Integrated component identification, network pharmacology, and experimental verification revealed mechanism of Dendrobium officinale Kimura et Migo against lung cancer.

BACKGROUND: Dendrobium officinale Kimura et Migo (DO), a valuable Chinese herbal medicine, has been reported to exhibit potential effects in the prevention and treatment of lung cancer. However, its material basis and mechanism of action have not been comprehensively analyzed. PURPOSE: The objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification. METHODS: The chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected. RESULTS: 249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway. CONCLUSIONS: This study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.

Can acupuncture increase microcirculation in peripheral artery disease and diabetic foot syndrome? - a pilot study.

Background: Globally, diabetes mellitus (DM) and peripheral artery disease (PAD) have an increasing incidence and a high prevalence and are both associated with high morbidity and complication rates, e.g., as chronic non-healing peripheral ulcers. Impaired macro- and microcirculation and peripheral neuropathy lead to an increased risk of foot ulcers and infections. These complications are difficult to treat, have a high risk of becoming chronic and often lead to lower limb amputation. The aim of this planned study was to investigate the potential effects of acupuncture on improving microcirculation in patients with Diabetic Foot Syndrome (DFS) and PAD. Materials and methods: In 18 patients with chronic non-healing peripheral ulcers and diagnosed DM or PAD, data on 8 microcirculatory parameters were collected simultaneously on intact skin close to the wound margin. Microcirculation was assessed using an O2C device combining laser Doppler shift and white light spectroscopy (LEA Medizintechnik GmbH, Giessen, Germany). Unilateral and bilateral acupuncture was performed on the connecting line between acupuncture points Stomach 14 and Stomach 15. Results: After unilateral acupuncture (ipsilateral to the wound side), a statistically significant improvement in 7 out of 8 microcirculatory parameters was demonstrated compared to baseline measurements before acupuncture. After bilateral acupuncture, there was an additional improvement and statistical significance in all parameters in both DFS and PAD patients. Discussion: These results show an improvement in the microcirculation and peripheral blood flow at the edges of the wound. As impaired micro- and macrocirculation is considered to be a critical prognostic factor for the healing of a peripheral lesion, the intervention could have a positive impact on the healing of (chronic) peripheral wounds.

Chromatography based profiling of feruloylated arabinans and galactans.

Profiling of pectic arabinans and galactans by analysis of the released oligosaccharides after backbone cleavage provides information on the complexity of the polymer structure. In plants of the family Amaranthaceae, arabinan and galactan substitution with ferulates extends the polysaccharide complexity, changing its chemical properties. Knowledge of the ferulate environment is crucial to understand structure-function-relationships of feruloylated pectins. Here, we present an approach to separate enzymatically generated feruloylated and non-feruloylated arabino- and galactooligosaccharides, followed by deesterification and semiquantitative analysis by HPAEC-PAD using previously reported relative response factors. Application of this approach to sugar beet pectins and insoluble and soluble dietary fiber preparations of amaranth and quinoa suggests that ferulates are preferably incorporated into more complex structures, as nicely demonstrated for feruloylated galactans. Also, ferulate substitution appears to negatively affect enzymatic cleavage by using endo-enzymes. As a consequence, we were able to tentatively identify new feruloylated tri- and tetrasaccharides of galactans isolated from sugar beet pectins.

Pharmacotherapy and revascularization strategies of peripheral artery disease.

The global epidemiological transition of atherosclerotic vascular diseases is witnessing a rapid redistribution of its burden, shifting from high-income to low- and middle-income countries. With a wide clinical spectrum, spanning from intermittent claudication to more complex critical limb threatening ischemia, nonhealing ulcers, gangrene as well as acute limb ischemia, peripheral artery disease is often faced with the challenges of under-diagnosis and under-treatment despite its high prevalence. The management of peripheral arterial disease in patients with multiple comorbidities presents a formidable challenge and remains a pressing global health concern. In this review, we aim to provide an in-depth overview of the pathophysiology of peripheral artery disease and explore evidence-based management strategies encompassing pharmacological, lifestyle, interventional, and surgical approaches. By addressing these challenges, the review contributes to a better understanding of the evolving landscape of peripheral artery disease, offering insights into effective and holistic management strategies.

