Rol comunicativo del cuidador en pacientes con accidente cerebrovascular, Sincelejo, Colombia / The communicative role of caregivers assisting stroke patients from Sincelejo, Colombia / Papel comunicativo do cuidador em pacientes com acidente vascular cerebral, Sincelejo, Colômbia

Introducción: Las enfermedades cerebrovasculares son consideradas un problema de salud pública que afectan muchas capacidades en el individuo, entre ellas la comunicación; de esta manera el cuidador cumple un papel fundamental en su recuperación. Objetivo: Describir el rol comunicativo del cuidador en la atención a pacientes con secuelas de accidente cerebrovascular en la ciudad de Sincelejo, Colombia. Materiales y métodos: Paradigma positivista, enfoque cuantitativo y estudio descriptivo de corte transversal realizado con 40 cuidadores, seleccionados según muestreo por criterios y reclutamiento en cadena. Se utilizó una encuesta sociodemográfica, una sobre favorecimiento y bienestar comunicativo y Escala Likert, se realizó análisis de fiabilidad y consistencia interna del instrumento. Resultados: Predominaron cuidadores de sexo femenino, sobresale el cuidador informal, con estudios de secundaria y estrato socioeconómico bajo. Se encontró una actitud favorable en la competencia del ser y saber hacer, prima el buen trato, justicia y respeto. La competencia del saber evidenció actitud desfavorable, caracterizada por un conocimiento limitado frente a la patología, insuficientes destrezas, técnicas y habilidades para cumplir sus funciones y estrategias empleadas. Conclusión: Es necesario cualificar al cuidador en la atención del paciente con accidente cerebrovascular, mediante programas de que dinamicen la competencia del ser, saber y saber hacer

Introduction: Cerebrovascular diseases are a public health problem affecting the different capabilities of patients, including communication. Thus, caregivers play a fundamental role in their recovery. Objective: To describe the communicative role of caregivers in the support of patients with stroke sequelae in the city of Sincelejo, Colombia. Materials and methods: A positivist paradigm, quantitative approach, and descriptive cross-sectional study was carried out with 40 caregivers, who were selected according to criteria sampling and chain recruitment. A sociodemographic survey about favorability and communicative well-being as well as the Likert Scale were applied. A reliability and internal consistency analysis was conducted. Results: The majority of caregivers were women. Informal caregivers, with high school education, and belonging to low socioeconomic status were also predominant. A positive attitude regarding competences such as being and knowing what to do; appropriate treatment of patients, with justice and respect, were observed as common features. The knowledge competence was considered unfavorable, which was characterized by limited understanding regarding pathology, strategies used, and insufficient skills, techniques, and abilities to fulfill their functions. Conclusions: Caregivers of stroke patients should be qualified through programs that improve the being, knowing, and knowing how to do competencies.

Introdução: As doenças cerebrovasculares são consideradas um problema de saúde pública que afeta diversas capacidades do indivíduo, incluindo a comunicação; desta forma, o cuidador desempenha um papel fundamental na sua recuperação. Objetivo: Descrever o papel comunicativo do cuidador no cuidado de pacientes com sequelas de acidente vascular cerebral na cidade de Sincelejo, Colômbia. Materiais e métodos: Paradigma positivista, abordagem quantitativa e estudo transversal descritivo realizado com 40 cuidadores, selecionados segundo critérios de amostragem e recrutamento em cadeia. Foi utilizado um inquérito sociodemográfico, um de favorabilidade e bem-estar comunicativo e uma Escala Likert, foi realizada uma análise da fiabilidade e consistência interna do instrumento. Resultados: Predominaram cuidadores do sexo feminino, destacando-se os cuidadores informais, com escolaridade média e baixo nível socioeconômico. Encontrou-se na competição uma atitude favorável por ser e saber fazer, prevalecendo o bom tratamento, a justiça e o respeito. A competência conhecimento apresentou atitude desfavorável, caracterizada por conhecimento limitado sobre a patologia, habilidades, técnicas e habilidades insuficientes para cumprir suas funções e estratégias utilizadas. Conclusões: É necessário qualificar o cuidador no cuidado ao paciente com AVC, por meio de programas que potencializem a competência de ser, saber e saber fazer.

