RESUMO
Intestinal macrophages with functional plasticity play essential roles in gut immune responses by increasing chemokines and cytokines, thereby contributing to the pathogenesis of inflammatory bowel disease (IBD). Poly(rC)-binding protein 1 (PCBP1), which is widely expressed in immune cells, binds to nucleic acids in mRNA processing, stabilization, translation and transcription. However, little is known about the influence of PCBP1 on macrophages and its specific mechanism in inflamed intestines. In this study, conditional depletion of Pcbp1 in macrophages protected mice from progression of dextran sulfate sodium induced colitis and resulted in significant alleviation of colitis. Pcbp1 deficiency markedly decreased C-C motif chemokine ligand 2 (CCL2) production by colonic CX3C motif chemokine receptor 1+ (CX3CR1+) macrophages and reduced accumulation of pro-inflammatory macrophages and production of pro-inflammatory cytokines, such as IL-6 and TNF-α, in the inflamed colon. RNA-immunoprecipitation analysis indicated that PCBP1 might interact with Ccl2 mRNA and regulate its expression in macrophages. PCBP1 expression in inflamed intestines also correlated significantly with IBD severity in patients, suggesting a critical involvement of PCBP1 in intestinal inflammation. We anticipate that our findings will facilitate the development of novel therapeutic approaches for IBD by targeting the specific function of immune cells in the local microenvironment, thereby helping to reduce adverse effects.
Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Camundongos , Ligantes , Macrófagos , Colo , Quimiocinas , Citocinas/metabolismo , RNA Mensageiro/metabolismo , Sulfato de Dextrana/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Quinoa, known as the "golden grain" for its high nutritional value, has polysaccharides as one of its sources of important nutrients. However, the biological functions of quinoa polysaccharides remain understudied. In this study, two crude polysaccharide extracts of quinoa (Q-40 and Q-60) were obtained through sequential precipitation with 40% and 60% ethanol, with purities of 58.29% (HPLC) and 62.15% (HPLC) and a protein content of 8.27% and 9.60%, respectively. Monosaccharide analysis revealed that Q-40 contained glucose (Glc), galacturonic acid (GalA), and arabinose (Ara) in a molar ratio of 0.967:0.027:0.006. Q-60 was composed of xylose (xyl), arabinose (Ara), galactose, and galacturonic acid (GalA) with a molar ratio of 0.889:0.036:0.034:0.020. The average molecular weight of Q-40 ranged from 47,484 to 626,488 Da, while Q-60 showed a range of 10,025 to 47,990 Da. Rheological experiments showed that Q-40 exhibited higher viscosity, while Q-60 demonstrated more elastic properties. Remarkably, Q-60 showed potent antioxidant abilities, with scavenging rates of 98.49% for DPPH and 57.5% for ABTS. Antibacterial experiments using the microdilution method revealed that Q-40 inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), while Q-60 specifically inhibited MRSA. At lower concentrations, both polysaccharides inhibited MDA (MD Anderson Cancer Center) cell proliferation, but at higher concentrations, they promoted proliferation. Similar proliferation-promoting effects were observed in HepG2 cells. The research provides important information in the application of quinoa in the food and functional food industries.
