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Cuproptosis is characterized by lipoylated protein aggregation and loss of iron-sulfur (Fe-S) proteins, which are crucial for a wide range of important cellular functions, including DNA replication and damage repair. Sirt2 and sirt4 are lipoamidases that remove the lipoyl moiety from lipoylated proteins using nicotinamide adenine dinucleotide (NAD+) as a cofactor. However, to date, it is not clear whether nicotinamide mononucleotide (NMN), a precursor of NAD+, affects cellular sensitivity to cuproptosis. Therefore, in the current study, cuproptosis was induced by the copper (Cu) ionophore elesclomol (Es) in HeLa cells. It was also found that Es/Cu treatment increased cellular DNA damage level. On the other hand, NMN treatment partially rescued cuproptosis in a dose-dependent manner, as well as reduced cellular DNA damage level. In addition, NMN upregulated the expression of Fe-S protein POLD1, without affecting the aggregation of lipoylated proteins. Mechanistic study revealed that NMN increased the expression of sirt2 and cellular reduced nicotinamide adenine dinucleotide phosphate (NADPH) level. Overexpression of sirt2 and sirt4 did not change the aggregation of lipoylated proteins, however, sirt2, but not sirt4, increased cellular NADPH levels and partially rescued cuproptosis. Inhibition of NAD+ kinase (NADK), which is responsible for generating NADPH, abolished the rescuing function of NMN and sirt2 for Es/Cu induced cell death. Taken together, our results suggested that DNA damage is a characteristic feature of cuproptosis. NMN can partially rescue cuproptosis by upregulating sirt2, increase intracellular NADPH content and maintain the level of Fe-S proteins, independent of the lipoamidase activity of sirt2.
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Daño del ADN , NADP , Mononucleótido de Nicotinamida , Sirtuina 2 , Regulación hacia Arriba , Humanos , Sirtuina 2/metabolismo , Sirtuina 2/genética , Células HeLa , NADP/metabolismo , Daño del ADN/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Mononucleótido de Nicotinamida/farmacología , Mononucleótido de Nicotinamida/metabolismo , Cobre/farmacología , Cobre/metabolismo , Sirtuinas/metabolismoRESUMEN
The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for a wide range of vital functions, including the modification, folding, and trafficking of proteins, as well as the biosynthesis of lipids and the maintenance of intracellular calcium homeostasis. A variety of factors can disrupt the function of the ER, leading to the aggregation of unfolded and misfolded proteins within its confines and the induction of ER stress. A conserved cascade of signaling events known as the unfolded protein response (UPR) has evolved to relieve the burden within the ER and restore ER homeostasis. However, these processes can culminate in cell death while ER stress is sustained over an extended period and at elevated levels. This review summarizes the potential role of ER stress and the UPR in determining cell fate and function in various diseases, including cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also puts forward that the manipulation of this intricate signaling pathway may represent a novel target for drug discovery and innovative therapeutic strategies in the context of human diseases.
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OBJECTIVE: Evidence of the associations between fine particulate matter (PM2.5) and diabetes risk from women of reproductive age, in whom diabetes may have adverse long-term health effects for both themselves and future generations, remains scarce. We therefore examined the associations of long-term PM2.5 exposure with fasting blood glucose (FBG) level and diabetes risk in women of reproductive age in China. RESEARCH DESIGN AND METHODS: This study included 20,076,032 women age 20-49 years participating in the National Free Preconception Health Examination Project in China between 2010 and 2015. PM2.5 was estimated using a satellite-based model. Multivariate linear and logistic regression models were used to examine the associations of PM2.5 exposure with FBG level and diabetes risk, respectively. Diabetes burden attributable to PM2.5 was estimated using attributable fraction (AF) and attributable number. RESULTS: PM2.5 showed monotonic relationships with elevated FBG level and diabetes risk. Each interquartile range (27 µg/m3) increase in 3-year average PM2.5 concentration was associated with a 0.078 mmol/L (95% CI 0.077, 0.079) increase in FBG and 18% (95% CI 16%, 19%) higher risk of diabetes. The AF attributed to PM2.5 exposure exceeding 5 µg/m3 was 29.0% (95% CI 27.5%, 30.5%), corresponding to an additional 78.6 thousand (95% CI 74.5, 82.6) diabetes cases. Subgroup analyses showed more pronounced diabetes risks in those who were overweight or obese, age >35 years, less educated, of minority ethnicity, registered as a rural household, and residing in western China. CONCLUSIONS: We found long-term PM2.5 exposure was associated with higher diabetes risk in women of reproductive age in China.
