RESUMO

Enhancement of Connexin43 (Cx43) and ferroptosis are respectively associated with the exacerbation of myocardial ischemia-reperfusion injury (MIRI) in diabetes. Myocardial vulnerability to ischemic insult has been shown to vary during early and later phases of diabetes in experimental settings. Whether or not Connexin43 (Cx43) and ferroptosis interplay during MIRI in diabetes is unknown. We, thus, aimed to investigate whether or not the content of myocardial Cx43 may be attributable to myocardial vulnerability to MIRI at different stages of diabetes and also to explore the potential interplay between Cx43 and ferroptosis in this pathology. Age-matched control and subgroups of Streptozotocin-induced diabetic mice were subjected to MIRI induced by 30 minutes coronary artery occlusion and 2 hours reperfusion respectively at 1, 2 and 5 weeks of diabetes. Rat cardiac H9C2 cells were exposed to high glucose (HG) for 48h in the absence or presence of Cx43 gene knockdown followed by hypoxia/reoxygenation (HR) respectively for 6 and 12 hours. Post-ischemic myocardial infarct size was reduced in 1 and 2 weeks DM mice concomitant with enhanced GPX4 and reduced cardiac Cx43 and ferroptosis as compared to control. By contrast, cardiac GPX4 was significantly reduced while Cx43 increased at DM 5 weeks (D5w) which was correspondent to significant increases in ferroptosis and myocardial infarction. Post-ischemic cardiac function was improved in 1 and 2 weeks but worsened in 5w DM mice as compared with non-diabetic control. GAP19 (Cx43 inhibitor) significantly attenuated ferroptosis and reduced myocardial infarction in D5w mice. Erastin (ferroptosis activator) reversed the cardioprotective effect of GAP19. In vitro, HR significantly reduced cell viability accompanied with reduced GPX4 but elevated Cx43 expression, MDA production and ferroptosis. Cx43 gene knockdown in H9C2 resulted in a significant increase in GPX4, reduction in MDA and ferroptosis, and subsequently reduced post-hypoxic cell viability. The beneficial effects of Cx43 gene knock-down was minified or eliminated by Erastin. It is concluded that Cx43 overexpression exacerbates MIRI under diabetic conditions via promoting ferroptosis, while its down-regulation at early state of diabetes is attributable to enhanced myocardial tolerance to MIRI.

Assuntos

Conexina 43 , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Ferroptose , Traumatismo por Reperfusão Miocárdica , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Animais , Ferroptose/genética , Conexina 43/metabolismo , Conexina 43/genética , Camundongos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Ratos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/genética , Masculino , Técnicas de Silenciamento de Genes , Humanos , Linhagem Celular , Miocárdio/patologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo

RESUMO

Background/purpose: External root resorption is a main side effect of orthodontic treatment and is more likely to occur on the pression side than the tension side. To explore the potential protective mechanisms on the tension side, this study investigated the influence of mechanical tension on cementoblast mineralization and elucidated the role of autophagy in mediating this process. Materials and methods: Mechanical tension was applied to cementoblasts using iStrain. The expression of mineralization-related and autophagy-related markers was detected by qRT-PCR, Western blot analysis, and immunofluorescence staining. RNA sequencing identified key regulators. Immunohistochemical staining assessed related markers expression in in vivo experiments. Results: Applying tension to cementoblasts increased mineralization-related gene expression in a force-dependent and time-dependent manner. The immunohistochemical staining result of in vivo experiments supported these findings, demonstrating elevated expression of mineralization markers under tension. Mechanical tension also enhanced autophagic activity in cementoblasts, which was demonstrated by the results of qRT-PCR, Western blot analysis, immunofluorescence staining, and in vivo experiments. Suppression of autophagy with chloroquine attenuated the mineralization of cementoblasts induced by tension stimulus. RNA-seq identified Postn as a key regulator, and the knockdown of Postn impaired the mechanical tension-promoted mineralization of cementoblasts. Conclusion: This study proposed the tension-induced promotion in mineralization of cementoblasts and emphasized the mediating role of autophagy in this process. Postn, a mediator connecting autophagy and mineralization, was identified as a key regulator. These discoveries helped elucidate orthodontic-related microprocesses on tooth roots and offer potential targets for therapeutic interventions to prevent and restore external root resorption clinically.