Assuntos
Chenopodium quinoa , Ácidos Hexurônicos , Staphylococcus aureus Resistente à Meticilina , Arabinose , Escherichia coli , Grão ComestívelRESUMO
BACKGROUND: Malvaceae is an economically important plant family of 4,225 species in nine subfamilies. Phylogenetic relationships among the nine subfamilies have always been controversial, especially for Brownlowioideae, whose phylogenetic position remains largely unknown due to the lack of samples in previous analysis datasets. To greatly clarify the phylogenetic relationship of Malvaceae, we newly sequenced and assembled the plastome of Diplodiscus trichospermus taxonomically located in Brownlowioideae, and downloaded the allied genomes from public database to build a dataset covering all subfamily members of Malvaceae. RESULTS: The annotation results showed that the plastome of Diplodiscus trichospermus has a typical quadripartite structure, comprising 112 unique genes, namely 78 protein-coding genes, 30 tRNA genes and 4 rRNA genes. The total length was 158,570 bp with 37.2% GC content. Based on the maximum likelihood method and Bayesian inference, a robust phylogenetic backbone of Malvaceae was reconstructed. The topology showed that Malvaceae was divided distinctly into two major branches which were previously recognized as Byttneriina and Malvadendrina. In the Malvadendrina clade, Malvoideae and Bombacoideae formed, as always, a close sister clade named as Malvatheca. Subfamily Helicteroideae occupied the most basal position and was followed by Sterculioideae which was sister to the alliance of Malvatheca, Brownlowioideae, Dombeyoideae, and Tilioideae. Brownlowioideae together with the clade comprising Dombeyoideae and Tilioideae formed a sister clade to Malvatheca. In addition, one specific conservation SSR and three specific palindrome sequences were observed in Brownlowioideae. CONCLUSIONS: In this study, the phylogenetic framework of subfamilies in Malvaceae has been resolved clearly based on plastomes, which may contribute to a better understanding of the classification and plastome evolution for Malvaceae.
Assuntos
Genoma de Cloroplastos , Malvaceae , Filogenia , Malvaceae/genética , Teorema de Bayes , Sequência de BasesRESUMO
Advanced glycation end products (AGEs) are formed in non-enzymatic reaction, oxidation, rearrangement and cross-linking between the active carbonyl groups of reducing sugars and the free amines of amino acids. The Maillard reaction is related to sensory characteristics in thermal processed food, while AGEs are formed in food matrix in this process. AGEs are a key link between carbonyl stress and neurodegenerative disease. AGEs can interact with receptors for AGEs (RAGE), causing oxidative stress, inflammation response and signal pathways activation related to neurodegenerative diseases. Neurodegenerative diseases are closely related to gut microbiota imbalance and intestinal inflammation. Polyphenols with multiple hydroxyl groups showed a powerful ability to scavenge ROS and capture α-dicarbonyl species, which led to the formation of mono- and di- adducts, thereby inhibiting AGEs formation. Neurodegenerative diseases can be effectively prevented by inhibiting AGEs production, and interaction with RAGEs, or regulating the microbiota-gut-brain axis. These strategies include polyphenols multifunctional effects on AGEs inhibition, RAGE-ligand interactions blocking, and regulating the abundance and diversity of gut microbiota, and intestinal inflammation alleviation to delay or prevent neurodegenerative diseases progress. It is a wise and promising strategy to supplement dietary polyphenols for preventing neurodegenerative diseases via AGEs-RAGE axis and microbiota-gut-brain axis regulation.
Assuntos
Produtos Finais de Glicação Avançada , Doenças Neurodegenerativas , Humanos , Produtos Finais de Glicação Avançada/metabolismo , Eixo Encéfalo-Intestino , Doenças Neurodegenerativas/prevenção & controle , Suplementos Nutricionais , Polifenóis/farmacologia , Inflamação/prevenção & controleRESUMO