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Glucemia , Material Particulado , Humanos , Femenino , Material Particulado/efectos adversos , Adulto , Glucemia/metabolismo , Glucemia/análisis , China/epidemiología , Persona de Mediana Edad , Adulto Joven , Diabetes Mellitus/epidemiología , Diabetes Mellitus/sangre , Ayuno/sangre , Exposición a Riesgos Ambientales/efectos adversos , Pueblos del Este de AsiaRESUMEN
Background: The purpose of the present study was to investigate the effect of erythropoietin (EPO) on lung ischemia-reperfusion injury (LIRI). Methods: Sprague Dawley rats and BEAS-2B cells were employed to construct an ischemia-reperfusion (I/R)-induced model in vivo and in vitro, respectively. Afterward, I/R rats and tert-butyl hydroperoxide (TBHP)-induced cells were treated with different concentrations of EPO. Furthermore, 40 patients with LIRI and healthy controls were enrolled in the study. Results: It was observed that lung tissue damage, cell apoptosis and the expression of BAX and caspase-3 were higher in the LIRI model in vivo and in vitro than in the control group, nevertheless, the Bcl-2, FGF23 and FGFR4 expression level was lower than in the control group. EPO administration significantly reduced lung tissue damage and cell apoptosis while also up-regulating the expression of FGF23 and FGFR4. Rescue experiments indicated that EPO exerted a protective role associated with the FGF23/FGFR4/p-ERK1/2 signal pathway. Notably, the expression of serum EPO, FGF23, FGFR4 and Bcl-2 was decreased in patients with LIRI, while the expression of caspase-3 and BAX was higher. Conclusion: EPO could effectively improve LIRI, which might be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway.
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Eritropoyetina , Daño por Reperfusión , Animales , Humanos , Ratas , Proteína X Asociada a bcl-2/metabolismo , Caspasa 3/genética , Epoetina alfa/metabolismo , Eritropoyetina/farmacología , Isquemia , Pulmón/metabolismo , Sistema de Señalización de MAP Quinasas , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas Sprague-Dawley , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/genética , Daño por Reperfusión/tratamiento farmacológico , Transducción de SeñalRESUMEN
Two novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (YPF and LLLP) were discovered from goat milk protein by peptidomics, in silico analysis, and in vitro assessment. A total of 698 peptides (<23 AA) were successfully identified by LC-MS/MS from goat milk hydrolysates (hydrolyzed by papaian plus proteinase K). Then, 105 potential DPP-IV inhibitory peptides were screened using PeptideRanker, the ToxinPred tool, Libdock, iDPPIV-SCM, and sequence characteristics. After ADME, physicochemical property evaluation, and a literature search, 12 candidates were efficiently selected and synthesized in vitro for functional validation. Two peptides (YPF and LLLP) were found to exert relatively high in vitro chemical system (IC50 = 368.54 ± 12.97 µM and 213.99 ± 0.64 µM) and in situ (IC50 = 159.46 ± 17.40 µM and 154.96 ± 8.41 µM) DPP-IV inhibitory capacities, and their inhibitory mechanisms were further explored by molecular docking. Our study showed that the formation of strong non-bonding interactions with the core residues from the pocket of DPP-IV (such as ARG358, PHE357, GLU205, TYR662, TYR547, and TYR666) might primarily account for the DPP-IV inhibitory activity of two identified peptides. Overall, the two novel DPP-IV inhibitory peptides rapidly identified in this study can be used as functional food ingredients for the control of diabetes.
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We tried to elucidate the possible roles of maternal embryonic leucine pull chain kinase (MELK) in lung adenocarcinoma (LUAD) growth and metastasis. Differentially expressed genes in LUAD samples were analysed by the GEPIA database. Clinical tissue samples and cells were collected for MELK, EZH2 and LATS2 expression determination. Co-IP assay was used to verify the interaction between EZH2 and MELK; CHX tracking assay and ubiquitination assay detected the degradation of MELK on EZH2 ubiquitination. ChIP assay detected the enrichment of EZH2 and H3K27me3 on the LATS2 promoter region. LUAD cells were selected for in vitro validation, and the tumorigenic ability of LUAD cells was also observed in a transplantation tumour model of LUAD nude mice. MELK and EZH2 were highly expressed in LUAD samples, while LATS2 was lowly expressed. MELK interacted with EZH2 to inhibit its ubiquitination degradation; EZH2 elevated H3K27me3 modification in the LATS2 promoter to lower LATS2 expression. Silencing MELK or EZH2 or overexpressing LATS2 restrained LUAD cell proliferation and invasion, and facilitated their apoptosis. Silencing MELK or EZH2 or overexpressing LATS2 suppressed tumour formation in nude mice. This study demonstrated that MELK aggravated LUAD by upregulating EZH2 and downregulating LATS2.