Calidad de vida relacionada con la salud y los estados de ánimo en estudiantes de instituciones educativas de Antioquia, Colombia / Quality of life related to the health and mood states of students in educational institutions from Antioquia, Colombia / Qualidade de vida relacionada à saúde e ao humor em estudantes de instituições de ensino em Antioquia, Colômbia

Introducción: La calidad de vida relacionada con la salud (CVRS) y los estados de ánimo son indicadores cruciales del bienestar en adolescentes, pero su relación con estudiantes de Antioquia, Colombia, no ha sido ampliamente estudiada. Objetivo: Determinar la CVRS y los estados de ánimo en escolares de Antioquia-Colombia. Materiales y métodos: Estudio transversal con 1957 escolares de 9 a 20 años. Se aplicaron mediciones de CVRS, ansiedad, depresión, hostilidad y alegría, actividad física, comportamiento sedentario, apoyo social de padres y nivel socioeconómico. Resultados: La calidad de vida alta (CVA) es más elevada en hombres, personas con alegría, estudiantes con apoyo de padres, activos físicamente y personas de nivel socioeconómico alto y medio. AL aumentar un año de edad, disminuye en un 15 % la CVA, y al aumentar la depresión, la ansiedad y el comportamiento sedentario disminuye la CVA. Además, los niveles de depresión y ansiedad son mayores en mujeres, estudiantes mayores, sin apoyo de los padres y personas sedentarias. Conclusiones: La CVRS se asocia con estados de ánimo, actividad física, comportamiento sedentario y apoyo de los padres; mientras que los estados de ánimo se asocian con el sexo, el apoyo de los padres, la CVS y el sedentarismo.

Introduction: Even though health-related quality of life (HRQL) and mood states are key indicators of the well-being of adolescents, their relationship has not been analyzed in students from Antioquia, Colombia. Objective: To determine HRQL and mood states in schoolchildren from Antioquia. Materials and methods: A cross-sectional study was conducted on 1,957 schoolchildren and adolescents aged between 9 and 20 years. Measurements of HRQL, anxiety, depression, hostility and happiness, physical activity, sedentary behavior, parental social support, and socioeconomic status were applied. Results: A high quality of life (HQL) was observed more frequently in male participants, students with parental support, physically active, and those belonging to medium and high socioeconomic status. HQL decreased 15% as their age increased by one year. Also, HQL was reduced when depression, anxiety, and sedentary behavior increased. Furthermore, depression and anxiety levels were higher in women, older students, as well as in those without parental control and with sedentary behavior. Conclusions: HRQL is associated with mood states, physical activity, sedentary behavior, and parental support. In contrast, mood states are related to gender, parental support, HQL, and sedentary lifestyle.

Introdução: A qualidade de vida relacionada à saúde (CVRS) e os estados de humor são indicadores cruciais de bem-estar em adolescentes, mas sua relação com estudantes de Antioquia, Colômbia, não foi amplamente estudada. Objetivo: Determinar a CVRS e os estados de humor em escolares de Antioquia-Colômbia. Materiais e métodos: Estudo transversal com 1.957 escolares de 9 a 20 anos. Foram aplicadas medidas de QVRS, ansiedade, depressão, hostilidade e felicidade, atividade física, comportamento sedentário, apoio social dos pais e nível socioeconômico. Resultados: A alta qualidade de vida (CVA) é maior em homens, pessoas com alegria, estudantes com apoio parental, fisicamente ativos e pessoas de nível socioeconômico alto e médio. À medida que a idade aumenta em um ano, diminui em 15% o CVA, e ao aumentar a depressão, a ansiedade e o comportamento sedentário aumentam, o CVA diminui. Além disso, os níveis de depressão e ansiedade são mais elevados nas mulheres, nos estudantes mais velhos, sem apoio dos pais e nas pessoas sedentárias. Conclusões: A QVRS está associada a estados de humor, atividade física, comportamento sedentário e apoio parental; enquanto os estados de humor estão associados ao sexo, apoio parental, CVS e estilo de vida sedentário.

