ABSTRACT
The ubiquitin-proteasome system (UPS), which involves E3 ligases and deubiquitinases (DUBs), is critical for protein homeostasis. The epigenetic reader ZMYND8 (zinc finger MYND-type containing 8) has emerged as an oncoprotein, and its protein levels are elevated in various types of cancer, including breast cancer. However, the mechanism by which ZMYND8 protein levels are increased in cancer remains elusive. Although ZMYND8 has been reported to be regulated by the E3 ligase FBXW7, it is still unknown whether ZMYND8 could be modulated by DUBs. Here, we identified USP7 (ubiquitin carboxyl-terminal hydrolase 7) as a bona fide DUB for ZMYND8. Mechanically, USP7 directly binds to the PBP (PHD-BRD-PWWP) domain of ZMYND8 via its TRAF (tumor necrosis factor receptor-associated factor) domain and UBL (ubiquitin-like) domain and removes F-box and WD repeat domain containing 7 (FBXW7)-catalyzed poly-ubiquitin chains on lysine residue 1034 (K1034) within ZMYND8, thereby stabilizing ZMYND8 and stimulating the transcription of ZMYND8 target genes ZEB1 (zinc finger E-box binding homeobox 1) and VEGFA (Vascular Endothelial Growth Factor A). Consequently, USP7 enhances the capacity of breast cancer cells for migration and invasion through antagonizing FBXW7-mediated ZMYND8 degradation. Importantly, the protein levels of USP7 positively correlates with those of ZMYND8 in breast cancer tissues. These findings delineate an important layer of migration and invasion regulation by the USP7-ZMYND8 axis in breast cancer cells.
ABSTRACT
With increasing production of kitchen waste, cooking oil gradually enters the soil, where it can negatively affect soil fauna. In this study, we explored the effects of soybean oil on the survival, growth, reproduction, tissue structure, biochemical responses, mRNA expression, and gut microbiome of earthworms (Eisenia fetida). The median lethal concentration of soybean oil was found to be 15.59%. Earthworm growth and reproduction were significantly inhibited following exposure to a sublethal concentration of soybean oil (1/3 LC50, 5.2%). The activity of the antioxidant enzymes total superoxide dismutase (T-SOD), peroxidase (POD), and catalase (CAT) were affected under soybean oil exposure. The glutathione (GSH) content decreased significantly, whereas that of the lipid peroxide malondialdehyde (MDA) increased significantly after soybean oil exposure. mRNA expression levels of the SOD, metallothionein (MT), lysenin and lysozyme were significantly upregulated. The abundance of Bacteroides species, which are related to mineral oil repair, and Muribaculaceae species, which are related to immune regulation, increased within the earthworm intestine. These results indicate that soybean oil waste is toxic to earthworms. Thus, earthworms deployed defense mechanisms involving antioxidant system and gut microbiota for protection against soybean oil exposure-induced stress.
Subject(s)
Gastrointestinal Microbiome , Oligochaeta , Soil Pollutants , Animals , Antioxidants/metabolism , Oligochaeta/physiology , Soybean Oil/metabolism , Soybean Oil/pharmacology , Soil Pollutants/analysis , Catalase/metabolism , Catalase/pharmacology , Oxidative Stress , Superoxide Dismutase/metabolism , Malondialdehyde/metabolism , Malondialdehyde/pharmacology , Reproduction , Soil/chemistry , RNA, Messenger/metabolism , RNA, Messenger/pharmacologyABSTRACT
Circular RNAs (circRNAs) function as modulators of microRNAs (miRNAs) and are often involved in cancer progression. This study aims to investigate the underlying mechanism by which circRNA hsa-circ-000684 promotes the progression of gastric cancer (GC). Expression of hsa-circ-000684 and that of ZEB1 mRNA were elevated while microRNA-186 (miR-186) expression was downregulated in GC cell lines and clinical tissues. In addition, the effects of hsa-circ-000684 on the proliferation, migration, invasion, and tube formation of GC cells were examined through gain-and loss-of-function experiments. Furthermore, we introduced tumor xenografts into nude mice to better understand these effects in vivo. Either knockdown of hsa-circ-000684 or upregulation of miR-186 inhibited GC cell proliferation, migration, invasion, and tube formation in vitro, and reduced the xenograft tumor growth in nude mice. Moreover, we found that hsa-circ-000684 and ZEB1 directly bound to miR-186. Hsa-circ-000684 increased the expression of ZEB1 by binding to miR-186. The tumor suppressive effects of hsa-circ-000684 knockdown were reversed by inhibition of miR-186. Collectively, our data show that hsa-circ-000684 reduces the miR-186 expression which leads to an increase in the ZEB1 expression and, consequently, promotion of GC progression.