RESUMO

BACKGROUND: Neolamarckia cadamba (Rubiaceae) is a well-recognized medicinal plant with recorded therapeutical attributes. However, a thorough assessment of active compounds in its fruits is lacking, limiting their use and valorization in pharmacological industries. METHODS: Thus, this study investigated variations in the fruits' secondary metabolite (SM) profiles, as well as antioxidant activities in aqueous (WA) and ethanol (ET) extracts. RESULTS: Liquid chromatography-electrospray ionization tandem mass spectrometry identified 541 SMs, of which 14 and 1 (di-O-glucosylquinic acid) were specifically detected in ET and WA, respectively. Phenolic acids (36.97%), flavonoids (28.10%), terpenoids (12.20%), and alkaloids (9.98%) were the dominant SMs. The SM profiles of the fruits in WA and ET were quite different. We revealed 198 differentially extracted (DE) metabolites between WA and ET, including 62 flavonoids, 57 phenolic acids, 45 terpenoids, 14 alkaloids, etc. Most DE flavones (36 out of 40), terpenoids (45 out of 45), and alkaloids (12 out of 14) had higher content in ET. Catechin and its derivatives, procyanidins, and tannins had higher content in WA. ABTS and DPPH assays showed that the antioxidant activity of ET was significantly higher than that of WA. CONCLUSIONS: Our findings will facilitate the efficient extraction and evaluation of specific active compounds in N. cadamba.

RESUMO

OBJECTIVES: To determine the difference between orthodontic camouflage and orthodontic-orthognathic surgery using the traditional cephalometric measurement IMPA and the newly proposed IA/PAMD, the angle between the long axis of the lower incisor (IA) and the principal axis of the mandibular alveolus (PAMD). MATERIALS AND METHODS: This study included 40 cases each in the orthodontic camouflage group (OG) and orthodontic-orthognathic surgery group (SG). The differences between the IMPA and IA/PAMD before and after treatment were compared between the two groups. T0 lateral cephalometric images of the 10 cases with the highest and lowest increase in the IA/PAMD were analyzed to identify characteristics associated with a higher risk of overdecompensation of the lower incisors during presurgical orthodontic treatment. RESULTS: Both the OG and SG showed a significant improvement in hard- and soft-tissue measurements. However, in the OG, there was significant lingual inclination of the lower incisor but only a small change in the IA/PAMD. In the surgical group, the IMPA was close to 90° after treatment, but the IA/PAMD significantly increased. CONCLUSIONS: In orthodontic camouflage, the lower anterior teeth were significantly moved lingually with a better root-bone relationship. However, this relationship deteriorated in some surgical patients. Therefore, it is important to conduct cephalometric or cone-beam computed tomography examinations during preoperative orthodontics to identify and prevent possible periodontal risks.

Assuntos

Cefalometria , Incisivo , Má Oclusão Classe III de Angle , Procedimentos Cirúrgicos Ortognáticos , Humanos , Incisivo/diagnóstico por imagem , Cefalometria/métodos , Má Oclusão Classe III de Angle/cirurgia , Má Oclusão Classe III de Angle/terapia , Má Oclusão Classe III de Angle/diagnóstico por imagem , Feminino , Masculino , Procedimentos Cirúrgicos Ortognáticos/métodos , Mandíbula/cirurgia , Mandíbula/diagnóstico por imagem , Adolescente , Adulto Jovem , Ortodontia Corretiva/métodos , Adulto

