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BACKGROUND: Extracorporeal shockwave therapy (ESWT) has been proven beneficial for post-stroke spasticity (PSS) of ankle plantar flexor muscles. This study aims to investigate the dose-response effectiveness of focused-ESWT and the duration of its effect on the treatment of ankle PSS in stroke patients. METHODS: In this double-blinded randomized controlled trial, stroke patients diagnosed with PSS in the ankle plantar flexor muscles were randomly assigned to two groups. The experimental group received double-dose ESWT (4000 pulses per session) targeting spastic calf muscles, while the control group received half the dose (2000 pulses per session). Both groups underwent four sessions over two weeks. The outcomes, including modified Ashworth Scale (MAS), modified Tardieu Scale (MTS), passive range of motion (PROM) of the ankle, Timed Up and Go (TUG) Test, Barthel index and strain elastography were evaluated at baseline, 1st, 4th, 12th, and 24th week after ESWT. RESULTS: Within-group analysis revealed significant improvements in MAS, PROM, TUG Test, and Barthel index for the double-dose ESWT group and improvements in Barthel index for the control group. Between-group analysis revealed greater improvements in TUG Test, Barthel Index and strain elastography for the double-dose ESWT group. Generalized estimating equations analysis indicated that the double-dose ESWT group achieved superior outcomes in the TUG Test, Barthel Index, and strain elastography across various time points and groups. CONCLUSIONS: Double-dose ESWT showed better functional improvement and elastography compared to the control group. ESWT demonstrated dose-response effectiveness for PSS of ankle-equinus. TRIAL REGISTRATION: NCT05878223.
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Tratamento por Ondas de Choque Extracorpóreas , Espasticidade Muscular , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Espasticidade Muscular/etiologia , Espasticidade Muscular/reabilitação , Espasticidade Muscular/terapia , Masculino , Tratamento por Ondas de Choque Extracorpóreas/métodos , Feminino , Pessoa de Meia-Idade , Método Duplo-Cego , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral/métodos , Tornozelo , Resultado do Tratamento , Adulto , Idoso , Amplitude de Movimento Articular , Articulação do TornozeloRESUMO
With cabozantinib as the precursor, a novel small molecule inhibitors of c-Met kinase with thieno [2,3-b] pyridine as the scaffold were designed, synthesized and evaluated for their biological activity against A549, Hela and MCF-7 cell lines. The in vitro activities of 16 compounds were tested by MTT method with cabozantinib as control drug. Most compounds had moderate to strong inhibitory activities on cells. Among them, compound 10 had the strongest inhibitory activity, which was superior to the lead compound cabozantinib. Its IC50 values for A549, Hela and MCF-7 cells were 0.005, 2.833 and 13.581 µM, respectively. The colony formation assay demonstrated that compound 10 significantly inhibited the colony formation of A549 cells and suppressed their growth in a concentration-dependent manner. The wound healing assay showed that compound 10 could effectively inhibit the migration of cancer cells compared to a blank control group. The AO/EB assay demonstrated that compound 10 possesses the capability to effectively trigger apoptosis in a concentration-dependent manner. The elementary structure-activity relationship, molecular docking and pharmacokinetics studies revealed the significance of thieno [2,3-b] pyridine derivatives in anti-tumor activity.
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BACKGROUND: Pediatric CKD is associated with a high risk of cardiovascular disease (CVD). Early detection of subclinical CVD in childhood CKD can be achieved through various cardiovascular (CV) assessments, including carotid intima-media thickness (cIMT), ambulatory blood pressure monitoring (ABPM), and arterial stiffness indices. Lactoferrin (LF), a key functional glycoprotein found in breast milk, has been linked to several diseases and has potential as a biomarker. METHODS: In our study of 102 children with CKD stages G1-G4, we explored the relationship between LF and CV risk markers. RESULTS: We found that LF concentration was not related to the severity or underlying causes of childhood CKD, but was positively correlated with overweight/obesity. Lower LF levels were correlated with increased cIMT and elevated arterial stiffness indices. Notably, abnormalities in ABPM profiles were observed in up to 60% of the children with CKD, with low LF levels linked to nighttime hypertension, nocturnal non-dipping, and ABPM abnormalities. CONCLUSIONS: In conclusion, LF shows promise as a biomarker for detecting subclinical CVD in children with CKD. Its potential utility in early detection could be instrumental in guiding timely interventions and improving long-term CV outcomes, although further research is needed to clarify the underlying mechanisms.