Screening of natural inhibitors against peptidyl arginine deiminase 4 from herbal extracts by a high-performance liquid chromatography ultraviolet-visible based method.

Peptidyl arginine deiminase 4 (PAD4) is an important biocatalytic enzymes involved in the conversion of protein arginine to citrulline, its dysregulation has a great impact on many physiological processes. Recently, PAD4 has emerged as a potential therapeutic target for the treatment of various diseases including rheumatoid arthritis (RA). Traditional Chinese Medicines (TCMs), also known as herbal plants, have gained great attention by the scientific community due to their good therapeutic performance and far fewer side effects observed in the clinical treatment. However, limited researches have been reported to screen natural PAD4 inhibitors from herbal plants. The color developing reagent (COLDER) or fluorescence based methods have been widely used in PAD4 activity assay and inhibitor screening. However, both methods measure the overall absorbance or fluorescence in the reaction solution, which are easy to be affected by the background interference due to colorful extracts from herbal plants. In this study, a simple, and robust high-performance liquid chromatography ultraviolet-visible (HPLC-UV) based method was developed to determine PAD4 activity. The proposed strategy was established based on COLDER principle, while used hydrophilic l-arginine instead of hydrophobic N-benzoyl-l-arginine ethyl ester (BAEE) as a new substrate to determine PAD4 inhibition activity of herbal extracts. The herbal extracts and PAD4 generated hydrophobic l-citrulline were successfully separated by the HPLC, and the developed method was optimized and validated with a known PAD4 inhibitor (GSK484) in comparison with COLDER assay. The IC50 value of GSK484 measured by HPLC-UV method was 153 nM, and the detection limit of the citrulline was 0.5 nmol, respectively, with a linear range of 0.5 nmol to 20 nmol. The IC50 value of the HPLC-UV method was improved by nearly three times compared with COLDER assay (527 nM), and the results indicated the reliability of PAD4 inhibition via HPLC-UV method. The inhibitory effect against PAD4 were fast and accurately screened for the twenty-four extracts from eight herbs. Among them, Ephedra Herba extracts showed significant inhibitory activity against the PAD4 with the IC50 values of three extracts (ethanol, ethyl acetate and water) ranging from 29.11 µg/mL to 41.36 µg/mL, which may help researchers to discover novel natural compounds holding high PAD4 inhibition activity.

Infra-patellar fat pad-derived mesenchymal stem cells maintain their chondrogenic differentiation potential after arthroscopic harvest with blood-product supplementation.

PURPOSE: Mesenchymal stem cells/medicinal signaling cells (MSCs) possess therapeutic potential and are used in regenerative orthopaedics. The infra-patellar fat pad (IFP) is partially resected during knee arthroscopy (KASC) and contains MSCs. Heat, irrigation, and mechanical stress during KASC may decrease MSC's therapeutic potential. This study assessed MSCs' regenerative potential after arthroscopic IFP harvest and potential effects of two blood products (BP) (platelet-rich plasma (PRP), hyperacute serum (HAS)) on MSCs' viability and chondrogenic differentiation capacity. METHODS: IFP was arthroscopically harvested, isolated, and counted (n = 5). Flow cytometry was used to assess cell viability via staining with annexin V/7-AAD and stemness markers via staining for CD90, CD73, and CD105. MSCs were incubated with blood products, and metabolic activity was determined via an XTT assay. Deposition of cartilage extracellular matrix was determined in histologic sections of chondrogenically differentiated 3D pellet cultures via staining with Alcian Blue. Expression of cartilage-specific genes (SOX9, MMP3/13, ACAN, COL1/2) was analyzed via quantitative PCR. RESULTS: MSC isolation from IFP yielded 2.66*106 ± 1.49*106 viable cells from 2.7 (0.748) g of tissue. MSC markers (CD 90/105/73) were successfully detected and annexin V staining showed 81.5% viable cells. XTT showed increased metabolic activity. Within the BP groups, this increase was significant (days 0-14, p < 0.05). PCR showed expression of cartilage-specific genes in each group. COL2 (p < 0.01) as well as ACAN (p < 0.001) expression levels were significantly higher in the HAS group. Histology showed successful differentiation. CONCLUSION: Arthroscopic harvest of IFP-MSCs yields sufficient cells with maintained regenerative potential and viability. Blood products further enhance MSCs' viability.