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Adenocarcinoma del Pulmón , Proliferación Celular , Proteína Potenciadora del Homólogo Zeste 2 , Regulación Neoplásica de la Expresión Génica , Histonas , Neoplasias Pulmonares , Ratones Desnudos , Proteínas Serina-Treonina Quinasas , Proteínas Supresoras de Tumor , Ubiquitinación , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Animales , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Histonas/metabolismo , Ratones , Proliferación Celular/genética , Metilación , Línea Celular Tumoral , Regiones Promotoras Genéticas/genética , Apoptosis/genética , Femenino , MasculinoRESUMEN
The angiotensin I-converting enzyme (ACE)-inhibitory peptide SQPK was selected by in silico digestion and virtual screening from goat ß-casein, and its effect and regulatory mechanism on function of endothelial cells was further evaluated. The results showed that SQPK exhibited relatively good ACE inhibition capacity (IC50 = 452.7 µg/mL). Treatment with 25 µg/mL SQPK for 12 h significantly elevated nitric oxide (NO) production, stimulated eNOS expression (p < 0.05) and affected the transcriptomic profiling of EA. Hy926 cells. In particular, SQPK stimulated the expression of genes encoding inflammatory cytokines (CXCL1/2 and IL6) but depressed encoding mesenchymal markers (FN1 and CNN3). Furthermore, SQPK modified the expression of genes involved in endothelial-to-mesenchymal transition (EndMT). Therefore, the selected peptide SQPK may exert potential protective effects on the function of endothelial cells by inhibiting the EndMT.
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Inhibidores de la Enzima Convertidora de Angiotensina , Caseínas , Animales , Caseínas/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Células Endoteliales/metabolismo , Cabras/metabolismo , Péptidos/farmacología , Péptidos/metabolismoRESUMEN
BACKGROUND AND AIMS: The beneficial effect of low-glycemic index (GI) diet on gestational diabetes mellitus (GDM) has been suggested in many observational studies; however, results from intervention trials remain inconsistent. This study aims to estimate the effect of interventions with low-GI dietary advice on pregnant outcomes in women with elevated risk of GDM. DESIGN: PubMed, Web of Science, Embase, and Cochrane Library databases were searched for randomized clinical trials (RCTs) through March 2022. Studies reporting the effect of low-GI diet advice intervention on maternal and fetal outcomes in pregnant women with increased risks of GDM were included. Random or fixed effects model was used to calculate combined treatment effects. Publication bias was assessed via Begg's and Egger's tests and funnel plot inspection. RESULTS: Nine RCTs recruiting 3416 participants were included. Low-GI diet advice did not modulate the risk of GDM. Compared with control diets, low-GI diet advice significantly reduced gestational weight gain (GWG) (weighted mean differences, WMD = -0.93 kg, 95% CI: -1.31, -0.55; p < 0.001; n = 7) and the risk of premature birth (RR = 0.55, 95% CI: 0.35, 0.88; p = 0.012; n = 5). In subgroup analyses, the effect of low-GI diet interventions on premature birth was significant only in women with BMI higher than 30 kg/m2 (RR = 0.28, 95% CI: 0.10, 0.77, p = 0.014; n = 3); the significant effect on GWG was not altered by stratification of BMI and the type of GDM risk factors. No significant changes in other maternal and newborn outcomes were found. CONCLUSIONS: Low-GI diet advice interventions during pregnancy decreased GWG and the risk of premature birth in women with elevated GDM risk; however, the interventions did not significantly prevent GDM development in these women.
