Recent advances in nanomaterial-based biosensor for periodontitis detection.

Periodontitis, a chronic inflammatory condition caused by bacteria, often causes gradual destruction of the components that support teeth, such as the alveolar bone, cementum, periodontal ligament, and gingiva. This ultimately results in teeth becoming loose and eventually falling out. Timely identification has a crucial role in preventing and controlling its progression. Clinical measures are used to diagnose periodontitis. However, now, there is a hunt for alternative diagnostic and monitoring methods due to the progress of technology. Various biomarkers have been assessed using multiple bodily fluids as sample sources. Furthermore, conventional periodontal categorization factors do not provide significant insights into the present disease activity, severity and amount of tissue damage, future development, and responsiveness to treatment. In recent times, there has been a growing utilization of nanoparticle (NP)-based detection strategies to create quick and efficient detection assays. Every single one of these platforms leverages the distinct characteristics of NPs to identify periodontitis. Plasmonic NPs include metal NPs, quantum dots (QDs), carbon base NPs, and nanozymes, exceptionally potent light absorbers and scatterers. These find application in labeling, surface-enhanced spectroscopy, and color-changing sensors. Fluorescent NPs function as photostable and sensitive instruments capable of labeling various biological targets. This article presents a comprehensive summary of the latest developments in the effective utilization of various NPs to detect periodontitis.

Autoregulated and Non-Autoregulated Blood Flow Restriction on Acute Arterial Stiffness.

This study aimed to investigate the acute effects of autoregulated and non-autoregulated applied pressures during blood flow restriction resistance exercise to volitional fatigue on indices of arterial stiffness using the Delfi Personalized Tourniquet System. Following a randomized autoregulated or non-autoregulated blood flow restriction familiarization session, 20 physically active adults (23±5 years; 7 females) participated in three randomized treatment-order sessions with autoregulated and non-autoregulated and no blood flow restriction training. Participants performed four sets of dumbbell wall squats to failure using 20% of one repetition maximum. Blood flow restriction was performed with 60% of supine limb occlusion pressure. Testing before and post-session included an ultrasonic scan of the carotid artery, applanation tonometry, and blood pressure acquisition.Carotid-femoral pulse wave velocity increased in the non-autoregulated and no blood flow restriction training groups following exercise while carotid-radial pulse wave velocity increased in the no blood flow restriction training group (all p<0.05). Carotid-femoral pulse wave velocity exhibited an interaction effect between autoregulated and non-autoregulated blood flow restriction in favor of autoregulated blood flow restriction (p<0.05). Autoregulated blood flow restriction training does not influence indices of arterial stiffness while non-autoregulated and no blood flow restriction training increases central stiffness.

Sprint Interval Training on Stationary Air Bike Elicits Cardiorespiratory Adaptations While Being Time-Efficient.

ABSTRACT: Moghaddam, M, Cervantes, M, Cheshier, B, and Jacobson, BH. Sprint interval training on stationary air bike elicits cardiorespiratory adaptations while being time-efficient. J Strength Cond Res 37(9): 1795-1801, 2023-Sprint interval training (SIT) refers to a set of brief intermittent exercises that are performed at maximal intensity. This study compared the effects of 2 SIT protocols (e.g., 10-5-SIT and 20-10-SIT) vs. moderate-intensity continuous training (MICT) on cardiovascular adaptations, using stationary air bikes. Thirty-two recreationally active individuals were randomly assigned to the 3 performance groups, such as 10-5-SIT (n = 11), 20-10-SIT (n = 10), and MICT (n = 11), to train 3 days per week for 4 weeks. Moderate-intensity continuous training included 30 minutes of cycling at 75% of maximal heart rate reserve, whereas the SIT protocols consisted of 3 sets of 8 intervals at all-out intensity. The 10-5-SIT and 20-10-SIT were performed with 10-second work:5-second rest and 20-second work:10-second rest, with 2.5- and 5-minute recovery periods between sets, respectively. A ramp protocol was used before and after the intervention via cycle ergometer to assess aerobic performance. Time to exhaustion (TTE), absolute V̇o2max (A-V̇o2max), relative V̇o2max (R-V̇o2max), and metabolic equivalents (METs) were measured and analyzed with 2-way mixed factorial analyses of variance (ANOVAs). In addition, total work (TW) during 12 sessions were recorded and analyzed with 1-way ANOVA. Significant (p < 0.05) differences were found for TW (10-5-SIT: 907.3 ± 332.0, 20-10-SIT: 1230.0 ± 188.1, and MICT: 2263.0 ± 896.9 calories) between groups. A significant main effect of time was observed for 10-5-SIT, 20-10-SIT, and MICT (p < 0.05) in TTE (increased by 7.3, 8.7, and 8.2%), A-V̇o2max (increased by 13.0, 11.8, and 13.6%), R-V̇o2max (increased by 12.6, 12.1, and 14.8%), and METs (increased by 12.7, 12.3, and 14.9%), respectively. Despite less volume and duration, both SIT protocols induced cardiorespiratory adaptations similar to MICT. These findings suggest that performing SIT on a stationary air bike is valuable because of time-efficiency and cardiorespiratory adaptations.