Subject(s)
MicroRNAs/genetics , Oncogenes/genetics , RNA, Circular/genetics , Stomach Neoplasms/genetics , Zinc Finger E-box-Binding Homeobox 1/genetics , Adult , Aged , Animals , Carcinogenesis/genetics , Cell Line , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Down-Regulation/genetics , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , RNA, Messenger/genetics , Up-Regulation/geneticsABSTRACT
BACKGROUND: Experimental and observational research suggests that combined epidural-general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural-general anesthesia improves long-term survival in elderly patients. METHODS: This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. RESULTS: Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural-general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural-general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural-general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural-general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. CONCLUSIONS: In elderly patients having major thoracic and abdominal surgery, combined epidural-general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference.
Subject(s)
Analgesia, Epidural/mortality , Anesthesia, General/mortality , Geriatric Assessment/methods , Surgical Procedures, Operative/mortality , Aged , Aged, 80 and over , Analgesia, Epidural/methods , Anesthesia, General/methods , China/epidemiology , Drug Therapy, Combination , Female , Follow-Up Studies , Geriatric Assessment/statistics & numerical data , Humans , Incidence , Male , Middle Aged , SurvivalABSTRACT
PURPOSE OF REVIEW: The goal of this review is to highlight the need for new biomarkers for the diagnosis and treatment of musculoskeletal disorders, especially osteoporosis and sarcopenia. These conditions are characterized by loss of bone and muscle mass, respectively, leading to functional deterioration and the development of disabilities. Advances in high-resolution lipidomics platforms are being used to help identify new lipid biomarkers for these diseases. RECENT FINDINGS: It is now well established that bone and muscle have important endocrine functions, including the release of bioactive factors in response to mechanical and biochemical stimuli. Bioactive lipids are a prominent set of these factors and some of these lipids are directly related to the mass and function of bone and muscle. Recent lipidomics studies have shown significant dysregulation of lipids in aged muscle and bone, including alterations in diacylglycerols and ceramides. Studies have shown that alterations in some types of plasma lipids are associated with aging including reduced bone mineral density and the occurrence of osteoporosis. Musculoskeletal disorders are a major burden in our society, especially for older adults. The development and application of new lipidomics methods is making significant advances in identifying new biomarkers for these diseases. These studies will not only lead to improved detection, but new mechanistic insights that could lead to new therapeutic targets and interventions.
