored to the normal level by B4, thereby showing good application prospects in the treatment of OU. KEY POINTS: • The first investigating the correlation between OU and gut microbiota. • A close correlation between metabolites and gut microbiota in OU disease was successfully identified. • Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.


Assuntos
Microbioma Gastrointestinal , Úlceras Orais , Humanos , Animais , Ratos , RNA Ribossômico 16S/genética , Mucosa Bucal , Biomarcadores
5.
Expert Opin Drug Saf ; : 1-9, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38646719

RESUMO

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

6.
World J Gastroenterol ; 30(11): 1524-1532, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38617452

RESUMO

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes. Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation. A large number of studies have shown that autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal (GI) cells. However, the role of autophagy in GI diseases remains controversial. This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases, in order to provide new ideas for their diagnosis and treatment.


Assuntos
Gastroenteropatias , Humanos , Autofagia , Microscopia Eletrônica de Transmissão
7.
Heliyon ; 10(6): e27423, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38496898

RESUMO

Global cerebral ischemia/reperfusion (GCI/R) injury poses a risk for cognitive decline, with neuroinflammation considered pivotal in this process. This study aimed to unravel the molecular mechanisms underlying GCI/R injury and propose a potential therapeutic strategy for associated cognitive deficits. Utilizing bioinformatics analysis of a public microarray profile (GSE30655 and GSE80681) in cerebral ischemic mice, it was observed that neuroinflammation emerged as a significant gene ontology item, with an increase in the expression of thioredoxin-interacting protein (TXNIP) and NLRP3 genes. Experimental models involving bilateral occlusion of the common carotid arteries in mice revealed that GCI/R induced cognitive impairment, along with a time-dependent increase in TXNIP and NLRP3 levels. Notably, TXNIP knockdown alleviated cognitive dysfunction in mice. Furthermore, the introduction of adeno-associated virus injection with TXNIP knockdown reduced the number of activated microglia, apoptosis neurons, and levels of oxidative stress and inflammatory cytokines in the hippocampus. Collectively, these findings underscore the significance of TXNIP/NLRP3 in the hippocampus in exacerbating cognitive decline due to GCI/R injury, suggesting that TXNIP knockdown holds promise as a therapeutic strategy.

8.
Blood Press Monit ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38502043

RESUMO

OBJECTIVES: This study was to explore blood pressure levels in Chinese adolescents with different genotypes of phosphatidylethanolamine N-methyltransferase (PEMT) gene (PEMT) rs7946, as well as effects of dietary intake on blood pressure levels with different genders and different genotypes of PEMT rs7946. METHODS: PEMT rs7946 genotypes were identified by PCR-restriction fragment length polymorphism and verified by DNA sequencing. Blood pressure was measured using a standard mercury sphygmomanometer. Dietary intakes were analyzed based on a 3-day diet diary, and dietary components were calculated using computer software. RESULTS: A total of 721 high school students (314 males and 407 females) at the age of 16.86 ±â€…0.59 years were included. The A allele carriers of PEMT rs7946 had increased levels of SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP) than the GG homozygotes in the female subjects. There were significant interactions between PEMT rs7946 and gender on SBP and MAP levels, regardless of whether an unadjusted or adjusted model was used. When dietary intake was taken into account, fat intake was positively associated with SBP and PP in the male GG homozygotes, while protein intake was positively associated with PP in the female A allele carriers of PEMT rs7946. CONCLUSION: This study suggests that PEMT rs7946 is significantly associated with blood pressure levels in human being. There might be interactions among PEMT rs7946, gender, and dietary intake on blood pressure levels in the adolescent population.

9.
Nucleic Acids Res ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554108

RESUMO

Recycling of parental histones is an important step in epigenetic inheritance. During DNA replication, DNA polymerase epsilon subunit DPB3/DPB4 and DNA replication helicase subunit MCM2 are involved in the transfer of parental histones to the leading and lagging strands, respectively. Single Dpb3 deletion (dpb3Δ) or Mcm2 mutation (mcm2-3A), which each disrupts one parental histone transfer pathway, leads to the other's predominance. However, the biological impact of the two histone transfer pathways on chromatin structure and DNA repair remains elusive. In this study, we used budding yeast Saccharomyces cerevisiae to determine the genetic and epigenetic outcomes from disruption of parental histone H3-H4 tetramer transfer. We found that a dpb3Δ mcm2-3A double mutant did not exhibit the asymmetric parental histone patterns caused by a single dpb3Δ or mcm2-3A mutation, suggesting that the processes by which parental histones are transferred to the leading and lagging strands are independent. Surprisingly, the frequency of homologous recombination was significantly lower in dpb3Δ, mcm2-3A and dpb3Δ mcm2-3A mutants, likely due to the elevated levels of free histones detected in the mutant cells. Together, these findings indicate that proper transfer of parental histones during DNA replication is essential for maintaining chromatin structure and that lower homologous recombination activity due to parental histone transfer defects is detrimental to cells.