Periodontal therapy for hopeless mandibular anterior teeth: a retrospective case report with a multidisciplinary approach and a 20-year follow-up

Introduction: This case report presents the intentional periodontal maintenance of two periodontal hopeless lower central incisors with a multidisciplinary approach and 20-year follow-up. Case presentation: A 36-year-old male, in 2001, was diagnosed with aggressive periodontitis, gingival swelling, bleeding, and mandibular central incisors with mobility and poor prognosis. Following periodontal therapy (phase I), root canal treatment, and occlusal adjustment, #31 and #41 were gently extracted to remove the granulation tissues, calculus, and infected cementum from the root surface. Then, tetracycline-HCl was applied for 5 minutes on the root surfaces. The teeth were repositioned into the sockets and splinted with a lingual bar. At 3 months, the bar was removed, and a free gingival autogenous graft was done to improve the local keratinized tissue width. Mobility scores, pocket depths, and clinical attachment levels were recorded, and radiographs were taken at 1, 5, and 20 years. The 5-year follow-up showed that the teeth were clinically and radiographically in function. There was a reduction in probing depth and a gain in clinical attachment and radiographic alveolar bone levels. After 20 years, #41 was stable, but #31 had external root resorption, leading to a new treatment plan (dental implants) and extraction. Conclusion: The clinical result of this case was satisfactory for 20 years. Intentional periodontal maintenance of the teeth may be an alternative treatment, even considering the high level of complexity.

Percepção profissional sobre tratamento endodôntico em sessão única e múltiplas sessões / Professional perception of single and multi-session endodontic treatment

Na odontologia a decisão do tratamento é exclusiva dos cirurgiões dentistas e suas percepções, incluindo filosofia de tratamento, fazendo com que a prática de novos conceitos, tratamentos ou técnicas dependam não apenas de sua lógica ou eficácia biológica. Sendo assim, este estudo teve como objetivo avaliar os parâmetros envolvidos na tomada de decisão de cirurgiões dentistas clínicos e especialistas para a realização do tratamento endodôntico em sessão única ou múltiplas sessões. Para tanto, este estudo contou com uma coleta de dados através de um questionário online, aplicado cirurgiões dentistas clínicos gerais e especialistas em endodontia. As respostas foram tabuladas e analisadas por meio de estatística descritiva. Os resultados revelaram que a maioria dos endodontistas e dos clínicos gerais prefere realizar tratamento endodôntico em sessão única, devido ao menor desperdício de material, além do melhor domínio da anatomia e tratamento em um único momento. O motivo mais comum para os endodontistas e clínicos gerais escolherem o tratamento com múltiplas visitas é para dentes com prognóstico duvidoso e os casos em que o profissional aguarda a remissão dos sintomas antes da obturação. Em conclusão, a maioria dos endodontistas e dos clínicos gerais preferiu realizar tratamento endodôntico em sessão única.

In dentistry, treatment decisions are made exclusively by dental surgeons and their perceptions, including treatment philosophy, which means that the practice of new concepts, treatments or techniques depends not only on their logic or biological efficacy. Therefore, the aim of this study was to evaluate the parameters involved in clinical and specialist dental surgeons' decision to carry out endodontic treatment in single or multiple sessions. To this end, data was collected using an online questionnaire administered to general dental surgeons and endodontic specialists. The answers were tabulated and analyzed using descriptive statistics. The results revealed that the majority of endodontists and general practitioners prefer to carry out endodontic treatment in a single session, due to less wastage of material, as well as better mastery of the anatomy and treatment at a single time. The most common reason for endodontists and general practitioners to choose treatment with multiple visits is for teeth with a doubtful prognosis and cases in which the professional is waiting for symptoms to remit before filling. In conclusion, the majority of endodontists and general practitioners preferred to carry out endodontic treatment in a single session.