Periodontitis and progression of gastrointestinal cancer: current knowledge and future perspective.

Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related to periodontitis pathogenesis and were found to be abundant in the intestinal mucosa of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. Besides, periodontal infections have been found in a variety of tissues and organs, indicating that periodontitis is not just an inflammation limited to the oral cavity. Considering the possible translocation of pathobiont from the oral cavity to the gastrointestinal (GI) tract, this study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the relationship between periodontitis and GI malignancies by focusing on the oral/gut axis.

Economic Burden of Asthma in Northwest Iran.

Background: The economic burden of asthma is a major public health concern. This study estimates the economic burden of asthma in Northwest of Iran. Methods: A longitudinal study was conducted between 2017 and 2018 in Tabriz (Iran) using the Persian version of the Work Productivity and Activity Impairment (WPAI) questionnaire. Direct and indirect costs associated with asthma were estimated based on the societal perspective, prevalence-based approach, and bottom-up method. Annual indirect costs were estimated using the human capital (HC) method. The structural equation model was used to evaluate the relationship between costs, sex, and asthma severity. Results: A total of 621 patients with asthma were enrolled in the study. Significant differences were found between female and male patients for the mean cost of radiology (P=0.006), laboratory (P=0.028), and diagnostic (P=0.017) tests at baseline, and for laboratory (P=0.012), and diagnostic (P=0.027) tests at one-year follow-up. The more severe asthma, the more significant the costs for annual physician office visits (P=0.040) and medications (P=0.013). As asthma severity increased, significantly higher expenditures were observed in women for days lost from work at baseline (P=0.009) and one-year follow-up (P=0.001), and in men for productivity loss at work due to impairment at baseline (P=0.045). A significant association between indirect costs and the cost of impairment-related lost productivity at work (ß=3.29, P<0.001), and between severe asthma and indirect costs (ß=32.36, P<0.001) was observed. Conclusion: High costs are incurred by Iranian asthma patients, especially because of impairment-related productivity loss at work associated with asthma exacerbation.

The effect of aerobic exercise on metabolic parameters of patients with non-alcoholic fatty liver disease: systematic review and meta-analysis.

INTRODUCTION: The aim of this study was to determine and evaluate the effect of aerobic exercise on fasting blood glucose, Insulin, Insulin resistance, Glycosylated hemoglobin (Hemoglobin A1C), Lipid profile as important indicators of non-alcoholic fatty liver disease. EVIDENCE ACQUISITION: This research is a systematic review and meta-analysis that was conducted in 2021. For the present study, databases, ScienceDirect, PubMed, Scopus, science of Web, SID, Magiran and Google Scholar from 2010 to 2021, were searched along with keywords. After the initial screening, the full text of the articles was evaluated and the articles that met the inclusion criteria were analyzed. A total of 120 articles were reviewed, of which 16 articles met the criteria for entering the systematic review and meta-analysis. Accordingly, 710 people with fatty liver disease were divided into two groups of control and experimental group of 307 and 403 people, respectively. The mean age of the subjects in the present study was 52±10 years. The intervention effects were evaluated using the mean difference (MD) and the random effects model. Data were analyzed using effect size tests, bias analysis and heterogeneity analysis and by STATA software. EVIDENCE SYNTHESIS: Meta-analysis results indicated that endurance training in general significantly reduced glucose levels (P=0.004, SDM=-0.26, SE=0.09), insulin (P=0.01, SDM=-0.29, SE=0.11), HOMA-IR (P=0.01, SDM=-0.28, SE=0.11), Hba1c (P=0.001, SDM=-0.33, SE=0.12), triglycerides (P=0.02, SDM=-0.31, SE=0.13) and LDL (P=0.03, SDM=-0.21, SE=0.1). CONCLUSIONS: The results of meta-analysis did not show a significant effect on HDL levels after aerobic exercise in patients with fatty liver (P=0.97, SDM=0, SE=0.09). Endurance training improves the levels of glucose, insulin, Hba1c, Homa-IR, triglyceride, and LDL; although, there was no significant change in HDL levels due to endurance training. However, there is still a need for further research in this area.

