Identification of novel pathogenic variants of CUBN in patients with isolated proteinuria.

BACKGROUND: Although proteinuria is long recognized as an independent risk factor for progressive chronic kidney diseases, not all forms of proteinuria are detrimental to kidney function, one of which is isolated proteinuria caused by cubilin (CUBN)-specific mutations. CUBN encodes an endocytic receptor, initially found to be responsible for the Imerslund-Gräsbeck syndrome (IGS; OMIM #261100) characterized by a combined phenotype of megaloblastic anemia and proteinuria. METHODS: After analyzing their clinical and pathological characterizations, next-generation sequencing for renal disease genes or whole-exome sequencing (WES) was performed on four patients with non-progressive isolated proteinuria. CUBN biallelic pathogenic variants were identified and further analyzed by cDNA-PCR sequencing, immunohistochemistry, minigene assay, and multiple in silico prediction tools, including 3D protein modeling. RESULTS: Here, we present four patients with isolated proteinuria caused by CUBN C-terminal biallelic pathogenic variants, all of which showed no typical IGS symptoms, such as anemia and vitamin B12 deficiency. Their urine protein levels fluctuated between +~++ and estimated glomerular filtration rate (eGFR) were normal or slightly higher. Mild mesangial hypercellularity was found in three children's renal biopsies. A homozygous splice-site variant of CUBN (c.6821+3 (IVS44) A>G) was proven to result in the exon 44 skipping and premature translation termination by cDNA sequencing and immunohistochemistry. Compound heterozygous mutations were identified among the other three children, including another novel splice-site variant (c.10764+1 (IVS66) G>A) causing the retention of first 4 nucleotides in intron 66 by minigene assay, two unreported missense mutations (c.4907G>A (p.R1636Q); c. 9095 A>G (p.Y3032C)), and two reported missense mutations in China (c.8938G>A (p.D2980N); c. 9287T>C (p.L3096P)), locating behind the vitamin B12-binding domain, affecting CUB11, CUB16, CUB22, CUB23, and CUB27 domains, respectively. CONCLUSION: These results demonstrate that above CUBN mutations may cause non-progressive and isolated proteinuria, expanding the variant spectrum of CUBN and benefiting our understanding of proteinuria and renal function.

Psychiatric disorders associated with PCSK9 inhibitors: A real-world, pharmacovigilance study.

BACKGROUND: The relationship between Protein Convertase Subtilisin Kexin Type 9 inhibitor (PCSK9i) and psychiatric adverse events (AEs) remains unclear due to the limitations of clinical trials. In this study, PCSK9i-related psychiatric AEs were realistically observed and systematically summarized in the real world by data mining the FDA AE Reporting System (FAERS). METHOD: Total AEs between the third quarter of 2015 and the first quarter of 2023 were obtained from FAERS. Psychiatric AEs were identified using disproportionality analysis and clinical prioritization of signals using a rating scale, followed by univariate logistic regression to explore factors influencing psychiatric AEs. RESULTS: Psychiatric AEs accounted for 6.7% of the total number of PCSK9i reports. Eighteen psychiatric AEs were defined as PCSK9i-related psychiatric adverse events (ppAEs) (lower 95% CI of both ROR >1 and IC025 > 0). The median age of ppAE reports was 68 years, and female patients accounted for 22.67% of reports, including 41.40% of reports with a serious outcome. Eleven (61.11%) and seven (38.89%) ppAEs were classified as weak and moderate clinical priority, respectively. The median time to onset of ppAEs was 149 and 196 days after treatment with evolocumab and alirocumab, respectively. Patients weighing ≥80 kg were 1.59 times more likely to experience ppAEs. CONCLUSION: The results of this study facilitate the prioritization of psychiatric AE signals by healthcare professionals with the goal of mitigating the risk of PCSK9i-related psychiatric AEs. However, as an exploratory study, our findings need to be confirmed in large-scale prospective studies.

Association between prenatal exposure to rare earth elements and the neurodevelopment of children at 24-months of age: A prospective cohort study.