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Dietary regulation has been recognized for its profound impact on human health. The convergence of cardiovascular, kidney, and metabolic disorders at the pathophysiological level has given rise to cardiovascular-kidney-metabolic (CKM) syndrome, which constitutes a significant global health burden. Maternal dietary nutrients play a crucial role in fetal development, influencing various programmed processes. This review emphasizes the effects of different types of dietary interventions on each component of CKM syndrome in both preclinical and clinical settings. We also provide an overview of potential maternal dietary strategies, including amino acid supplementation, lipid-associated diets, micronutrients, gut microbiota-targeted diets, and plant polyphenols, aimed at preventing CKM syndrome in offspring. Additionally, we discuss the mechanisms mediated by nutrient-sensing signals that contribute to CKM programming. Altogether, we underscore the interaction between maternal dietary interventions and the risk of CKM syndrome in offspring, emphasizing the need for continued research to facilitate their clinical translation.
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Doenças Cardiovasculares , Fenômenos Fisiológicos da Nutrição Materna , Humanos , Feminino , Gravidez , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/etiologia , Animais , Dieta , Microbioma Gastrointestinal , Nefropatias/metabolismo , Nefropatias/prevenção & controle , Nefropatias/etiologia , Nefropatias/dietoterapia , Rim/metabolismo , Síndrome Metabólica/prevenção & controle , Síndrome Metabólica/dietoterapia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/etiologiaRESUMO
BACKGROUND: Offspring hypertension arising from adverse maternal conditions can be mitigated through dietary nutritional supplementation, including resveratrol. Previously, we identified derivatives of resveratrol butyrate ester (RBE), specifically 3,4'-di-O-butanoylresveratrol (ED2) and 3-O-butanoylresveratrol (ED4), demonstrating their superior antioxidant capabilities compared to RBE itself. This study sought to assess the protective impact of maternal supplementation with ED2 or ED4 on offspring hypertension in a rat model subjected to a high-fructose (HF) diet during pregnancy and lactation. METHODS: Female Sprague-Dawley rats were distributed into distinct dietary groups throughout pregnancy and lactation: (1) standard chow; (2) HF diet (60%); (3) HF diet supplemented with ED2 (25 mg/L); and (4) HF diet supplemented with ED4 (25 mg/L). Male offspring were euthanized at the age of 12 weeks. RESULTS: The maternal HF diet induced hypertension in the offspring, which was mitigated by perinatal supplementation with either ED2 or ED4. These protective effects were attributed to the antioxidant properties of ED2 and ED4, resulting in an increased availability of nitric oxide (NO). Additionally, supplementation with ED2 was connected to an increased abundance of Bifidobacterium and Clostridium genera, which was accompanied by a decrease in Angelakisella and Christensenella. On the other hand, ED4 supplementation shielded rat offspring from hypertension by elevating concentrations of short-chain fatty acids (SCFAs) and their receptors while reducing trimethylamine-N-oxide (TMAO) levels. CONCLUSIONS: These findings highlight the potential of purified RBE monomers, ED2 and ED4, as preventive measures against hypertension resulting from a maternal high-fructose diet. Further research is warranted to explore their clinical applications based on these promising results.
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Suplementos Nutricionais , Frutose , Hipertensão , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal , Ratos Sprague-Dawley , Resveratrol , Animais , Feminino , Gravidez , Hipertensão/prevenção & controle , Hipertensão/etiologia , Resveratrol/farmacologia , Ratos , Antioxidantes/farmacologia , Masculino , Butiratos , Microbioma Gastrointestinal/efeitos dos fármacos , Lactação , Óxido Nítrico/metabolismoRESUMO
BACKGROUND: The convergence of cardiovascular, kidney, and metabolic disorders at the pathophysiological level has led to the recognition of cardiovascular-kidney-metabolic (CKM) syndrome, which represents a significant global health challenge. Polyphenols, a group of phytochemicals, have demonstrated potential health-promoting effects. METHODS: This review highlights the impact of maternal polyphenol supplementation on the CKM health of offspring. RESULTS: Initially, we summarize the interconnections between polyphenols and each aspect of CKM syndrome. We then discuss in vivo studies that have investigated the use of polyphenols during pregnancy and breastfeeding, focusing on their role in preventing CKM syndrome in offspring. Additionally, we explore the common mechanisms underlying the protective effects of maternal polyphenol supplementation. CONCLUSIONS: Overall, this review underscores the potential of early-life polyphenol interventions in safeguarding against CKM syndrome in offspring. It emphasizes the importance of continued research to advance our understanding and facilitate the clinical translation of these interventions.