Anti-inflammatory mechanisms of polyphenols in adipose tissue: role of gut microbiota, intestinal barrier integrity and zinc homeostasis.

Obesity is associated with an imbalance of micro-and macro-nutrients, gut dysbiosis, and a "leaky" gut phenomenon. Polyphenols, such as curcumin, resveratrol, and anthocyanins may alleviate the systemic effects of obesity, potentially by improving gut microbiota, intestinal barrier integrity (IBI), and zinc homeostasis. The essential micronutrient zinc plays a crucial role in the regulation of enzymatic processes, including inflammation, maintenance of the microbial ecology, and intestinal barrier integrity. In this review, we focus on IBI- which prevents intestinal lipopolysaccharide (LPS) leakage - as a critical player in polyphenol-mediated protective effects against obesity-associated white adipose tissue (WAT) inflammation. This occurs through mechanisms that block the movement of the bacterial endotoxin LPS across the gut barrier. Available research suggests that polyphenols reduce WAT and systemic inflammation via crosstalk with inflammatory NF-κB, the mammalian target of rapamycin (mTOR) signaling and zinc homeostasis.

Anti-Inflammatory Mechanisms of Curcumin and Its Metabolites in White Adipose Tissue and Cultured Adipocytes.

The plant-derived polyphenol curcumin alleviates the inflammatory and metabolic effects of obesity, in part, by reducing adipose tissue inflammation. We hypothesized that the benefits of curcumin supplementation on diet-induced obesity and systemic inflammation in mice occur through downregulation of white adipose tissue (WAT) inflammation. The hypothesis was tested in adipose tissue from high-fat diet-induced obese mice supplemented with or without curcumin and in 3T3-L1 adipocytes treated with or without curcumin. Male B6 mice were fed a high-fat diet (HFD, 45% kcal fat) with or without 0.4% (w/w) curcumin supplementation (HFC). Metabolic changes in these mice have been previously reported. Here, we determined the serum levels of the curcumin metabolites tetrahydrocurcumin (THC) and curcumin-O-glucuronide (COG) using mass spectrometry. Moreover, we determined interleukin 6 (IL-6) levels and proteomic changes in LPS-stimulated 3T3-L1 adipocytes treated with or without curcumin by using immunoassays and mass spectrometry, respectively, to gain further insight into any altered processes. We detected both curcumin metabolites, THC and COG, in serum samples from the curcumin-fed mice. Both curcumin and its metabolites reduced LPS-induced adipocyte IL-6 secretion and mRNA levels. Proteomic analyses indicated that curcumin upregulated EIF2 and mTOR signaling pathways. Overall, curcumin exerted anti-inflammatory effects in adipocytes, in part by reducing IL-6, and these effects may be linked to the upregulation of the mTOR signaling pathway, warranting additional mechanistic studies on the effects of curcumin and its metabolites on metabolic health.

Identification of a novel secreted metabolite cyclo(phenylalanyl-prolyl) from Batrachochytrium dendrobatidis and its effect on Galleria mellonella.