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Diabetes Gestacional , Nacimiento Prematuro , Femenino , Humanos , Recién Nacido , Embarazo , Terapia Combinada , Bases de Datos Factuales , Índice Glucémico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Women with antenatal depression often have a higher risk of developing postpartum depression (PPD) after delivery. A number of factors associated with the PDD in those previously reporting antenatal depression have been suggested, but further research is needed. This study aimed to investigate factors associated with developing subsequent postnatal depression in women who had screened positive for antenatal depression. METHODS: This study was carried out in Hangzhou women's Hospital. 578 women who experienced antenatal depression from this cohort were enrolled in this study. The sociodemographic and clinical characteristics of the participants were collected and tabulated against the incidence of postnatal depression. Binary logistic regression was used to estimate the effects of the principal underlying variables. The Chinese-version Edinburgh Postnatal Depression Scale (EPDS) was used to screen for PPD. Antenatal screening for depression was conducted at 28-34 weeks during pregnancy and postpartum depressive symptoms were assessed at 6 weeks after childbirth in the women. Path Analysis of Structural Equation Model (SEM) was employed to explore the direct, indirect, and total effects of risk factors of PPD. RESULTS: 57.6% (n = 333) of the participants subsequently developed PPD in our study. The results of the logistic analysis indicated that ages ≤ 35 years old (OR = 1.852; 95%CI: 1.002-3.423), non-one-child families (OR = 1.518; 95%CI: 1.047-2.200), and rare care from partner during pregnancy (OR = 2.801; 95%CI: 1.038-7.562), the antenatal EPDS score (OR = 1.128; 95%CI: 1.052-1.209), pyrexia during pregnancy (OR = 2.43; 95%CI: 1.358-4.345), fairly good (OR = 1.836; 95%CI: 1.009-3.340), fairly bad (OR = 3.919; 95%CI:2.072-7.414) and very bad postpartum sleep quality (OR = 9.18; 95%CI: 2.335-36.241) were associated with increased risk of PPD (compared to very good postpartum sleep quality). In path analysis model, antenatal EPDS score (standardized total ß = 0.173) and pyrexia during pregnancy (standardized total ß = 0.132) had both direct and indirect effects (the impact on outcome variables needs to be determined through other variables) on PPD. Sleep quality after delivery (standardized ß = 0.226) and one-child family (standardized ß = 0.088) had direct effects only on PPD. CONCLUSION: The results from our study indicated that more than 50% of the women who experienced antepartum depression would subsequently develop PPD. Depressive symptoms and pyrexia during pregnancy increase PPD scores, and these effects were in part mediated via poor sleep quality during the postpartum period.
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Depresión Posparto , Embarazo , Femenino , Humanos , Adulto , Depresión Posparto/diagnóstico , Depresión Posparto/epidemiología , Depresión Posparto/etiología , Depresión/epidemiología , Periodo Posparto , Parto , Factores de RiesgoRESUMEN
BACKGROUND: Aero-otitis media (AOM), also known as aural barotrauma or barotitis media, is categorized into primary AOM and secondary AOM. Because conservative treatment was ineffective, primary AOM was one of the main reasons for grounding. In 2014, the team successfully treated a pilot with primary AOM using balloon Eustachian tuboplasty (BET). Now, this case is reported.CASE REPORT:The patient was a 40-yr-old male transport pilot who joined a flight after catching a cold. During the descent, the right ear appeared to have stuffiness and hearing loss, accompanied by tinnitus and ear pain. The local hospital's acoustic immittance test showed an "A" curve in the left ear and a "B" curve in the right ear. According to "secretory otitis media", right tympanic membrane puncture and drugs were performed. After he recovered, he continued to fly, and the symptoms reappeared again. Then he was transferred to our hospital, and right BET was performed. Equalization of ear pressure in the hypobaric chamber returned to normal 2 mo after the operation. The pilot was found fit to fly. The pilot is still qualified, with more than 6000 h of flight time.DISCUSSION: AOM is linked to Eustachian tube dysfunction. BET has been a minimally invasive treatment of Eustachian tube lesions in recent years. If conservative treatments for primary AOM are ineffective, BET can be selected. While the postoperative symptoms disappeared, pure tone audiometry, tympanometry, and ear pressure function tests met the standards for the physical examination of pilots, allowing the determination of flight qualification.Zhang M, Liu X, Wang B, Jin Z, Xu X. Qualification of pilots with aero-otitis media after balloon Eustachian tuboplasty. Aerosp Med Hum Perform. 2023; 94(8):629-633.
