In-depth LC-MS and in-vitro studies of a triterpenoid saponin capilliposide-A metabolism modulation in gut microbiota of mice.

Introduction: Some herbal ingredients can reshape the composition of the gut microbiome as well as its metabolites. At the same time, the gut microbiota can also affect drug metabolism. A large number of studies have reported that saponins are biotransformed under the action of intestinal microorganisms to improve drug efficacy and bioavailability. Capilliposide A is a triterpenoid saponin, which is derived from Lysimachia capillipes Hemsl. CPS-A has anti-inflammatory pharmacological activity, but the substance basis in vivo is unknown at present, so studies on the interaction between intestinal microorganisms and CPS-A may clarify the pharmacodynamic substance basis of CPS-A. Methods: This study established a colitis mouse model, collected sterile feces from normal mice and colitis mice, and incubated CPS-A with two different intestinal flora in vitro. Based on LC-MS, the metabolic process of CPS-A mediated by intestinal microbes and the intervention effect of CPS-A on intestinal microbiome derived metabolites were studied. Results: The results of experiments indicate that intestinal microorganisms can mediate the biotransformation of CPS-A and metabolize it into corresponding deglycosylation products, thereby promoting its drug effect. Not only that, CPS-A can also promote metabolites such as Deoxycholic acid, Histamine, 3-Hydroxytridecanoic acid, and Indole-3-acetic acid in the intestinal microbiota of mice with colitis. This may result in anti-colitis effects. CPS-A mainly involved in metabolic pathways such as azathioprine and mercaptopurine, which may also have beneficial or adverse effects. Discussion: This study on the interaction between CPS-A and microbiota provides a new idea for the study of traditional Chinese medicine with poor oral bioavailability. The regulatory effect of CPS-A on the metabolites of intestinal flora in colitis mice was also found. It laid a foundation for exploring the mechanism of action of saponins on colitis mice.

Correlation between diabetic retinopathy and diabetic nephropathy: a two-sample Mendelian randomization study.

Rationale & objective: A causal relationship concerning diabetic retinopathy (DR) and diabetic nephropathy (DN) has been studied in many epidemiological observational studies. We conducted a two-sample mendelian randomization study from the perspective of genetics to assess these associations. Methods: 20 independent single nucleotide polymorphisms (SNPs) associated with diabetic retinopathy were selected from the FinnGen consortium. Summary-level data for diabetic nephropathy were obtained from the publicly available genome-wide association studies (GWAS) database, FinnGen and CKDGen consortium. Inverse variance weighted (IVW) was selected as the primary analysis. MR-Egger, weighted median (WM), simple mode and weighted mode were used as complementary methods to examine causality. Additionally, sensitivity analyses including Cochran's Q test, MR-Egger, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analyses were conducted to guarantee the accuracy and robustness of our MR analysis. Results: Our current study demonstrated positive associations of genetically predicted diabetic retinopathy with diabetic nephropathy (OR=1.32; P=3.72E-11), type 1 diabetes with renal complications (OR=1.96; P= 7.11E-11), and type 2 diabetes with renal complications (OR=1.26, P=3.58E-04). Further subtype analysis and multivariate mendelian randomization (MVMR) also reached the same conclusion. A significant casualty with DN was demonstrated both in non-proliferative DR (OR=1.07, P=0.000396) and proliferative DR (OR=1.67, P=3.699068E-14). All the findings were robust across several sensitivity analyses. Conclusion: Consistent with previous clinical studies, our findings revealed a positive correlation between DR and DN, providing genetic evidence for the non-invasive nature of DR in predicting DN.

Corrigendum: Coffee intake and risk of diabetic nephropathy: a Mendelian randomization study.

[This corrects the article DOI: 10.3389/fendo.2023.1169933.].

Coffee intake and risk of diabetic nephropathy: a Mendelian randomization study.

Rationale and objective: A causal relationship concerning coffee intake and diabetic nephropathy (DN) is controversial. We conducted a Mendelian randomization study to assess the causal nature of these associations. Methods: 40 independent single nucleotide polymorphisms (SNPs) associated with coffee intake were selected from the UK Biobank study. Summary-level data for diabetic nephropathy were obtained from publicly available genome-wide association studies (GWAS) and the FinnGen consortium. Inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods were used to examine a causal association. Sensitivity analyses included Cochran's Q test, the intercept of MR-Egger, MR-PRESSO, and the Outlier method. Leave-One-Out sensitivity analyses were also conducted to reduce the heterogeneity. Results: Our current study demonstrated positive associations of genetically predicted coffee intake with diabetic nephropathy (OR=1.939; P = 0.045 and type 2 diabetes with renal complications (OR = 2.787, P= 0.047). These findings were robust across several sensitivity analyses. Conclusions: This study found a positive correlation between coffee consumption and the risk of diabetic nephropathy using genetic data. For a more accurate and trustworthy conclusion, subgroup analysis on coffee intake, including preparing method, variety of coffee, and quantity, is required.

PM sensors as an indicator of overall air quality: Pre-COVID and COVID periods.