RESUMO

Mycotoxins are toxic secondary metabolites produced by different fungal species under specific environmental conditions. The common and regulated mycotoxins are such as deoxynivalenol (DON), zearalenone (ZEN), ochratoxin (OTA), aflatoxin B1 (AFB1), and fumonisins (FB). These mycotoxins are highly regulated in feed and food because their effects start to exert from their lowest exposures and are abundant in our common environment. However, there are other emerging mycotoxins such as apicidin, beauvericin, aurofusarin, and enniatins which are also harmful. Thus, making a total of around 500 forms of mycotoxins. The existence of mycotoxins in feed and food has a significant impact on animal and human health, which ultimately, slows down economic growth globally. According to this review, different approaches to removing multi-mycotoxin separately or simultaneously have been stated. Mostly, the review focused on the simultaneous removal of different multiple mycotoxins. This is because the current studies show a growing trend in reporting the co-existence of multiple mycotoxins in feed and food materials, however, most detoxifying approaches are for singular mycotoxins. Therefore, the physical, chemical, and biological approaches to remove multi-mycotoxin have been elucidated as well as their advantages and limitations. Furthermore, the authors give suggestions on the way forward to reduce exposure to mycotoxins and diminish their health effects in society. Lastly, the authors emphasized introducing more stringent limits for co-existing mycotoxins, especially those that have the same health effects by acting synergistically, such as AFB1 and OTA, which both act as carcinogenic agents.

RESUMO

Treatment strategies for hard tissue defects aim to establish a mineralized microenvironment that facilitates tissue remodeling. As a mineralized tissue, cementum shares a similar structure with bone and exhibits an excellent capacity to resist resorption under compression. Macrophages are crucial for mineralized remodeling; however, their functional alterations in the microenvironment of cementum remain poorly understood. Therefore, this study explores the mechanisms by which cementum resists resorption under compression and the regulatory roles of cementoblasts in macrophage functions. As a result, extracellular vesicles from compression-loaded cementoblasts (Comp-EVs) promote macrophage M2 polarization and enhance the clearance of apoptotic cells (efferocytosis) by 2- to 3-fold. Local injection of Comp-EVs relieves cementum destruction in mouse root resorption model by activating the tissue repair function of macrophages. Moreover, Comp-EV-loaded hydrogels achieve significant bone healing in calvarial bone defect. Unexpectedly, under compression, EV secretion in cementoblasts is reduced by half. RNA-Seq analysis and verification reveal that Rab35 expression decreases by 60% under compression, thereby hampering the release of EVs. Rab35 overexpression is proposed as a modification of cementoblasts to boost the yield of Comp-EVs. Collectively, Comp-EVs activate the repair function of macrophages, which will be a potential therapeutic strategy for hard tissue repair and regeneration.

Assuntos

Cemento Dentário , Modelos Animais de Doenças , Vesículas Extracelulares , Macrófagos , Animais , Vesículas Extracelulares/metabolismo , Camundongos , Macrófagos/metabolismo , Cemento Dentário/metabolismo , Cicatrização/fisiologia , Camundongos Endogâmicos C57BL

RESUMO

Objective: To analyze the kinematic changes of the hip joint after total hip arthroplasty (THA) through three-dimensional gait analysis. Methods: Patients with hip joint diseases admitted between October 2022 and June 2023 were selected as the subjects. The patients who met the selective criteria were finally included in the THA group. The healthy volunteers matched with the THA group in the same age were included as the control group. Baseline data including age, gender, body mass index (BMI), and laterality were compared between the two groups. The Harris hip score (HHS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were recorded preoperatively and at last follow-up in the THA group. Three-dimensional motion capture system was utilized to collect spatiotemporal parameters and kinematic data during walking, including stride length, cadence, and maximum/minimum values, range of motion (ROM) in hip joint abduction/adduction, external/internal rotation, and flexion/extension, as well as gait scores. Differences between the two groups were analyzed. Additionally, the correlation between gait scores and postoperative HHS and WOMAC scores were analyzed in the THA group. Finally, the kinematic data of each degree of freedom (DOF) were fitted into a gait diagram, and the dynamic changes of the 3-DOF of the hip joint during the gait cycle were quantitatively analyzed. Results: There was no significant difference in gender, age, laterality, and BMI between the two groups ( n=20, P>0.05). The mean follow-up time in the THA group was 9.9 months (range, 6-12 months). The HHS and WOMAC scores at last follow-up in the THA group showed significant improvement when compared with preoperative scores ( P<0.05). Gait scores were positively correlated with postoperative HHS score ( r=0.585, P=0.007) and negatively correlated with WOMAC score ( r=-0.619, P=0.004). There was no significant difference in stride length and cadence between the THA and control groups ( P>0.05), but gait score was significantly lower in the THA group than in the control group ( P<0.05). There was no significant difference in maximum and minimum values of flexion/extension, external/internal rotation, and abduction/adduction between the two groups ( P>0.05); however, ROM in the THA group was significantly lower than that in the control group ( P<0.05). There were significant differences between the two groups of flexion/extension in multiple phases of the gait cycle ( P<0.05). Conclusion: Early post-THA hip joint kinematics exhibit relative adduction, external rotation, and flexion during the gait cycle compared to normal individuals, with incomplete recovery of kinematic parameters in three degrees of freedom. Significant differences in flexion are observed at multiple phases of the gait cycle compared to normal individuals.