10.
Biomed Pharmacother ; 173: 116309, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479180

RESUMO

As the leading killer of life and health, stroke leads to limb paralysis, speech disorder, dysphagia, cognitive impairment, mental depression and other symptoms, which entail a significant financial burden to society and families. At present, physiology, clinical medicine, engineering, and materials science, advanced biomaterials standing on the foothold of these interdisciplinary disciplines provide new opportunities and possibilities for the cure of stroke. Among them, hydrogels have been endowed with more possibilities. It is well-known that hydrogels can be employed as potential biosensors, medication delivery vectors, and cell transporters or matrices in tissue engineering in tissue engineering, and outperform many traditional therapeutic drugs, surgery, and materials. Therefore, hydrogels become a popular scaffolding treatment option for stroke. Diverse synthetic hydrogels were designed according to different pathophysiological mechanisms from the recently reported literature will be thoroughly explored. The biological uses of several types of hydrogels will be highlighted, including pro-angiogenesis, pro-neurogenesis, anti-oxidation, anti-inflammation and anti-apoptosis. Finally, considerations and challenges of using hydrogels in the treatment of stroke are summarized.


Assuntos
Técnicas Biossensoriais , Acidente Vascular Cerebral , Humanos , Hidrogéis/uso terapêutico , Materiais Biocompatíveis , Engenharia Tecidual , Acidente Vascular Cerebral/tratamento farmacológico
11.
Zool Res ; 45(2): 355-366, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38485505

RESUMO

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, cyp17a1-/- zebrafish ( Danio rerio) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/- fish compared to cyp17a1+/+ male fish, including stearoyl-CoA desaturase ( scd) and fatty acid synthase ( fasn). Androgen response element (ARE) motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+ male fish but not in cyp17a1-/- fish. Both androgen receptor ( ar)-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis enzymes. The Ar agonist BMS-564929 reduced the content of VAT and lipid content, and down-regulated acetyl-CoA carboxylase a ( acaca), fasn, and scd expression. Mechanistically, the rescue effect of testosterone on cyp17a1-/- fish in terms of phenotypes was abolished when ar was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.


Assuntos
Androgênios , Lipogênese , Masculino , Animais , Androgênios/farmacologia , Lipogênese/genética , Peixe-Zebra/genética , Testosterona , Lipídeos , Transdução de Sinais , Cromatina
12.
Sci Rep ; 14(1): 5095, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429374

RESUMO

The clinical application of conventional doxorubicin (CDOX) was constrained by its side effects. Liposomal doxorubicin was developed to mitigate these limitations, showing improved toxicity profiles. However, the adverse events associated with liposomal doxorubicin and CDOX have not yet been comprehensively evaluated in clinical settings. The FAERS data from January 2004 to December 2022 were collected to analyze the adverse events of liposomal doxorubicin and CDOX. Disproportionate analysis and Bayesian analysis were employed to quantify this association. Our analysis incorporated 68,803 adverse event reports related to Doxil/Caelyx, Myocet and CDOX. The relative odds ratios (RORs, 95%CI) for febrile neutropenia associated with CDOX, Doxil/Caelyx, and Myocet were 42.45 (41.44; 43.48), 17.53 (16.02; 19.20), and 34.68 (26.63; 45.15) respectively. For cardiotoxicity, they were 38.87(36.41;41.49), 17.96 (14.10; 22.86), and 37.36 (19.34; 72.17). For Palmar-Plantar Erythrodysesthesia (PPE), the RORs were 6.16 (5.69; 6.68), 36.13 (32.60; 40.06), and 19.69 (11.59; 33.44). Regarding onset time, significant differences adverse events including neutropenia, PPE, pneumonia and malignant neoplasm progression. This study indicates that clinical monitoring for symptoms of cardiotoxicity of CDOX and Myocet, and PPE and interstitial lung disease of Doxil should be performed. Additionally, the onset time of febrile neutropenia, malignant neoplasm progression, and pneumonia associated with Doxil and Myocet merits particular attention. Continuous surveillance, risk evaluations, and additional comparative studies between liposomal doxorubicin and CDOX were recommended.