Analysis of Forsythia suspensa fruit and leaf extracts using UHPLC-Q-Exactive-Orbitrap/MS: In vivo antioxidant activity on D-galactose-induced aging mice.

Making health-enhancing tea from Forsythia suspensa leaves has been a tradition of Chinese folk culture for centuries. However, these leaves were not officially recognized as a new food source until 2017 by the Chinese government. In this study, ethyl acetate fractions from Forsythia suspensa fruit and leaves exhibited excellent antioxidant activity in vitro antioxidant assays and in vivo D-galactose-induced aging mice model. The antioxidant activity of the leaves was higher than that of fruit both in vitro and in vivo. The chemical constituents present in these ethyl acetate fractions were comprehensively analyzed using UHPLC-Q-Exactive-Orbitrap/MS. A total of 20 compounds were identified, among which forsythoside E, (+)-epipinoresinol, dihydromyricetin, chlorogenic acid, and ursolic acid were exclusively detected in the ethyl acetate fraction of Forsythia suspensa leaves, but absent in the ethyl acetate fraction derived from its fruit. This study provides theoretical support for the utilization of Forsythia suspensa fruit and leaves.

Insights into the flavor endowment of aroma-active compounds in cloves (Syzygium aromaticum) to stewed beef.

Clove (Syzygium aromaticum) is one of the most commonly used spices in stewed beef to enrich and improve its aroma during the stewing process. Gas chromatography ion mobility spectroscopy (GC-IMS), Q Exactive GC-Orbitrap-MS-O (QE-GC-MS/O), combined with sensory evaluation were employed to analyze the flavor endowment of aroma-active compounds in cloves to stewed beef. A total of 173 volatiles were identified in the clove powder (CP), stewed beef with clove (SBC), and stewed beef with salt (SBS), of which 21 volatiles were considered as aroma-active compounds. The concept of flavor endowment of aroma-active compounds in cloves was defined innovatively, and the endowment rate values (ERVs) of stewed beef were calculated. Nine aroma-active compounds in cloves were found to have a flavor endowment effect on stewed beef, while the terpenoids exhibited high ERVs. Despite the low ERV of eugenol, it still significantly impacted the aroma profile of SBC due to its high odor activity value (OAV) and flavor dilution (FD) factor. These volatiles offered mainly the clove, herbal, anise, and floral odor to stewed beef, which was also confirmed by sensory evaluation. These findings indicated that the terpenoids, phenolics and ethers in cloves had a significant influence on the overall aroma of stewed beef through the flavor endowment, which contributed to the precise use of cloves and improved the aroma of stewed beef.

Dietary sn-2 palmitate influences cognitive behavior by increasing the transport of liver-produced lysophosphatidylcholine VLCPUFAs to the brain.

Investigations indicated that sn-2 palmitate have positive effects on brain development, although its mechanism remains largely unexamined. This research delved into how a diet abundant in sn-2 palmitate influenced the cognitive behavior of mice and elucidated the associated mechanisms using metabolomics and lipidomics. The study demonstrated that dietary sn-2 palmitate led to improved working memory and cognition in mice, as well as an increase in brain BDNF concentration when compared to those fed blend vegetable oil (BVO). This was because sn-2 palmitate feeding promoted the synthesis of very long-chain fatty acids (VLCPUFAs) for the lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) in the liver. This led to more efficient delivery of VLCPUFAs to the brain, as indicated by elevated concentration of LPC/LPE-VLCPUFAs in the liver and heightened expression of the major facilitator superfamily domain containing 2a (MFSD2A). In essence, this paper offered a potential mechanism by which sn-2 palmitate enhanced mouse neurodevelopment.