Evaluation of coffee husks in pellet bedding, performance characteristics, footpad dermatitis scoring, and meat quality of broiler ducks.

The study aimed to analyze the chemical composition of pellet bedding made of straw or coffee husks (10, 25, 50%) and the performance characteristics of broiler ducks and footpad dermatitis. During rearing, the properties of the bedding and utility features of ducks were analyzed, and the frequency of footpad dermatitis (FPD) in ducks was verified. There was a decrease in dry matter from the 28th day of rearing. The crude fiber, NDF, ADF, and nitrogen content decreased compared to fresh bedding, while phosphorus and potassium increased. The highest pH was found in the CH25 and CH50 groups in fresh bedding on day 42 and in CH50 on day 14. High adj. R2 was found due to rearing time and bedding material (0.817-0.985). The ducks' growth rate in the CH25 group was higher at week 6 than in the other groups. In CH10 and CH25 groups, higher carcass weight was found than in group C. In group CH10, a higher weight of pectoral muscles and lower wing proportion was found than in C. In CH25, a higher remains weight was shown than in C and CH50. In CH50, lower water-holding capacity in the pectoral muscles was found than in the other groups. Considering the bedding (the content of nitrogen, phosphorus, and potassium), carcass features, and meat quality (water-holding capacity, intramuscular fat, and water content), it is possible to use 10, 25 or 50% of coffee husks in straw pellets in the rearing of broiler ducks. Due to the FPD, the moisture should be lowered.

Omega-3 Polyunsaturated Fatty Acids are not associated with Peripheral Artery Disease in a Meta-Analysis from the Multi-Ethnic Study of Atherosclerosis and Atherosclerosis Risk in Communities Study Cohorts.

BACKGROUND: Research suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce. OBJECTIVES: We evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts. METHODS: Omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined. RESULTS: In the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y. CONCLUSION: This study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk.

Simple procedure to enhance pulsed amperometric detector (PAD) response stability for inulin-type fructans analysis. Application to a case study with chicory taproot.

A new electrode management, within the HPAEC-PAD systems, was proposed to measure inulin-type fructans in chicory roots, grown under two lighting periods: 12 h (T-12 h) and 24 h continuous lighting (T-24 h-CL), with the same daily light integral (DLI). The amperometric cell turn-off (PAD-Off) after elution of carbohydrate of interest, allowed the stabilization of the PAD response, avoiding excessive electrode surface oxidation. The enhanced signal stability allowed the application of fucose as internal standard (ISTD) for data normalization, improving the correctness of linear calibration curves and the quantification of fructans in the case study of chicory plants. T-24 h-CL decreased FW and DW of chicory leaves while increasing these parameters in roots. Fructans amount in chicory roots was significantly higher in the T-24-CL photoperiod. The accuracy of prebiotics quantification by PAD-Off emphasized significant differences between light treatments. CL can improve the yield and quality of chicory roots.

Evaluation of arthrokinematics and posterior soft tissues of the ankle during ankle dorsiflexion using ultrasound.

BACKGROUND: Arthrokinematics (caudal and posterior movements of the talus) and posterior soft tissues of the ankle during ankle dorsiflexion have not been objectively evaluated in detail. This study aimed to investigate the characteristics of arthrokinematics and posterior soft tissues of the ankle during ankle dorsiflexion using ultrasound. METHODS: Thirteen healthy adults participated in the study. Participants whose passive dorsiflexion range of motion (ROM) of the ankle joint was <35° were classified as the restricted group (n = 6), and participants whose passive ankle dorsiflexion ROM was ≥35° were classified as the control group (n = 7). Passive ankle dorsiflexion was performed to measure the ankle arthrokinematics. Strain elastography was performed to measure the elasticity of the flexor hallucis longus (FHL) and Kager's fat pad (KFP) at each dorsiflexion angle. RESULTS: A significant difference in the posterior movement of the talus at the ankle dorsiflexion of 30° was observed between the two groups (P = 0.04). The elasticity of the restricted group was increased at all angles in both FHL and KFP (P < 0.05). CONCLUSION: This study showed that it is possible to objectively evaluate the direction of ankle arthrokinematics and posterior ankle soft-tissue restrictions using ultrasound.