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Doenças Cardiovasculares , Nefropatias , Polifenóis , Polifenóis/farmacologia , Humanos , Feminino , Gravidez , Doenças Cardiovasculares/prevenção & controle , Nefropatias/prevenção & controle , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal , Síndrome Metabólica , Suplementos Nutricionais , Animais , Rim/efeitos dos fármacos , Rim/metabolismo , Aleitamento MaternoRESUMO
Oxaliplatin is effective against colorectal cancer (CRC), but resistance hampers treatment. We found upregulated Dickkopf-1 (DKK1, a secreted protein) in oxaliplatin-resistant (OR) CRC cell lines and DKK1 levels increased by more than 2-fold in approximately 50% of oxaliplatin-resistant CRC tumors. DKK1 activates AKT via cytoskeleton-associated protein 4 (CKAP4, a DKK1 receptor), modulating oxaliplatin responses in vitro and in vivo. The leucine zipper (LZ) domain of CKAP4 and cysteine-rich domain 1 (CRD1) of secreted DKK1 are crucial for their interaction and AKT signaling. By utilizing the LZ protein, we disrupted DKK1 signaling, enhancing oxaliplatin sensitivity in OR CRC cells and xenograft tumors. This suggests that DKK1 as a chemoresistant factor in CRC via AKT activation. Targeting DKK1 with the LZ protein offers a promising therapeutic strategy for oxaliplatin-resistant CRC with high DKK1 levels. This study sheds light on oxaliplatin resistance mechanisms and proposes an innovative intervention for managing this challenge.
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Importance: The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. Objectives: To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. Design, Setting, and Participants: This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Exposure: Body mass index, calculated as weight in kilograms divided by height in meters squared. Main Outcomes and Measures: The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. Results: To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). Conclusions and Relevance: In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.
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Índice de Massa Corporal , Neoplasias Colorretais , Humanos , Masculino , Feminino , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/epidemiologia , Pessoa de Meia-Idade , Incidência , Ásia/epidemiologia , Fatores de Risco , Adulto , Obesidade/epidemiologia , Obesidade/complicações , Estudos Prospectivos , Idoso , Estudos de Coortes , Modelos de Riscos ProporcionaisRESUMO
Lactoferrin, a glycoprotein derived from breastmilk, is recognized for its health benefits in infants and children; however, its protective effects when administered during gestation and lactation against offspring hypertension remain unclear. This study aimed to investigate whether maternal lactoferrin supplementation could prevent hypertension in offspring born to mothers with chronic kidney disease (CKD), with a focus on nitric oxide (NO), renin-angiotensin system (RAS) regulation, and alterations in gut microbiota and short-chain fatty acids (SCFAs). Prior to pregnancy, female rats were subjected to a 0.5% adenine diet for 3 weeks to induce CKD. During pregnancy and lactation, pregnant rats received one of four diets: normal chow, 0.5% adenine diet, 10% lactoferrin diet, or adenine diet supplemented with lactoferrin. Male offspring were euthanized at 12 weeks of age (n = 8 per group). Supplementation with lactoferrin during gestation and lactation prevented hypertension in adult offspring induced by a maternal adenine diet. The maternal adenine diet caused a decrease in the index of NO availability, which was restored by 67% with maternal LF supplementation. Additionally, LF was related to the regulation of the RAS, as evidenced by a reduced renal expression of renin and the angiotensin II type 1 receptor. Combined maternal adenine and LF diets altered beta diversity, shifted the offspring's gut microbiota, decreased propionate levels, and reduced the renal expression of SCFA receptors. The beneficial effects of lactoferrin are likely mediated through enhanced NO availability, rebalancing the RAS, and alterations in gut microbiota composition and SCFAs. Our findings suggest that maternal lactoferrin supplementation improves hypertension in offspring in a model of adenine-induced CKD, bringing us closer to potentially translating lactoferrin supplementation clinically for children born to mothers with CKD.