Shuangdan Jiedu Decoction improved LPS-induced acute lung injury by regulating both cGAS-STING pathway and inflammasome.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangdan Jiedu Decoction (SJD) is a formula composed of six Chinese herbs with heat-removing and detoxifying, antibacterial, and anti-inflammatory effects, which is clinically used in the therapy of various inflammatory diseases of the lungs including COVID-19, but the therapeutic material basis of its action as well as its molecular mechanism are still unclear. AIM OF THE STUDY: The study attempted to determine the therapeutic effect of SJD on LPS-induced acute lung injury (ALI), as well as to investigate its mechanism of action and assess its therapeutic potential for the cure of inflammation-related diseases in the clinical setting. MATERIALS AND METHODS: We established an ALI model by tracheal drip LPS, and after the administration of SJD, we collected the bronchoalveolar lavage fluid (BALF) and lung tissues of mice and examined the expression of inflammatory factors in them. In addition, we evaluated the effects of SJD on the cyclic guanosine monophosphate-adenosine monophosphate synthase -stimulator of interferon genes (cGAS-STING) and inflammasome by immunoblotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: We demonstrated that SJD was effective in alleviating LPS-induced ALI by suppressing the levels of pro-inflammatory cytokines in the BALF, improving the level of lung histopathology and the number of neutrophils, as well as decreasing the inflammatory factor-associated gene expression. Importantly, we found that SJD could inhibit multiple stimulus-driven activation of cGAS-STING and inflammasome. Further studies showed that the Chinese herbal medicines in SJD had no influence on the cGAS-STING pathway and inflammasome alone at the formulated dose. By increasing the concentration of these herbs, we observed inhibitory effects on the cGAS-STING pathway and inflammasome, and the effect exerted was maximal when the six herbs were combined, indicating that the synergistic effects among these herbs plays a crucial role in the anti-inflammatory effects of SJD. CONCLUSIONS: Our research demonstrated that SJD has a favorable protective effect against ALI, and its mechanism of effect may be associated with the synergistic effect exerted between six Chinese medicines to inhibit the cGAS-STING and inflammasome abnormal activation. These results are favorable for the wide application of SJD in the clinic as well as for the development of drugs for ALI from herbal formulas.

Naoxintong capsule accelerates mitophagy in cerebral ischemia-reperfusion injury via TP53/PINK1/PRKN pathway based on network pharmacology analysis and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence and mortality of cerebrovascular diseases are increasing year by year. Cerebral ischemia-reperfusion injury (CIRI) is common in patients with ischemic stroke. Naoxintong (NXT) is composed of a variety of Chinese medicines and has the ability to treat CIRI. AIM OF THE STUDY: The aim of this study is to investigate whether NXT regulates mitophagy in CIRI based on network pharmacology analysis and experimental validation. MATERIALS AND METHODS: Oxygen and glucose deprivation/re-oxygenation (OGD/R, 2/22 h) model of PC12 cells and transient middle cerebral artery occlusion (tMCAO, 2/22 h) model of rats were established. Pharmacodynamic indicators include neurological deficit score, 2,3,5-triphenyte-trazoliumchloride (TTC) staining, hematoxylin-eosin (HE) staining and cell viability. Network pharmacology was used to predict pharmacological mechanisms. Pharmacological mechanism indexes include transmission electron microscopy (TEM), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), immunohistochemistry (IHC), western blot (WB) and immunofluorescence (IF). Kevetrin (an agonists of p53) and pifithrin-α (an inhibitor of p53) used to detect the key role of p53 in mitophagy of NXT. RESULTS: NXT (1% serum containing NXT and 110 mg/kg) improved the damage of OGD/R PC12 cells and tMCAO rats, and this protective effect was related to the anti-oxidation and ability to promote mitophagy of NXT. NXT and pifithrin-α increased the expression of promoting-mitophagy targets (PINK1, PRKN and LC3B) and inhibited the expression of inhibiting-mitophagy targets (p52) via restraining p53, and finally accelerated mitophagy caused by CIRI. CONCLUSION: This study demonstrates that NXT promotes mitophagy in CIRI through restraining p53 and promoting PINK1/PRKN in vivo and in vitro.