Assuntos

Artroplastia de Quadril , Marcha , Articulação do Quadril , Amplitude de Movimento Articular , Humanos , Artroplastia de Quadril/métodos , Fenômenos Biomecânicos , Articulação do Quadril/cirurgia , Marcha/fisiologia , Feminino , Masculino , Estudos de Casos e Controles , Osteoartrite do Quadril/cirurgia , Pessoa de Meia-Idade , Análise da Marcha , Período Pós-Operatório , Idoso

RESUMO

Aflatoxin B1 is a notorious mycotoxin with mutagenicity and carcinogenicity, posing a serious hazard to human and animal health. In this study, an AFB1-degrading dipeptidyl-peptidase III mining from Aspergillus terreus HNGD-TM15 (ADPP III) with a molecular weight of 79 kDa was identified. ADPP III exhibited optimal activity toward AFB1 at 40 °C and pH 7.0, maintaining over 80% relative activity at 80 °C. The key amino acid residues that affected enzyme activity were identified as H450, E451, H455, and E509 via bioinformatic analysis and site-directed mutagenesis. The degradation product of ADPP III toward AFB1 was verified to be AFD1. The zebrafish hepatotoxicity assay verified the toxicity of the AFB1 degradation product was significantly weaker than that of AFB1. The result of this study proved that ADPP III presented a promising prospect for industrial application in food and feed detoxification.

Assuntos

Aflatoxina B1 , Aspergillus , Dipeptidil Peptidases e Tripeptidil Peptidases , Proteínas Fúngicas , Peixe-Zebra , Aflatoxina B1/metabolismo , Aflatoxina B1/química , Aspergillus/enzimologia , Aspergillus/genética , Aspergillus/química , Aspergillus/metabolismo , Animais , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Estabilidade Enzimática , Cinética , Peso Molecular , Concentração de Íons de Hidrogênio , Especificidade por Substrato

RESUMO

BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign bone tumor, it is also called "Nora's lesion". The lesion is characterized by heterotopic ossification of the normal bone cortex or parosteal bone. The etiology of BPOP is unclear and may be related to trauma. In most BPOPs, the lesion is not connected to the medullary cavity. Here we report an atypical case, characterized by reversed features compared to the typical BPOP, which demonstrated continuity of the lesion with the cavity. CASE PRESENTATION: An 11-year-old female child had a slow-growing mass on her right wrist for 8 months with forearm rotation dysfunction. Plain X-rays showed an irregular calcified mass on the right distal ulna, and computed tomography (CT) showed a pedunculated mass resembling a mushroom protruding into the soft tissue at the distal ulna. The medulla of this lesion is continuous with the medulla of the ulna. A surgical resection of the lesion, together with a portion of the ulnar bone cortex below the tumor was performed, and the final pathology confirmed BPOP. After the surgery, the child's forearm rotation function improved significantly, and there was no sign of a recurrence at 1-year follow-up. CONCLUSION: It is scarce for BPOP lesions to communicate with the medullary cavity. However, under-recognition of these rare cases may result in misdiagnosis or inappropriate treatment thereby increasing the risk of recurrence. Therefore, special cases where BPOP lesions are continuous with the medulla are even more important to be studied to understand better and master these lesions. Although BPOP is a benign tumor with no evidence of malignant transformation, the recurrence rate of surgical resection is high. We considered the possibility of this particular disease prior to surgery and performed a surgical resection with adequate safety margins. Regular postoperative follow-up is of utmost importance, without a doubt.