Low-intensity resistance exercise with blood flow restriction for patients with claudication: A randomized controlled feasibility trial.

BACKGROUND: Claudication is a common and debilitating symptom of peripheral artery disease, resulting in poor exercise performance and quality of life (QoL). Supervised exercise programs are an effective rehabilitation for patients with claudication, but they are poorly adhered to, in part due to the high pain and effort associated with walking, aerobic, and resistance exercise. Low-intensity resistance exercise with blood flow restriction (BFR) represents an alternative exercise method for individuals who are intolerant to high-intensity protocols. The aim of this study was to evaluate the feasibility of a supervised BFR program in patients with claudication. METHODS: Thirty patients with stable claudication completed an 8-week supervised exercise program and were randomized to either BFR (n = 15) or a control of matched exercise without BFR (control; n = 15). Feasibility, safety, and efficacy were assessed. RESULTS: All success criteria of the feasibility trial were met. Exercise adherence was high (BFR = 78.3%, control = 83.8%), loss to follow up was 10%, and there were no adverse events. Clinical improvement in walking was achieved in 86% of patients in the BFR group but in only 46% of patients in the control group. Time to claudication pain during walking increased by 35% for BFR but was unchanged for the control. QoL for the BFR group showed improved mobility, ability to do usual activities, pain, depression, and overall health at follow up. CONCLUSION: A supervised blood flow restriction program is feasible in patients with claudication and has the potential to increase exercise performance, reduce pain, and improve QoL. (Clinicaltrials.gov Identifier: NCT04890275).

Low-dose peripheral leptin infusion produces selective activation of ventromedial hypothalamic and hindbrain STAT3.

Previous studies have shown that very low dose, acute, single peripheral leptin injections fully activate arcuate nucleus signal transducer and activator of transcription 3 (STAT3), but ventromedial hypothalamus (VMH) pSTAT3 continues to increase with higher doses of leptin that inhibit food intake. The lowest dose that inhibited intake increased circulating leptin 300-fold whereas food intake is inhibited by chronic peripheral leptin infusions that only double circulating leptin. This study examined whether the pattern of hypothalamic pSTAT3 was the same in leptin-infused rats as in leptin-injected rats. Male Sprague-Dawley rats received intraperitoneal infusions of 0, 5, 10, 20, or 40 µg leptin/day for 9 days. The highest dose of leptin increased serum leptin by 50-100%, inhibited food intake for 5 days, but inhibited weight gain and retroperitoneal fat mass for 9 days. Energy expenditure, respiratory exchange ratio, and brown fat temperature did not change. pSTAT3 was quantified in hypothalamic nuclei and the nucleus of the solitary tract (NTS) when food intake was inhibited and when it had returned to control levels. There was no effect of leptin on pSTAT3 in the medial or lateral arcuate nucleus or in the dorsomedial nucleus of the hypothalamus. VMH pSTAT3 was increased only at day 4 when food intake was inhibited, but NTS pSTAT3 was increased at both 4 and 9 days of infusion. These results suggest that activation of leptin VMH receptors contributes to the suppression of food intake, but that hindbrain receptors contribute to a sustained change in metabolism that maintains a reduced weight and fat mass.NEW & NOTEWORTHY Low-dose, chronic peripheral infusions of leptin produced an initial, transient inhibition of food intake that correlated with signal transducer and activator of transcription 3 (STAT3) activation in the ventromedial hypothalamus (VMH) and nucleus of the solitary tract (NTS). When intake normalized, but weight remained suppressed, the NTS was the only area that remained activated. These data suggest that leptin's primary function is to reduce body fat, that hypophagia is a means of achieving this and that different areas of the brain are responsible for the progressive response.

