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Chemical Biology & Drug Design Sep 2023In this paper, the purification, structure, and antioxidant activity of Rehmannia Radix Praeparata polysaccharide (RRPP) were studied. The RRPP was separated using...
In this paper, the purification, structure, and antioxidant activity of Rehmannia Radix Praeparata polysaccharide (RRPP) were studied. The RRPP was separated using DEAE-52 cellulose and Sephadex G-100. The RRPP consisted of xylose, glucose, rhamnose, galactose, and mannose in ratios of 10.64:5.58:3.52:1.39:1.0. No protein was detected in the RRPP fraction, and the molecular weight of RRPP was about 1.75 × 10 Da. The basic skeleton information was obtained using periodic acid oxidation-Smith degradation, and RRPP contained 1→, 1 → 2, 1 → 3, 1 → 4, 1 → 2,6, 1 → 4,6 or 1 → 6, 1 → 2,3, 1 → 2,3,4, and other glycosidic bonds. Fourier transform infrared spectroscopy also showed that RRPP has both α- and β-glycosidic bonds. The in vitro antioxidant activity test showed that RRPP could potentialize scavenging effect on ABTS and its scavenging rate was 91.3%.
Topics: Antioxidants; Rehmannia; Polysaccharides; Oxidation-Reduction; Galactose; Spectroscopy, Fourier Transform Infrared; Molecular Weight
PubMed: 37286527
DOI: 10.1111/cbdd.14261 -
Diabetes Research and Clinical Practice Feb 2024Robust evidence exists regarding initiation, intensification or modification of treatments. Recommendations to de-escalate therapy are lacking, specifically in diabetes.... (Review)
Review
INTRODUCTION
Robust evidence exists regarding initiation, intensification or modification of treatments. Recommendations to de-escalate therapy are lacking, specifically in diabetes. A successful treatment de-intensification reduces overtreatment, polypharmacy, and risk of adverse effects.
OBJECTIVE
To encompass current recommendations for deprescribing common drugs and create a consensus among health professionals.
METHODS
We reviewed four databases for deprescribing approaches published between 2010 and 2022. Articles were divided into different groups of drugs (for uric-acid, hypoglycemic, lipid-lowering, and psychotropic drugs).
RESULTS
Hypoglycemic agents: strategies were limited to newer agents and insulin regimens for elderly individuals. Reducing insulin was associated with 1.1% reduction of A1c over time. SGLT2i and GLP-1RAs dose reduction depends on adverse events. Lipid-lowering agents: studies show that patients with very low cholesterol have fewer cardiovascular events without associated increased risk. Antihypertensive agents: Younger patients, lower systolic blood pressure, and few comorbidities are ideal characteristics for discontinuation. Uric acid therapy: we found no recommendation for dose de-escalation. Poor treatment adherence is associated with episodes of gout and deforming arthritis in the long term.
CONCLUSION
Deprescribing hypoglycemic, statins, antihypertensives, and urate-lowering agents may be feasible in selected patients, but periodic surveillance is important. More evidence is necessary to support this decision entirely.
Topics: Humans; Aged; Goals; Hypoglycemic Agents; Diabetes Mellitus; Antihypertensive Agents; Insulin; Lipids
PubMed: 38244782
DOI: 10.1016/j.diabres.2024.111096 -
Journal of Cachexia, Sarcopenia and... Feb 2024Mice lacking vitamin D receptor (VDR) exhibit a glycogen storage disorder, disrupting carbohydrate utilization in muscle. Here, we asked if the defective carbohydrate...
BACKGROUND
Mice lacking vitamin D receptor (VDR) exhibit a glycogen storage disorder, disrupting carbohydrate utilization in muscle. Here, we asked if the defective carbohydrate metabolism alters the fat utilization by the skeletal muscles of vdr mice.
METHODS
To check the effect of high-fat-containing diets on muscle mass and metabolism of vdr mice, we subjected them to two different milk fat-based diets (milk fat diet with 60% of energy from milk fat and milk-based diet [MBD] with 37% of energy from milk fat) and lard-based high-fat diet (HFD) containing 60% of energy from lard fat. Skeletal muscles and pancreas from these mice were analysed using RNA sequencing, quantitative reverse transcription polymerase chain reaction and western blot to understand the changes in signalling and metabolic pathways. Microscopic analyses of cryosections stained with haematoxylin and eosin, BODIPY, succinate dehydrogenase and periodic acid-Schiff reagent were performed to understand changes in morphology and metabolism of muscle fibres and pancreatic islets.