The increasing consumption of rare earth elements (REEs) has resulted in a considerable risk of environmental exposure. However, the adverse effects of prenatal REEs exposure on children's neurodevelopment are not yet fully recognized. Therefore, we investigated the individual and joint effects of prenatal exposure to 13 REEs on children's neurocognitive development based on 809 mother-child pairs from a large birth cohort in Wuhan, China. Maternal urinary concentrations of 13 REEs were repeatedly measured by inductively coupled plasma mass spectrometry. Children's neurodevelopment [e.g., mental and psychomotor development index (MDI/PDI)] at 24-months was assessed using Bayley Scales of Infant Development of Chinese Revision. GEE and BKMR models were applied to estimate the individual and joint effects of prenatal REE exposure on child neurodevelopment level. After controlling for typical confounders, we observed that exposure to 9 REEs during the first trimester were significantly associated with decreased MDI scores [ßs and 95% confidence intervals (CIs) ranging from -2.24 (-3.86 âˆ¼ -0.63) to -1.44 (-2.26∼ -0.26)], and 7 REEs during third trimester were significantly associated decreased PDI scores [ß and 95% CIs ranging from -1.95 (-3.19 âˆ¼ -0.71) to -1.25 (-2.34 âˆ¼ -0.16)]. Higher quantiles of REE mixture in first and third trimester were associated with decreased MDI and PDI score. Thulium, erbium in the first trimester and cerium, lanthanum in the third trimester accounted most importance to joint effects on MDI and PDI, respectively. In conclusion, prenatal exposure to higher concentrations of REEs during the first and third trimester were negative associated with children's neurodevelopment.

Predicted lean body mass in relation to cognitive function in the older adults.

Background: Previous findings about lean body mass (LBM) and cognitive function remain unclear. We aimed to examine this association by using data from the National Health and Nutrition Examination Survey (NHANES). Methods: Using data from the NHANES 2011-2014, we conducted logistic regression models to investigate the relation between the predicted LBM and domain-specific cognitive function assessed by Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer's Disease Word Learning test (CERAD-WL) and Delayed Recall test (CERAD-DR), and Animal Fluency (AF) for information processing speed, memory, and executive function, respectively. Cognitive impairment was defined as the lowest quartile of each cognitive test in the total population. Sex-stratified analysis was further made. Results: A total of 2955 participants aged 60 and above (mean [SD] age, 69.17[0.20] years; 1511 female [51.13%]) were included in the study. After being adjusted for social economic factors, anthropometric parameters, and diseases, we found a positive association between predicted LBM and information processing speed (Odds ratio of DSST impairment= 0.95, 95%CI= 0.91 to 0.99) regardless of body mass index and sex. Compared with patients in the first quartile of predicted LBM, those in the fourth quartile had an odds ratio of 0.355 (95% confidence interval 0.153-0.822) for DSST impairment. No significant relation in other cognitive tests and predicted LBM was found whether stratified by sex or not. Conclusion: Our findings point to the association between predicted lean body mass and cognitive dysfunction in information processing speed, which could be used for early detection and prevention of deterioration of cognitive function among older adults.

Piperine ameliorates psoriatic skin inflammation by inhibiting the phosphorylation of STAT3.

Psoriasis is a common chronic inflammatory skin disease that is easy to relapse and difficult to cure. Piperine is the main alkaloid extracted from black pepper, and its role in psoriasis has not been previously reported. We identified that piperine ameliorated M5-induced psoriatic skin lesions. Furthermore, piperine alleviated psoriasis pathological features including epidermal hyperplasia and inflammatory cell infiltration, decreased the expression of psoriasis-characteristic cytokines, chemokines and proteins in IMQ-induced psoriasiform dermatitis. Moreover, we determined that piperine inhibited the phosphorylation of STAT3 in M5- and IMQ-induced psoriasis-like skin lesions. Our data demonstrated that piperine ameliorated psoriatic skin inflammation by inhibiting the phosphorylation of STAT3. Therefore, piperine may be one potential compound candidate for psoriasis therapy, providing new strategies for clinical intervention.

Deep eutectic solvent-based manganese dioxide nanosheets composites for determination of DNA by a colorimetric method.