BACKGROUND: The fungus, Batrachochytrium dendrobatidis, is the causative agent of chytridiomycosis and a leading cause of global decline in amphibian populations. The first stages of chytridiomycosis include: inflammation, hyperkeratosis, lethargy, loss of righting reflex, and disruption of internal electrolyte levels leading to eventual death of the host. Previous work indicates that B. dendrobatidis can produce immunomodulatory compounds and other secreted molecules that regulate the growth of the fungus. In this study, filtrates of the fungus grown in media and water were subjected to ultra-performance liquid chromatography-mass spectrometry and analyzed using Compound Discoverer 3.0. RESULTS: Identification of cyclo(phenylalanyl-prolyl), chitobiose, and S-adenosylmethionine were verified by their retention times and fragmentation patterns from B. dendrobatidis supernatants. Previous studies have analyzed the effects of B. dendrobatidis on amphibian models, in vitro, or in cell culture. We studied the effects of live B. dendrobatidis cells, spent culture filtrates containing secreted metabolites, and cyclo(pheylalanyl-prolyl) on wax moth larvae (Galleria mellonella). Concentrated filtrates caused melanization within 24 h, while live B. dendrobatidis caused melanization within 48 h. CONCLUSIONS: Here we show B. dendrobatidis produces secreted metabolites previously unreported. The impacts of these chemicals were tested on an alternate non-amphibian model system that has been used for other fungi to study pathogenicity traits in this fungus.

Branched-Chain Amino Acids Are Linked with Alzheimer's Disease-Related Pathology and Cognitive Deficits.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder with a complex pathophysiology. Type 2 diabetes (T2D) is a strong risk factor for AD that shares similar abnormal features including metabolic dysregulation and brain pathology such as amyloid and/or Tau deposits. Emerging evidence suggests that circulating branched-chain amino acids (BCAAs) are associated with T2D. While excess BCAAs are shown to be harmful to neurons, its connection to AD is poorly understood. Here we show that individuals with AD have elevated circulating BCAAs and their metabolites compared to healthy individuals, and that a BCAA metabolite is correlated with the severity of dementia. APPSwe mouse model of AD also displayed higher plasma BCAAs compared to controls. In pursuit of understanding a potential causality, BCAA supplementation to HT-22 neurons was found to reduce genes critical for neuronal health while increasing phosphorylated Tau. Moreover, restricting BCAAs from diet delayed cognitive decline and lowered AD-related pathology in the cortex and hippocampus in APP/PS1 mice. BCAA restriction for two months was sufficient to correct glycemic control and increased/restored dopamine that were severely reduced in APP/PS1 controls. Treating 5xFAD mice that show early brain pathology with a BCAA-lowering compound recapitulated the beneficial effects of BCAA restriction on brain pathology and neurotransmitters including norepinephrine and serotonin. Collectively, this study reveals a positive association between circulating BCAAs and AD. Our findings suggest that BCAAs impair neuronal functions whereas BCAA-lowering alleviates AD-related pathology and cognitive decline, thus establishing a potential causal link between BCAAs and AD progression.

Mattress Coil Spring Fatigue and Weight-Bearing Support: Comparison of Weight-Bearing and Non-Weight-Bearing Springs.

OBJECTIVE: The purpose of this study was to compare the firmness of used mattress coil springs from the areas bearing greatest body weight versus areas subjected to little compression. METHODS: Weight-bearing springs (WBS) extracted from the center of the mattresses (N = 32), and non-weight-bearing springs (NWBS) extracted from the head/foot were of the same mattresses. To determine spring weakness, a 1296-g ingot was placed on the coil, and the compression distance was measured (cm). In addition, a gauge was used to measure the amount of pressure required to compress the coil springs a distance of 2 cm. Comparison between WBS and NWBS data were statistically treated using independent t tests and a 1-way analysis of variance. RESULTS: There were no significant group differences in weight or height in unloaded coils. However, there were significant (P < .05) differences in coil spring compression distance under load (WBS = 2.78 ± 0.34 cm; NWBS = 1.52 ± 0.39 cm) and force gauge compression (WBS = 1090.51 ± 88.42 g; NWBS = 1213.12 ± 71.38 g) between groups. CONCLUSION: This study found that WBSs were weaker when compressed than the NWBS from used mattresses, and such characteristics may not be visually apparent in a mattress when not in use. Thus, coil springs in bedding systems may eventually fail to provide the initial structural support after use. Such sagging may compromise sleep posture with accompanying poor sleep quality and quantity.