BACKGROUND: Alignment is indispensable for the foot and ankle function, especially in the hindfoot alignment. In the preoperative planning of patients with varus or valgus deformity, the precise measurement of the hindfoot alignment is important. A new method of photographing and measuring hindfoot alignment based on X-ray was proposed in this study, and it was applied in the assessment of flatfoot. METHODS: This study included 28 patients (40 feet) with flatfeet and 20 volunteers (40 feet) from January to December 2018. The hindfoot alignment shooting stand independently designed by our department was used to take hindfoot alignment X-rays at 10 degree, 15 degree, 20 degree, 25 degree, and 30 degree. We measured the modified tibio-hindfoot angle (THA) at the standard hindfoot aligment position (shooting at 20 degree) and evaluated consistency with the van Dijk method and the modified van Dijk method. In addition, we observed the visibility of the tibiotalar joint space from all imaging data at five projection angles and evaluated the consistency of the modified THA method at different projection angles. The angle of hindfoot valgus of flatfoot patients was measured using the modified THA method. RESULTS: The mean THA in the standard hindfoot aligment view in normal people was significantly different among the three evaluation methods (P < .001). The results from the modified THA method were significantly larger than those from the Van Dijk method (P < .001) and modified Van Dijk method (P < .001). There was no significant difference between the results of the modified THA method and the weightbearing CT (P = .605), and the intra- and intergroup consistency were the highest in the modified THA group. The tibiotalar space in the normal group was visible in all cases at 10 degree, 15 degree, and 20 degree; visible in some cases at 25 degree; and not visible in all cases at 30 degree. In the flatfoot group, the tibiotalar space was visible in all cases at 10 degree, visible in some cases at 15 degree and 20 degree, and not visible in all cases at 25 degree and 30 degree. In the normal group, the modified THA was 4.84 ± 1.81 degree at 10 degree, 4.96 ± 1.77 degree at 15 degree, and 4.94 ± 2.04 degree at 20 degree. No significant differences were found among the three groups (P = .616). In the flatfoot group, the modified THA of 18 feet, which was visible at 10 degree, 15 degree and 20 degree, was 13.58 ± 3.57 degree at 10 degree, 13.62 ± 3.83 degree at 15 degree and 13.38 ± 4.06 degree at 20 degree. There were no significant differences among the three groups (P = .425). CONCLUSIONS: The modified THA evaluation method is simple to use and has high inter- and intragroup consistency. It can be used to evaluate hindfoot alignment. For patients with flatfeet, the 10 degree position view and modified THA measurement can be used to evaluate hindfoot valgus.
Assuntos
Pé Chato , Humanos , Pé Chato/diagnóstico por imagem , Pé , Radiografia , Extremidade Inferior , Articulação do TornozeloRESUMO
With advances and developments in hysteroscopy, cystoscopy, transurethral resection of bladder tumor, and arthroscopy, transurethral resection of prostate (TURP) syndrome has been increasingly reported. TURP syndrome is often accompanied by severe hyponatremia, fluid overload, and a plasma hypotonic state, resulting in heart failure and pulmonary and cerebral edema. Conventional treatment methods, such as intravenous infusion of hyperosmotic saline, can rapidly reverse the downward trend of serum sodium levels in efforts to prevent and treat cerebral edema. However, this may not be suitable for patients with cardiac and renal insufficiency and may induce central pontine myelinolysis due to the possibility of worsening volume load and difficulty in controlling the correction rate of serum sodium. The patient described in this report presented with severe hyponatremia (sodium<100 mmol/L) combined with intraoperative pulmonary edema; his cardiac function and oxygenation status deteriorated after an intravenous infusion of 3% hypertonic saline. He underwent continuous renal replacement therapy (CRRT) to prevent the progression of multiple-organ edema and cardiac insufficiency. CRRT has demonstrated efficacy in the treatment of chronic hyponatremia in patients with renal failure, and can slowly and continuously correct water-electrolyte imbalance, acid-base imbalance, and volume overload. TURP syndrome with severe hyponatremia and pulmonary edema was diagnosed; accordingly, the patient was treated with 3% hypertonic saline, furosemide, and CRRT, without the development of overt neurological sequelae.