RESULTS
Transcriptomic analyses showed that the skeletal muscles of vdr mice exhibit upregulation of the fatty acid oxidation pathways, suggesting a shift towards increased lipid utilization even in a carbohydrate-enriched regular chow diet (chow). Two different milk fat-enriched diets restored body weight (12.01 ± 0.33 g in chow vs. 17.99 ± 0.62 g in MBD) and muscle weights (38.58 ± 3.84 mg in chow vs. 110.72 ± 1.96 mg in MBD for gastrocnemius [GAS]) of vdr mice. Muscle ATP levels (0.56 ± 0.18 μmol in chow vs. 1.48 ± 0.08 μmol in MBD) and protein synthesis (0.25 ± 0.04 A.U. in chow vs. 2.02 ± 0.06 A.U. in MBD) were upregulated by MBD. However, despite increasing muscle energy levels, HFD failed to restore the muscle mass and cross-sectional area to that of wild-type (WT) mice (104.95 ± 2.6 mg for WT mice on chow vs. 77.26 ± 1.7 mg for vdr mice on HFD for GAS). Moreover, HFD disrupted glucose homeostasis in vdr mice, while MBD restored it. We further analysed insulin response and pancreatic insulin levels of these mice to show that HFD led to reduced insulin levels in pancreatic beta cells of vdr mice (mean intensity of 1.5 × 10 for WT mice on chow vs. 4.3 × 10 for vdr mice on HFD). At the same time, MBD restored glucose-stimulated pancreatic insulin response (mean intensity of 9.2 × 10 ).
CONCLUSIONS
Skeletal muscles of vdr mice are predisposed to utilize fatty acids as their primary energy source to circumvent their defective carbohydrate utilization. Thus, HFDs could restore energy levels in the skeletal muscles of vdr mice. This study reveals that when mice are subjected to a lard-based HFD, VDR signalling is essential for maintaining insulin levels in pancreatic islets. Our data show a critical role of VDR in muscle metabolic flexibility and pancreatic insulin response.
Topics: Mice; Animals; Vitamin D; Muscle, Skeletal; Insulin; Diet, High-Fat; Vitamins; Glucose; Oxidative Stress; Carbohydrates
PubMed: 38041597
DOI: 10.1002/jcsm.13378 -
International Immunopharmacology Mar 2024Saikosaponin F (SsF) is one of the major active ingredients of Radix Bupleuri, an herb widely used in the treatment of depression. Studies have shown that dry eye...
AIMS
Saikosaponin F (SsF) is one of the major active ingredients of Radix Bupleuri, an herb widely used in the treatment of depression. Studies have shown that dry eye disease often occurs together with depression. The aim of this study is to investigate whether SsF can improve depression-associated dry eye disease and explore the underlying mechanism.
METHODS
Behavioral test was used to verify the effect of SsF on CUMS-induced depression-like behaviors in mice. Corneal fluorescein staining, phenol red cotton thread test and periodic acid-Schiff (PAS) staining were used to observe the effect of SsF on depression-associated dry eye disease. Western blot (WB) was performed to observe the expression of TAK1 protein and key proteins of NF-κB and MAPK (P38) inflammatory pathways in the hippocampus and cornea. Immunohistochemical staining was used to observe the expression of microglia, and immunoprecipitation was used to observe K63-linked TAK1 ubiquitination. Subsequently, we constructed a viral vector sh-TAK1 to silence TAK1 protein to verify whether SsF exerted its therapeutic effect based on TAK1. The expression of inflammatory factors such as IL-1β, TNF-α and IL-18 in hippocampus and cornea were detected by ELISA. Overexpression of TRIM8 (OE-TRIM8) by viral vector was used to verify whether SsF improved depression-associated dry eye disease based on TRIM8.
RESULTS
SsF treatment significantly improved the depression-like behavior, increased tear production and restored corneal injury in depression-related dry eye model mice. SsF treatment downregulated TAK1 expression and TRIM8-induced K63-linked TAK1 polyubiquitination, while inhibiting the activation of NF-κB and MAPK (P38) inflammatory pathways and microglial expression. In addition, selective inhibition of TAK1 expression ameliorated depression-associated dry eye disease, while overexpression of TRIM8 attenuated the therapeutic effect of SsF on depression-associated dry eye disease.
