Association between fecal incontinence and cardiovascular disease in adult Americans: evidence from NHANES 2005-2010.

Objectives: There is limited amount of research on the association between fecal incontinence (FI) and cardiovascular disease (CVD). This study aims to evaluate whether there is a relationship between FI and CVD among adults in the United States. Methods: This study employed a cross-sectional design, encompassing 11,237 adults aged 20 years and older, drawn from the National Health and Nutrition Survey conducted from 2005 to 2010. FI was defined as the involuntary monthly leakage of solid, liquid, or mucus stool. The presence of CVD was evaluated through a questionnaire. Adjusted odds ratios (OR) were computed utilizing a multivariate logistic regression model. Subgroup analyses were conducted to ascertain the stability of the results. Results: Following adjustments for population characteristics, lifestyle habits, laboratory tests, and comorbidities, a significant association was observed between FI and elevated CVD risk (OR: 1.47, 95% CI: 1.21-1.79, P < 0.001). Subgroup analysis uncovered a strong correlation between FI and CVD among participants aged 45-65 years (OR: 1.78, 95%CI: 1.31-2.43). In the participants to aged 66 and above, this correlation persisted (OR: 1.31, 95% CI: 1.01-1.70). Conclusions: This study reveals a significant positive correlation between FI and CVD. Middle-aged and older adults are considered high-risk population for developing CVD, thus emphasizing the importance of screening and timely intervention.

Effects of WN1703 on Cardiovascular Function in Chronic Hyperuricemia Rats and Myocardial Injury Mechanism Exploration in H9C2 Cells.

Hyperuricemia, a prevalent condition, is typically preceded by disturbances in purine metabolism and is frequently associated with hyperlipidemia and other dysfunctions of metabolism. WN1703 demonstrated an inhibitory activity against xanthine oxidoreductase (XOR) that was comparable to febuxostat in our prior investigation. In this study, we assessed the cardiovascular safety of WN1703 in a chronic hyperuricemia rat model induced by potassium oxonate in combination with hypoxanthine. We investigated the changes in cardiovascular biomarkers in chronic hyperuricemia rats treated with febuxostat and WN1703, including creatine kinase (CK), CK-MB, B type natriuretic peptide (BNP), Corin protein (CRN), Neprilysin (NEP), myeloperoxidase (MPO), 8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), and interleukin-8 (IL-8). Additionally, we validated the potential mechanism of cardiac injury induced by WN1703 in H9C2 cells, guided by cardiotoxicity predictions from the cardioToxCSM database and network pharmacology. We observed that excessively rapid urate-lowering, oxidative stress, and inflammation could disrupt myocardial functional homeostasis and increase the risk of cardiovascular injury in hyperuricemia rats, and WN1703 treatment effectively reduced the levels oxidative stress marker 8-OHdG and inflammatory factor TNF-α. Despite the absence of organic damage to the heart with prolonged treatment of febuxostat and WN1703, potential hazard of cardiovascular injury could be associated with the modulation of the TGFß and RHO/ROCK signaling pathways by febuxostat and WN1703. This could offer new insights into the mechanisms underlying the adverse effects caused by XOR inhibitors.

O-linked ß-N-acetylglucosamine (O-GlcNAc) modification: Emerging pathogenesis and a therapeutic target of diabetic nephropathy.

AIMS: O-Linked ß-N-acetylglucosamine (O-GlcNAc) modification, a unique post-translational modification of proteins, is elevated in diabetic nephropathy. This review aims to summarize the current knowledge on the mechanisms by which O-GlcNAcylation of proteins contributes to the pathogenesis and progression of diabetic nephropathy, as well as the therapeutic potential of targeting O-GlcNAc modification for its treatment. METHODS: Current evidence in the literature was reviewed and synthesized in a narrative review. RESULTS: Hyperglycemia increases glucose flux into the hexosamine biosynthesis pathway, which activates glucosamino-fructose aminotransferase expression and activity, leading to the production of O-GlcNAcylation substrate UDP-GlcNAc and an increase in protein O-GlcNAcylation in kidney cells. Protein O-GlcNAcylation regulates the function of kidney cells including mesangial cells, podocytes, and proximal tubular cells, and promotes renal interstitial fibrosis, resulting in kidney damage. Current treatments for diabetic nephropathy, such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and renin-angiotensin-aldosterone system (RAAS) inhibitors, delay disease progression, and suppress protein O-GlcNAcylation. CONCLUSIONS: Increased protein O-GlcNAcylation mediates renal cell damage and promotes renal interstitial fibrosis, leading to diabetic nephropathy. Although the full significance of inhibition of O-GlcNAcylation is not yet understood, it may represent a novel target for treating diabetic nephropathy.

Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious complication of chronic obstructive pulmonary disease, often characterized by increased morbidity and mortality. In traditional Chinese medicine, AECOPD is linked to phlegm-heat and blood-stasis, presenting symptoms like thick sputum, fever, and chest pain. It has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD, suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type AECOPD. AIM: To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type AECOPD. METHODS: One hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two groups. The treatment group received acetylcysteine inhalation (10% solution, 5 mL, twice daily) along with conventional therapy, whereas the control group received only conventional therapy. The treatment duration was 14 d. Inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) in the serum and sputum as well as lung function parameters (forced expiratory volume in one second, forced vital capacity, and peak expiratory flow) were assessed pre- and post-treatment. Acetylcysteine inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group (P < 0.05). This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type AECOPD. RESULTS: Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control group. These differences were statistically significant (P < 0.05). The study concluded that acetylcysteine inhalation had a positive effect on microinflammation and lung ventilation function in patients with this type of AECOPD, suggesting its potential as an adjuvant therapy for such cases. CONCLUSION: Acetylcysteine inhalation demonstrated significant improvements in reducing inflammatory markers in the serum and sputum, as well as enhancing lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD. These findings suggest that acetylcysteine could serve as a valuable adjuvant therapy for individuals with this specific type of AECOPD, offering benefits for managing microinflammation and optimizing lung function.

Elevated RHAMM as a biomarker for predicting diabetic kidney disease in patients with type 2 diabetes.

Background: Diabetic kidney disease (DKD) poses a significant challenge globally as a complication of diabetes. Hyaluronan (HA), a critical non-sulfated glycosaminoglycan in the extracellular matrix, plays a pivotal role in the progression of DKD. This study assesses the predictive significance of HA's corresponding receptor, RHAMM (receptor for HA-mediated motility), in DKD pathogenesis in type 2 diabetes (T2DM) patients. Methods: Enzyme-linked immunosorbent assays were utilized to measure plasma and urine levels of HA, CD44 and RHAMM in 99 diabetic patients. Immunohistochemistry staining was employed to examine HA deposition, CD44 and RHAMM expressions from 18 biopsy-proven DKD patients. Spearman correlation analysis, linear regression and receiver operating characteristic (ROC) analysis were conducted to establish associations between plasma HA, CD44 and RHAMM levels, and clinical parameters in DKD patients with T2DM. Results: Elevated plasma and urine HA, CD44 and RHAMM levels were notably observed in the severe renal dysfunction group. Plasma RHAMM exhibited positive correlations with HA (r = 0.616, P < .001) and CD44 (r = 0.220, P < .001), and a negative correlation with estimated glomerular filtration rate (eGFR) (r = -0.618, P < .001). After adjusting for other potential predictors, plasma RHAMM emerged as an independent predictor of declining eGFR (ß = -0.160, P < .05). Increased HA, CD44 and RHAMM levels in kidney biopsies of DKD patients were closely associated with heightened kidney injury. The ROC curve analysis highlighted an area under the curve (AUC) of 0.876 for plasma RHAMM, indicating superior diagnostic efficacy compared to CD44 in predicting DKD pathogenesis. The combined AUC of 0.968 for plasma RHAMM, HA and CD44 also suggested even greater diagnostic potential for DKD pathogenesis. Conclusion: These findings provide initial evidence that elevated RHAMM levels predict DKD pathogenesis in T2DM patients. The formation of a triple complex involving HA, CD44 and RHAMM on the cell surface shows promise as a targetable biomarker for early intervention to mitigate severe renal dysfunctions.

Cognitive impairment in major depressive disorder with non-suicidal self-injury: Association with the functional connectivity of frontotemporal cortex.