Zhongfeng decoction attenuates cerebral ischemia-reperfusion injury by inhibiting autophagy via regulating the AGE-RAGE signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tackling phlegm and improving blood circulation is vital in the treatment of ischemic stroke (IS), culminating in the development of Zhongfeng Decoction (ZFD), a method grounded in this approach and serving as an effective therapy for IS. Nonetheless, the defensive mechanism of the ZFD in preventing cerebral ischemia-reperfusion damage remains ambiguous. AIM OF THE STUDY: Determine the active ingredients in ZFD that have neuroprotective effects, and identify its mechanism of action against IS. MATERIALS AND METHODS: A cerebral ischemia model in rats was developed, utilizing TTC, Nissl staining, and an oxidative stress kit to evaluate the neuroprotective impact of ZFD on this rat model. Following this, an amalgamation of LC-MS and network pharmacology techniques was employed to pinpoint potential active components, primary targets, and crucial action mechanisms of ZFD in treating IS. Finally, key targets and signaling pathways were detected using qRT-PCR, ELISA, Western blotting, electron microscopy, and other methods. RESULTS: Through LC-MS and network analysis, 15 active ingredients and 6 hub targets were identified from ZFD. Analysis of pathway enrichment revealed that ZFD predominantly engages in the AGE-RAGE signaling route. Kaempferol, quercetin, luteolin, baicalein, and nobiletin in ZFD are the main active ingredients for treating IS. In vivo validation showed that ZFD can improve nerve damage in cerebral ischemic rats, reduce the mRNA expression of IL6, SERPINE1, CCL2, and TGFB1 related to inflammation. Furthermore, we also confirmed that ZFD can inhibit the protein expression of AGEs, RAGE, p-IKBα/IKBα, p-NF-κB p65/NF-κB p65, reduce autophagy levels, and thus decrease neuronal apoptosis. CONCLUSIONS: The mechanism of action of ZFD in treating IS primarily includes inflammation suppression, oxidative stress response alleviation, post-stroke cell autophagy and apoptosis regulation, and potential mediation of the AGE-RAGE signaling pathway. This study elucidates how ZFD functions in treating IS, establishing a theoretical basis for its clinical application.

Emergency department clinical performance of ADVIA Centaur n-terminal prohormone of B-type natriuretic peptide assay.

BACKGROUND: Natriuretic peptide testing is guideline recommended as an aid to the diagnosis of heart failure (HF). We sought to evaluate the performance of the ADVIA Centaur (Siemens Healthcare Diagnostics, Tarrytown, NY) NT-proBNPII assay (PBNPII) in emergency department (ED) dyspneic patients. METHODS: Eligible patients presented to the ED with dyspnea, with their gold standard diagnosis determined by up to 3 cardiologists blinded to the PBNPII results. Patients were stratified into 3 groups based on PBNPII resultsa rule out group of NT-proBNP<300  pg/mL, an age-specific rule in group using cutoffs of 450, 900, and 1800 pg/mL, for <50, 50-75, and > 75 years respectively, and an intermediate cohort for results between the rule out and rule in groups. RESULTS: Of 3128 eligible patients, 1148 (36.7 %) were adjudicated as acute heart failure (AHF). The gold standard AHF diagnosis rate was 3.7, 24.3, and 67.2 % for patients with NTproBNPII in the negative, indeterminate, and positive groups, respectively. Overall likelihood ratios (LR) were 0.07 (95 % CI: 0.05,0.09), 0.55 (0.45,0.67), and 3.53 (3.26,3.83) for the same groups, respectively. Individual LR+for age dependent cutoffs were 5.01 (4.25,5.91), 3.71 (3.25,4.24), and 2.38 (2.10,2.69), respectively. NTproBNPII increased with increasing severity of HF when stratified by NYHA classification. CONCLUSIONS: The ADVIA Centaur PBNPII assay demonstrates acceptable clinical performance using the recommended single rule out and age dependent rule in cutoffs for an AHF diagnosis in dyspneic ED patients.

The effect of genetic polymorphisms in STIM1 and ORAI1 on erythropoietin resistance in Egyptian patients with end-stage renal disease.