Assuntos

Neoplasias Ósseas , Ulna , Humanos , Feminino , Criança , Ulna/cirurgia , Ulna/diagnóstico por imagem , Ulna/patologia , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Tomografia Computadorizada por Raios X , Osteocondroma/cirurgia , Osteocondroma/diagnóstico por imagem , Osteocondroma/patologia , Resultado do Tratamento

RESUMO

Phytoremediation is a low-cost, environmentally friendly, and sustainable technology that can utilize vegetation and microorganisms to avoid eutrophication and purifying water environment. The ability of five different living aquatic plants of nitrogen (N), phosphorus (P), and chemical oxygen demand (CODcr) removal were investigated in pilot scale constructed wetlands (CWs). Aquatic plant mixes significantly improved CODcr removal and plant tissue uptake of nitrogen and phosphorus. The wetland performance of mixed plantings was also influenced by the specific species. The mixed planting of Phragmites australi, Nymphaea Colorado and Myriophyllum verticillatum (PNM)When assessing pollutant removal in CWs, PNM performed better within mixtures, a possible synergistic effect, while TNV Typha orientalis, Nymphaea Colorado, and Vallisneria natans (TNV) performed poorly, a possible antagonist effect. The nutrient uptake within plant tissues byunder mixed plants planting was always ahad synergistic effect. Mixed plantingAquatic plant mixes significantly increased the rhizosphere microbial diversity and promoted the growth of functional denitrifying flora.

Assuntos

Biodegradação Ambiental , Nitrogênio , Fósforo , Rizosfera , Áreas Alagadas , Fósforo/metabolismo , Nitrogênio/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/análise , Análise da Demanda Biológica de Oxigênio , Projetos Piloto , Microbiota , Plantas/metabolismo , Nymphaea/metabolismo , Microbiologia do Solo

RESUMO

BACKGROUND: Mediation analysis is a powerful tool to identify factors mediating the causal pathway of exposure to health outcomes. Mediation analysis has been extended to study a large number of potential mediators in high-dimensional data settings. The presence of confounding in observational studies is inevitable. Hence, it's an essential part of high-dimensional mediation analysis (HDMA) to adjust for the potential confounders. Although the propensity score (PS) related method such as propensity score regression adjustment (PSR) and inverse probability weighting (IPW) has been proposed to tackle this problem, the characteristics with extreme propensity score distribution of the PS-based method would result in the biased estimation. METHODS: In this article, we integrated the overlapping weighting (OW) technique into HDMA workflow and proposed a concise and powerful high-dimensional mediation analysis procedure consisting of OW confounding adjustment, sure independence screening (SIS), de-biased Lasso penalization, and joint-significance testing underlying the mixture null distribution. We compared the proposed method with the existing method consisting of PS-based confounding adjustment, SIS, minimax concave penalty (MCP) variable selection, and classical joint-significance testing. RESULTS: Simulation studies demonstrate the proposed procedure has the best performance in mediator selection and estimation. The proposed procedure yielded the highest true positive rate, acceptable false discovery proportion level, and lower mean square error. In the empirical study based on the GSE117859 dataset in the Gene Expression Omnibus database using the proposed method, we found that smoking history may lead to the estimated natural killer (NK) cell level reduction through the mediation effect of some methylation markers, mainly including methylation sites cg13917614 in CNP gene and cg16893868 in LILRA2 gene. CONCLUSIONS: The proposed method has higher power, sufficient false discovery rate control, and precise mediation effect estimation. Meanwhile, it is feasible to be implemented with the presence of confounders. Hence, our method is worth considering in HDMA studies.

Assuntos

Análise de Mediação , Pontuação de Propensão , Humanos , Estudos Observacionais como Assunto/métodos , Fatores de Confusão Epidemiológicos , Epigenômica/métodos , Simulação por Computador , Algoritmos

RESUMO

The enzymatic biodegradation of mycotoxins in food and feed has attracted the most interest in recent years. In this paper, the laccase gene from Bacillus swezeyi was cloned and expressed in Escherichia coli BL 21(D3). The sequence analysis indicated that the gene consisted of 1533 bp. The purified B. swezeyi laccase was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis -12% with an estimated molecular weight of 56.7 kDa. The enzyme is thermo-alkali-tolerant, displaying the optimal degradation of zearalenone (ZEN) and aflatoxin B1 (AFB1) at pH 8 and 9, with incubation temperatures of 55 and 50 °C, respectively, within 24 h. The degradation potentials of the 50 µg of the enzyme against ZEN (5.0 µg/mL) and AFB1 (2.5 µg/mL) were 99.60 and 96.73%, respectively, within 24 h. To the best of our knowledge, this is the first study revealing the recombinant production of laccase from B. swezeyi, its biochemical properties, and potential use in ZEN and AFB1 degradation in vitro and in vivo.