Assuntos
Doxorrubicina/análogos & derivados , Neoplasias , Neutropenia , Pneumonia , Humanos , Cardiotoxicidade/tratamento farmacológico , Teorema de Bayes , Doxorrubicina/efeitos adversos , Lipossomos , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Pneumonia/tratamento farmacológico , Polietilenoglicóis
13.
Biochem Genet ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478147

RESUMO

This study aims to elucidate the role and mechanisms of Death Receptor 6 (DR6), a member of the tumor necrosis factor receptor superfamily, in the malignant progression of colorectal cancer (CRC). The association of DR6 expression levels and CRC patient survival was examined using the CRC cohort data from GEPIA database. The functional role of DR6 in CRC cells was investigated by performing loss-of-function and gain-of-function experiments based on CCK-8 proliferation assay, transwell migration and invasion assay, and sphere-forming assays. Xenograft model of CRC cells in nude mouse was established to evaluate the impact of DR6 knockdown on CRC tumorigenesis. Elevated expression of DR6 was correlated with an unfavorable prognosis in CRC patients. In vitro functional assays demonstrated that silencing DR6 considerably suppressed the proliferation, migration, invasion, and stemness of CRC cells, whereas its overexpression showed an opposite effect. DR6 knockdown also attenuated tumor formation of CRC cells in the nude mice. Mechanistically, silencing DR6 reduced the phosphorylation of AKT and NF-κB in CRC cells, and the treatment with an AKT activator (SC79) abrogated the inhibitory effects of DR6 knockdown on the malignant features of CRC cells. Our data suggest that DR6 contributes to the malignant progression of CRC by activating AKT/NF-κB pathway, indicating its clinical potential as a prognostic marker and therapeutic target for CRC.

14.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469761

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic spread rapidly with considerable morbidity nationwide since China's liberalization in December 2022. Our work has focused on identifying different predictive factors from the laboratory examination of critically ill patients, and forecasting the unfavorable outcome of critically ill patients with COVID-19 through a combined diagnosis of biological markers. METHODS: We conducted a retrospective study at the Department of First Affiliated Hospital of Wenzhou Medical University, China, from December 24, 2022, to January 10, 2023, where 434 critically ill patients who met the inclusion criteria were involved. Machine analysis was employed to search for the parameters with the highest predictive value to calculate COVID-19 mortality by exploiting 66 typical laboratory results. RESULTS: Combined diagnosis of serum albumin (ALB), lactate dehydrogenase (LDH), direct bilirubin (Dbil), ferritin, pulse oxygen saturation (SpO2), and neutrophil count (NEUT#) was evaluated, and the result with the highest predictive value (NEUT#) was selected as the predictor for COVID-19 mortality with a sensitivity of 89.2% and a specificity of 77.4%. CONCLUSIONS: The increased levels of LDH, Dbil, ferritin, and NEUT#, along with lowered ALB and SpO2 levels are the most decisive variables for forecasting the mortality for COVID-19 according to our machine-learning-based model. The combined diagnosis could be used to improve further diagnostic performance.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Estudos Retrospectivos , Estado Terminal , Ferritinas
15.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469764

RESUMO

BACKGROUND: Normal hemoglobin is a tetrameric structure, consisting of two alpha-globin chains and two nonalpha (beta, gamma, delta) chains. Hemoglobinopathies occur when the presence of gene mutations affect the molecular structure or expression of the globin chains. METHODS: We reported the case of a 9-year-old Chinese girl who presented with abnormal low oxygen saturation values on pulse oximetry and no oximetry results were obtained during blood gas analysis (BGA). RESULTS: High-performance liquid chromatography (HPLC) and capillary electrophoresis demonstrated that the presence of a low oxygen affinity hemoglobin variant, characterized as hemoglobin Titusville, was proven by gene sequencing. The patient's mother and aunt also carry the hemoglobin variant, representing the first Chinese family case reported. CONCLUSIONS: Hemoglobin Titusville is a rare genetic hemoglobin structural defect. early diagnosis can help patients and clinicians avoid unnecessary anxiety and costly or excessive clinical investigations.