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Lesiones Accidentales , Barotrauma , Trompa Auditiva , Otitis Media con Derrame , Pilotos , Masculino , Humanos , Barotrauma/etiología , Trompa Auditiva/cirugía , Pruebas de Impedancia AcústicaRESUMEN
Objectives: This study aimed to investigate the effect of vascular risk factors on the outcomes of endolymphatic sac decompression (ESD) surgery in patients with Meniere's disease. Methods: The study included 56 patients with Meniere's disease, who had undergone unilateral ESD surgery. The patients' vascular risk factors were assessed based on the preoperative 10-year atherosclerotic cardiovascular diseases risk classification. Those with no or low risk were defined as the low-risk group, while those with medium, high, or very high risk were defined as the high-risk group. The correlation between the vascular risk factors and ESD efficacy was evaluated by the comparison of vertigo control grade between the two groups. The functional disability score was also assessed to investigate whether ESD improved the quality of life in Meniere's disease patients with vascular risk factors. Results: After ESD, 78.95 and 81.08% of patients from the low-risk and high-risk groups, respectively, demonstrated at least grade B vertigo control; no statistically significant difference was observed (p = 0.96). The postoperative functional disability scores in both groups were significantly lower compared with those before surgery (p < 0.01), with a median decrease of two (1, 2) points in both groups. No statistically significant difference between the two groups was observed (p = 0.65). Conclusion: Vascular risk factors have little effect on the efficacy of ESD in patients with Meniere's disease. Patients with one or more vascular risk factors can still experience a not poor vertigo control and improved quality of life after ESD.
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BACKGROUND: The aim of this study was to investigate the effectiveness of the mental rotation test (MRT) based on virtual reality (VR) in predicting pilots' spatial visualization ability (SVA).METHODS: Based on VR, 118 healthy pilots' SVA were evaluated by MRT. The pilot flight ability evaluation scale was used as the criterion of test validity. According to the scale score, pilots were divided into high, middle, or low spatial ability groups pursuant to the 27% allocation principle. Differences in reaction time (RT), correct rate (CR), and correct number per second (CNPS) of MRT between groups were compared. Correlations between scale scores and MRT scores were analyzed. RT, CR, and CNPS of MRT among different age groups and between genders were also compared.RESULTS: The RT of the high spatial ability group was remarkably slower than that of the low spatial ability group (363.4 ± 140.2 s, 458.1 ± 151.7 s). The CNPS of the high spatial ability group was dramatically higher than that of the low spatial ability group (0.111 ± 0.045 s, 0.086 ± 0.001 s). There were no significant differences in RT, CR, and CNPS between different genders. Pilots in the 29-35 yr old age group had considerably slower RT than those in the 22-28 yr old age group (330.8 ± 140.3 s, 417.2 ± 132.7 s). Pilots in the 29-35 yr old age group had conspicuously higher CNPS than pilots in the 22-28 yr old age group (0.119 ± 0.040 s, 0.096 ± 0.036 s). All pilots' scale scores were positively correlated with CNPS (r = 0.254) and negatively correlated with RT (r = -0.234).DISCUSSION: MRT based on VR has a good discrimination efficacy for SVA of pilots and is a good indicator for the SVA component measurement.Zhang M, Wang M, Feng H, Liu X, Zhai L, Xu X, Jin Z. Pilots' spatial visualization ability assessment based on virtual reality. Aerosp Med Hum Perform. 2023; 94(6):422-428.
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Medicina Aeroespacial , Personal Militar , Pilotos , Navegación Espacial , Realidad Virtual , Humanos , Masculino , FemeninoRESUMEN
This study aimed to analyze the changes in brain networks functional connectivity of pilots exposed to simulated hypoxia using resting-state functional magnetic resonance imaging (fMRI). A total of 35 healthy male pilots exposed to 14.5% oxygen concentration (corresponding to an altitude of 3000 m) underwent resting-state fMRI scans. The independent component analysis (ICA) approach was used to analyze changes in the resting-state brain networks functional connectivity of pilots after hypoxic exposure, and 9 common components in brain functional networks were identified. In the functional connections that showed significant group differences, linear regression was used to examine the association between functional connectivity and clinical characteristics. The brain networks functional connectivity after hypoxia exposure decreased significantly, including the left frontoparietal network and visual network 1-area, left frontoparietal network and visual network 2-area, right frontoparietal network and visual network 2-area, dorsal attention network and ventral attention network, dorsal attention network and auditory network, and ventral attention network and visual network 1-area. We found no correlation between the altered functional connectivity and arterial oxygen saturation level. Our findings provide insights into the mechanisms underlying hypoxia-induced cognitive impairment in pilots.