Assuntos

Aflatoxina B1 , Bacillus , Proteínas de Bactérias , Estabilidade Enzimática , Lacase , Proteínas Recombinantes , Zearalenona , Lacase/genética , Lacase/metabolismo , Lacase/química , Aflatoxina B1/metabolismo , Aflatoxina B1/química , Zearalenona/metabolismo , Zearalenona/química , Bacillus/enzimologia , Bacillus/genética , Bacillus/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Concentração de Íons de Hidrogênio , Temperatura , Peso Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Clonagem Molecular , Álcalis/metabolismo , Álcalis/química

RESUMO

Neem leaves have long been used in traditional medicine for promoting longevity. However, the precise mechanisms underlying their anti-aging effects remain elusive. In this study, we investigated the impact of neem leaf extract (NLE) extracted from a 50% ethanol solution on the chronological lifespan of Saccharomyces cerevisiae, revealing an extension in lifespan, heightened oxidative stress resistance, and a reduction in reactive oxygen species. To discern the active compounds in NLE, LC/MS and the GNPS platform were employed. The majority of identified active compounds were found to be flavonoids. Subsequently, compound-target pharmacological networks were constructed using the STP and STITCH platforms for both S. cerevisiae and Homo sapiens. GOMF and KEGG enrichment analyses of the predicted targets revealed that "oxidoreductase activity" was among the top enriched terms in both yeast and human cells. These suggested a potential regulation of oxidative stress response (OSR) by NLE. RNA-seq analysis of NLE-treated yeast corroborated the anti-oxidative effect, with "oxidoreductase activity" and "oxidation-reduction process" ranking high in enriched GO terms. Notably, CTT1, encoding catalase, emerged as the most significantly up-regulated gene within the "oxidoreductase activity" cluster. In a ctt1 null mutant, the enhanced oxidative stress resistance and extended lifespan induced by NLE were nullified. For human cells, NLE pretreatment demonstrated a decrease in reactive oxygen species levels and senescence-associated ß-galactosidase activity in HeLa cells, indicative of anti-aging and anti-oxidative effects. This study unveils the anti-aging and anti-oxidative properties of NLE while delving into their mechanisms, providing novel insights for pharmacological interventions in aging using phytochemicals.

Assuntos

Antioxidantes , Estresse Oxidativo , Extratos Vegetais , Folhas de Planta , Espécies Reativas de Oxigênio , Saccharomyces cerevisiae , Humanos , Saccharomyces cerevisiae/efeitos dos fármacos , Folhas de Planta/química , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento/efeitos dos fármacos , Flavonoides/farmacologia

RESUMO

INTRODUCTION: Over the past decade, numerous studies have described the types of pathogens and their antibiotic resistance patterns in patients with burn injuries in China; however, the findings have generally been inconsistent. We conducted a literature search and meta-analysis to summarize the infection spectra and antimicrobial resistance patterns in patients with burn injuries. METHODS: We searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Biomedical Literature, Wanfang, and Weipu databases for relevant articles published between January 2010 and December 2023. The DerSimonian-Laird random-effects model was used to estimate the proportions and 95% confidence intervals (CIs) of pathogens among Chinese patients with burn injuries. Meta-regression analyses were performed to explore differences in the proportions of pathogens among different subgroups and their resistance patterns. This study was registered with PROSPERO (CRD42024514386). RESULTS: The database searches yielded 2017 records; after removing duplicates and conducting initial screening, 219 articles underwent full-text screening. Ultimately, 60 studies comprising a total of 62,819 isolated strains reported the proportions of pathogens in patients with burn injuries and were included in this meta-analysis. Meta-analyses were conducted on 18 types of pathogens. The most common pathogens causing infections in Chinese patients with burn injuries were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus epidermidis. Similar results were observed in the subgroup analysis focusing on wound infections. Since 2015, there has been a significant decrease in the proportion of Pseudomonas aeruginosa (R2 = 4.89%) and a significant increase in the proportion of Klebsiella pneumoniae (R2 = 9.60%). In terms of antibiotic resistance, there has been a significant decrease in the resistance of Staphylococcus aureus to multiple antibiotics and an increasing trend in the resistance of Klebsiella pneumoniae. CONCLUSIONS: We systematically summarized the epidemiological characteristics and antibiotic resistance patterns of pathogens among individuals suffering from burns in China, thus providing guidance for controlling wound infections and promoting optimal empirical antimicrobial therapy. The observed high levels of antibiotic resistance underscore the need for ongoing monitoring of antibiotic usage trends.