Nowadays, there has been a substantial proliferation in the use of low-cost particulate matter (PM) sensors and facilitating as an indicator of overall air quality. However, during COVID-19 epidemics, air pollution sources have been deteriorated significantly, and given offer to evaluate the impact of COVID-19 on air quality in the world's most polluted city: Delhi, India. To address low-cost PM sensors, this study aimed to a) conduct a long-term field inter-comparison of twenty-two (22) low-cost PM sensors with reference instruments over 10-month period (evaluation period) spanning months from May 2019 to February 2020; b) trend of PM mass and number count; and c) probable local and regional sources in Delhi during Pre-CVOID (P-COVID) periods. The comparison of low-cost PM sensors with reference instruments results found with R2 ranging between 0.74 and 0.95 for all sites and confirm that PM sensors can be a useful tool for PM monitoring network in Delhi. Relative reductions in PM2.5 and particle number count (PNC) due to COVID-outbreaks showed in the range between (2-5%) and (4-13%), respectively, as compared to the P-COVID periods. The cluster analysis reveals air masses originated ∼52% from local, while ∼48% from regional sources in P-COVID and PM levels are encountered 47% and 66-70% from local and regional sources, respectively. Overall results suggest that low-cost PM sensors can be used as an unprecedented aid in air quality applications, and improving non-attainment cities in India, and that policy makers can attempt to revise guidelines for clean air.

Novel mutation in the SALL1 gene in a four-generation Chinese family with uraemia: A case report.

BACKGROUND: Approximately 10% of adults and nearly all children who receive renal replacement therapy have inherited risk factors or are related to genetic factors. In the past, due to the limitations of detection technology and the nonspecific manifestations of uraemia, the etiological diagnosis is unclear. In addition to common monogenic diseases and complex disorders, advanced testing techniques have led to the recognition of more hereditary renal diseases. Here, we report a four-generation Chinese family in which four individuals had a novel SALL1 mutation and presented with uraemia or abnormal urine tests. CASE SUMMARY: A 32-year-old man presented with end-stage renal disease with a 4-year history of dialysis. His father and paternal aunt both had a history of unexplained renal failure with haemodialysis, and his 10-year-old daughter presented with proteinuria. The patient had multiple congenital abnormalities, including bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss. His family members also presented with similar defects. Genetic testing revealed that the proband carried a novel heterozygous shift mutation in SALL1_exon 2 (c.3437delG), and Sanger sequencing confirmed the same mutation in all affected family members. CONCLUSION: We report a novel SALL1 exon 2 (c.3437delG) mutation and clinical syndrome with kidney disease, bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss in a four-generation Chinese family.

Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion.

Background: Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease worldwide. Its pathological features include IgA immune complex deposition, accompanied by mesangial cell proliferation and mesangial matrix expansion. This study was conducted to investigate the effects of Liuwei Dihuang pills (LWDHW) on IgAN in mice and human podocytes, as well as to determine their underlying mechanisms of action. Methods: For in vitro experiments, podocytes were exposed to the human mesangial cell culture medium supernatant of glomerular cells treated with aggregated IgA1 (aIgA1) and LWDHW-containing serum. Cell viability and the proportion of positive cells were evaluated using CCK-8 and flow apoptosis kits, respectively. The cells were collected for western blot analysis. Twenty-four mice with IgAN induced by oral bovine serum albumin administration combined with tail vein injection of staphylococcal enterotoxin B were randomly divided into four groups of six mice each: untreated model group, model + LWDHW group, model + rapamycin group, and model + LWDHW + rapamycin group. The normal control group contained six mice. The red blood cell count in the urine, urine protein, blood urea nitrogen, serum creatinine, and IgA deposition were determined, and TUNEL and western blotting were performed in the mouse kidney tissues. Results: In vitro experiments showed that LWDHW promoted autophagy by regulating the PI3K/Akt/mTOR signalling pathway and improved the damage to podocytes caused by the aIgA1-treated mesangial cell supernatant. This study demonstrates the effectiveness of LWDHW for treating IgAN. In the animal experiments, LWDHW significantly reduced the urine red blood cell count, serum creatinine and urea nitrogen contents, and 24 h urinary protein function and improved IgA deposition in the kidney tissues, glomerular volume, glomerular cell proliferation and polysaccharide deposition, and glomerular cell apoptosis. The pills also reversed the changes in the LC3II/I ratio and p62 content in the kidney tissues. The combination of LWDHW and rapamycin showed stronger inhibitory effects compared to those of LWDHW or rapamycin alone. Conclusion: LWDHW may improve regulation of the PI3K-Akt-mTOR pathway and inhibit autophagy in podocytes, as well as alleviate IgA nephropathy by directly altering mesangial cell exosomes.

Deployment of networked low-cost sensors and comparison to real-time stationary monitors in New Delhi.