BACKGROUND: Non-suicidal self-injury (NSSI) may be related to serious cognitive impairment in patients with major depressive disorder (MDD), but the specific mechanism is still unclear. This study attempts to identify the neurobiological process alterations of cognitive impairment in MDD patients with NSSI by examining the functional connectivity of the frontotemporal cortex in MDD patients with or without NSSI. METHOD: Thirty MDD patients with NSSI, 36 MDD patients without NSSI, and 35 healthy controls (HC) were included in the study. The MATRICS Consensus Cognitive Battery (MCCB) was used to comprehensively assess the cognitive function of the subjects and functional near-infrared spectroscopy (fNIRS) was used to detect the functional connectivity of the frontotemporal cortex and its brain regions of interest. RESULTS: MDD patients with or without NSSI had multi-domain cognitive impairments. MDD patients with NSSI showed the lowest score in performance of attention/alertness and the weakest functional connectivity of frontotemporal when compared with the MDD patients without NSSI and the HC. In addition, the functional connectivity of the bilateral frontotemporal cortex was positively correlated with verbal learning and working memory in MDD patients with NSSI. CONCLUSION: In MDD patients, the appearance of NSSI is often accompanied by further impairment of attention/alertness and a decline in functional connectivity of the frontotemporal cortex. The impairment of verbal learning and working memory was associated with decreased functional connectivity of the frontotemporal cortex in MDD patients with NSSI.

Sex-differential cognitive performance on MCCB of youth with BD-II depression.

BACKGROUND: Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression. METHOD: This cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted. RESULT: ​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression. CONCLUSION: Our study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients.

A survey of skin failure perceptions amongst pressure injury management staff in China: A cross-sectional study.

This study sought to evaluate the perceptions of pressure injury (PI) management staff regarding skin failure (SF). Additionally, an analysis of influencing factors based on the collected data was conducted to establish a foundation for targeted SF training. A descriptive, cross-sectional survey was undertaken in October-November 2023, utilising a convenience sampling method involving selected management staff of PI from 16 provinces in China. A total of 501 nursing participants were included, exhibiting an overall perception level that was moderately low. Although the majority were aware of the possibility of SF (n = 417, 83.23%), only 60% reported an understanding of the fundamentals of SF, with the lowest level of comprehension observed in differentiating between SF and PI (n = 212, 42.31%). Overall attitudes were generally positive. Regarding behaviour, active learning was more prevalent (n = 340, 67.86%), but training is less (n = 287, 57.29%). Family education (n = 401, 80.04%) and nursing record monitoring (n = 426, 85.03%) demonstrated better behaviour. Further analysis revealed that training (t = 13.937, p < 0.001) and professional title (F = 4.681, p = 0.010) had a significant effect on participants' perceptions. These findings underscore that there remains a substantial lack of perception about SF amongst participants. Overall, participants exhibited a positive attitude towards SF, highlighting the need for future improvements in SF training.

Correlations of Aflatoxin Exposure from Cooking Oil and Dietary Foods During Pregnancy with Birth Weight and Gestational Age at Birth in Guangxi, China.

Background: Cooking oil and dietary foods are easily contaminated by aflatoxins (AFs) in Guangxi, China where low birth weight and preterm birth were prevalent. However, there are no data on AF exposure in pregnant women or their impact on newborn birth outcomes. This study aims to measure the levels and correlations of AFs in cooking oil, estimated dietary intake (EDI) of AFs in dietary foods, and serum AFB1 albumin adducts (AFB1-alb) with newborn birthweight and gestational age at birth. Methods: A prospective study was conducted among 126 pregnant women in Guangxi, China. All recruited women were interviewed for demographic data and behavior and obstetric information and then followed up until giving birth. AF measurements were obtained from cooking oil, dietary foods, maternal serum, and cord blood and the correlations of AF levels with newborn birthweight and gestational age at birth were tested using correlation analysis. Results: The median EDI of AFs in cooking oil was 2.61 ng/kg.bw/day and in dietary foods 2.95 ng/kg.bw/day. High positive correlations among EDI of aflatoxin B1 (AFB1) from cooking oil and dietary foods were found (r > 0.7). Low positive correlations of AFB1-alb in maternal serum and cord blood and both EDI of AFB1 in both cooking oil and dietary foods were shown (r ≈0.3). Significant correlations between AF levels in both cooking oil and dietary foods with birth weight were found, but very low negative correlations (r = - 0.244 ~ -0.285). AFB1 levels in foods, maternal serum and cord blood levels were high in pregnant women with newborn low birth weight and preterm birth. Conclusion: The EDIs of AFB1 from both cooking oil and dietary foods were significantly correlated with AFB1-alb in maternal serum and cord blood. Negative correlations of AFs from cooking oils and foods with newborn birth weight should be paid more attention.

