<i>PIK3CA</i> mutation and clinicopathological features of colorectal cancer: a systematic review and Meta-Analysis

Background: There is conflicting evidence regarding the association between PIK3CA mutations and clinicopathological features of colorectal cancer (CRC). We performed a comprehensive meta-analysis investigating the association between PIK3CA mutations and clinicopathological features in CRC, including subgroup analysis of mutations in exons 9 and 20, to elucidate the role of PIK3CA mutations in CRC. Materials and Methods: A detailed literature search was performed within the PubMed, Web of Science, and Embase databases, examining the associations between PIK3CA mutations and demographic characteristics, clinicopathologic parameters, and molecular features in patients with CRC. The odds ratios with 95% confidence intervals were used to estimate the effect of PIK3CA mutations on outcome parameters. Results: Forty-four studies enrolling 17621 patients were eligible for inclusion. PIK3CA mutations were associated with proximal tumor location, mucinous differentiation, KRAS mutations, and microsatellite instability (MSI). Subgroup analysis demonstrated that PIK3CA exon 9 mutations were positively associated with proximal tumor location and KRAS mutations, and negatively associated with BRAF mutations and MSI; exon 20 mutations were associated with proximal tumor location, KRAS mutations, BRAF mutations and MSI. Conclusions: Our findings suggest that overall or exon-specific PIK3CA mutations showed null associations with key clinicopathological parameters, including disease stage and tumor differentiation, indicating that PIK3CA mutations do not predict aggressive clinicopathological characteristics in CRC. As PIK3CA mutations were found to be closely associated with KRAS mutations, their relationship warrants further investigation. Since PIK3CA exon 9 and 20 mutations showed different tendencies with regard to BRAF mutation and MSI status, they may have distinct molecular impacts on CRC.</p

Bulk Nanobubbles Fabricated by Repeated Compression of Microbubbles

Nanobubbles (NBs), given its extraordinary properties, have drawn keen attention in the field of nanotechnology worldwide. However, compared to that of surface NBs, generation of stable bulk NBs remains an arduous task with the prevailing method. In this study, we developed a pressure-driven method to prepare bulk NBs by repeatedly compressing sulfur hexafluoride (SF6) gas into water. The results show that NBs with a mean diameter of 240 ± 9 nm and a polydispersity index of 0.25 were successfully prepared. The generated NBs had a high negative zeta potential (−40 ± 2 mV) with stability of more than 48 h. Under the condition of 600 times repeated compression, the NB concentration could reach about 1.92 × 1010 bubbles/mL. Furthermore, we examine the possible formation mechanism involved in NB generation by virtue of optical microscopy and attenuated total reflectance Fourier transform infrared (ATR–FTIR) spectroscopy. The microscopic results showed that microbubbles about 10–50 μm formed first and then decreased to be nanoscale-sized. A stronger hydrogen bond was detected by ATR–FTIR spectroscopy during the shrinking of microbubbles into NBs. It is speculated that the disappearance of microbubbles contributes to the formation of NBs, and the strong hydrogen bond at the gas–water interface prompts the stability of NBs. Therefore, repeated compression of the gas in aqueous solution could be a new method to prepare stable nanosized bubbles for wide applications in the future

Bulk Nanobubbles Fabricated by Repeated Compression of Microbubbles

Nanobubbles (NBs), given its extraordinary properties, have drawn keen attention in the field of nanotechnology worldwide. However, compared to that of surface NBs, generation of stable bulk NBs remains an arduous task with the prevailing method. In this study, we developed a pressure-driven method to prepare bulk NBs by repeatedly compressing sulfur hexafluoride (SF6) gas into water. The results show that NBs with a mean diameter of 240 ± 9 nm and a polydispersity index of 0.25 were successfully prepared. The generated NBs had a high negative zeta potential (−40 ± 2 mV) with stability of more than 48 h. Under the condition of 600 times repeated compression, the NB concentration could reach about 1.92 × 1010 bubbles/mL. Furthermore, we examine the possible formation mechanism involved in NB generation by virtue of optical microscopy and attenuated total reflectance Fourier transform infrared (ATR–FTIR) spectroscopy. The microscopic results showed that microbubbles about 10–50 μm formed first and then decreased to be nanoscale-sized. A stronger hydrogen bond was detected by ATR–FTIR spectroscopy during the shrinking of microbubbles into NBs. It is speculated that the disappearance of microbubbles contributes to the formation of NBs, and the strong hydrogen bond at the gas–water interface prompts the stability of NBs. Therefore, repeated compression of the gas in aqueous solution could be a new method to prepare stable nanosized bubbles for wide applications in the future

Additional file 1 of The bacterial consortia promote plant growth and secondary metabolite accumulation in Astragalus mongholicus under drought stress

Supplementary Material

DataSheet1_Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion.ZIP

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.</p

miR-188-3p abolishes germacrone-mediated podocyte protection in a mouse model of diabetic nephropathy in type I diabetes through triggering mitochondrial injury