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Adenina , Suplementos Nutricionais , Microbioma Gastrointestinal , Hipertensão , Lactação , Lactoferrina , Fenômenos Fisiológicos da Nutrição Materna , Sistema Renina-Angiotensina , Animais , Lactoferrina/administração & dosagem , Lactoferrina/farmacologia , Feminino , Gravidez , Masculino , Hipertensão/prevenção & controle , Hipertensão/induzido quimicamente , Hipertensão/etiologia , Ratos , Sistema Renina-Angiotensina/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Óxido Nítrico/metabolismo , Insuficiência Renal Crônica/prevenção & controle , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/induzido quimicamente , Ácidos Graxos Voláteis/metabolismo , Ratos Sprague-Dawley , DietaRESUMO
Pregnant women with chronic kidney disease (CKD) face increased risks of adverse outcomes in their adult offspring. Offspring rats born to dams fed an adenine diet develop hypertension, coinciding with dysregulated hydrogen sulfide (H2S) and nitric oxide (NO) pathways, as well as alterations in gut microbiota. Chondroitin sulfate (CS) is a multifunctional food known for its diverse bioactivities. As a sulfate prebiotic, CS has shown therapeutic potential in various diseases. Here, we investigated the protective effects of maternal CS supplementation against hypertension in offspring induced by an adenine diet. Mother rats were administered regular chow, 0.5% adenine, 3% CS, or a combination throughout gestation and lactation. Maternal CS supplementation effectively protected offspring from hypertension induced by the adenine diet. These beneficial effects of CS were connected with increased renal mRNA and protein levels of 3-mercaptopyruvate sulfurtransferase, an enzyme involved in H2S production. Furthermore, maternal CS treatment significantly enhanced alpha diversity and altered beta diversity of gut microbiota in adult offspring. Specifically, perinatal CS treatment promoted the abundance of beneficial microbes such as Roseburia hominis and Ruminococcus gauvreauii. In conclusion, perinatal CS treatment mitigates offspring hypertension associated with maternal adenine diet, suggesting that early administration of sulfate prebiotics may hold preventive potential. These findings warrant further translational research to explore their clinical implications.
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RATIONALE AND OBJECTIVE: There is a notable absence of robust evidence on the efficacy of ultrasound-based breast cancer screening strategies, particularly in populations with a high prevalence of dense breasts. Our study addresses this gap by evaluating the effectiveness of such strategies in Chinese women, thereby enriching the evidence base for identifying the most efficacious screening approaches for women with dense breast tissue. METHODS: Conducted from October 2018 to August 2022 in Central China, this prospective cohort study enrolled 8996 women aged 35-64 years, divided into two age groups (35-44 and 45-64 years). Participants were screened for breast cancer using hand-held ultrasound (HHUS) and automated breast ultrasound system (ABUS), with the older age group also receiving full-field digital mammography (FFDM). The Breast Imaging Reporting and Data System (BI-RADS) was employed for image interpretation, with abnormal results indicated by BI-RADS 4/5, necessitating a biopsy; BI-RADS 3 required follow-up within 6-12 months by primary screening strategies; and BI-RADS 1/2 were classified as negative. RESULTS: Among the screened women, 29 cases of breast cancer were identified, with 4 (1.3) in the 35-44 years age group and 25 (4.2) in the 45-64 years age group. In the younger age group, HHUS and ABUS performed equally well, with no significant difference in their AUC values (0.8678 vs. 0.8679, P > 0.05). For the older age group, ABUS as a standalone strategy (AUC 0.9935) and both supplemental screening methods (HHUS with FFDM, AUC 0.9920; ABUS with FFDM, AUC 0.9928) outperformed FFDM alone (AUC 0.8983, P < 0.05). However, there was no significant difference between HHUS alone and FFDM alone (AUC 0.9529 vs. 0.8983, P > 0.05). CONCLUSION: The findings indicate that both HHUS and ABUS exhibit strong performance as independent breast cancer screening strategies, with ABUS demonstrating superior potential. However, the integration of FFDM with these ultrasound techniques did not confer a substantial improvement in the overall effectiveness of the screening process.