Risk Factors of Enternal Nutrition Intolerance in Septic Patients: A Case-control Study.

OBJECTIVE: This study aimed to investigate the incidence of enteral nutrition intolerance (ENI) in patients with sepsis and explore potential risk factors. METHODS: A case-control study was conducted in patients with sepsis who were receiving enteral nutrition (EN) at a tertiary hospital in China. The included patients were divided into the ENI group and the non-ENI group. Univariate and multivariate analyses were performed to identify the risk factors for ENI. RESULTS: A total of 859 patients were included in the study. Among them, 288 (33.53%) patients experienced symptoms of ENI, including diarrhea, vomiting, bloating, and gastric retention. Logistic regression analysis revealed that the Acute Physiology and Chronic Health Evaluation H (APACHE H) score, thoracocentesis, and usage of cardiotonic drugs (namely, inotropes) were independent predictors of the ENI. CONCLUSION: The incidence of ENI is relatively high in patients with sepsis, especially in those who have higher APACHE H scores, have undergone thoracocentesis, and have received inotropes.

The relationship between human blood metabolites and preeclampsia-eclampsia: A Mendelian randomization study.

Preeclampsia and eclampsia are serious complications of pregnancy, leading to high rates of maternal and neonatal mortality. During pregnancy, there are changes in relevant serum metabolites in women. However, it remains unclear if these serum metabolites contribute to the development of associated disorders during pregnancy. Therefore, we conducted a Mendelian randomization study to explore the causal relationship between serum metabolites and preeclampsia and eclampsia. We utilized the inverse variance weighted model as our primary analysis approach. We complemented this with sensitivity analyses, including the heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis, to ensure the robustness of our findings. Furthermore, we conducted linkage disequilibrium score regression, multivariable Mendelian randomization, and metabolic pathway analysis to further explore the genetic data. The Mendelian randomization analysis has identified γ-glutamylglutamine, inosine, and isoleucine 10 metabolites that are significantly associated with preeclampsia, and γ-glutamylglutamine and phenylacetate 8 metabolites that may potentially contribute to the development of eclampsia. Notably, γ-glutamylglutamine has been found to have a causal relationship with both preeclampsia and eclampsia. In the multivariable Mendelian randomization analysis, our research findings suggest that both isoleucine and X-14304-leucylalanine directly impact preeclampsia within the context of amino acids and peptides. Moreover, our observations reveal that carbohydrates can also have a direct effect on preeclampsia. Importantly, it should be emphasized that only 3-lactate in amino acids has been shown to have a direct influence on eclampsia. This research has the potential to enhance our understanding of the biological variances related to disease status, providing a foundation for future investigations.

Curative effect of the total saponins of Panax japonicus (TSPJ) on type 2 diabetes: Focusing on VEGFA.

OBJECTIVE: The objective of this study was to assess the impact of the total saponins of Panax japonicus (TSPJ) on Type 2 diabetes mellitus (T2DM). RESULTS: The intervention of TSPJ was found to have the ability to reverse physiological indicators associated with T2DM, while also enhancing the expression of genes involved in glucose metabolism and intestinal homeostasis. Additionally, alterations in the composition of the gut microbiota were observed. Based on the findings of experimental results and network pharmacology analysis, it is evident that vascular endothelial growth factor A (VEGFA) serves as a prominent shared target between TSPJ and diabetes. The outcomes observed in T2DM mice overexpressing VEGFA align with those observed in T2DM mice treated with TSPJ. CONCLUSIONS: TSPJ administration and VEGFA overexpression yield similar effects on T2DM in mice. Thus, in terms of mechanism, by upregulating the expression of VEGFA, TSPJ may ameliorate metabolic imbalance, preserve intestinal homeostasis, and lessen the symptoms of type 2 diabetes. The findings demonstrated the viability of using VEGFA as a type 2 diabetes therapy option and offered important insights into the therapeutic mechanisms by TSPJ in the management of T2DM. To determine the exact mechanisms behind the effects of TSPJ and VEGFA and to assess their potential therapeutic uses, more research efforts are necessary.

The effectiveness of vortioxetine on neurobiochemical metabolites and cognitive of major depressive disorders patients: A 8-week follow-up study.