Subject(s)
Lipid Metabolism , Lipidomics/methods , Musculoskeletal Diseases/diagnosis , Musculoskeletal Diseases/metabolism , Biomarkers/metabolism , HumansABSTRACT
BACKGROUND: The relation between neighbourhood built environment and obesity has been described as both nuanced and complex. AIM: The objective of this study was to examine the relationship between the built environment, physical activity, and obesity in a rapidly urbanised area of China. SUBJECTS AND METHODS: This is a cross-sectional study. Descriptive statistics were used to describe the socio-demographic variables, physical activity levels and BMI status. Multivariable logistic regression models were used to examine the association between neighbourhood environment, the likelihood of engaging in different types of physical activity, and BMI. RESULTS: A total of 842 respondents completed the questionnaires and were included (84.1% response rate). Among them, 56.4% reported meeting high physical activity levels, while 40.7% were overweight or obese. Multivariable regression analysis showed that better road conditions (ß = 0.122, t = 2.999, p = 0.003) and access to physical activity facilities (ß = 0.121, t = 3.193, p = 0.001) were significantly associated with higher levels of physical activity. Physical activity levels were inversely associated with the likelihood of being overweight (OR = 0.565, 95%CI: 0.3 4 9-0.917) or obese (OR = 0.614, 95%CI: 0.3 9 0-0.966). CONCLUSION: The built environment has an important impact on physical activity. However, the direct impact of leisure physical activity on BMI is not significant. This research provides a summary of recent evidence in Pingshan District on built environments that are most favourable for physical activity and obesity.
Subject(s)
Built Environment/statistics & numerical data , Exercise , Obesity/epidemiology , Adult , Aged , China/epidemiology , Cities , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Obesity/etiology , Overweight/epidemiology , Overweight/etiology , Young AdultABSTRACT
Honey bees provide essential pollination services to the terrestrial ecosystem and produce important agricultural products. As a beneficial lactic acid bacterium, Enterococcus faecium is often supplied as a probiotic for honey bees and other animals. However, the underlying mechanisms of its actions and possible safety risks are not well understood. We present the first complete genome sequence of E. faecium isolated from the honey bee gut using nanopore sequencing, and investigate the effects and mechanisms of interactions between E. faecium and honey bees via transcriptome and miRNA analysis. E. faecium colonization increased honey bee gut weight. Transcriptome analysis showed that developmental genes were up-regulated. In accordance, the target genes of the down-regulated miRNAs were enriched in developmental pathways. We describe how E. faecium increases honey bee gut weight at the transcriptional and post-transcriptional levels, and add insights about how miRNAs mediate host and bacteria interactions.
Subject(s)
Bees/microbiology , Ecosystem , Enterococcus faecium/genetics , Host-Pathogen Interactions/genetics , Animals , Bees/genetics , Gastrointestinal Microbiome/genetics , Gene Expression Regulation, Developmental/genetics , MicroRNAs/genetics , Transcriptome/geneticsABSTRACT
Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial-mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway.
Subject(s)
Epithelial-Mesenchymal Transition , MicroRNAs/metabolism , Osteopontin/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Animals , Apoptosis/genetics , Base Sequence , Carcinogenesis/genetics , Carcinogenesis/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Down-Regulation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Mice, Nude , MicroRNAs/genetics , Models, Biological , Neoplasm Invasiveness , Osteopontin/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Up-Regulation/geneticsABSTRACT
Colorectal cancer (CRC) is the fourth most common cancer in the world, with the second highest incidence rate after lung cancer. Oxaliplatin (OXA) is a broad-spectrum anti-tumor agent with significant therapeutic efficacy in colorectal cancer, and as a divalent platinum analog, it is not selective in its distribution in the body and has systemic toxicity with continued use. Interleukin-12 (IL12) is an immunostimulatory cytokine with cytokine monotherapy that has made advances in the fight against cancer, limiting the clinical use of cytokines due to severe toxicity. Here, we introduced a long alkyl chain and N-methyl-2,2-diaminodiethylamine to the ligand of OXA to obtain OXA-LIP, which effectively reduces its toxicity and improves the uptake of the drug by tumor cells. We successfully constructed IL12 mRNA and used LNPs to deliver IL12 mRNA, and in vivo pharmacodynamic studies demonstrated that OXA-LIP combined with IL12 mRNA had better tumor inhibition and higher biosafety. In addition, it was investigated by pharmacokinetic experiments that the OXA-LIP drug could accumulate in nude mice at the tumor site, which prolonged the half-life and enhanced the anti-tumor efficiency of OXA. It is hoped that these results will provide an important reference for the subsequent research and development of OXA-LIP with IL12 mRNA, as well as provide new therapeutic approaches for the treatment of colon cancer.