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Resveratrol, acting as a prebiotic, and propionate, functioning as a postbiotic, hold promise for preventing hypertension in chronic kidney disease (CKD). Previously, we employed propionate to enhance the bioavailability of resveratrol through esterification, resulting in the production of a resveratrol propionate ester (RPE) mixture. In this study, we purified 3-O-propanoylresveratrol (RPE2) and 3,4'-di-O-propanoylresveratrol (RPE4) and investigated their protective effects in a juvenile rat adenine-induced CKD model. To this end, male Sprague Dawley rats aged three weeks (n = 40) were divided into five groups: control; CKD (rats fed adenine); CKRSV (CKD rats treated with 50 mg/L resveratrol); CDRPE2 (CKD rats treated with 25 mg/L RPE2); and CKRPE4 (CKD rats treated with 25 mg/L RPE 4). RPE2 and PRE4 similarly exhibited blood pressure-lowering effects comparable to those of resveratrol, along with increased nitric oxide (NO) availability. Furthermore, RPE2 and RPE4 positively influenced plasma short-chain fatty acid (SCFA) levels and induced distinct alterations in the gut microbial composition of adenine-fed juvenile rats. The supplementation of RPE2 and RPE4, by restoring NO, elevating SCFAs, and modulating the gut microbiota, holds potential for ameliorating CKD-induced hypertension.
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Adenina , Anti-Hipertensivos , Pressão Sanguínea , Suplementos Nutricionais , Microbioma Gastrointestinal , Hipertensão , Ratos Sprague-Dawley , Insuficiência Renal Crônica , Resveratrol , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Resveratrol/farmacologia , Masculino , Adenina/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Ratos , Hipertensão/tratamento farmacológico , Propionatos , Óxido Nítrico/metabolismo , Ácidos Graxos Voláteis/metabolismo , Modelos Animais de Doenças , DietaRESUMO
We hypothesized and investigated whether prenatal exposure to preeclampsia (PE) would simultaneously affect perinatal cardiovascular features and angiotensin system expressions. This prospective study was composed of mother-neonate dyads with (n = 49) and without maternal preeclampsia (n = 48) in a single tertiary medical center. The neonates exposed to PE had significantly larger relative sizes for the left and right coronary arteries and a higher cord plasma level of aminopeptidase-N, which positively correlated with the maternal diastolic blood pressures and determined the relative sizes of the left and right coronary arteries, whereas the encoding aminopeptidase-N (ANPEP) mRNA level in the PE cord blood leukocytes was significantly decreased, positively correlated with the neonatal systolic blood pressures (SBPs), and negatively correlated with the cord plasma-induced endothelial vascular cell adhesion molecule-1 mRNA levels. The PE cord plasma significantly induced higher endothelial mRNA levels of angiotensin II type 1 receptor (AT1R) and AT4R, whereas in the umbilical arteries, the protein expressions of AT2R and AT4R were significantly decreased in the PE group. The endothelial AT1R mRNA level positively determined the maternal SBPs, and the AT4R mRNA level positively determined the neonatal chamber size and cardiac output. In conclusion, PE may influence perinatal angiotensin system and cardiovascular manifestations of neonates across placentae. Intriguing correlations between these two warrant further mechanistic investigation.
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Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/genética , Adulto , Recém-Nascido , Sangue Fetal/metabolismo , Pressão Sanguínea , Estudos Prospectivos , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Sistema Cardiovascular/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
To investigate the positive feed-forward regulatory mechanism of nitrate uptake by rice, its responses to various light and carbohydrates were compared. In order to measure nitrate uptake in real time, the non-invasive method was used. The results showed that net nitrate uptake increased in the light and decreased in the dark, and finally reached a steady state after about 5 h. Based on it, carbohydrates effects could be investigated without considering light effects. After sucrose addition for 2 h, net nitrate uptake increased by about 80% without a lag, while glucose, fructose and raffinose had a slight effect with a lag and other sugars had no effect. It provided an evidence that sucrose was a positive feed-forward signal molecule of nitrate uptake by rice roots. To further analyze the effect of sucrose on the expression of high affinity nitrate transporter genes OsNRT2.1, OsNRT2.2, OsNRT2.3a and OsNRT2.3b, qRT-PCR was used to further verify after treated with 10 mM sucrose. The results revealed that these genes expression was immediately up-regulated, which indicated that these genes were post transcriptionally regulated. Further, 15N exchange dynamics analyzed N transport. It is benefit for increasing nitrate uptake by rice and improving its yield.