Assuntos
Hemoglobinopatias , Hemoglobinas Anormais , Feminino , Humanos , Criança , Saturação de Oxigênio , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Oximetria , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/análise , Oxigênio , Gasometria
16.
Biomaterials ; 306: 122483, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38330742

RESUMO

Bromodomain-containing protein 4 (BRD4) is the most well-studied BET protein that is important for the innate immune response. We recently revealed that targeting BRD4 triggers apoptosis in tumor-associated macrophages, but its role in synovial macrophages and joint inflammation is largely unknown. Herein, we demonstrated that BRD4 was highly expressed in the iNOS-positive M1 macrophages in the human and mouse osteoarthritis (OA) synovium, and conditional knockout of BRD4 in the myeloid lineage using Lyz2-cre; BRD4flox/flox mice significantly abolished anterior cruciate ligament transection (ACLT)-induced M1 macrophage accumulation and synovial inflammation. Accordingly, we successfully constructed apoptotic body-inspired phosphatidylserine-containing nanoliposomes (PSLs) loaded with the BRD4 inhibitor JQ1 to regulate inflammatory macrophages. JQ1-loaded PSLs (JQ1@PSLs) exhibited a higher cellular uptake by macrophages than fibroblast-like synoviocytes (FLSs) in vitro and in vivo, as well as the reduction in proinflammatory M1 macrophage polarization. Intra-articular injections of JQ1@PSLs showed prolonged retention within the joint, and remarkably reduced synovial inflammation and joint pain via suppressing M1 polarization accompanied by reduced TRPA1 expression by targeted inhibition of BRD4 in the macrophages, thus attenuating cartilage degradation during OA development. The results show that BRD4-inhibiting JQ1@PSLs can targeted-modulate macrophage polarization, which opens a new avenue for efficient OA therapy via a "Trojan horse".


Assuntos
Osteoartrite , Fatores de Transcrição , Animais , Humanos , Camundongos , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Proteínas Nucleares/metabolismo , Osteoartrite/metabolismo , Membrana Sinovial/metabolismo , Fatores de Transcrição/metabolismo
17.
Nurs Health Sci ; 26(1): e13091, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38356113

RESUMO

During home isolation due to the coronavirus disease, family caregivers assumed the responsibility of caring for infected family members; however, the full extent of the difficulties and challenges they encountered remains unclear. This study applied a descriptive phenomenology approach, using semi-structured, one-on-one, in-depth interviews to explore the experiences of 16 primary family caregivers during home isolation amid the coronavirus disease. The key themes identified were as follows: (1) protecting family, comprising anxiety over preventing infection and bearing the responsibility of caregiving and a concern about the diagnosis; (2) seeking stability, encompassing the impact of epidemic control policies on daily routines, strategies to overcome obstacles caused by quarantine measures, and gathering resources and receiving support; and (3) reflections on life, including favoring love over discrimination, rediscovering oneself, cherishing family, and acknowledging personal growth and dedication. This study highlights that family members who took on caregiving roles due to obstacles or health risks faced significant pressure to protect their family members during isolation and actively sought professional consultation and acquired caregiving skills to enhance their confidence and adaptability.


Assuntos
COVID-19 , Cuidadores , Humanos , Isolamento de Pacientes , Família , Ansiedade
18.
Org Lett ; 26(9): 1807-1812, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38393343

RESUMO

We have identified the biosynthetic gene cluster (hvm) for the sterol O-acyltransferase inhibitor helvamide (1) from the genome of Aspergillus rugulosus MST-FP2007. Heterologous expression of hvm in A. nidulans produced a previously unreported analog helvamide B (5). An α-ketoglutarate-dependent oxygenase Hvm1 was shown to catalyze intramolecular cyclization of 1 to yield 5. The biosynthetic branch to the related hancockiamides and helvamides was found to be controlled by the substrate selectivity of monomodular nonribosomal peptide synthetases.