OBJECTIVE: Vortioxetine has been shown to improve cognitive performance in people with depression. This study will look at the changes in neurobiochemical metabolites that occur when vortioxetine improves cognitive performance in MDD patients, with the goal of determining the neuroimaging mechanism through which vortioxetine improves cognitive function. METHODS: 30 depressed patients and 30 demographically matched healthy controls (HC) underwent MCCB cognitive assessment and 1H-MRS. After 8 weeks of vortioxetine medication, MCCB and 1H-MRS tests were retested in the MDD group. Before and after therapy, changes in cognitive performance, NAA/Cr, and Cho/Cr were examined in the MDD group. RESULTS: Compared with the HC group, the MDD group had significant reduced in verbal learning, social cognition, and total cognition (all p < 0.05). And the MDD group had lower NAA/Cr in Right thalamus and Left PFC; the Cho/Cr in Right thalamus was lower than HC; the Cho/Cr in Left ACC had significantly increase (all p < 0.05). The MDD group showed significant improvements in the areas of verbal learning, attention/alertness, and total cognitive function before and after Vortioxetine treatment (all p < 0.05). The NAA/Cr ratio of the right PFC before and after treatment (t = 2.338, p = 0.026) showed significant changes. CONCLUSIONS: Vortioxetine can enhance not just the depression symptoms of MDD patients in the initial period, but also their verbal learning, social cognition, and general cognitive capacities after 8 weeks of treatment. Furthermore, vortioxetine has been shown to enhance cognitive function in MDD patients by altering NAA/Cr and Cho/Cr levels in the frontal-thalamic-ACC.

Assessment of the Adverse Health Effects of Aflatoxin Exposure from Unpackaged Peanut Oil in Guangdong, China.

Aflatoxins are liver carcinogens and are common contaminants in unpackaged peanut (UPP) oil. However, the health risks associated with consuming aflatoxins in UPP oil remain unclear. In this study, aflatoxin contamination in 143 UPP oil samples from Guangdong Province were assessed via liquid chromatography-tandem mass spectrometry (LC-MS). We also recruited 168 human subjects, who consumed this oil, to measure their liver functions and lipid metabolism status. Aflatoxin B1 (AFB1) was detected in 79.72% of the UPP oil samples, with levels ranging from 0.02 to 174.13 µg/kg. The average daily human intake of AFB1 from UPP oil was 3.14 ng/kg·bw/day; therefore, the incidence of liver cancer, caused by intake of 1 ng/kg·bw/day AFB1, was estimated to be 5.32 cases out of every 100,000 persons per year. Meanwhile, Hepatitis B virus (HBV) infection and AFB1 exposure exerted a synergistic effect to cause liver dysfunction. In addition, the triglycerides (TG) abnormal rate was statistically significant when using AFB1 to estimate daily intake (EDI) quartile spacing grouping (p = 0.011). In conclusion, high aflatoxin exposure may exacerbate the harmful effects of HBV infection on liver function. Contamination of UPP oil with aflatoxins in Guangdong urgently requires more attention, and public health management of the consumer population is urgently required.

Structure and Antidiabetic Activity of a Glycoprotein from Porphyra haitanensis.

A novel antidiabetic glycoprotein (PG) was isolated and purified from Porphyra haitanensis, and its structure and inhibiting activity on α-amylase and α-glucosidase were analyzed. The purity of the PG was 95.29 ± 0.21%, and its molecular weight was 163.024 ± 5.55 kDa. The PG had a tetramer structure with α- and ß-subunits, and it contained 54.12 ± 0.86% protein (with highly hydrophobic amino acids) and 41.19% ± 0.64% carbohydrate (composed of galactose). The PG was linked via an O-glycosidic bond, exhibiting an α-helical structure and high stability. In addition, the PG inhibited the activities of α-amylase and α-glucosidase, by changing the enzyme's structure toward the PG's structure in a noncompetitive inhibition mode. Molecular docking results showed that the PG inhibited α-amylase activity by hydrophobic interaction, whereas it inhibited α-glucosidase activity by hydrogen bonds and hydrophobic interaction. Overall, the PG was linked to polysaccharides via O-glycosidic bonds, showing an α-helical configuration and a hydrophobic effect, which altered the configuration of α-amylase and α-glucosidase and exerted hypoglycemic activity. This study provides insights into analyzing the structure and antidiabetic activity of glycoproteins.

Gut microbiome-serum metabolic profiles: insight into the hypoglycemic effect of Porphyra haitanensis glycoprotein on hyperglycemic mice.