The Effects of Vision-Deprived Progressive Resistance Training on One-Repetition Maximum Bench Press Performance: An Exploratory Study.

The objective of this study was to determine whether vision-occluded progressive resistance training would increase upper-extremity movement performance using the one-repetition maximum (1-RM) bench press. Participants (n = 57) were recruited from a historically black college and university (HBCU), cross-matched by sex, age (±1 year), 1-RM (±2.27 kg), 1-RM/weight (±0.1), and 1-RM/lean mass ratio (±0.1), and randomly assigned to either the experimental group (vision occluded) or the control group. Participants performed resistance training for 6 weeks prior to beginning the study, and 1-RM was assessed the week prior to the beginning of the study. Weight and body composition were measured using a BOD POD. Of the 57 participants who started the study, 34 completed the study (Experimental = 16, Control = 18) and were reassessed the week after completing the 6-week-long training protocol. Using a combination of Mann−Whitney U and Wilcoxon signed-rank tests, we found that when accounting for changes in lean muscle mass, individuals who trained with their vision occluded reported significantly greater improvements in 1-RM strength compared to those who did not (p < 0.05). The findings from our study suggest that vision-occluded progressive resistance training increases upper-extremity performance when assessed using the bench press. These findings may have significant practical implications in both sports and rehabilitation, as these techniques may be used to enhance performance in athletes and/or improve rehabilitation effectiveness.

Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the ß1 integrin-RhoA-formin axis.

Lymphangiogenesis is an essential physiological process but also a determining factor in vascular-related pathological conditions. Angiopoietin-2 (Ang2) plays an important role in lymphatic vascular development and function and its upregulation has been reported in several vascular-related diseases, including cancer. Given the established role of the small GTPase RhoA on cytoskeleton-dependent endothelial functions, we investigated the relationship between RhoA and Ang2-induced cellular activities. This study shows that Ang2-driven human dermal lymphatic endothelial cell migration depends on RhoA. We demonstrate that Ang2-induced migration is independent of the Tie receptors, but dependent on ß1 integrin-mediated RhoA activation with knockdown, pharmacological approaches, and protein sequencing experiments. Although the key proteins downstream of RhoA, Rho kinase (ROCK) and myosin light chain, were activated, blockade of ROCK did not abrogate the Ang2-driven migratory effect. However, formins, an alternative target of RhoA, were identified as key players, and especially FHOD1. The Ang2-RhoA relationship was explored in vivo, where lymphatic endothelial RhoA deficiency blocked Ang2-induced lymphangiogenesis, highlighting RhoA as an important target for anti-lymphangiogenic treatments.

Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation.

Neuroinflammation is a central factor in neuropathic pain (NP). Ginger is a promising bioactive compound in NP management due to its anti-inflammatory property. Emerging evidence suggests that gut microbiome and gut-derived metabolites play a key role in NP. We evaluated the effects of two ginger root extracts rich in gingerols (GEG) and shogaols (SEG) on pain sensitivity, anxiety-like behaviors, circulating cell-free mitochondrial DNA (ccf-mtDNA), gut microbiome composition, and fecal metabolites in rats with NP. Sixteen male rats were divided into four groups: sham, spinal nerve ligation (SNL), SNL+0.75%GEG in diet, and SNL+0.75%SEG in diet groups for 30 days. Compared to SNL group, both SNL+GEG and SNL+SEG groups showed a significant reduction in pain- and anxiety-like behaviors, and ccf-mtDNA level. Relative to the SNL group, both SNL+GEG and SNL+SEG groups increased the relative abundance of Lactococcus, Sellimonas, Blautia, Erysipelatoclostridiaceae, and Anaerovoracaceae, but decreased that of Prevotellaceae UCG-001, Rikenellaceae RC9 gut group, Mucispirillum and Desulfovibrio, Desulfovibrio, Anaerofilum, Eubacterium siraeum group, RF39, UCG-005, Lachnospiraceae NK4A136 group, Acetatifactor, Eubacterium ruminantium group, Clostridia UCG-014, and an uncultured Anaerovoracaceae. GEG and SEG had differential effects on gut-derived metabolites. Compared to SNL group, SNL+GEG group had higher level of 1'-acetoxychavicol acetate, (4E)-1,7-Bis(4-hydroxyphenyl)-4-hepten-3-one, NP-000629, 7,8-Dimethoxy-3-(2-methyl-3-buten-2-yl)-2H-chromen-2-one, 3-{[4-(2-Pyrimidinyl)piperazino]carbonyl}-2-pyrazinecarboxylic acid, 920863, and (1R,3R,7R,13S)-13-Methyl-6-methylene-4,14,16-trioxatetracyclo[11.2.1.0∼1,10∼.0∼3,7∼]hexadec-9-en-5-one, while SNL+SEG group had higher level for (±)-5-[(tert-Butylamino)-2'-hydroxypropoxy]-1_2_3_4-tetrahydro-1-naphthol and dehydroepiandrosteronesulfate. In conclusion, ginger is a promising functional food in the management of NP, and further investigations are necessary to assess the role of ginger on gut-brain axis in pain management.