BACKGROUND: Nucleic acid is the carrier of genetic information and the keymolecule in life science. It is important to establish a simple and feasible method for nucleic acid quantification in complex biological samples. METHODS: Four kinds of hydrogen bond acceptors (choline chloride (ChCl), L-carnitine, tetrabutylammonium chloride (TBAC) and cetyltrimethylammonium bromide (CTAB)) were used to synthesize deep eutectic solvents (DESs) with hexafluoroisopropanol (HFIP). DESs based manganese dioxide (MnO2) nanosheets composites was synthesized and characterized. DNA concentration was determined by a UVVis spectrometer. The mechanism of DNA-DES/MnO2 colorimetric system was further discussed. RESULTS: The composite composed of DES/MnO2 exhibited excellent oxidase-like activity and could oxidize 3,3',5,5' -tetramethylbenzidine (TMB) to produce a clear blue change with an absorbance maximum at 652 nm. When DNA is introduced, the DNA can interact with the DES by hydrogen bonding and electrostatic interactions, thereby inhibiting the color reaction of DES/MnO2 with TMB. After condition optimization, ChCl/HFIP DES in 1:3 molar ratio was used for the colorimetric method of DNA determination. The linear range of DNA was 10-130 µg/mL and exhibited good selectivity. CONCLUSION: A colorimetric method based on DES/MnO2 was developed to quantify the DNA concentration. The proposed method can be successfully used to quantify DNA in bovine serum samples.

Structure characteristics of low molecular weight pectic polysaccharide and its anti-aging capability by modulating the intestinal homeostasis.

Pectic polysaccharide has attracted increasing attention for their potential biological properties and applications in health industries. In this study, a low-molecular-weight pectic polysaccharide, POS4, was obtained from citrus peel. The structure of POS4 was preliminarily analyzed by gel-permeation chromatography, monosaccharide analysis, infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Results showed that the molecular weight of POS4 was 4.76 kDa and it was a galacturonic acid enriched pectic polysaccharide. The anti-aging activity in vivo showed that POS4 could notably prolong the average lifespan of fruit flies by suppressing the generation of reactive oxygen species (ROS). Further studies demonstrated that POS4 could enhance intestinal homeostasis by modulating gut microbiota in a positive way and regulating autophagy associated genes. Taken together, we proposed that galacturonic acid enriched low molecular weight pectic polysaccharide have great potential in the development of healthy foods such as anti-aging health care products.

Relationship Between Weight-Change Patterns and Cognitive Function: A Retrospective Study.

BACKGROUND: Obesity has been linked to cognitive impairment. However, how changes in body mass index (BMI) over the life course influence cognitive function remains unclear. OBJECTIVE: The influence of distinct weight-change patterns from young adulthood to midlife and late adulthood on cognitive function in older adults was explored. METHODS: A total of 5,809 individuals aged≥60 years were included and categorized into four groups on the basis of BMI change patterns. Cognitive function was assessed using four cognition tests in the baseline survey. The relationship between the weight-change patterns and cognition was evaluated using regression models. RESULTS: In comparison with participants who remained at non-obese, those moving from the non-obese to obese weight-change pattern from young (25 years of age) to middle adulthood showed lower Digit Symbol Substitution Test (DSST) scores (ß= -1.28; 95% confidence interval [CI]: -2.24 to -0.32). A non-obese to obese change pattern from age 25 years of age to 10 years before baseline was associated with a higher risk of DSST impairment (odds ratio = 1.40; 95% CI: 1.09 to 1.79). In comparison with participants whose heaviest weight was recorded after 60 years of age, those with the heaviest weight between 18 and 40 years of age had lower DSST scores (ß= -1.46; 95% CI: -2.77 to -1.52). CONCLUSION: Our results suggest that the transition from the non-obese to obese category in early adulthood and appearance of the heaviest weight between 18 and 40 years of age are associated with lower cognitive function in later life.