Assuntos
Edema Encefálico , Terapia de Substituição Renal Contínua , Hiponatremia , Edema Pulmonar , Ressecção Transuretral da Próstata , Masculino , Humanos , Hiponatremia/etiologia , Hiponatremia/terapia , Hiponatremia/diagnóstico , Ressecção Transuretral da Próstata/efeitos adversos , Edema Pulmonar/etiologia , Edema Encefálico/complicações , Terapia de Substituição Renal Contínua/efeitos adversos , SódioRESUMO
With its complicated pathobiology and pathophysiology, heart failure (HF) remains an increasingly prevalent epidemic that threatens global human health. Ferroptosis is a form of regulated cell death characterized by the iron-dependent lethal accumulation of lipid peroxides in the membrane system and is different from other types of cell death such as apoptosis and necrosis. Mounting evidence supports the claim that ferroptosis is mainly regulated by several biological pathways including iron handling, redox homeostasis, and lipid metabolism. Recently, ferroptosis has been identified to play an important role in HF induced by different stimuli such as myocardial infarction, myocardial ischemia reperfusion, chemotherapy, and others. Thus, it is of great significance to deeply explore the role of ferroptosis in HF, which might be a prerequisite to precise drug targets and novel therapeutic strategies based on ferroptosis-related medicine. Here, we review current knowledge on the link between ferroptosis and HF, followed by critical perspectives on the development and progression of ferroptotic signals and cardiac remodeling in HF.
Assuntos
Ferroptose , Insuficiência Cardíaca , Humanos , Morte Celular , Apoptose , Ferro/metabolismo , Peroxidação de LipídeosRESUMO
MAIN CONCLUSION: The proteome and its time-dependent effects reveal the importance of stress response (including expression regulation of heat-shock proteins) and fatty acid metabolism in cold adaptation and preservation of Hami melon. To better understand the molecular mechanism of how Hami melons respond to low-temperature stress, this study investigated the relevant physiological characteristics, catalytic antibody activity, and quantitative proteomics of Hami melon (Jiashi muskmelon) during low-temperature storage. Jiashi muskmelon was stored inside two refrigerators set at 21 °C (control group) and 3 °C, respectively, for 24 days. Low-temperature storage led to a significantly reduced decay rate, weight loss rate, and loss of relative conductivity. It also maintained fruit firmness, inhibited the production rate of malondialdehyde and H2O2, and induced over-expression of antioxidant enzyme and ATPase. A total of 1064 differentially expressed proteins (DEPs) were identified during low-temperature storage. Stimulation response was the main process in response to low-temperature. To further verify the proteome data, we selected four heat-shock proteins (HSP) displaying relatively high expression levels. Real-time fluorescence PCR results confirmed that HmHSP90 I, HmHSP90 II, HmHSP70, and HmsHSP were significantly up-regulated upon low-temperature induction. These proteins may protect the Hami melon from physiological and cellular damage due to the low-temperature stress by acting alone or synergistically. Additionally, the main enrichment term of the fatty acid metabolism-related DEPs was fatty acid beta oxidation at 21 °C in contrast to fatty acid biosynthesis processes at 3 °C. It is speculated that Hami melon enhances low-temperature adaptability by slowing down the oxidative degradation of fatty acids and synthesizing new fatty acids at low temperatures. This study provides new insights into the mechanism of low-temperature adaptation and preservation in post-harvest Hami melon during cold storage.
Assuntos
Cucurbitaceae , Temperatura Baixa , Cucurbitaceae/genética , Peróxido de Hidrogênio , ProteomaRESUMO
PURPOSE: Open reduction and internal fixation (ORIF) is the most commonly used surgical technique for talar neck fracture, but there are high risks for complications and poor functional outcomes. In this study, we reported the closed reduction and percutaneous internal fixation (CRPIF) technique of the bilateral approach of the Achilles tendon for simple displaced talar neck fracture, in comparison with ORIF. METHODS: Data of 15 patients in the CRPIF group and 22 in the ORIF group were included. The American Orthopaedic Foot and Ankle Society (AOFAS) score, Visual Analog Scale (VAS) score, 12-item Short-Form Survey (SF-12) score, range of motion (ROM), complications, and radiographic results were recorded and compared. RESULTS: The mean follow-up in the CRPIF group was 33.9 months. Complications included two cases of avascular necrosis (AVN) and two cases of osteoarthritis. All patients achieved bony union and recovered their pre-operative mobility. The mean follow-up in the ORIF group was 39 months. Complications included two cases of bony nonunion, nine AVN, and seven cases of osteoarthritis. Moreover, the mobility of the ORIF group was significantly lower than the CRPIF group post-operatively. The AOFAS score, VAS score, and SF-12 physical component score (PCS) for the CRPIF group were better improved than those for the ORIF group (ALL, P < 0.05). CONCLUSIONS: The CRPIF technique of the bilateral approach of the Achilles tendon was an effective method for the treatment of simple displaced talar neck fractures. Compared with the ORIF, the limited blood supply of the talus was protected, provide better functional outcomes and biomechanical fixation, and lower incidence of resurgery and complication in the CRPIF.