Mitochondrial injury-triggered podocyte apoptosis is a major risk factor for diabetic nephropathy (DN). However, the detailed relationship between mitochondrial homeostasis and podocyte apoptosis remains unclear. The present study aimed to explore the role and functional mechanism of germacrone in DN in type I diabetes (type I DN). A mouse model of type I DN was established by injecting streptozocin, and a podocyte injury model was constructed using high glucose (HG) induction. Histopathology was detected by hematoxylin and eosin and periodic acid-Schiff staining. Transmission electron microscopy and flow cytometry were used to evaluate the mitochondrial function. Germacrone simultaneously reduced blood glucose, 24 h proteinuria, and other nephrotic symptoms in a type 1 DN mouse model. Moreover, germacrone protected against mitochondrial damage, limited reactive oxygen species (ROS) accumulation, and restored glutathione peroxidase (GPX) activity and GPX4 protein expression, subsequently preventing podocyte apoptosis. Mechanistically, the increased miR-188-3p expression in type I DN mice was reversed in germacrone-challenged DN mice. HG induced miR-188-3p expression and the miR-188-3p antagonist abolished the HG-mediated increase in ROS. Notably, miR-188-3p was found to have a therapeutic effect against DN by aggravating mitochondrial damage and podocyte apoptosis. Germacrone alleviates DN progression in type I diabetes by limiting podocyte apoptosis, which was partly counteracted by miR-188-3p upregulation. The combination of germacrone and miR-188-3p antagonists is expected to be an effective therapeutic strategy for DN. Abbreviations DN: diabetic nephropathy; Type I DN: DN in Type I diabetes; STZ: streptozocin; ROS: reactive oxygen species; NcRNAs: non-coding RNAs; UTR: untranslated regions; NC: negative control; BUN: blood urea nitrogen; BUA: blood uric acid; Ucr: urine creatinine; Scr: serum creatinine; PAS: Periodic Acid-Schiff; IF: Immunofluorescence; FISH: Fluorescence in situ hybridization; TUG1: taurine upregulated gene 1; GPX: Glutathione Peroxidase; GPX4: glutathione peroxidase 4; EMT: epithelial-mesenchymal transition</p

Exosomes from miR-374a-5p-modified mesenchymal stem cells inhibit the progression of renal fibrosis by regulating MAPK6/MK5/YAP axis

Chronic kidney disease (CKD) in clinical is defined as a gradual loss of kidney function for more than 3 months. The pathologic course of CKD is characterized by extensive renal fibrosis; thus, preventing renal fibrosis is vital for the treatment of CKD. It has been reported that microRNA (miR)-374a-5p was under-expressed in renal venous blood samples from patients with CKD. In addition, it exhibited anti-apoptotic effects in renal tissues suggesting that miR-374a-5p may play an important role in CKD. However, it is not clear whether miR-374a-5p could be delivered to renal cells by exosomes and exerts anti-renal fibrosis effects. To mimic renal fibrosis in vitro, human renal tubular epithelial cell lines (HK-2 cells) were treated by transforming growth factor-β (TGF-β) 1. Reverse transcription-quantitative polymerase-chain reaction (RT-qPCR) or Western blot was carried out to evaluate the mechanism by which miR-374a-5p regulated the development of renal fibrosis. Next, exosomes were isolated using with ultracentrifugation method, and the relationship between miR-374a-5p and MAPK6 was evaluated using dual-Luciferase a reporter assay system. The results indicated TGF-β1 significantly down-regulated the expression of miR-374a-5p in HK-2 cells and miR-374a-5p agomir remarkably inhibited the progression of fibrosis in vitro. In addition, exosomal miR-374a-5p could be internalized by HK-2 cells and obviously enhanced the level of miR-374a-5p in HK-2 cells. Furthermore, exosomal miR-374a-5p prevented the progression of renal fibrosis in vivo by regulating MAPK6/MK5/YAP axis. In conclusion, exosomal miR-374a-5p inhibited the progression of renal fibrosis by regulating MAPK6/MK5/YAP axis.</p

Table_1_Effect of different feeding methods and gut microbiota on premature infants and clinical outcomes.pdf

Premature infants require special care, and clinical feeding methods for this patient group are generally divided into breastfeeding and formula milk. This retrospective study investigated the effects of these two feeding methods on premature infants admitted to the neonatal intensive care unit between 2017 and 2018. Data regarding the duration of complete enteral feeding, weight gain, and postnatal infections were collected, categorized, and compared. Pearson’s correlation coefficient was used to determine the correlation between the intestinal flora and clinical outcomes. Results revealed no differences between the two feeding methods, and neither had significant effects on clinical indicators in premature infants, although the gut microbiota may be an important factor influencing many clinical indicators. Results of this study suggest an important role for the gut microbiota in the care of premature infants and provide a basis for promoting the healthy development of this patient population.</p

Additional file 1 of Reporting quality of randomized controlled trials evaluating non-vitamin K oral anticoagulants in atrial fibrillation: a systematic review

Supplementary Material 1: Supplementary Appendix to the 62 RCTs included in this systematic revie

DataSheet2_Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion.ZIP

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.</p