Identification of a novel TNNI3 synonymous variant causing intron retention in autosomal recessive dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy type 2A (DCM2A, MIM: #611880) is a rare autosomal recessive heart disease leading to heart failure and sudden cardiac death. However, the causative role of TNNI3 in DCM2A is still questioned due to few cases reported and the conflicting molecular biological evidence. METHODS: Trio whole-exome sequencing (trio-WES) was performed in a Chinese family with dilated cardiomyopathy. Sanger sequencing and real-time quantitative PCR were used to confirm the variants identified. Expression outcome caused by the synonymous mutation was validated by minigene splicing analyses. RESULTS: The one-year-old girl presented severe left ventricular enlargement and significantly reduced left ventricular systolic function and she died of respiratory and heart failure soon after her diagnosis. Trio-WES revealed a compound heterozygous variants of TNNI3, a novel c.24G＞A (p.Ala8Ala) (NM_000363.4) in exon 2 and a deletion of entire gene. Minigene splicing analyses showed it led to an intron retention (c.24 + 1_24 + 45ins) by intron 2 cryptic splicing. CONCLUSIONS: Our study describes and characterizes a synonymous mutation in TNNI3 gene, supporting the clinical diagnosis of an autosomal recessive DCM. Our study emphasizes the importance of functional analysis to assess the potential pathogenicity of synonymous mutations, especially when the synonymous variants are not annotated as benign.

Prenatal exposure to perfluorooctane sulfonate alternatives and associations with neonatal thyroid stimulating hormone concentration: A birth cohort study.

BACKGROUND: Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESA) and perfluorobutane sulfonate (PFBS), used as perfluorooctanesulfonate (PFOS) alternatives, were indicated as thyroid hormone disruptive toxicants in experimental studies. However, it is unclear whether prenatal exposure to Cl-PFESA and PFBS affects neonatal thyroid stimulating hormone (TSH) in human. OBJECTIVE: To disclose the relationships between prenatal Cl-PFESAs and PFBS exposure and neonatal thyroid-stimulating hormone (TSH) levels based on a perspective cohort study. METHODS: A total of 1015 pairs of mother and newborn were included from an ongoing birth cohort study in Wuhan, China, between 2013 and 2014. Six PFASs in cord blood sera and TSH concentration in neonatal postpartum heel sticks blood were quantified. Mixed linear and weighted quantile sum (WQS) regression models were applied to assess the individual and combination effects of PFASs exposure on neonatal TSH levels with multiple covariates adjustments. RESULTS: After adjusting for potential confounders and other five PFASs, for each 1-ng/mL increase of PFBS or 8:2 Cl-PFESA, was negatively associated with 25.90% (95%CI: 37.37%, -12.32%; P < 0.001) and 27.19% (95%CI: 46.15%, -1.55%; P = 0.033) change in TSH in male but not female infants, respectively. No significant association was found between other PFASs exposure and neonatal TSH. Higher PFAS mixture in cord blood was significantly associated with decrease TSH concentration in all newborns (ß = -0.36; 95%CI: 0.58, -0.13; P = 0.001) identified by WQS regression model. PFBS, PFOS and 6:2 Cl-PFESA were the major contributors to the neonatal TSH decrement with the weights of 56.50%, 18.71%, 12.81% among PFAS mixture, respectively. CONCLUSIONS: our prospective cohort study suggested a negative association of cord serum PFBS and 8:2 CI-PFESA with TSH concentration in newborns, especially for boys. Additional studies are required to elaborate on the underlying biological mechanisms, especially for PFBS.

Association of kidney function and brain health: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: This study aimed to evaluate the bidirectional association between the kidney dysfunction and the brain health, including structural and functional abnormalities. DESIGN: Systematic review and meta-analysis with network meta-analysis for outcomes with different estimated glomerular filtration rate (eGFR) ranges. DATA SOURCES: PubMed, Embase database, Cochrane library and Web of Science (up to Dec. 2021). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Longitudinal studies that provided evidence of the impact of kidney function estimated from eGFR and urine albumin-to-creatinine ratio (UACR) or chronic kidney disease (CKD) on structural and functional brain abnormalities, and those that provided evidence of the opposite relationship. Studies with study population mean age under 18 years old were excluded. MAIN OUTCOME MEASURES: Two independent reviewers screened the included studies, extracted the data, and assessed the risk of bias. We performed a random-effects meta-analysis and a network meta-analysis for outcomes with compatible data. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale criteria (NOS). Subgroup and sensitivity analyses were conducted to explore heterogeneity in the meta-analyses. Inconsistency analyses using the node-splitting method were performed to confirm the results of network meta-analysis. RESULTS: A total of 53 studies with 3037,357 participants were included in the current systematic review. Among these, 16 provided evidence of structural brain abnormalities, and 38 provided evidence of cognitive impairment and dementia. Analysis of evidence of categorical kidney function showed a positive association between kidney dysfunction and cerebral small vessel disease (cSVD) (relative risk (RR) 1.77, 95% confidence interval (CI) 1.40-2.24, I2 = 0.0%), but such results were not found in the analyses of evidence where the kidney function was measured as a continuous variable. Meanwhile, analysis of 28 prior longitudinal studies with 194 compatible sets of data showed that the worse kidney function as categorical variables was related to a greater risk of global brain cognitive disorder (RR 1.28, 95% CI 1.20-1.36, I2 = 82.5%). CONCLUSIONS: In this systematic review and meta-analysis, we found a positive association between CKD and functional brain disorders. However, the relationship between the kidney dysfunction and structural abnormalities in the brain remains controversial. As for the opposite relationship, structural brain abnormalities, especially cerebral microbleeds and silent infarction, but not functional brain abnormalities, are associated with worse renal function. In addition, a higher UACR, but not a lower eGFR, was associated with a higher risk of Alzheimer's disease and vascular dementia.