The hypoglycemic activity of natural algal glycoproteins has attracted interest, but studies of their mechanism of regulating glucose metabolism are lacking. This study investigated the hypoglycemic activity of Porphyra haitanensis glycoprotein (PG) in a mouse hyperglycemia model. The underlying mechanism was elucidated by monitoring changes in the gut microbiome and untargeted serum metabolomics. The results indicated that 30-300 mg kg-1 PG regulated blood glucose levels by increasing insulin secretion, reducing glycated hemoglobin, and improving streptozotocin-induced hyperglycemia in a concentration-dependent manner. In particular, 300 mg kg-1 PG decreased fasting blood glucose by 63.11% and glycosylated hemoglobin by 24.50% and increased insulin secretion by 163.97%. The mechanism of the improvement of hyperglycemia by PG may involve regulating beneficial intestinal bacteria (e.g., norank_f__Muribaculaceae and Lachnospiraceae) and altering the serum metabolic profile (e.g., upregulation of hypotaurine, 3-hydroxy-2-naphthoic acid, and L-glycine), to regulate taurine and hypotaurine, the TCA cycle, AMPK, and pyruvate metabolism. Our findings supported the development of Porphyra haitanensis and its glycoprotein as novel natural antidiabetic compounds to regulate the glycemic balance.

Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy.

BACKGROUND: DJ-1 is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength. However, underlying activity mechanisms are not fully explored. METHODS: Western blotting and quantitative real-time polymerase chain reaction approaches were adopted to analyse DJ-1 expression in skeletal muscle from aged humans or mice and compared with young subjects. Skeletal muscle-specific-DJ-1 knockout (MDKO) mice were generated, followed by an assessment of the physical activity phenotypes (grip strength, maximal load capacity, and hanging, rotarod, and exercise capacity tests) of the MDKO and control mice on the chow diet. Muscular atrophy phenotypes (cross-sectional area and fibre types) were determined by imaging and quantitative real-time polymerase chain reaction. Mitochondrial function and skeletal muscle morphology were evaluated by oxygen consumption rate and electron microscopy, respectively. Tail suspension was applied to address disuse atrophy. RNA-seq analysis was performed to indicate molecular changes in muscles with DJ-1 ablation. Dual-luciferase reporter assays were employed to identify the promoter region of Trim63 and Fbxo32 genes, which were indirectly regulated by DJ-1 via the FoxO1 pathway. Cytoplasmic and nuclear fractions of DJ-1-deleted muscle cells were analysed by western blotting. Compound 23 was administered into the gastrocnemius muscle to mimic the of DJ-1 deletion effects. RESULTS: DJ-1 expression decreased in atrophied muscles of aged human (young men, n = 2; old with aged men, n = 2; young women, n = 2; old with aged women, n = 2) and immobilization mice (n = 6, P < 0.01). MDKO mice exhibited no body weight difference compared with control mice on the chow diet (Flox, n = 8; MDKO, n = 9). DJ-1-deficient muscles were slightly dystrophic (Flox, n = 7; MDKO, n = 8; P < 0.05), with impaired physical activities and oxidative capacity (n = 8, P < 0.01). In disuse-atrophic conditions, MDKO mice showed smaller cross-sectional area (n = 5, P < 0.01) and more central nuclei than control mice (Flox, n = 7; MDKO, n = 6; P < 0.05), without alteration in muscle fibre types (Flox, n = 6; MDKO, n = 7). Biochemical analysis indicated that reduced mitochondrial function and upregulated of atrogenes induced these changes. Furthermore, RNA-seq analysis revealed enhanced activity of the FoxO1 signalling pathway in DJ-1-ablated muscles, which was responsible for the induction of atrogenes. Finally, compound 23 (an inhibitor of DJ-1) could mimic the effects of DJ-1 ablation in vivo. CONCLUSIONS: Our results illuminate the crucial of skeletal muscle DJ-1 in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle wasting diseases.

Prediction of intracranial hemorrhage after internal carotid artery stenting in patients with symptomatic severe carotid stenosis by computed tomography perfusion.