Air quality is a global challenge issue, and many regions of the world, such as India, are experiencing daunting challenges. An important aspect is to identify and then control the emissions from major contributing sources. To advance this aspect, this paper describes an air quality network that has been set up in the National Capital Territory of Delhi (NCT-Delhi) to identify major contributing source categories in real-time. The various components include an innovative cloud-based dashboard to compile the data in real-time from a series of PM instruments (Beta Attenuation Monitors (BAM)) and a low-cost sensor network (22 APT- MAXIMA sensors). Furthermore, at one of the locations (urban site), three real-time chemical speciation monitors are installed to provide elemental speciation (30 elements), elemental carbon (EC), and organic carbon (OC) data. PM2.5 concentrations at different sites (urban, industrial, and background) were compared to the BAM measurements over an 8-month period from May 2019 to February 2020; spanning the summer, monsoon, autumn, and winter seasons in Delhi. The APT sensor measurements were well correlated to the BAM measurements, with R2 values ranging between 0.84 and 0.95 for all sites. This validated that the APT-MAXIMA low-cost sensors can be a useful tool for distributed monitoring of PM2.5 levels. The mean PM2.5 concentrations showed a trend with winter (Dec, Jan, Feb: 205.2 ± 95.1 µg m-3) and autumn (Oct, Nov: 171.7 ± 128.3 µg m-3) highs and summer (May, Jun: 64.6 ± 57.2 µg m-3) and monsoon (Jul, Aug, Sep: 27.6 ± 16.7 µg m-3) lows. The bivariate polar plot reveals high PM2.5 levels originated from local/regional combustion sources located east and south-west of the urban site, especially when high PM2.5 episodes are encountered during the festival season and other smog episodes.Implications: Low-cost sensors are useful for distributed monitoring under both low and high pollution conditions. A cloud-based dashboard system provided real-time, remote access to the data and in the visualization of air quality in the entire region. The real-time data availability on the cloud enabled establishing hot-spot regions of air pollution, spatial variation of PM2.5, real-time source apportionment, and health risk estimates to benefit both policy makers, and the general public.

Hyaluronic acid (HA)-based hydrogels for full-thickness wound repairing and skin regeneration.

In this work, two kinds of hyaluronic acid (HA)-based hydrogels were fabricated: one is made from physical freezing-thawing of HA solution (HA1), and the other is from chemical cross-linking of HA and polysaccharide (HA2). They were applied to repair full-thickness skin defects with New Zealand rabbits as the test animals, using powder HA and cotton dress as the references. The wound starts to heal after wounds were disinfected with iodine followed by coating with HA2, HA1, HA and cotton dress (the control), respectively. They were recorded as 4 treatments (groups), HA2, HA1, HA and the control. The healing progress was followed and tested in the duration of 56 days, and the biological repairing mechanism was explored. From the wound area alteration, white blood cell (WBC) measurements and H&E staining, HA2 was the most promising treatment in promoting the wound healing with least serious scar formation. Immunochemistry analyses and real-time PCR tests of the bio-factors involved in the wound healing, vascular endothelial growth factor (VEGF), alpha-smooth muscle actin (α-SMA) and transforming growth factor beta-1 (TGF-ß1), exhibited that HA2 enhanced VEGF and α-SMA secretion but reduced TGF-ß1 expression at early stage, which alleviated the wound inflammation, improved the skin regeneration and relieved the scar formation.

Real-time measurement of size-resolved elemental composition ratio for flame synthesized composite nanoparticle aggregates using a tandem SMPS-ICP-OES.

Composite nanoparticles find application in catalysis, drug delivery, and energy storage and require increasingly fine control of their physical properties and composition. While composite nanoparticles have been widely synthesized and characterized, little work has systematically correlated the initial concentration of precursors and the final composition of flame synthesized composite nanoparticles. This relationship is explored in a diffusion flame aerosol reactor by coupling a scanning mobility particle sizer (SMPS) with an inductively coupled plasma optical emission spectrometer (ICP-OES). A framework for studying the relationship between the initial precursor concentrations of different elements and the final nanoparticle composition is explored. The size-resolved elemental composition was measured by directly injecting size-selected fractions of aggregated magnetite and silicon dioxide composite nanoparticles into the ICP-OES plasma. This work showed a correlation between precursor molar ratio and the measured elemental ratio in the mobility size range of 50 to 140 nm. Building on previous work studying size resolved elemental composition of engineered nanoparticles, the analysis is extended to flame synthesized composite nanoparticle aggregates in this work.

Measurement of sub-2 nm clusters of pristine and composite metal oxides during nanomaterial synthesis in flame aerosol reactors.

Measuring stable clusters to understand particle inception will aid the synthesis of well-controlled nanoparticles via gas-phase aerosol routes. Using a Half Mini differential mobility analyzer, the presence of monomers, dimers, trimers, and tetramers was detected for the first time in a flame aerosol reactor during the synthesis of pristine TiO2 and TiO2/SiO2 nanocomposites. Atomic force microscopy confirmed the presence and the size of sub-2 nm clusters. The detection of these clusters elucidated the initial stages of particle formation during combustion synthesis and supported previous hypotheses that collisional growth from stable monomers of metal oxides is the first step of particle growth.