Cerebral Blood Flow Alterations and Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Reduction in cerebral blood flow (CBF) plays an essential role in the cognitive impairment and dementia in obesity. However, current conclusions regarding CBF changes in patients with obesity are inconsistent. OBJECTIVE: A systematic review and meta-analysis was performed to evaluate the relationship between obesity and CBF alterations. METHODS: We systematically screened published cross-sectional and longitudinal studies focusing on the differences in CBF between obese and normal-weight individuals. Eighteen studies including 24,866 participants, of which seven articles reported longitudinal results, were evaluated in the present study. RESULTS: The results of the meta-analysis showed that in cross-sectional studies, body mass index (BMI) was negatively associated with CBF (ß= -0.31, 95% confidence interval [CI]: -0.44, -0.19). Moreover, this systematic review demonstrated that obese individuals showed global and regional reductions in the CBF and increased CBF in diverse functional areas of the frontal lobe, including the prefrontal cortex, left frontal superior orbital, right frontal mid-orbital cortex, and left premotor superior frontal gyrus. CONCLUSION: Our findings suggest that BMI, rather than waist circumference and waist-to-hip ratio, is inversely associated with CBF in cross-sectional studies. The CBF of obese individuals showed global and regional reductions, including the frontal lobe, temporal and parietal lobes, cerebellum, hippocampus, and thalamus.

Perfluorononanoate and Perfluorobutane Sulfonate Induce Cardiotoxic Effects in Zebrafish.

Globally, per- and polyfluoroalkyl substances are common artificial ingredients in industrial and consumer products. Recently, they have been shown to be an emerging human health risk. Perfluorononanoic acid (PFNA)/perfluorononanoate and perfluorobutane sulfonic acid (PFBS)/perfluorobutane sulfonate cause reproductive toxicity and hepatotoxicity, disrupt thyroid functions, and damage embryonic development in zebrafish. However, the cardiotoxic effects of PFNA and PFBS have not been fully established. We found that PFNA and PFBS exposures repress hatchability while increasing malformation and mortality in zebrafish embryos. Hematoxylin and eosin staining as well as assessment of the transgenic zebrafish line Tg(myl7:nDsRed) revealed that exposure of embryos to PFNA increases the occurrence of severe cardiac malformations relative to exposure to PFBS. Moreover, we evaluated the differential expressions of cardiac development-associated genes in response to PFNA and PFBS, which validated the potential cardiotoxic effects, consistent with cardiac dysfunctions. Overall, our findings reveal novel cardiotoxic effects of PFNA and PFBS in zebrafish, implying that they may exert some cardiotoxic effect in humans. To the best of our knowledge, ours is the first study to show that PFNA exerts more severe cardiotoxic effects in zebrafish when compared with PFBS. Based on these findings, studies should evaluate the mechanisms of their cardiotoxic effects. Environ Toxicol Chem 2022;41:2527-2536. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Association of Sarcopenia and A Body Shape Index With Overall and Cause-Specific Mortality.