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Mapeo Encefálico , Red Nerviosa , Encéfalo/patología , Mapeo Encefálico/métodos , Humanos , Hipoxia , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas , OxígenoRESUMEN
Objective: Acute lung injury (ALI) is a severe respiratory disorder causing alveolar-capillary barrier, leading to a high rate of morbidity and death in critically ill individuals. microRNAs (miRNAs)-mediated mechanism in the pathogenesis of ALI has attracted much interest. Herein, we attempt to characterize a candidate miRNA and its downstream target that is linked to the pathogenesis of ALI. Methods: LPS-conditioned MH-S cells were treated with miR-29a-1-5p mimic, inhibitor, and RNT4 expression vector, and the ALI animal model was injected with agomir and antagomir of miR-29b-1-5p and RNT4 expression vector, in which the pro-inflammatory cytokine production, cell viability and apoptosis, myeloperoxidase (MPO) activity, wet/dry (W/D) ratio, and expression of TGF-ß1, α-smooth muscle actin (α-SMA), E-cadherin, and vimentin were examined. miR-29a-1-5p inhibition of RTN4 translation was confirmed by luciferase activity assays. Results: An elevated miR-29a-1-5p expression was demonstrated in LPS-conditioned MH-S cells. miR-29a-1-5p inhibitor transfection attenuated the production of pro-inflammatory cytokines and MH-S cell viability but enhanced the apoptosis. miR-29a-1-5p inhibition of RTN4 translation was demonstrated in the setting of LPS-induced ALI. LPS-induced murine models demonstrated upregulated miR-29a-1-5p. Intravenous injection of miR-29b-1-5p agomir attenuated mouse lung injury and pulmonary fibrosis. RTN4 overexpression resisting to miR-29a-1-5p overexpression was demonstrated in LPS-induced murine models. Conclusion: The findings obtained from the study that disturbing the action of miR-29a-1-5p may be a novel therapeutic strategy for preventing ALI.
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Arsenic-based therapeutic strategies, even though promising for acute promyelocytic leukemia (APL), are limited by arsenic-related toxic effect and resistance with unknown mechanisms. The purpose of this study is to better understand the different sensitivities of hepatocellular carcinoma cells to arsenic and its mechanism. Arsenic-sensitive liver cancer cell line (HepG2) and arsenic-resistant HepG2 (AsHepG2) cells are employed to study the role of aquaporin 9 (AQP9) in arsenic uptake and tolerance. The half-maximal inhibitory concentration (IC50) value of arsenic in AsHepG2 cells (15.59 ± 1.36 µM) is significantly higher than that in HepG2 cells (7.33 ± 0.93 µM; p= 0.0288). We demonstrated that, with the treatment of sodium arsenite (NaAsO2), arsenic was accumulated at a significantly lower level in AsHepG2 cells in comparison with HepG2 cells (p= 0.00549). Further, arsenic level in AsHepG2 cells reaches a plateau after six hours of treatment, whereas arsenic continues to increase in HepG2 cells during the entire experimental period. Mechanistic study showed that the expression of AQP9 is decreased in a dose-dependent manner in AsHepG2 cells, but no significant difference in HepG2 cells. Furthermore, NaAsO2 dramatically increases AQP9 and p38 phosphorylation, which may partially regulate arsenic sensitivity in both cell lines. In conclusion, the expression and phosphorylation of AQP9 regulated by p38 kinase are involved in the arsenic uptake, thus regulating cellular arsenic sensitivity.
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Background: The preventive effects of probiotic supplementation against gestational diabetes mellitus (GDM) in pregnant women remain unclear. The objective of this review was to investigate the effect of probiotic supplementation on the profiles of glucose metabolism in pregnant women without diabetes. The published literature was retrieved and screened from PubMed, Embase, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang, and Cochrane Center Register of Controlled Trails up to April 1st, 2021. Random controlled trials (RCTs) of probiotic supplementation on pregnant women without GDM were included. Results: 12 RCTs (2213 participants) were eligible for meta-analyses. Overall, probiotic supplementation significantly reduced GDM incidence (Risk Ratio (RR) = 0.62, 95% CI: 0.39-0.99), serum fasting blood glucose (FBG) (Mean Difference (MD) = -0.14 mmol L-1; 95% CI: -0.26 mmol L-1, -0.01 mmol L-1), insulin concentration (MD = -1.91 pmol L-1, 95% CI: -2.41 to -1.41), the homeostasis model assessment of insulin resistance (HOMA-IR) (MD = -0.32 mmol L-1; 95% CI: -0.42 mmol L-1, -0.22 mmol L-1), and Quantitative Insulin sensitivity Check Index (QUICKI) (MD = 0.02, 95% CI: 0.01,0.03) in pregnant women. Probiotic supplementation had no significant effects on the results of the oral glucose tolerance test (OGTT) (1 h OGTT, MD = -0.10, 95% CI: -0.30, 0.09; 2 h OGTT, MD = -0.06, 95% CI: -0.31, 0.20). Conclusion: This meta-analysis suggested that probiotic supplementation may lead to an improvement in glycemic control and reduction of GDM incidence in pregnant women.