Chronic renal failure (CRF) is an incurable disease with unique challenges. Anemia is a frequent complication affecting dialysis patients. Erythropoietin (EPO) is used to treat anemia, but a poor response may result. We investigated genetic polymorphisms of store-operated calcium channel (SOC) signaling, an important erythropoietin-activated pathway that may induce EPO resistance in patients with renal failure. A total of 108 end stage renal disease (ESRD) patients were selected for this study. Patients were divided into two groups according to their erythropoietin resistance index (ERI): 39 patients with an ERI>10 and 69 patients with an ERI<10. We selected four tagging single nucleotide polymorphisms (tSNPs) in STIM1 and five in ORAI1 in our study. A polymerase chain reaction was performed, and genotyping against EPO resistance was correlated. Patients with the AG genotype of rs1561876 in STIM1, the TC genotype of rs6486795 in ORAI1, and the TG or GG genotypes of rs12320939 in ORAI1 were associated with an increased risk of erythropoietin resistance. Overall, we reported a moderately significant relationship between genetic polymorphisms of STIM1 and EPO resistance. We also reported a highly significant relationship between genetic polymorphisms of ORAI1 and EPO resistance. The (A-A-G) haplotype of STIM1 and the (G-T-G-T-A, G-C-G-C-G, or G-T-T-C-G) haplotypes of ORAI1 were significantly associated with EPO resistance.

T-2 toxin induces cardiac fibrosis by causing metabolic disorders and up-regulating Sirt3/FoxO3α/MnSOD signaling pathway-mediated oxidative stress.

T-2 toxin, an omnipresent environmental contaminant, poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity. This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin. Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0, 10, and 100 nanograms per gram body weight per day (ng/(g·day)), respectively. Morphological, pathological, and ultrastructural alterations in cardiac tissue were meticulously examined. Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites. The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected. The results showed that exposure to T-2 toxin elicited myocardial tissue disorders, interstitial hemorrhage, capillary dilation, and fibrotic damage. Mitochondria were markedly impaired, including swelling, fusion, matrix degradation, and membrane damage. Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiac metabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway. T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress. In conclusion, the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway. This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.

Hypotensive effect of potent angiotensin-I-converting enzyme inhibitory peptides from corn gluten meal hydrolysate: Gastrointestinal digestion and transepithelial transportation modifications.

The study examined the antihypertensive effect of peptides derived from pepsin-hydrolyzed corn gluten meal, namely KQLLGY and PPYPW, and their in silico gastrointestinal tract digested fragments, KQL and PPY, respectively. KQLLGY and PPYPW showed higher angiotensin I-converting enzyme (ACE)-inhibitory activity and lower ACE inhibition constant (Ki) values when compared to KQL and PPY. Only KQL showed a mild antihypertensive effect in spontaneously hypertensive rats with -7.83 and - 5.71 mmHg systolic and diastolic blood pressure values, respectively, after 8 h oral administration. During passage through Caco-2 cells, KQL was further degraded to QL, which had reduced ACE inhibitory activity. In addition, molecular dynamics revealed that the QL-ACE complex was less stable compared to the KQL-ACE. This study reveals that structural transformation during peptide permeation plays a vital role in attenuating antihypertensive effect of the ACE inhibitor peptide.

Ultrasound-responsive microfibers promoted infected wound healing with neuro-vascularization by segmented sonodynamic therapy and electrical stimulation.