Aim: This observational study aimed to examine the association between the A Body Shape Index (ABSI) and/or sarcopenia and total, cardiovascular, and cancer mortality. Methods: The associations of sarcopenia and ABSI with all-cause, cardiovascular, and cancer mortality were assessed in 4,488 participants from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) who were followed up until December 31, 2015. Models were analyzed separately for men and women and adjusted for age, race, and other confounding factors. ABSI was assessed as a continuous measurement by quartile for men and women. Population attributable fractions (PAFs) were calculated to assess mortality caused by sarcopenia and/or ABSI in the study population. Results: When ABSI was assessed as a continuous variable, the ABSI quartile showed a linear trend for total (p = 0.0001), cardiovascular (p = 0.04), and cancer (p = 0.02) mortality in men and for total (p = 0.06) and cardiovascular (p = 0.06) mortality in women. The hazard ratios (HRs) of the fourth ABSI quartile were 1.51 [95% confidence interval (CI): 1.20-1.89] in men and 1.23 (95% CI: 0.93-1.64) in women, compared with those in the first quartile. When ABSI was assessed by quartile, the appendicular skeletal mass index (ASMI) was lower in the groups with high ABSI. When high ABSI was combined with sarcopenia, the HRs of all-cause mortality were 2.05 (95% CI: 1.60-2.62) in men and 1.51 (95% CI: 1.19-1.92) in women. In the subpopulation (sarcopenia group or higher ABSI), the PAFs of mortality due to sarcopenia were 26.16% (95% CI: 12.68-37.56) in men and 21.89% (95% CI: 5.64-35.35) in women, and the PAF of mortality due to higher ABSI was 23.70% (95% CI: 12.11-33.77) in men. Conclusion: The ABSI value was significantly associated with all-cause and cardiovascular mortality, and the co-existence of higher ABSI values and sarcopenia can contribute to a more significant death risk in comparison with high ABSI values or sarcopenia. Moreover, the ABSI values in combination with the ASMI can be used to preliminarily evaluate the content and distribution of fat and muscle and to predict the risk of death in obese and sarcopenic populations.

Association Between Diabetic Retinopathy, Brain Structural Abnormalities, and Cognitive Impairment for Accumulated Evidence in Observational Studies.

PURPOSE: To evaluate the association between diabetic retinopathy (DR) and cerebral disease or cognitive impairment. DESIGN: Systematic review and meta-analysis. METHOD: The hypothesis was formulated prior to data collection. Cross-sectional studies and cohort studies that assessed the association between any measure of DR and cerebral small vessel disease or any type of cognitive impairment in diabetic participants were included. The data were independently extracted by two investigators. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines RESULTS: A total of 27 studies were included. The combined odds ratio of 5 cross-sectional/cohort studies that reported that the associations between DR and cerebral structural changes was 1.75 (95% confidence interval [CI]: 1.36-2.25). The combined hazard ratio of 4 cohort studies that examined the association between DR and cognitive impairment events was 1.47 (95% CI: 1.22-1.78). The combined odds ratio of 14 cross-sectional/cohort studies that examined the association between DR and different cognitive impairment events was 1.43 (95% CI: 1.06-1.93). The overall coefficient (ß) of 4 studies that examined the relationship between DR and specific cognitive performance was 0.09 (95% CI: 0.00-0.18). Considering the quality of the data, we have performed subgroup analysis in studies scored >7 and studies scored ≤7, respectively, according to the Newcastle-Ottawa scale. CONCLUSION: The present meta-analysis suggests that DR is associated with an increased risk of structural abnormalities in the brain and cognitive impairment. This association remained significant after adjusting for blood glucose, and the presence of hypertension, indicating that DR is an important danger signal for cerebral abnormalities.

The Association Between Diabetes Mellitus and Risk of Sarcopenia: Accumulated Evidences From Observational Studies.

Aim: We performed a meta-analysis of observational studies to evaluate the association between the presence of sarcopenia and HbA1c, prediabetes, diabetes and diabetic complications. Method: The PubMed, Embase, Cochrane and Web of Science databases were searched from inception to May 2021. We included full-text English language articles that reported the prevalence of sarcopenia in patients with and without diabetes. Quality assessment was performed according to the Newcastle- Ottawa scale for observational studies. Results: Sixteen studies were included in the meta-analysis. Three studies showed that high HbA1c levels lead to loss of muscle mass, and one study involving prediabetes showed that people with prediabetes had lower muscle mass, strength, and performance than non-diabetic population. Seven studies showed that people with diabetes had a higher risk of sarcopenia than those without diabetes (combined OR: 2.09, 95% CI:1.62-2.70). The remaining five studies suggested that diabetic complications increased the risk of sarcopenia (combined OR: 2.09,95% CI:1.62-2.70). Conclusion: High HbA1c levels, prediabetes, diabetes and diabetes complications were associated with an increased risk of sarcopenia. Therapeutic strategies addressed to avoid the conversion of IGT to diabetes and to optimize glycemic control are warranted to prevent or arrest sarcopenia in the diabetic population.