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Diabetes Gestacional , Resistencia a la Insulina , Probióticos , Glucemia/metabolismo , Diabetes Gestacional/metabolismo , Femenino , Humanos , Embarazo , Mujeres EmbarazadasRESUMEN
BACKGROUND: Studies have demonstrated the associations between pre-pregnancy obesity, thyroid dysfunction, dyslipidemia, and increased risk of gestational diabetes mellitus (GDM) in pregnant women. This study was designed to investigate whether and to what extent, the interactions between these factors contribute to the risk of GDM. METHODS: A case-control study of 232 GDM cases and 696 controls was conducted among pregnant women from Hangzhou, China. Multiple logistic regression analysis was applied to identify independent risk factors of GDM. Crossover analysis was performed to assess the interactive effects of pre-pregnancy body mass index (pBMI), thyroid hormones, and blood lipid profiles on the risk of GDM. The indexes including attributable proportion (AP) to the interaction and the relative excess risk due to interaction (RERI) were calculated. RESULTS: Chinese pregnant women with pBMI > 23 kg/m2 (adjusted: OR = 4.162, p < 0.001), high triglyceride levels (> 2.30 mmol/L) (adjusted: OR = 1.735, p < 0.001), and the free triiodothyronine/free thyroxine (FT3/FT4) ratio ≥ 0.502 (OR = 4.162, p < 0.001) have significantly increased risk of GDM. Crossover analysis indicated that there were significant interactions between pre-pregnancy overweight/obesity and FT3/FT4 ≥ 0.502 (AP = 0.550, p < 0.001; RERI = 7.586, p = 0.009), high TG levels and FT3/FT4 ≥ 0.502 (AP = 0.348, 95%CI = 0.081-0.614, P = 0.010; RERI = 2.021, 95%CI = 0.064-3.978, p = 0.043) on the risk of GDM. CONCLUSION: The interactions between pBMI and FT3/FT4 ratio, TG level and FT3/FT4 ratio may have significant impacts on the risk of GDM in pregnant women. Such findings may help improve our understanding of the pathogenesis of GDM as well as develop comprehensive strategies for the management of GDM.
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Diabetes Gestacional , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Lípidos , Obesidad , Embarazo , Glándula Tiroides , TriyodotironinaRESUMEN
The present study evaluated the effect of Shenqi Jiangtang Granules(SJG) combined with western medicine on the adverse pregnancy outcomes in women with gestational diabetes mellitus(GDM). PubMed, Web of Science, CNKI, Wanfang, and VIP were searched for clinical randomized controlled trials(RCTs) of SJG combined with western medicine against GDM. The included RCTs were assessed for risks using the assessment criteria recommended by the Cochrane handbook for systematic reviews of interventions. Meta-analysis was performed using Stata 12.0 and RevMan 5.3. Nineteen RCTs were included, with 1 647 patients involved, including 824 cases treated with western medicine alone, and 823 cases treated with SJG combined with western medicine. The course of treatment ranged from 2 to 12 weeks. As revealed by Meta-analysis results, compared with western medicine treatment alone, SJG combined with western medicine could reduce the incidence of postpartum hemorrhage(OR=0.23, 95%CI[0.10, 0.53], P=0.000 6), gestational hypertension(OR=0.24, 95%CI[0.13, 0.45], P<0.000 01), polyhydramnios(OR=0.24, 95%CI[0.12, 0.45], P<0.000 1), premature rupture of membranes(OR=0.20, 95%CI[0.09, 0.45], P<0.000 1), cesarean section(OR=0.40, 95%CI[0.29, 0.55], P<0.000 01), macrosomia(OR=0.19, 95%CI[0.08, 0.47], P<0.000 3), neonatal asphyxia(OR=0.22, 95%CI[0.12, 0.40], P<0.000 01), premature delivery(OR=0.19, 95%CI[0.12, 0.30], P<0.000 01), proteinuria(OR=0.19, 95%CI[0.06, 0.58], P=0.004) and hypoglycemia(OR=0.28, 95%CI[0.16, 0.50], P<0.000 1). The funnel plots and Egger's test showed that except macrosomia, there was no significant publication bias in the results of other indicators. Therefore, as indicated by the findings, SJG combined with western medicine can reduce the incidence of adverse pregnancy outcomes in GDM patients. However, due to the uneven quality of the included trials, the clinical application of this protocol requires caution.