The Effectiveness of Whole-Body Vibration and Heat Therapy on the Muscle Strength, Flexibility, and Balance Abilities of Elderly Groups.

Whole-body vibration (WBV) is a novel exercise training measure that promotes the muscle strength, flexibility, and balance abilities of elderly groups. The feasibility and applicability of 20-30 min (lowering a heat pack at 73 °C by wrapping it in multiple layers of towels to 40-43 °C before it touched the skin) thermotherapy are increasingly being demonstrated by applications and clinical trials. Studies show that it increases the flexibility of macules and ligament. However, no studies have examined the interactions between the pre-exercise and post-exercise application of heat therapy (duration a training course). Therefore, this study investigates the effects of WBV and heat therapy on the muscle strength, flexibility, and balance abilities of elderly groups. Eighty middle-age and elderly participants with no regular exercise habits were enrolled in this study. They were randomly assigned to a WBV group, a WBV plus heat therapy group, a heat therapy alone group, and a control group. The WBV groups underwent 5-min, fixed-amplitude (4 mm), thrice-weekly WBV training sessions for 3 consecutive months on a WBV training machine. Participants' balance was measured using the limits of stability (LOS) test on a balance system. The pretest and posttest knee extensor and flexor strength were tested using an isokinetic lower extremity dynamometer. Pretest and posttest flexibility changes were measured using the sit-and-reach test. Significantly larger pretest and posttest differences in flexibility and muscle strength were observed in the WBV and WBV plus heat therapy groups. The addition of heat therapy to WBV resulted in the largest flexibility improvements.

Structural compositions and biological activities of cell wall polysaccharides in the rhizome, stem, and leaf of Polygonatum odoratum (Mill.) Druce.

Polygonatum odoratum is a perennial rhizomatous medicinal plant and different plant parts have been used in the treatment of various ailments. Herein, we have investigated the structural compositions of rhizome, leaf, and stem cell walls. We found 30-44% of polysaccharides in these wall preparations were cyclohexanediaminetetraacetic acid (CDTA) extractable, the proportion of heteromannans (HMs) in the rhizome is nearly three-fold compared to that of the leave and stem. The pectic polysaccharides of the rhizome are also structurally more diverse, with arabinans and type I and type II arabinogalactans being richest as shown by linkage study of the sodium carbonate (Na2CO3) extract. In addition, the 2-linked Araf was rhizome-specific, suggesting the cell walls in the rhizome had adapted to a more complex structure compared to that of the leaf and stem. Water-soluble polysaccharide fractions were also investigated, high proportion of Man as in 4-linked Manp indicated high proportion of HMs. The 21.4 kDa pectic polysaccharides and HMs derived from rhizome cell walls induced specific immune response in mice macrophage cells producing IL-1α and hematopoietic growth factors GM-CSF and G-CSF in vitro.

Huang Qin Decoction inhibits the initiation of experimental colitis associated carcinogenesis by controlling the PAD4 dependent NETs.

BACKGROUND: Colorectal cancer is associated with ulcerative colitis (UC). The infiltration of neutrophils is the main cause of DNA damage produced by inflammation in the intestinal epithelium. Under the action of peptidyl arginine deaminase 4 (PAD4), neutrophils dissociate chromatin and form neutrophil extracellular traps (NETs), which can aggravate tissue inflammation and encourage tumor development. Although Huang Qin Decoction (HQD) was found to be useful in treating UC and was used to gradually prevent and treat digestive tract cancers, the underlying reasons were unclear. METHODS: To demonstrate HQD could inhibits the initiation of colitis associated carcinogenesis by controlling NETs related inflammation, we first performed an AOM/DSS-generated colitis-associated carcinogenesis model to assess the efficacy of HQD in reducing neutrophil infiltration and anti-tumor activity. Then, using network pharmacology research, we investigated the potential mechanisms underlying those medicinal effects, as demonstrated by the detection of NETs aggregation and PAD4 expression changes in the colon. RESULTS: HQD substantially reduced the number of colon cancers and the expression of Ki67, restored the level of intestinal tight junction protein occludin and ZO-1, and relieved the intestinal inflammation caused by TNF-α, IL-1ß. At the same time, it inhibited neutrophil infiltration in the colon and improved the immunosurveillance of CD8+T cells. The potential mechanisms of HQD intervention against UC and UC with neoplasia (UCN) were studied using network pharmacology, and 156 conjunct genes as well as numerous inflammation-related pathways were identified. Protein-protein interaction (PPI) analysis indicated that HQD inhibition of intestinal tumors might be related to the deactivation of PAD4, which was verified by the down-regulation of NETs, MPO-DNA complex levels, and PAD4 expression after HQD treatment. CONCLUSION: Huang Qin Decoction inhibits the initiation of colitis associated carcinogenesis by controlling PAD4-dependent neutrophil extracellular traps.