Assuntos
Ácidos Cetoglutáricos , Oxigenases , Oxigenases/genética , Oxigenases/metabolismo , Esterol O-Aciltransferase/genética , Esterol O-Aciltransferase/metabolismo , Ciclização , Família Multigênica , Peptídeo Sintases/metabolismo
19.
Int J Ophthalmol ; 17(2): 339-347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371252

RESUMO

AIM: To explore the brain mechanism of acupuncture for children with anisometropic amblyopia using the voxel-mirror homotopic connectivity (VMHC) analysis method of resting functional magnetic resonance imaging (rs-fMRI) technology based on clinical effectiveness. METHODS: Eighty children with anisometropic monocular amblyopia were randomly divided into two groups: control (40 cases, 1 case of shedding) and acupuncture (40 cases, 1 case of shedding) groups. The control group was treated with glasses, red flash, grating, and visual stimulations, with each procedure conducted for 5min per time. Based on routine treatment, the acupuncture group underwent acupuncture of "regulating qi and unblocking meridians to bright eyes", Jingming (BL1), Cuanzhu (BL2), Guangming (GB37), Fengchi (GB20) acupoints were taken on both sides, with the needle kept for 30min each time. Both groups were treated once every other day, three times per week, for a total of 4wk. After the treatment, the overall curative effect of the two groups and the latency and amplitude changes of P100 wave of pattern visual-evoked potential were counted. At the same time, nine children with left eye amblyopia were randomly selected from the two groups and were scanned with rs-fMRI before and after treatment. The differences in the brain regions between the two groups were compared and analyzed with VMHC. RESULTS: Chi-square test showed a notable difference in the total efficiency rate between the acupuncture (94.87%) and control groups (79.49%). Regarding the P100 wave latency and amplitude, the acupuncture group had significantly shorter latency and higher amplitude of P100 wave than the control group. Moreover, the VMHC values of the bilateral temporal lobe, superior temporal gyrus, and middle temporal gyrus were notably increased in the acupuncture group after treatment. CONCLUSION: Acupuncture combined with conventional treatment can significantly improve the corrected visual acuity and optic nerve conduction in children with anisometropic amblyopia. Compared with the conventional treatment, the regulation of acupuncture on the functional activities of the relevant brain areas in the anterior cerebellum may be an effective acupuncture mechanism for anisometropic amblyopia.

20.
Zhongguo Zhen Jiu ; 44(2): 153-157, 2024 Feb 12.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38373760

RESUMO

OBJECTIVES: To observe the clinical efficacy of Tiaoqi Tongjing Mingmu acupuncture (acupuncture for regulating qi, unblocking meridians and brightening eyes) combined with conventional treatment for anisometropic amblyopia children. METHODS: A total of 76 children with monocular anisometropic amblyopia were randomized into an observation group (38 cases, 2 cases dropped out) and a control group (38 cases). The lens covering therapy was adopted in both groups. The conventional treatment i.e. red flash, grating and visual stimulation was given in the control group, 5 min for one item each time; on the basis of the treatment in the control group, acupuncture was applied at bilateral Jingming (BL 1), Cuanzhu (BL 2), Fengchi (GB 20) and Guangming (GB 37) in the observation group. Both groups were treated once every other day, 3 times a week for 4 weeks. Before and after treatment, the best corrected visual acuity, the latency and amplitude of P100 wave of pattern visual evoked potential (P-VEP), the diopter (spherical equivalent [SE]) were observed, the stereoacuity was measured by Titmus stereoscopic examination, and the clinical efficacy was evaluated in both groups. RESULTS: Compared with those before treatment, the best corrected visual acuity improved (P<0.05), the latency of P-VEP P100 wave was shortened and the amplitude of P-VEP P100 wave was increased (P<0.05), and the SE and Titmus values were decreased (P<0.05) after treatment in both groups. After treatment, in the observation group, the best corrected visual acuity was higher (P<0.05), the latency of P-VEP P100 wave was shorter and the amplitude of P-VEP P100 wave was higher (P<0.05), SE and Titmus values were lower (P<0.05) than those in the control group. The total effective rate was 86.1% (31/36) in the observation group, which was superior to 65.8% (25/38) in the control group (P<0.05). CONCLUSIONS: During the visual plasticity period, Tiaoqi Tongjing Mingmu acupuncture combined with conventional treatment can effectively improve the best corrected vision, diopter and stereoacuity in children with anisometropic amblyopia, and enhance the nerve conduction function from retina to visual cortex. Its effect is superior to that of simple conventional treatment.


Assuntos
Terapia por Acupuntura , Ambliopia , Criança , Humanos , Ambliopia/terapia , Potenciais Evocados Visuais , Visão Ocular , Retina
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