Bacteria-infected wounds pose challenges to healing due to persistent infection and associated damage to nerves and vessels. Although sonodynamic therapy can help kill bacteria, it is limited by the residual oxidative stress, resulting in prolonged inflammation. To tackle these barriers, novel 4 octyl itaconate-coated Li-doped ZnO/PLLA piezoelectric composite microfibers are developed, offering a whole-course "targeted" treatment under ultrasound therapy. The inclusion of Li atoms causes the ZnO lattice distortion and increases the band gap, enhancing the piezoelectric and sonocatalytic properties of the composite microfibers, collaborated by an aligned PLLA conformation design. During the infection and inflammation stages, the piezoelectric microfibers exhibit spatiotemporal-dependent therapeutic effects, swiftly eliminating over 94.2 % of S. aureus within 15 min under sonodynamic therapy. Following this phase, the microfibers capture reactive oxygen species and aid macrophage reprogramming, restoring mitochondrial function, achieving homeostasis, and shortening inflammation cycles. As the wound progresses through the healing stages, bioactive Zn2+ and Li + ions are continuously released, improving cell recruitment, and the piezoelectrical stimulation enhances wound recovery with neuro-vascularization. Compared to commercially available dressings, our microfibers accelerate the closure of rat wounds (Φ = 15 mm) without scarring in 12 days. Overall, this "one stone, four birds" wound management strategy presents a promising avenue for infected wound therapy.

MSCs biomimetic ultrasonic phase change nanoparticles promotes cardiac functional recovery after acute myocardial infarction.

Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.

NIR responsive scaffold with multistep shape memory and photothermal-chemodynamic properties for complex tissue defects repair and antibacterial therapy.

Complex tissue damage accompanying with bacterial infection challenges healthcare systems globally. Conventional tissue engineering scaffolds normally generate secondary implantation trauma, mismatched regeneration and infection risks. Herein, we developed an easily implanted scaffold with multistep shape memory and photothermal-chemodynamic properties to exactly match repair requirements of each part from the tissue defect by adjusting its morphology as needed meanwhile inhibiting bacterial infection on demand. Specifically, a thermal-induced shape memory scaffold was prepared using hydroxyethyl methacrylate and polyethylene glycol diacrylate, which was further combined with the photothermal agent iron tannate (FeTA) to produce NIR light-induced shape memory property. By varying ingredients ratios in each segment, this scaffold could perform a stepwise recovery under different NIR periods. This process facilitated implantation after shape fixing to avoid trauma caused by conventional methods and gradually filled irregular defects under NIR to perform suitable tissue regeneration. Moreover, FeTA also catalyzed Fenton reaction at bacterial infections with abundant H2O2, which produced excess ROS for chemodynamic antibacterial therapy. As expected, bacteriostatic rate was further enhanced by additional photothermal therapy under NIR. The in vitro and vivo results showed that our scaffold was able to perform high efficacy in both antibiosis, inflammation reduction and wound healing acceleration, indicating a promising candidate for the regeneration of complex tissue damage with bacterial infection.

"All in one" lipid-polymer nanodelivery system for gene therapy of ischemic diseases.

Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.

Fluorescence and photoacoustic (FL/PA) dual-modal probe: Responsive to reactive oxygen species (ROS) for atherosclerotic plaque imaging.

Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O-OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.

Intravascular delivery of an MK2 inhibitory peptide to prevent restenosis after angioplasty.

Peripheral artery disease is commonly treated with balloon angioplasty, a procedure involving minimally invasive, transluminal insertion of a catheter to the site of stenosis, where a balloon is inflated to open the blockage, restoring blood flow. However, peripheral angioplasty has a high rate of restenosis, limiting long-term patency. Therefore, angioplasty is sometimes paired with delivery of cytotoxic drugs like paclitaxel to reduce neointimal tissue formation. We pursue intravascular drug delivery strategies that target the underlying cause of restenosis - intimal hyperplasia resulting from stress-induced vascular smooth muscle cell switching from the healthy contractile into a pathological synthetic phenotype. We have established MAPKAP kinase 2 (MK2) as a driver of this phenotype switch and seek to establish convective and contact transfer (coated balloon) methods for MK2 inhibitory peptide delivery to sites of angioplasty. Using a flow loop bioreactor, we showed MK2 inhibition in ex vivo arteries suppresses smooth muscle cell phenotype switching while preserving vessel contractility. A rat carotid artery balloon injury model demonstrated inhibition of intimal hyperplasia following MK2i coated balloon treatment in vivo. These studies establish both convective and drug coated balloon strategies as promising approaches for intravascular delivery of MK2 inhibitory formulations to improve efficacy of balloon angioplasty.