Curcumin Reduces Adipose Tissue Inflammation and Alters Gut Microbiota in Diet-Induced Obese Male Mice.

SCOPE: Obesity prevalence continues to increase and contribute to metabolic diseases, potentially by driving systemic inflammation. Curcumin is an anti-inflammatory spice with claimed health benefits. However, mechanisms by which curcumin may reduce obesity-associated inflammation are poorly understood; thus, it is hypothesized that benefits of curcumin consumption may occur through reduced white adipose tissue (WAT) inflammation and/or beneficial changes in gut bacteria. METHODS AND RESULTS: Male B6 mice are fed high-fat diets (HFD, 45% kcal fat) or HFD supplemented with 0.4% (w/w) curcumin (HFC) for 14 weeks. Curcumin supplementation significantly reduces adiposity and total macrophage infiltration in WAT, compared to HFD group, consistent with reduced mRNA levels of M1 (Cd80, Cd38, Cd11c) and M2 (Arginase-1) macrophage markers. Moreover, curcumin supplementation reduces expression of other key pro-inflammatory genes, such as NF-κB p65 subunit (p65), Stat1, Tlr4, and Il6, in WAT (p < 0.05). Using microbial 16S RNA sequencing, it is demonstrated that the relative abundance of the Lactococcus, Parasutterella, and Turicibacter genera are increased in the HFC group versus HFD. CONCLUSIONS: Curcumin exerts protective metabolic effects in dietary obesity, in part through downregulation of adipose tissue inflammation, which may be mediated by alterations in composition of gut microbiota, and metabolism of curcumin into curcumin-O-glucuronide.

Drug-Induced Lipid Remodeling in Leishmania Parasites.

Leishmania parasites efficiently develop resistance against several types of drugs including antimonials, the primary antileishmanial drug historically implemented. The resistance to antimonials is considered to be a major risk factor for effective leishmaniasis treatment. To detect biomarkers/biopatterns for the differentiation of antimony-resistant Leishmania strains, we employed untargeted global mass spectrometry to identify intracellular lipids present in antimony sensitive and resistant parasites before and after antimony exposure. The lipidomic profiles effectively differentiated the sensitive and resistant phenotypes growing with and without antimony pressure. Resistant phenotypes were characterized by significant downregulation of phosphatidylcholines, sphingolipid decrease, and lysophosphatidylcholine increase, while sensitive phenotypes were characterized by the upregulation of triglycerides with long-chain fatty acids and a tendency toward the phosphatidylethanolamine decrease. Our findings suggest that the changes in lipid composition in antimony-resistant parasites contribute to the physiological response conducted to combat the oxidative stress unbalance caused by the drug. We have identified several lipids as potential biomarkers associated with the drug resistance.

Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease.