Background: To explore the risk of intracranial hemorrhage (ICH) after internal carotid artery stenting (CAS) in patients with symptomatic severe carotid stenosis by computed tomography perfusion (CTP). Methods: The clinical and imaging data of 87 patients with symptomatic severe carotid stenosis who underwent CTP before CAS were retrospectively analyzed. The absolute values of the cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) were calculated. The relative values (i.e., the rCBF, rCBV, rMTT, and rTTP), defined as the comparison between ipsilateral and contralateral hemispheres, were also derived. The degree of carotid artery stenosis was divided into 3 grades, and the Willis' circle was classified into 4 types. The relationship between the occurrence of the ICH and CTP parameters, the Willis' circle type, and the clinical baseline data were evaluated. A receiver operating characteristic (ROC) curve analysis was performed to determine the most effective CTP parameter for the prediction of ICH. Results: In total, 8 patients (9.2%) developed ICH after CAS. The results showed that the CBF (P=0.025), MTT (P=0.029), rCBF (P=0.006), rMTT (P=0.004), rTTP (P=0.006), and the degree of carotid artery stenosis (P=0.021) differed significantly between the ICH group and non-ICH group. The ROC curve analysis showed that the CTP parameter with the maximal area under the curve (AUC) for ICH was rMTT (AUC =0.808), which indicated that patients with an rMTT >1.88 were more likely to develop ICH (sensitivity: 62.5%, specificity: 96.2%). The occurrence of ICH after CAS was not related to the type of Willis' circle (P=0.713). Conclusions: CTP can be used to predict ICH after CAS in patients with symptomatic severe carotid stenosis, and patients with a preoperative rMTT >1.88 should be closely monitored for evidence of ICH after CAS.

Biochemical metabolism in the anterior cingulate cortex and cognitive function in major depressive disorder with or without insomnia syndrome.

BACKGROUND: Major depressive disorder (MDD) and insomnia have been linked to deficiencies in cognitive performance. However, the underlying mechanism of cognitive impairment in MDD patients with insomnia symptoms (IS) remains unclear. This study aimed to explore the effects of IS in patients with MDD by comparing cognitive function indices among those with IS, those without insomnia symptoms (NIS), and healthy controls (HCs). In addition, we assessed whether the dysfunction of central nervous system (CNS) is one of the important pathophysiologic mechanisms of IS in patients with MDD by comparing the biochemical metabolism ratios in the anterior cingulate cortex (ACC). METHOD: Fifty-five MDD with IS, 39 MDD without IS, and 47 demographically matched HCs underwent the MATRICS Consensus Cognitive Battery (MCCB) assessment and proton magnetic resonance spectroscopy (1H-MRS). MCCB cognitive scores and biochemical metabolism in ACC were assessed and compared between groups. RESULTS: Compared to the HCs group, IS and NIS groups scored significantly lower in seven MCCB cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning problem solving and social cognition). IS group showed a lower speed of processing and lower Cho/Cr ratio in the left ACC vs. NIS group and HCs. Also, in IS group, the Cho/Cr ratio in the left ACC was positively correlated with the composite T-score. CONCLUSION: Patients with comorbidity of MDD with IS may exhibit more common MCCB cognitive impairments than those without IS, particularly speed of processing. Also, dysfunction of ACC may underlie the neural substrate of cognitive impairment in MDD with IS.

Marine glycoproteins: a mine of their structures, functions and potential applications.

Many bioactive compounds are reported from marine organisms, which are significantly different from those found in terrestrial organisms regarding their chemical structures and pharmacological activities. Marine glycoproteins (MGs) have aroused increasing attention as a good nutrient source owing to their potential applications in medicine, cosmetics and food. However, there is a lack of a comprehensive study on MGs to help readers understand the current state of research on marine-derived glycoproteins. The current review compiles the recent progress made on the structures and functions of MGs with future perspectives to maximize their value and applications via bibliometric analysis methods for the first time. The current research on MGs appears mostly limited to the laboratory, with no large-scale production of marine glycoproteins developed. The sugar chains are bound to proteins through covalent bonds that can readily be cleaved leading to difficultly in their separation and purification. Health effects attributed to MGs include treatment of inflammatory diseases, as well as anti-oxidant, immune modulation, anti-tumor, hypolipidemic, hypoglycemic, anti-bacterial and anti-freeze activities. This review can not only deepen the understanding of the functions of MGs, but also lay an important foundation for the further development and utilization of marine resources.

Overview on isolation, structural and functional properties of marine glycoproteins (MGs) via bibliometric analysis methods for the first time.Marine glycoproteins (MGs) have various biological activities and potential health applications.glycoproteins from marine organisms (MGs) significantly enhanced anti-oxidant and anti-inflammatory activities.