ABSTRACT
Honeybees and bumblebees play a crucial role as essential pollinators. The special gut microbiome of social bees is a key factor in determining the overall fitness and health of the host. Although bees harbor relatively simple microbial communities at the genus level, recent studies have unveiled significant genetic divergence and variations in gene content within each bacterial genus. However, a comprehensive and refined genomics-based taxonomic database specific to social bee gut microbiomes remains lacking. Here, we first provided an overview of the current knowledge on the distribution and function of social bee gut bacteria, as well as the factors that influence the gut population dynamics. We then consolidated all available genomes of the gut bacteria of social bees and refined the species-level taxonomy, by constructing a maximum-likelihood core genome phylogeny and calculating genome-wide pairwise average nucleotide identity. On the basis of the refined species taxonomy, we constructed a curated genomic reference database, named the bee gut microbe genome sequence database (BGM-GDb). To evaluate the species-profiling performance of the curated BGM-GDb, we retrieved a series of bee gut metagenomic data and inferred the species-level composition using metagenomic intra-species diversity analysis system (MIDAS), and then compared the results with those obtained from a prebuilt MIDAS database. We found that compared with the default database, the BGM-GDb excelled in aligned read counts and bacterial richness. Overall, this high-resolution and precise genomic reference database will facilitate research in understanding the gut community structure of social bees.
ABSTRACT
STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHgâ min, 1-30 mmHgâ min, and > 30 mmHgâ min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHgâ min was associated with a shortened overall survival when compared with the < 1 mmHgâ min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHgâ min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.
ABSTRACT
High concentrations of unconjugated bilirubin (UCB) have toxic effects. The aim of our study was to find a way to elevate UCB tolerance or inhibit its toxicity in neurocytes. It has been reported that cystatin C (CST3) concentrations have a significant positive correlation with total bilirubin (TB) levels and a negative correlation with albumin levels. In addition, CST3 can directly bind UCB, decrease human umbilical vein endothelial cells' permeability, improve blood-brain barrier integrity after ischemic brain injury in mice, and induce autophagy. We hypothesized that CST3 could increase the solubility of UCB, decrease permeability of neurocytes, induce autophagy of neurocytes, and alleviate bilirubin-induced damage. To verify our hypothesis, we measured TB and conjugated bilirubin levels, and the permeability and autophagy of neurocytes treated with UCB and CST3. Our findings suggest that CST3 can protect against UCB-induced damage in neurocytes and that autophagy played an important role in this process.
ABSTRACT
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with varied clinical and histopathological features between individuals, particularly across races. As an autoimmune disease, IgAN arises from consequences of increased circulating levels of galactose-deficient IgA1 and mesangial deposition of IgA-containing immune complexes, which are recognized as key events in the widely accepted "multi-hit" pathogenesis of IgAN. The emerging evidence further provides insights into the role of genes, environment, mucosal immunity and complement system. These developments are paralleled by the increasing availability of diagnostic tools, potential biomarkers and therapeutic agents. In this review, we summarize current evidence and outline novel findings in the prognosis, clinical trials and translational research from the updated perspectives of IgAN pathogenesis.
ABSTRACT
We report the case of a 31-year-old male who presented with repeated episodes of nephritic-nephrotic syndrome in concomitance with infection. IgA was diagnosed and was initially responsive to treatment with immunosuppressors but further disease flare did not respond to treatment. Based on three consecutive renal biopsies over 8 years, a pattern switch from endocapillary proliferative IgA nephropathy to membranous proliferative glomerulonephritis with monoclonal IgAκ deposits was observed. Bortezomib-dexamethasone combination therapy finally led to a favorable renal response. This case provides new insights into the pathophysiological mechanisms of proliferative glomerulonephritis with monoclonal immunoglobin deposits (PGNMID), highlighting the importance of repeat renal biopsies and routine evaluation of monoclonal immunoglobin deposits in proliferative glomerulonephritis with refractory nephrotic syndrome.