Assuntos
Fraturas Ósseas , Osteoartrite , Tálus , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Estudos Retrospectivos , Tálus/cirurgia , Resultado do TratamentoRESUMO
Chenopodium quinoa Willd. is recognized to be an excellent nutrient with high nutritional content. However, few genotypes of quinoa were analyzed, so we found a knowledge gap in the comparison of quinoa seeds of different genotypes. This study aims to compare the physicochemical, antioxidant, and anticancer properties of seed oil from three C. quinoa genotypes. Seeds of three genotypes (white, red, and black) were extracted with hexane and compared in this study. The oil yields of these quinoa seeds were 5.68-6.19% which contained predominantly polyunsaturated fatty acids (82.78-85.52%). The total tocopherol content ranged from 117.29 to 156.67 mg/kg and mainly consisted of γ-tocopherol. Total phytosterols in the three oils ranged from 9.4 to 12.2 g/kg. Black quinoa seed oil had the highest phytosterols followed by red and white quinoas. The chemical profile of quinoa seed oils paralleled by their antioxidant and anticancer activities in vitro was positively correlated with the seed coat color. Black quinoa seed oil had the best antioxidant and anti-proliferation effect on HCT 116 cells by the induction of apoptosis in a dose-dependent manner, which may play more significant roles in the chemoprevention of cancer and other diseases related to oxidative stress as a source of functional foods.
Assuntos
Chenopodium quinoa , Fitosteróis , Antioxidantes/análise , Antioxidantes/farmacologia , Chenopodium quinoa/química , Genótipo , Fitosteróis/análise , Fitosteróis/farmacologia , Óleos de Plantas/química , Sementes/químicaRESUMO
BACKGROUND: The bioavailability of curcumin (Cur) is generally limited by its poor stability. However, it is beneficial to improve the stability of Cur by using self-assembled zein hydrolysate (ZH) as delivery carrier. This paper aimed to explore the formation mechanism of zein hydrolysate-curcumin nanocomplexes as a function of critical micelle concentration (CMC). RESULTS: In this work, The CMC of ZH (0.535 mg mL-1 ) was obtained by the pyrene fluorescent probe method. ZH-Cur nanocomplexes undergo hydrogen bonding and hydrophobic interactions, and the fluorescence quenching effect was concentration dependent with the process of static quenching. Moreover, the differences of colloidal properties on ZH and ZH-Cur nanocomplexes were systematically compared by dynamic light scattering and scanning electron microscopy near CMC. ZH presented irregular spherical shapes and would aggregate to form micelles at the CMC and above. The tight micellar structure promoted more uniform size distribution (double peaks reduced) and higher potentials (over -30 mV) within 10 days. In addition, the nanocomplexes demonstrated an obvious core-shell structure. Within 10 days of storage, the particle size distributions were uniform and the potentials increased significantly, indicating that the micellar nanostructure made the Cur stably embedded in the hydrophobic core of ZH. Finally, ZH-Cur nanocomplexes effectively improved the water solubility and encapsulation rate (over 70%) of Cur. Moreover, over 90% of Cur was released steadily within 91 h. CONCLUSION: This work provided a theoretical basis for the application of amphiphilic peptide micellar nanostructure as novel food-grade nanocarriers to transport hydrophobic bioactive substances. © 2022 Society of Chemical Industry.