CONCLUSION
SsF inhibited the polyubiquitination of TAK1 by acting on TRIM8, resulting in the downregulation of TAK1 expression, inhibition of inflammatory response, and improvement of CUMS-induced depression-associated dry eye disease.
Topics: Animals; Male; Mice; Depression; Dry Eye Syndromes; Inflammation; MAP Kinase Kinase Kinases; Mice, Inbred C57BL; Nerve Tissue Proteins; NF-kappa B; Oleanolic Acid; Saponins; Ubiquitin-Protein Ligases; Ubiquitination; Antidepressive Agents
PubMed: 38430804
DOI: 10.1016/j.intimp.2024.111749 -
FP Essentials Jun 2024Tinea infections are caused by dermatophytes, except for tinea versicolor, which is caused by yeasts in the genus. If available, potassium hydroxide preparation should... (Review)
Review
Tinea infections are caused by dermatophytes, except for tinea versicolor, which is caused by yeasts in the genus. If available, potassium hydroxide preparation should be performed to confirm diagnosis of tinea capitis or onychomycosis. In some cases, fungal culture, UV light examination, or periodic acid-Schiff stain can be helpful. Topical drugs are effective for tinea corporis, tinea cruris, and tinea pedis. Tinea incognito is an atypical presentation that usually requires systemic treatment. Management of tinea capitis always requires oral drugs. Oral drugs are preferred for onychomycosis treatment but should not be prescribed without confirmation of fungal infection. Localized cases of tinea versicolor can be managed with topical drugs, but oral drugs might be needed for severe, widespread, or recurrent cases. Warts are superficial human papillomavirus infections. Common treatments include irritant, destructive (eg, cryotherapy), immune stimulant (eg, intralesional antigen), and debridement and excision methods. Scabies infestation results in intensely itchy papules, nodules, or vesicles. Mites and burrows on the skin are pathognomonic but difficult to identify. Dermoscopy, particularly with UV light, can make identification easier. Topical permethrin and oral ivermectin are two of the most commonly used treatments. All household and close contacts should be treated regardless of the presence or absence of symptoms.
Topics: Humans; Child; Adolescent; Scabies; Warts; Tinea; Antifungal Agents; Onychomycosis; Papillomavirus Infections; Mite Infestations; Dermoscopy
PubMed: 38896827
DOI: No ID Found -
Computer Methods and Programs in... Dec 2023The Oxford Classification for IgA nephropathy is the most successful example of an evidence-based nephropathology classification system. The aim of our study was to...
BACKGROUND AND OBJECTIVE
The Oxford Classification for IgA nephropathy is the most successful example of an evidence-based nephropathology classification system. The aim of our study was to replicate the glomerular components of Oxford scoring with an end-to-end deep learning pipeline that involves automatic glomerular segmentation followed by classification for mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S) and active crescents (C).
METHODS
A total number of 1056 periodic acid-Schiff (PAS) whole slide images (WSIs), coming from 386 kidney biopsies, were annotated. Several detection models for glomeruli, based on the Mask R-CNN architecture, were trained on 587 WSIs, validated on 161 WSIs, and tested on 127 WSIs. For the development of segmentation models, 20,529 glomeruli were annotated, of which 16,571 as training and 3958 as validation set. The test set of the segmentation module comprised of 2948 glomeruli. For the Oxford classification, 6206 expert-annotated glomeruli from 308 PAS WSIs were labelled for M, E, S, C and split into a training set of 4298 glomeruli from 207 WSIs, and a test set of 1908 glomeruli. We chose the best-performing models to construct an end-to-end pipeline, which we named MESCnn (MESC classification by neural network), for the glomerular Oxford classification of WSIs.
RESULTS
Instance segmentation yielded excellent results with an AP50 ranging between 78.2-80.1 % (79.4 ± 0.7 %) on the validation and 75.1-77.7 % (76.5 ± 0.9 %) on the test set. The aggregated Jaccard Index was between 73.4-75.9 % (75.0 ± 0.8 %) on the validation and 69.1-73.4 % (72.2 ± 1.4 %) on the test set. At granular glomerular level, Oxford Classification was best replicated for M with EfficientNetV2-L with a mean ROC-AUC of 90.2 % and a mean precision/recall area under the curve (PR-AUC) of 81.8 %, best for E with MobileNetV2 (ROC-AUC 94.7 %) and ResNet50 (PR-AUC 75.8 %), best for S with EfficientNetV2-M (mean ROC-AUC 92.7 %, mean PR-AUC 87.7 %), best for C with EfficientNetV2-L (ROC-AUC 92.3 %) and EfficientNetV2-S (PR-AUC 54.7 %). At biopsy-level, correlation between expert and deep learning labels fulfilled the demands of the Oxford Classification.