Subject(s)
Glomerulonephritis, IGA , Glomerulonephritis, Membranoproliferative , Glomerulonephritis , Nephrotic Syndrome , Male , Humans , Adult , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, Membranoproliferative/diagnosis , Glomerulonephritis, Membranoproliferative/drug therapy , Immunoglobulin G , Glomerulonephritis/pathologyABSTRACT
Mucilages are natural compounds consisting mainly of polysaccharides with complex chemical structures. Mucilages also contain uronic acids, proteins, lipids, and bioactive compounds. Because of their unique properties, mucilages are used in various industries, including food, cosmetics, and pharmaceuticals. Typically, commercial gums are composed only of polysaccharides, which increase their hydrophilicity and surface tension, reducing their emulsifying ability. As a result of the presence of proteins in combination with polysaccharides, mucilages possess unique emulsifying properties due to their ability to reduce surface tension. In recent years, various studies have been conducted on using mucilages as emulsifiers in classical and Pickering emulsions because of their unique emulsifying feature. Studies have shown that some mucilages, such as yellow mustard, mutamba, and flaxseed mucilages, have a higher emulsifying capacity than commercial gums. A synergistic effect has also been shown in some mucilages, such as Dioscorea opposita mucilage when combined with commercial gums. This review article investigates whether mucilages can be used as emulsifiers and what factors affect their emulsifying properties. A discussion of the challenges and prospects of using mucilages as emulsifiers is also presented in this review.
Subject(s)
Emulsifying Agents , Polysaccharides , Polysaccharides/chemistry , Emulsifying Agents/chemistry , Emulsions/chemistry , Proteins , FoodABSTRACT
Chronic kidney disease (CKD) is one of the major and exacerbating global health burdens, which is characterized by no curative treatments and high morbidity and mortality. Since malnutrition has become an important factor determining the final clinical outcomes of CKD, soy products, high-quality plant-based sources of proteins and other nutrients, are recommended by many physicians for CKD patients. However, it has been reported that adherence to this dietary advice among those patients is low. In order to dissect the potential reasons behind this phenomenon and to subsequently develop target intervention to improve the current situation, we designed and conducted a self-administered questionnaire survey in 3 medical centers in China. Total 570 patients responded to our survey and data analysis reveals that 85.6% of the respondents were aware of the necessaries of high-quality protein diets for CKD patients, but only 41.9% of patients knew that soy foods provide high-quality proteins needed. In contrast, up to 90.4% of patients were affected by the notion that patients with CKD should avoid soy products. Besides, comparing with other groups, higher percentage of patients undergoing peritoneal dialysis recognized soy products as foods with high-quality proteins, however, as many as 68.8% of them did not consume any soy foods due to the concerns of adverse effects on the progress of CKD. Our data suggest that a significant portion of patients with CKD do not consume soy foods, which could be mainly resulted from their misconception towards soy products delivered by medical workers or social media. Evidence-based updated education of patients and medical workers on soy foods would be a necessary strategy for improving nutrition status of CKD patients and their clinical outcomes.
Subject(s)
Renal Insufficiency, Chronic , Soy Foods , China , Female , Humans , Male , Nutritional Status , Surveys and QuestionnairesABSTRACT
Although Corni Fructus (CF) is a fruit with great economic value and development potential in medicine and food, too much reliance on personal experience for quality evaluation seriously limits the trading and circulation of CF. In the present study, through the research on the correlation between the chemical composition and the appearance color, a standard colorimetric card related to CF quality was established, which simplified the quality evaluation process and improved the accuracy of the visual evaluation of CF. Firstly, a total of 29 batches of CF from different places were collected. Then, "imread" in the MATLAB software was used to convert the color of all samples into RGB values, and HPLC-DVD was used to measure the content of the main chemical components in CF. Thereafter, the correlation between the content and color was studied by using MLR, BP-ANNs and SVM chemometric tools to screen the Q-marker of CF, which was further confirmed by in vivo and in vitro experiments. Finally, the Q-marker standard colorimetric card with the best fitting degree is established according to the prediction model. Thus, this study provides an auxiliary reference for the color evaluation of CF and a reference for the standardization and quantification of the macro characteristics of traditional Chinese medicine and food.