A one step method for isolation of genomic DNA using multi-amino modified magnetic nanoparticles.

A simple and efficient approach for the rapid extraction of genomic DNA from blood using various amino-modified magnetic nanoparticles (AMNPs) has been described. The salmon sperm DNA was isolated from aqueous solution based on electrostatic interaction between the positively charged amino-groups of AMNPs and the negatively charged phosphate groups of the DNA. The results of ultraviolet-visible (UV-Vis) spectrometry showed that increasing number of amino groups on the AMNPs surface resulted in an improvement in DNA adsorption efficiency. Several variables including the extraction pH, adsorption time, ionic strength and quantity of AMNPs were optimized to achieve the best extraction efficiency with the proposed method. Acceptable adsorption efficiency of 92% and recovery of 91% were achieved using multi-amino modified MNPs (mAMNPs) with an extraction time of 10 min and an overall processing time of 30 min. The mAMNPs enabled genomic DNA capture from human whole blood, and the resulting mAMNP/DNA complexes could be directly used as templates for PCR amplification without the need for complex and time-consuming DNA elution and purification steps. Our results imply that this method can be used as an effective strategy for genomic DNA extraction and may be extended to other types of biological samples.

Δ133p53/FLp53 Predicts Poor Clinical Outcome in Esophageal Squamous Cell Carcinoma.

BACKGROUND: p53 isoform Δ133p53 is directly transactivated by p53 and antagonizes p53 activities in cancer progression. However, its correlation with prognosis and cancer recurrence in esophageal squamous cell carcinoma (ESCC) is still unclear. PATIENTS AND METHODS: Expression of Δ133p53 and Δ133p53/full-length p53 (FLp53) in tissues and serums of 180 ESCC patients was evaluated using qRT-PCR. Patients were divided into high- and low-expression groups according to the cutoff value determined by X-tile 3.6.1 software. Survival analysis was performed by the Kaplan-Meier method. Univariate and multivariate Cox survival analyses were applied to assess the hazard ratios (HRs). RESULTS: Tissue Δ133p53 expression and Δ133p53/FLp53 ratio were significantly increased in ESCC tissue compared with adjacent normal tissue. Pre-operative Δ133p53 expression and Δ133p53/FLp53 ratio in tissue or serum samples were positively associated with TNM stage and post-operative recurrence. Kaplan-Meier curve and multivariate cox regression analyses revealed that the tissue and serum Δ133p53/FLp53 ratios (cutoff value: 2.9160) were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) in ESCC patients and showed no statistical difference in receiver-operating characteristic curve (ROC) analysis, while serum Δ133p53 showed no significant prognostic value. More importantly, the serum Δ133p53/FLp53 ratio in ESCC patients was significantly decreased within 72 h post tumor resection and patients with a consistently high serum Δ133p53/FLp53 ratio (≥2.9160) had higher recurrence rates than those with consistently low ratio values. In addition, dynamic detection in each follow-up timepoint showed that serum Δ133p53/FLp53 ratios were higher than 2.9160 upon recurrence, and they even increased prior to radiologic progression. CONCLUSION: The serum Δ133p53/FLp53 ratio can be a novel predictor for survival outcome and may serve as a real-time parameter for monitoring recurrence in ESCC patients after surgery.

A newborn with normal IgM and elevated IgG antibodies born to an asymptomatic infection mother with COVID-19.

Pregnant women are susceptible population of COVID-19 which are more likely to have complications and even progress to severe illness. Pregnancy with COVID-19 and neonates are rarely reported. We report a newborn with normal IgM and elevated IgG antibodies born to an asymptomatic infection mother with COVID-19. We assessed whether there was intrauterine vertical transmission potential of COVID-19.