CONCLUSION
We designed an end-to-end pipeline for glomerular Oxford Classification on both a granular glomerular and an entire biopsy level. Both the glomerular segmentation and the classification modules are freely available for further development to the renal medicine community.
Topics: Humans; Glomerulonephritis, IGA; Deep Learning; Glomerular Filtration Rate; Kidney Glomerulus; Kidney
PubMed: 37722311
DOI: 10.1016/j.cmpb.2023.107814 -
Nano Letters Nov 2023To mimic natural photonic crystals having color regulation capacities dynamically responsive to the surrounding environment, periodic assembly structures have been...
To mimic natural photonic crystals having color regulation capacities dynamically responsive to the surrounding environment, periodic assembly structures have been widely constructed with response materials. Beyond monocomponent materials with stimulus responses, binary and multiphase systems generally offer extended color space and complex functionality. Constructing a rule for predicting response sensitivity can provide great benefits for the tailored design of intelligently responsive photonic materials. Here, we elucidate mathematical relationships between the response sensitivity of dynamically structural-color changes and the location distances of photonic co-phases in three-dimensional Hansen space that can empirically express the strength of their interaction forces, including dispersion force, polarity force, and hydrogen bonding. Such an empirical rule is proven to be applicable for some typical alcohols, acetone, and acetic acid regardless of their molecular structures, as verified by angle resolution spectroscopy, infrared spectroscopy, and molecular simulation. The theoretical method we demonstrate provides rational access to custom-designed responsive structural coloration.
PubMed: 37737087
DOI: 10.1021/acs.nanolett.3c02671 -
Life Sciences May 2024Central hypothyroidism (CH) is characterized by low T levels and reduced levels or bioactivity of circulating TSH. However, there is a lack of studies on CH-related...
BACKGROUND
Central hypothyroidism (CH) is characterized by low T levels and reduced levels or bioactivity of circulating TSH. However, there is a lack of studies on CH-related intestinal maldevelopment. In particular, the roles of TH and TSH/TSHR signaling in CH-related intestinal maldevelopment are poorly understood. Herein, we utilized Tshr mice as a congenital hypothyroidism model with TH deprival and absence of TSHR signaling.
METHODS
The morphological characteristics of intestines were determined by HE staining, periodic acid-shiff staining, and immunohistochemical staining. T was administrated into the offspring of homozygous mice from the fourth postnatal day through weaning or administrated after weaning. RT-PCR was used to evaluate the expression of markers of goblet cells and intestinal digestive enzymes. Single-cell RNA-sequencing analysis was used to explore the cell types and gene profiles of metabolic alternations in early-T-injected Tshr mice.
KEY FINDINGS
Tshr deletion caused significant growth retardation and intestinal maldevelopment, manifested as smaller and more slender small intestines due to reduced numbers of stem cells and differentiated epithelial cells. Thyroxin supplementation from the fourth postnatal day, but not from weaning, significantly rescued the abnormal intestinal structure and restored the decreased number of proliferating intestinal cells in crypts of Tshr mice. Tshr mice with early-life T injections had more early goblet cells and impaired metabolism compared to Tshr mice.
SIGNIFICANCE
TH deprival leads to major defects of CH-associated intestinal dysplasia while TSH/TSHR signaling deficiency promotes the differentiation of goblet cells and impairs nutrition metabolism.
Topics: Animals; Mice; Hypothyroidism; Receptors, G-Protein-Coupled; Receptors, Thyrotropin; Signal Transduction; Thyroid Hormones; Thyrotropin; Intestines
PubMed: 38521387
DOI: 10.1016/j.lfs.2024.122577 -
Molecular Immunology Aug 2023Houttuynia cordata is an herbal compound that grows in China and exhibits anti-inflammatory, antiviral, and antioxidant properties. Additionally, pyroptosis is mediated...
BACKGROUND
Houttuynia cordata is an herbal compound that grows in China and exhibits anti-inflammatory, antiviral, and antioxidant properties. Additionally, pyroptosis is mediated by the activated NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome after stimulation by various inflammatory factors in asthma.