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Regulação da Expressão Gênica de Plantas , Nitratos , Oryza , Raízes de Plantas , Sacarose , Oryza/metabolismo , Oryza/genética , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Nitratos/metabolismo , Sacarose/metabolismo , Transporte Biológico , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Transporte de Ânions/metabolismo , Proteínas de Transporte de Ânions/genética , Luz , Transportadores de NitratoRESUMO
Spontaneous intracerebral hemorrhage (ICH) constitutes a significant portion of acute stroke incidents worldwide, often leading to post-stroke dysphagia (PSD), affecting 50-77% of survivors and worsening patient morbidity. This study aimed to identify predictive variables for PSD among patients with spontaneous ICH. A retrospective cohort study was conducted on adult patients with acute spontaneous ICH, confirmed by brain computed tomography, from June 2019 to June 2023. We analyzed demographic, neuroimaging, and stroke-specific characteristics and rehabilitation indicators. PSD was evaluated using nasogastric (NG) tube retention and the Functional Oral Intake Scale (FOIS) levels at 4 and 12 weeks post-ICH. Statistical analyses involved univariate and multivariate logistic regression to identify PSD predictors. A total of 310 ICH patients were included in the study. At 4 weeks, significant predictors for NG tube retention included 24-hour National Institute of Health Stroke Scale (NIHSS) scores, estimated glomerular filtration rate and sitting balance. At 12 weeks, hospital stay duration and ICH score were significant predictors for NG tube retention. Regarding the FOIS, significant predictors at 4 weeks included higher 24-hour NIHSS scores, compromised sitting balance, immobility-related complications, initial hematoma volume and intraventricular hemorrhages. At 12 weeks, older age and higher 24-hour NIHSS scores significantly predicted lower FOIS levels. Our findings demonstrate that PSD in ICH patients is influenced by a complex interplay of factors, including stroke severity, renal function, and physical impairment. The study highlights the importance of early neurological assessment, physical function, and comprehensive management in improving swallowing outcomes, emphasizing a multifaceted approach to enhancing outcomes for ICH survivors.
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Amino acids are essential for normal pregnancy and fetal development. Disruptions in maternal amino acid metabolism have been associated with various adult diseases later in life, a phenomenon referred to as the developmental origins of health and disease (DOHaD). In this review, we examine the recent evidence highlighting the significant impact of amino acids on fetal programming, their influence on the modulation of gut microbiota, and their repercussions on offspring outcomes, particularly in the context of cardiovascular-kidney-metabolic (CKM) syndrome. Furthermore, we delve into experimental studies that have unveiled the protective effects of therapies targeting amino acids. These interventions have demonstrated the potential to reprogram traits associated with CKM in offspring. The discussion encompasses the challenges of translating the findings from animal studies to clinical applications, emphasizing the complexity of this process. Additionally, we propose potential solutions to overcome these challenges. Ultimately, as we move forward, future research endeavors should aim to pinpoint the most effective amino-acid-targeted therapies, determining the optimal dosage and mode of administration. This exploration is essential for maximizing the reprogramming effects, ultimately contributing to the enhancement of cardiovascular-kidney-metabolic health in offspring.
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Aminoácidos , Doenças Cardiovasculares , Desenvolvimento Fetal , Microbioma Gastrointestinal , Rim , Humanos , Gravidez , Feminino , Aminoácidos/metabolismo , Rim/metabolismo , Animais , Microbioma Gastrointestinal/fisiologia , Efeitos Tardios da Exposição Pré-Natal , Nefropatias , Fenômenos Fisiológicos da Nutrição MaternaRESUMO
The intricate currents of the Northwest Pacific Ocean, with strong manifestations along the westside rim, connect tropical and subtropical gyres and significantly influence East Asian and global climates. The El Niño/Southern Oscillation (ENSO) originates in the tropical Pacific Ocean and disrupts this ocean circulation system. However, the spatiotemporal dependence of the impact of ENSO events has yet to be elucidated because of the complexities of both ENSO events and circulation systems, as well as the increased availability of observational data. We thus combined altimeter and drifter observations to demonstrate the distinct tropical and subtropical influences of the circulation system on ENSO diversity. During El Niño years, the North Equatorial Current, North Equatorial Countercurrent, Mindanao Current, Indonesian Throughflow, and the subtropical Kuroshio Current and its Extension region exhibit strengthening, while the tropical Kuroshio Current weakens. The tropical impact is characterized by sea level changes in the warm pool, whereas the subtropical influence is driven by variations in the wind stress curl. The tropical and subtropical influences are amplified during the Centra Pacific El Niño years compared to the Eastern Pacific El Niño years. As the globe warms, these impacts are anticipated to intensify. Thus, strengthening observation systems and refining climate models are essential for understanding and projecting the enhancing influences of ENSO on the Northwest Pacific Oceanic circulation.