RESUMO

BACKGROUND: Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. METHODS: A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. RESULTS: The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. CONCLUSIONS: Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

Assuntos

Artroplastia do Joelho , Dexametasona , Glucocorticoides , Dor Pós-Operatória , Humanos , Artroplastia do Joelho/efeitos adversos , Masculino , Glucocorticoides/administração & dosagem , Feminino , Injeções Intra-Articulares , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/diagnóstico , Dexametasona/administração & dosagem , Injeções Intravenosas , Medição da Dor , Cuidados Intraoperatórios/métodos , Resultado do Tratamento , Amplitude de Movimento Articular

RESUMO

Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. STATEMENT OF SIGNIFICANCE: The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression.

Assuntos

Administração Cutânea , Ácido Hialurônico , Lipossomos , Envelhecimento da Pele , Pele , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Lipossomos/química , Animais , Humanos , Pele/patologia , Pele/efeitos dos fármacos , Pele/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Camundongos , Peso Molecular , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Sistemas de Liberação de Medicamentos , Células HaCaT

RESUMO

BACKGROUND: Outliers, data points that significantly deviate from the norm, can have a substantial impact on statistical inference and provide valuable insights in data analysis. Multiple methods have been developed for outlier detection, however, almost all available approaches fail to consider the spatial dependence and heterogeneity in spatial data. Spatial data has diverse formats and semantics, requiring specialized outlier detection methodology to handle these unique properties. For now, there is limited research exists on robust spatial outlier detection methods designed specifically under the spatial error model (SEM) structure. METHOD: We propose the Spatial-Θ-Iterative Procedure for Outlier Detection (Spatial-Θ-IPOD), which utilizes a mean-shift vector to identify outliers within the SEM. Our method enables an effective detection of spatial outliers while also providing robust coefficient estimates. To assess the performance of our approach, we conducted extensive simulations and applied it to a real-world empirical study using life expectancy data from multiple countries. RESULTS: Simulation results showed that the masking and JD (Joint Detection) indicators of our Spatial-Θ-IPOD method outperformed several commonly used methods, even in high-dimensional scenarios, demonstrating stable performance. Conversely, the Θ-IPOD method proved to be ineffective in detecting outliers when spatial correlation was present. Moreover, our model successfully provided reliable coefficient estimation alongside outlier detection. The proposed method consistently outperformed other models (both robust and non-robust) in most cases. In the empirical study, our proposed model successfully detected outliers and provided valuable insights in the modeling process. CONCLUSIONS: Our proposed Spatial-Θ-IPOD offers an effective solution for detecting spatial outliers for SEM while providing robust coefficient estimates. Notably, our approach showcases its relative superiority even in the presence of high leverage points. By successfully identifying outliers, our method enhances the overall understanding of the data and provides valuable insights for further analysis.

RESUMO

The massive use of paper has resulted in significant negative impacts on the environment. Fortunately, recent progress has been made in the field of rewritable paper, which has great potential in solving the increasing demand for paper while minimizing its environmental footprint. In this work, we report a green and economic strategy to develop ink-free rewritable paper by introducing hydrochromic covalent organic frameworks (COFs) in paper and using water as the sole trigger. When exposed to water or acidic solvents, two kinds of imino COFs change their colors reversibly from red to black. Additionally, a new visible absorption band appears, indicating that it can be transformed into another structure reversibly. This reversibility may be due to the isomerization from the diiminol to an iminol/cisketoenamine and its inability to doubly tautomerize to a diketoenamine. Specifically, we prepared the rewritable paper by loading these two COFs onto filter paper by using the decompression filtration method. When exposed to water, the paper undergoes a color change from red to black, which shows promising potential for applications in water-jet printing. Additionally, there is no significant performance degradation after 20 uses and 10 days between, further highlighting their potential as rewritable papers. To further improve its uniformity, we take the interface polymerization strategy to yield highly crystalline and more compact membranes, which are then transferred to paper to prepare writable papers. Our research has opened up a way for the application of COFs as a water-based printing material.