Assuntos
Antineoplásicos , Curcumina , Nanopartículas , Zeína , Curcumina/química , Interações Hidrofóbicas e Hidrofílicas , Micelas , Nanopartículas/química , Tamanho da Partícula , Zeína/químicaRESUMO
Ferroptosis has been identified as an important role in damaged heart. Meanwhile, statin therapy has been reported to be beneficial for the treatment of heart failure(HF) under different conditions. However, the beneficial effects of statin treatment on regulation of ferroptosis in failing heart is unveiled. The aim of this study is to explore the protective efficacy of atorvastatin against the ferroptosis related signaling pathway in isoproterenol(ISO)-induced HF. We found that ATV and ferrostatin-1(Fer-1,as a positive control) significantly improved ISO-decreased cell viability and cell survival by reducing oxidative stress and Fe2+-dependent lipid peroxidation in H9C2 cells. Additionally, ISO triggered marked ferritinophagy accompanied by up-regulating protein levels of LC3BII,NCOA4 and Beclin1 and down-regulating protein levels of P62 and FTH1 in damaged cells, which nevertheless was significantly blocked by administration of ATV and these results were in parallel with the results obtained after 3-methyadenine(3-MA) treatment. Consistently, C57BL/6J mice were used in used in this study and administered 5 mg/kg/day ISO for 2 weeks to simulate cardiac injury. 20 mg/kg/day ATV treatment for 2 weeks simultaneously markedly improved cardiac dysfunction and remodeling induced by ISO attack. ATV showed significantly protective effects through suppressing the activation of ferroptosis related signaling, as evidenced by decreasing the mRNA levels of PTGS2(a marker of ferroptosis), contents of malonaldehyde and protein levels of NOX4 and increasing the contents of glutathione(GSH), the ratio of GSH/GSSG and protein levels of GPX4 and SLC7A11. Moreover, ISO evidently triggered degradation of FTH1 in failing heart. However, ATV significantly prevented these changes in damaged heart. Overall, these results reveal atorvastatin suppresses ferroptosis and exhibits protective effect on failing myocardium of mice after ISO insult though inhibiting ferritinophagy-mediated ferroptosis, which might be a potential therapeutic strategy in the prevention of ISO-associated cardiomyopathy.
Assuntos
Atorvastatina/farmacologia , Ferroptose/efeitos dos fármacos , Isoproterenol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Miócitos Cardíacos/metabolismo , RatosRESUMO
Current studies aimed at investigating the association between atorvastatin therapy and insulin resistance (IR) appear to be controversial. IR is considered to be an important contributor to inducing cardiac dysfunction through multiple signals. The paradoxical cardiotoxicity of atorvastatin reported under different conditions suggests that the association between atorvastatin treatment, insulin resistance and cardiac function should be clarified further. In this study, C57BL/6 J male mice were fed a high-fat diet (HD) or standard chow diet (SD) for 12 weeks and subsequently randomly divided into four groups: the SD-Control (SD-C) and HD-Control (HD-C) groups treated with saline for 10 months and the HD-A and HD-A + N groups treated with atorvastatin (20 mg/kg/day) alone or atorvastatin combined with nicotinamide (NAM, 1 g/kg/day) for 10 months. Although no significant changes in systolic function and structure were observed between the four groups of mice at an age of 46 or 58 weeks, respectively, long-term treatment with atorvastatin alone or atorvastatin and NAM combination significantly retarded the HD-induced IR and diastolic dysfunction and attenuated both cardiac and hepatic fibrosis in obese mice possibly by regulating the cleavage of osteopontin and then controlling profibrotic activity. Changes in cardiac function and structure were similar between the HD-A and HD-A + N groups; however, mice in the HD-A + N group exhibited better glucose control and marked reduction in body weight and hepatic lipid accumulation. Thus, these results suggest that long-term treatment with atorvastatin or the combination of atorvastatin and nicotinamide may be alternative therapies due to their beneficial effects on IR and diastolic function.