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The effects of gut microbiota on the association between carbohydrate intake during pregnancy and neonatal low birth weight (LBW) were investigated. A prospective cohort study was conducted with 257 singleton-born mother-child pairs in Taiwan, and maternal dietary intake was estimated using a questionnaire, with each macronutrient being classified as low, medium, or high. Maternal fecal samples were collected between 24 and 28 weeks of gestation, and gut microbiota composition and diversity were profiled using 16S rRNA amplicon gene sequencing. Carbohydrates were the major source of total energy (56.61%), followed by fat (27.92%) and protein (15.46%). The rate of infant LBW was 7.8%, which was positively correlated with maternal carbohydrate intake. In the pregnancy gut microbiota, Bacteroides ovatus and Dorea spp. were indirectly and directly negatively associated with fetal growth, respectively; Rosenburia faecis was directly positively associated with neonatal birth weight. Maternal hypertension during pregnancy altered the microbiota features and was associated with poor fetal growth. Microbiota-accessible carbohydrates can modify the composition and function of the pregnancy gut microbiota, thus providing a potential marker to modulate deviations from dietary patterns, particularly in women at risk of hypertension during pregnancy, to prevent neonatal LBW.
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Carboidratos da Dieta , Fezes , Microbioma Gastrointestinal , Recém-Nascido de Baixo Peso , Humanos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Gravidez , Recém-Nascido , Adulto , Estudos Prospectivos , Fezes/microbiologia , Fenômenos Fisiológicos da Nutrição Materna , Taiwan , RNA Ribossômico 16S/genética , Desenvolvimento FetalRESUMO
Early life exposure lays the groundwork for the risk of developing cardiovascular-kidney-metabolic (CKM) syndrome in adulthood. Various environmental chemicals to which pregnant mothers are commonly exposed can disrupt fetal programming, leading to a wide range of CKM phenotypes. The aryl hydrocarbon receptor (AHR) has a key role as a ligand-activated transcription factor in sensing these environmental chemicals. Activating AHR through exposure to environmental chemicals has been documented for its adverse impacts on cardiovascular diseases, hypertension, diabetes, obesity, kidney disease, and non-alcoholic fatty liver disease, as evidenced by both epidemiological and animal studies. In this review, we compile current human evidence and findings from animal models that support the connection between antenatal chemical exposures and CKM programming, focusing particularly on AHR signaling. Additionally, we explore potential AHR modulators aimed at preventing CKM syndrome. As the pioneering review to present evidence advocating for the avoidance of toxic chemical exposure during pregnancy and deepening our understanding of AHR signaling, this has the potential to mitigate the global burden of CKM syndrome in the future.
Assuntos
Doenças Cardiovasculares , Efeitos Tardios da Exposição Pré-Natal , Receptores de Hidrocarboneto Arílico , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Humanos , Gravidez , Animais , Feminino , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/induzido quimicamente , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/etiologia , Exposição Materna/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Rim/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Desenvolvimento Fetal/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Poluentes Ambientais/efeitos adversos , Reprogramação MetabólicaRESUMO
This study investigated the impact of ultrasound treatment on dioscorin, the primary storage protein found in yam tubers. Three key factors, namely ultrasound power, duration, and frequency, were focused on. The research revealed that ultrasound-induced cavitation effects disrupted non-covalent bonds, resulting in a reduction in α-helix and ß-sheet contents, decreased thermal stability, and a decrease in the apparent hydrodynamic diameter (Dh) of dioscorin. Additionally, previously hidden amino acid groups within the molecule became exposed on its surface, resulting in increased surface hydrophobicity (Ho) and zeta-potential. Under specific ultrasound conditions (200 W, 25 kHz, 30 min), Dh decreased while Ho increased, facilitating the adsorption of dioscorin molecules onto the oil-water interface. Molecular dynamics (MD) simulations showed that at lower frequencies and pressures, the structural flexibility of dioscorin's main chain atoms increased, leading to more significant fluctuations between amino acid residues. This transformation improved dioscorin's emulsifying properties and its oil-water interface affinity.