Subject(s)
Cornus , Drugs, Chinese Herbal , Chemometrics , Chromatography, High Pressure Liquid , Cornus/chemistry , Drugs, Chinese Herbal/chemistry , Fruit/chemistry , Medicine, Chinese TraditionalABSTRACT
BACKGROUND: The role of Numb, a protein that is important for cell fate and development and that, in human muscle, is expressed at reduced levels with advanced age, was investigated; adult mice skeletal muscle and its localization and function within myofibres were determined. METHODS: Numb expression was evaluated by western blot. Numb localization was determined by confocal microscopy. The effects of conditional knock out (cKO) of Numb and the closely related gene Numb-like in skeletal muscle fibres were evaluated by in situ physiology, transmission and focused ion beam scanning electron microscopy, three-dimensional reconstruction of mitochondria, lipidomics, and bulk RNA sequencing. Additional studies using primary mouse myotubes investigated the effects of Numb knockdown on cell fusion, mitochondrial function, and calcium transients. RESULTS: Numb protein expression was reduced by ~70% (P < 0.01) at 24 as compared with 3 months of age in gastrocnemius and tibialis anterior muscle. Numb was localized within muscle fibres as bands traversing fibres at regularly spaced intervals in close proximity to dihydropyridine receptors. The cKO of Numb and Numb-like reduced specific tetanic force by 36% (P < 0.01), altered mitochondrial spatial relationships to sarcomeric structures, increased Z-line spacing by 30% (P < 0.0001), perturbed sarcoplasmic reticulum organization and reduced mitochondrial volume by over 80% (P < 0.01). Only six genes were differentially expressed in cKO mice: Itga4, Sema7a, Irgm2, Vezf1, Mib1, and Tmem132a. Several lipid mediators derived from polyunsaturated fatty acids through lipoxygenases were up-regulated in Numb cKO skeletal muscle: 12-HEPE was increased by ~250% (P < 0.05) and 17,18-EpETE by ~240% (P < 0.05). In mouse primary myotubes, Numb knockdown reduced cell fusion (~20%, P < 0.01) and delayed the caffeine-induced rise in cytosolic calcium concentrations by more than 100% (P < 0.01). CONCLUSIONS: These findings implicate Numb as a critical factor in skeletal muscle structure and function and suggest that Numb is critical for calcium release. We therefore speculate that Numb plays critical roles in excitation-contraction coupling, one of the putative targets of aged skeletal muscles. These findings provide new insights into the molecular underpinnings of the loss of muscle function observed with sarcopenia.
Subject(s)
Membrane Proteins , Muscle, Skeletal , Nerve Tissue Proteins , Sarcoplasmic Reticulum , Animals , Calcium/metabolism , Excitation Contraction Coupling , Gene Knockout Techniques , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Sarcoplasmic Reticulum/metabolismABSTRACT
Monoclonal gammopathy of renal significance (MGRS) is a pathological state which presents with a spectrum of renal lesions. MGRS is characterized by pathogenic monoclonal immunoglobulins or light chains produced by a premalignant plasma cell or B cell clone. In view of inadequate understanding in the past, the low detection rate of MGRS often results in poor outcomes and reduces quality of life of patients. Thus, MGRS stands for a group of clinical refractory renal diseases. To date, no standard treatment strategy for MGRS is available. Current consensus suggests a clone-directed approach that aims to eradicate the offending clone, but its long-term prognosis is not clear. In this article, we discuss the diagnostic methods, highlight treatment advances, and introduce integrated Chinese and Western medicine in the management of MGRS.