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Diabetes Gestacional , Cesárea , Diabetes Gestacional/tratamiento farmacológico , Medicamentos Herbarios Chinos , Femenino , Macrosomía Fetal , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo , Revisiones Sistemáticas como AsuntoRESUMEN
Grandparenting is known to impact psychological health in older people. However, the extent to which the effect is altered by migration-related and sociodemographic determinants is less clear. Therefore, we conducted this cross-sectional study to investigate whether the association between grandparenting and psychological distress differs between rural-urban migrants and local older adults from May to September 2019. A total of 373 rural-urban migrants and 602 local older adults involved in grandparenting in Hangzhou completed measurements assessing sociodemographic characteristics, childcare burden and psychological distress. In total, 22.2% of the grandparents reported psychological distress. Rural-urban migrant grandparents had a lower socioeconomic status (SES), a higher childcare burden (23.6 ± 9.2 vs. 20.7 ± 9.5, p < 0.001) and higher levels of psychological distress (29.8% vs. 17.4%, p < 0.001) than local grandparents. Childcare burden and pressure from adult children were the most significant predictors for psychological distress in both groups (ps < 0.05). Psychological distress was also significantly associated with self-rated health status (ß = -0.276, p = 0.033) and willingness to participate in grandparenting (ß = -0.659, p = 0.024) in migrant grandparents but associated with female gender (ß = 0.346, p = 0.022), caring for children at night (ß = 0.424, p = 0.011), conflict with adult children (ß = 0.432, p < 0.001) and annual income (ß = -0.237, p < 0.001) in local grandparents. Migrant status showed a statistically significant moderating effect between childcare burden and psychological distress. These results may be of assistance in comprehensively understanding the social determinants of mental health of grandparents involved in grandparenting.
Asunto(s)
Abuelos , Distrés Psicológico , Migrantes , Femenino , Humanos , Anciano , Niño , Abuelos/psicología , Cuidado del Niño , Estudios Transversales , China/epidemiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: alopecia is a hair disorder that can add a significant medical and psychological burden to patients. Currently, the FDA-approved drugs for the treatment of androgenetic alopecia (AGA) are minoxidil and finasteride and immunosuppressives are therapeutic options for alopecia areata (AA), but the objective adverse effects and high cost of these treatments reduce patient compliance and thus the effectiveness of the drugs. Traditional Chinese medicine (TCM) has good efficacy, a high safety profile and low treatment costs, but its mechanism of action is still not fully understood. The use of signaling pathways to modulate hair loss is a major direction in the study of the pathogenesis and pharmacology of alopecia. AIM OF THE STUDY: This review aims to collect the results of experimental studies related to alopecia, to screen previously documented combinations of herbs claimed to be effective based on the herbs and their constituent compounds used in the identified studies, and to uncover other useful information that we hope will better guide the clinical application and scientific research of drug combinations or individual herbs for the treatment of alopecia. MATERIALS AND METHODS: We have reviewed experimental studies to determine the methods used and the mechanisms of action of the herbs and constituent compounds. The following keywords were searched in databases, including PubMed, EMBASE, CNKI and CSTJ." Medicinal plants" "Chinese herbal medicine", "hair loss", " alopecia", "androgenetic alopecia" and " alopecia areata ". We also collected combinations of drugs from books approved by various schools for screening. RESULTS: Using known combinations of compounds within herbal medicine to match the documented combinations, 34 topical combinations and 74 oral combinations were identified, and among the 108 herbal combinations screened Angelica, Rehmannia glutinosaLigusticum chuanxiong hort, Radix Rehmanniae, etc. The number of occurrences was very high, and the association with vascular drugs was also found to be very close. CONCLUSIONS: This review further elucidates the therapeutic mechanisms of the compounds within the herbal components associated with alopecia and screens for other combinations that may be dominated by this component for the treatment of alopecia, uncovering compounds from other drugs that may be key factors in the treatment of alopecia. This improvement will provide a better quality of evidence for the effectiveness of herbs and compounds used to treat alopecia.