Advances in large-scale proteomics analysis have been very useful in understanding pathogenesis of diseases and elaborating therapeutic strategies. Proteomics has been employed to study Parkinson disease (PD); however, sparse studies reported proteome investigation after cell therapy approaches. In this study, we used liquid chromatography-tandem mass spectrometry and systems biology to identify differentially expressed proteins in a translational mouse model of PD after cell therapy. Proteins were extracted from five nigrostriatal-related brain regions of mice previously lesioned with 6-hydroxydopamine in the substantia nigra. Protein expression was compared in non-grafted brain to 1 and 7 days after intranigral grafting of E12.5 embryonic ventral mesencephalon (VM). We found a total of 277 deregulated proteins after transplantation, which are enriched for lipid metabolism, oxidative phosphorylation and PD, thus confirming that our animal model is similar to human PD and that the presence of grafted cells modulates the expression of these proteins. Notably, seven proteins (Acta1, Atp6v1e1, Eci3, Lypla2, Pip4k2a, Sccpdh, and Sh3gl2) were commonly down-regulated after engraftment in all studied brain regions. These proteins are known to be involved in the formation of lipids and recycling of dopamine (DA) vesicle at the synapse. Moreover, intranigral transplantation of VM cells decreased the expression of proteins related to oxidative stress, especially in the nigrostriatal pathway containing the DA grafted neurons. In the same regions, an up-regulation of several proteins including α-synuclein and tyrosine hydroxylase was observed, whereas expression of tetraspanin 7 was shut down. Overall, these results suggest that intranigral transplantation of VM tissue in an animal model of PD may induce a decrease of oxidative stress in the nigrostriatal pathway and a restoration of the machinery of neurotransmitters, particularly DA release to promote DA transmission through a decrease of D2 DA receptors endocytosis. Identification of new mechanistic elements involved in the nigrostriatal reconstruction process, using translational animal models and systems biology, is a promising approach to enhance the repair of this pathway in PD patients undergoing cell therapy.

Browning white adipose tissue using adipose stromal cell-targeted resveratrol-loaded nanoparticles for combating obesity.

Enhancing thermogenic energy expenditure via promoting the browning of white adipose tissue (WAT) is a potential therapeutic strategy to manage energy imbalance and the consequent comorbidities associated with excess body weight. Adverse effects and toxicities of currently available methods to induce browning of WAT have retarded exploration of this promising therapeutic approach. Targeted delivery of browning agents to adipose stromal cells (ASCs) in subcutaneous WAT to induce differentiation into beige adipocytes may overcome these barriers. Herein, we report for the first time, ASC-targeted delivery of trans-resveratrol (R), a representative agent, using ligand-coated R-encapsulated nanoparticles (L-Rnano) that selectively bind to glycanation site-deficient decorin receptors on ASCs. After biweekly intravenous administration of L-Rnano to obese C57BL/6 J mice for 5 weeks targeted R delivery significantly induced ASCs differentiation into beige adipocytes, which subsequently resulted in 40% decrease in fat mass, accompanied by improved glucose homeostasis and decreased inflammation. Our results suggest that the ASC-targeted nanoparticle delivery of browning agents could be a transformative technology in combating obesity and its comorbidities with high efficacy and low toxicity.

Novel and Transgressive Salinity Tolerance in Recombinant Inbred Lines of Rice Created by Physiological Coupling-Uncoupling and Network Rewiring Effects.

The phenomenon of transgressive segregation, where a small minority of recombinants are outliers relative to the range of parental phenotypes, is commonly observed in plant breeding populations. While this phenomenon has been attributed to complementation and epistatic effects, the physiological and developmental synergism involved have not been fully illuminated by the QTL mapping approach alone, especially for stress-adaptive traits involving highly complex interactions. By systems-level profiling of the IR29 × Pokkali recombinant inbred population of rice, we addressed the hypothesis that novel salinity tolerance phenotypes are created by reconfigured physiological networks due to positive or negative coupling-uncoupling of developmental and physiological attributes of each parent. Real-time growth and hyperspectral profiling distinguished the transgressive individuals in terms of stress penalty to growth. Non-parental network signatures that led to either optimal or non-optimal integration of developmental with stress-related mechanisms were evident at the macro-physiological, biochemical, metabolic, and transcriptomic levels. Large positive net gain in super-tolerant progeny was due to ideal complementation of beneficial traits while shedding antagonistic traits. Super-sensitivity was explained by the stacking of multiple antagonistic traits and loss of major beneficial traits. The synergism uncovered by the phenomics approach in this study supports the modern views of the Omnigenic Theory, emphasizing the synergy or lack thereof between core and peripheral components. This study also supports a breeding paradigm rooted on genomic modeling from multi-dimensional genetic, physiological, and phenotypic profiles to create novel adaptive traits for new crop varieties of the 21st century.