Citrullination is linked to reduced Ca2+ sensitivity in hearts of a murine model of rheumatoid arthritis.

AIMS: Cardiac contractile dysfunction is prevalent in rheumatoid arthritis (RA), with an increased risk for heart failure. A hallmark of RA has increased levels of peptidyl arginine deaminases (PAD) that convert arginine to citrulline leading to ubiquitous citrullination, including in the heart. We aimed to investigate whether PAD-dependent citrullination in the heart was linked to contractile function in a mouse model of RA during the acute inflammatory phase. METHODS: We used hearts from the collagen-induced arthritis (CIA) mice, with overt arthritis, and control mice to analyze cardiomyocyte Ca2+ handling and fractional shortening, the force-Ca2+ relationship in isolated myofibrils, the levels of PAD, protein post-translational modifications, and Ca2+ handling protein. Then, we used an in vitro model to investigate the role of TNF-α in the PAD-mediated citrullination of proteins in cardiomyocytes. RESULTS: Cardiomyocytes from CIA mice displayed larger Ca2+ transients than controls, whereas cell shortening was similar in the two groups. Myofibrils from CIA hearts required higher [Ca2+ ] to reach 50% of maximum shortening, ie Ca2+ sensitivity was lower. This was associated with increased PAD2 expression and α-actin citrullination. TNF-α increased PAD-mediated citrullination which was blocked by pre-treatment with the PAD inhibitor 2-chloroacetamide. CONCLUSION: Using a mouse RA model we found evidence of impaired cardiac contractile function linked to reduced Ca2+ sensitivity, increased expression of PAD2, and citrullination of α-actin, which was triggered by TNF-α. This provides molecular and physiological evidence for acquired cardiomyopathy and a potential mechanism for RA-associated heart failure.

Gestational and Lactational Exposure to the Emergent Alternative Plasticizer 1,2-Cyclohexane Dicarboxylic Acid Diisononyl Ester (DINCH) Impairs Lipid Metabolism to a Greater Extent Than the Commonly Used Di(2-Ethylhexyl) Phthalate (DEHP) in the Adult Rat Mammary Gland.

Due to their endocrine disruption properties, phthalate plasticizers such as di(2-ethylhexyl) phthalate (DEHP) can affect the hormone-dependent development of the mammary gland. Over the past few years, DEHP has been partially replaced by 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) which also have potential endocrine disrupting properties. The goal of the present study is to understand the impact of a gestational and lactational exposure to DEHP and DINCH on mammary gland development using Sprague Dawley rats. Both plasticizers altered the adipocytes of the mammary gland fat pad of adult progeny, as demonstrated by a decrease in their size, folding of their membrane, and modulations of the lipid profiles. DEHP treatments decreased the expression of Rxrα and Scd1 at the low and high dose, respectively, but did not affect any of the other genes studied. DINCH modulation of lipid metabolism could be observed at puberty by a decreased expression of genes implicated in triglyceride synthesis, lipid transport, and lipolysis, but by an increased expression of genes of the ß-oxidation pathway and of genes involved in lipid storage and fatty acid synthesis at adulthood, compared with control and DEHP-treated rats. A strong upregulation of different inflammatory markers was observed following DINCH exposure only. Together, our results indicate that a gestational and lactational exposure to DINCH has earlier and more significant effects on lipid homeostasis, adipogenesis, and the inflammatory state of the adult mammary gland than DEHP exposure. The long-term consequence of these effects on mammary gland health remained to be determined.