OBJECTIVE
To investigate the effect of sodium houttuyfonate on NLRP3 inflammasome-related pyroptosis and Th1/Th2 immune imbalance in asthma.
METHODS
Asthmatic mice model were made, sodium houttuyfonate was injected intraperitoneally to treat the asthmatic mice. Airway reactivity, cell classification and counting in the bronchoalveolar lavage fluid were measured. Hematoxylin-eosin and periodic acid-Schiff staining were used to analyze airway inflammation and mucus hypersecretion. Beas-2b cells were cultured, LPS, NLRP3 antagonist (Mcc950) and sodium houttuyfonate were used to intervene the Beas-2b cells, NLRP3, ASC, caspase-1, GSDMD, IL-1β, and IL-18 expression in the lung tissue and cells were analyzed using immunohistochemistry and western blot, while qRT- PCR was performed to analyze the mRNA contents in the pulmonary and the cells, respectively. Th1 and Th2 cytokines (IL-4 and IFN-γ) were detected with ELISA and the proportions of Th1 and Th2 in splenocyte were detected by flow cytometry.
RESULTS
Airway reactivity decreased in sodium houttuyfonate group when compared with asthmatic group mice. In the BALF, the numbers of leukocytes, eosinophils, neutrophils, lymphocytes, and macrophages were significantly lower in sodium houttuyfonate group mice than in asthmatic group mice. The proportion of TH1/TH2 cells in spleen cells and IFN-γ /IL-4 in plasma increased in sodium houttuyfonate treatment group when compared with asthma group. Immunohistochemistry, western blot and RT-PCR showed that the expressions of NLRP3, ASC, caspase-1, GSDMD, IL-1β and IL-18 were decreased in the lung tissue of mice after treated with sodium houttuyfonate when compared with those in the asthma group. However, sodium houttuyfonate combined with dexamethasone induced a stronger effect on NLRP3-related pyroptosis and Th1/Th2 immune imbalance compared to sodium houttuyfonate or dexamethasone alone. Beas-2b cells were cultured in vitro, sodium houttuyfonate can alleviate LPS-induced ASC, casepase-1, GSDMD, IL-18 and IL-1β increasing, especially in SH (10 μg/ml) treated group, but the effect less than Mcc950.
CONCLUSIONS
Sodium houttuyfonate can alleviated NLRP3-related pyroptosis and Th1/Th2 immune imbalance to reduce asthma airway inflammation and airway reactivity.
Topics: Mice; Animals; Interleukin-18; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Pyroptosis; Interleukin-4; Lipopolysaccharides; Asthma; Inflammation; Dexamethasone; Caspases
PubMed: 37413910
DOI: 10.1016/j.molimm.2023.06.013 -
Clinical Nutrition Research Jul 2023Bariatric surgery is the most effective treatment for sustained weight reduction, and it can result in substantial improvements in the severity of type 2 diabetes,...
Bariatric surgery is the most effective treatment for sustained weight reduction, and it can result in substantial improvements in the severity of type 2 diabetes, metabolic syndrome, nonalcoholic fatty liver disease, and quality of life. However, sleeve gastrectomy, a weight loss surgery that removes two-thirds of the stomach, reduces appetite and nutrient absorption, impairing digestion and the absorption of nutrients like iron, vitamin B, and protein-bound nutrients. This case study aims to demonstrate that patients undergoing sleeve gastrectomy require long-term and periodic monitoring of biochemical data, weight changes, and caloric and protein intake by a professional nutritionist to prevent malnutrition and nutritional deficiencies. In this case study, a 48-year-old woman was diagnosed with morbid obesity, hypertension, sleep apnea syndrome, and chronic gastritis. At initial evaluation, she was 160 cm tall and weighed 89 kg, with a body mass index of 34.8 kg/m. At 1 postoperative year, she consumed 650 kcal and 25 g of protein per day, the percentage of excess weight loss was 141.1%, and body mass index was 21 kg/m. Compared to preoperative levels, calcium and folic acid levels did not decrease after 1 postoperative year, but hemoglobin, ferritin, and vitamin B levels decreased. In conclusion, when patients experience rapid weight loss after sleeve gastrectomy, follow-up should be frequent and long. Dietary education should be conducted according to digestive symptoms, and oral nutritional supplements, including vitamins and minerals.
PubMed: 37593213
DOI: 10.7762/cnr.2023.12.3.177