RESUMO

The hearts of subjects with diabetes are vulnerable to ischemia-reperfusion injury (IRI). In contrast, experimentally rodent hearts have been shown to be more resistant to IRI at the very early stages of diabetes induction than the heart of the non-diabetic control mice, and the mechanism is largely unclear. Ferroptosis has recently been shown to play an important role in myocardial IRI including that in diabetes, while the specific mechanisms are still unclear. Non-diabetic control (NC) and streptozotocin-induced diabetic (DM) mice were treated with the antioxidant N-acetylcysteine (NAC) in drinking water for 4 week starting at 1 week after diabetes induction. Mice were subjected to myocardial IRI induced by occluding the coronary artery for 30 min followed by 2 h of reperfusion, subsequently at 1, 2, and 5 week of diabetes induction. The post-ischemic myocardial infarct size in the DM mice was smaller than that in NC mice at 1 week of diabetes but greater than that in the NC mice at 2 and 5 week of diabetes, which were associated with a significant increase of ferroptosis at 2 and 5 week but a significant reduction of ferroptosis at 1 week of diabetes. NAC significantly attenuated post-ischemic ferroptosis as well as oxidative stress and reduced infarct size at 2 and 5 week of diabetes. Application of erastin, a ferroptosis inducer, reversed the cardioprotective effects of NAC. It is concluded that increased oxidative stress and ferroptosis are the major factors attributable to the increased vulnerability to myocardial IRI in diabetes and that attenuation of ferroptosis represents a major mechanism whereby NAC confers cardioprotection against myocardial IRI in diabetes.

Assuntos

Acetilcisteína , Antioxidantes , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Ferroptose , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica , Animais , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Acetilcisteína/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Masculino , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Antioxidantes/farmacologia , Ferroptose/efeitos dos fármacos , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/patologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/tratamento farmacológico , Fatores de Tempo , Miocárdio/patologia , Miocárdio/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos

RESUMO

The resource recovery and reuse of precious metal-laden wastewater is widely recognized as crucial for sustainable development. Superalloy electrolytes, produced through the electrolysis of superalloy scrap, contain significant quantities of precious metal ions, thereby possessing substantial potential for recovery value. This study first explores the feasibility of utilizing fungi to treat Superalloy electrolytes. Five fungi resistant to high concentrations of heavy metals in electrolytes (mainly containing Co, Cr, Mo, Re, and Ni) were screened from the soil of a mining area to evaluate their adsorption characteristics. All five fungi were identified by ITS sequencing, and among them, Paecilomyces lilacinus showed the best adsorption performance for the five heavy metals; therefore, we conducted further research on its adsorption characteristics. The best adsorption effect of Co, Cr, Mo, Re, and Ni was 37.09, 64.41, 47.87, 41.59, and 25.38%, respectively, under the conditions of pH 5, time 1 h, dosage 26.67 g/L, temperature 25-30°C, and an initial metal concentration that was diluted fivefold in the electrolyte. The biosorption of Co, Mo, Re, and Ni was better matched by the Langmuir model than by the Freundlich model, while Cr displayed the opposite pattern, showing that the adsorption process of P. lilacinus for the five heavy metals is not a single adsorption mechanism, but may involve a multi-step adsorption process. The kinetics study showed that the quasi-second-order model fitted better than the quasi-first-order model, indicating that chemical adsorption was the main adsorption process of the five heavy metals in P. lilacinus. Fourier transform infrared spectroscopy revealed that the relevant active groups, i.e., hydroxyl (-OH), amino (-NH2), amide (- CONH2), carbonyl (-C = O), carboxyl (-COOH), and phosphate (PO43-), participated in the adsorption process. This study emphasized the potential application of P. lilacinus in the treatment of industrial wastewater with extremely complex background values.