Development of functional glow-in-the-dark photoluminescence linen fabrics with ultraviolet sensing and shielding.

Linen fibres were coated with a glow-in-the-dark photoluminescence, flame-retarding, and hydrophobic smart nanocomposite using the pad-dry-curing process. Ecologically friendly ammonium polyphosphate and lanthanide-activated strontium aluminium oxide (LSAO) nanoparticles were immobilized into linen fabric using eco-friendly room-temperature-vulcanizing silicone rubber. Different analytical techniques were used to examine the morphological characteristics and elemental compositions of LSAO nanoparticles and treated linen textiles. The self-extinguishing properties of the treated linen textiles were tested for their fire resistance. After 24 washing cycles, the coated linen samples retained their flame-retarding properties. The treated linen's superhydrophobicity rose in direct proportion to the LSAO concentration. After being excited at 365 nm, the colourless luminescent film that was coated on linen surface gave out an emission wavelength of 519 nm. The photoluminescent linen was monitored to create a range of different colours, including off-white in daytime light and green under ultraviolet (UV) light radiation, according to the Commission Internationale de l'éclairage laboratory colorimetric coordinates and photoluminescence spectra. Emission, excitation, and lifetime spectral analysis of the treated linen revealed persistent phosphorescence. For mechanical and comfort evaluation, the coated linen textiles' bending length and air permeability were assessed. Good UV light shielding and enhanced antibacterial activity were detected in the treated linens.

Vitamin D: The Missing Nutrient Behind the Two Deadly Pandemics, COVID-19 and Cardiovascular Diseases.

The coronavirus (COVID-19) pandemic is claiming millions of lives and creating an additional burden on health care, which is already affected by the rise of non-communicable diseases (NCDs). The scientific community, on the other side, is enormously engaged with studies to best identify the characteristics of the virus and minimize its effect while supporting the fight to contain NCDs, mainly cardiovascular diseases (CVDs), which are contributing hugely to the global death toll. Hence, the roles of vitamin D in COVID-19 immunity and cardiovascular health are gaining traction recently.  This literature review will mainly focus on summarizing pertinent studies and scientific publications which highlight the association of vitamin D levels with the various outcomes of COVID-19 and CVDs. It will also address how low vitamin D correlates with the epidemiology of CVDs and the inflammatory mechanisms attributed to COVID-19 severity. We believe that our review may open up hindsight perspectives and further discussions among the physicians in tapping the potential of vitamin D supplementation to tackle the morbidity, mortality, and health care cost of the two deadly diseases, COVID-19 and CVDs.

The Effectiveness of Pelvic Floor Muscle Training in Men after Radical Prostatectomy Measured with the Insert Test.

A commonly used physiotherapeutic method for the treatment of urinary incontinence (UI) after radical prostatectomy (RP) is pelvic floor muscle training (PFMT). The aim of this study was to evaluate the effectiveness of PFMT by enhanced biofeedback using the 1h pad-weighing test. The following factors were taken into consideration in the analysis of PFMT effectiveness: the relevance of the patients' age, time from RP, BMI, mental health, functional state, and depression. A total of 60 post-RP patients who underwent 10-week PFMT were studied. They were divided into groups: A (n = 20) and B (n = 20) (random division, time from RP: 2−6 weeks) and group C (time from RP > 6 weeks). Group B had enhanced training using EMG biofeedback. UI improved in all groups: A, p = 0.0000; B, p = 0.0000; and C, p = 0.0001. After the completion of PFMT, complete control over miction was achieved by 60% of the patients in group A, 85% in group B, and 45% in group C. There was no correlation between the results of PFMT efficacy and patients' age, BMI, time from RP, mental health, functional state, and depression. PFMT is highly effective in UI treatment. The enhancement of PFMT by EMG biofeedback seems to increase the effectiveness of the therapy.