Rapid Rebound of the Treg Compartment in DEREG Mice Limits the Impact of Treg Depletion on Mycobacterial Burden,but Prevents Autoimmunity

The development of an effective vaccine against tuberculosis (Tb) represents one of the major medical challenges of this century. Mycobacterium bovis Bacille Calmette-Guerin (BCG), the only vaccine available at present, is mostly effective at preventing disseminated Tb in children, but shows variable protection against pulmonary Tb, the most common form in adults. The reasons for this poor efficacy are not completely understood, but there is evidence that T regulatory cells (Tregs) might be involved. Similarly, Tregs have been associated with the immunosuppression observed in patients infected with Tb and are therefore believed to play a role in pathogen persistence. Thus, Treg depletion has been postulated as a novel strategy to potentiate M. bovis BCG vaccination on one side, while on the other, employed as a therapeutic approach during chronic Tb infection. Yet since Tregs are critically involved in controlling autoimmune inflammation, elimination of Tregs may therefore also incur the danger of an excessive inflammatory immune response. Thus, understanding the dynamics and function of Tregs during mycobacterial infection is crucial to evaluate the potential of Treg depletion as a medical option. To address this, we depleted Tregs after infection with M. bovis BCG or Mycobacterium tuberculosis (Mtb) using DEREG mice, which express the diphtheria toxin (DT) receptor under the control of the FoxP3 locus, thereby allowing the selective depletion of FoxP3⁺ Tregs. Our results show that after depletion, the Treg niche is rapidly refilled by a population of DT-insensitive Tregs (diTregs) and bacterial load remains unchanged. On the contrary, impaired rebound of Tregs in DEREG × FoxP3^GFP mice improves pathogen burden, but is accompanied by detrimental autoimmune inflammation. Therefore, our study provides the proof-of-principle that, although a high degree of Treg depletion may contribute to the control of mycobacterial infection, it carries the risk of autoimmunity.     

Nitrate Reductase is Needed for Methyl Jasmonate-Mediated Arsenic Toxicity Tolerance of Rice by Modulating the Antioxidant Defense System,Glyoxalase System and Arsenic Sequestration Mechanism

Journal of Plant Growth Regulation - The study was conducted to consider the role of nitrate reductase (NR)-synthesized nitric oxide (NO) in the methyl jasmonate (MJ)-induced tolerance of arsenic...     

Diversity of Medicinal and Food Plants as Non-timber Forest Products in Naban River Watershed National Nature Reserve (China): Implications for Livelihood Improvement and Biodiversity Conservation

Diversity of Medicinal and Food Plants as Non-timber Forest Products in Naban River Watershed National Nature Reserve (China): Implications for Livelihood Improvement and Biodiversity Conservation. Non-timber forest products (NTFPs) play an important role in rural livelihoods. People living in and around forests are dependent on a variety of NTFPs for their subsistence and for income generation. This paper gives a general overview on the diversity of NTFPs in the Naban River Watershed National Nature Reserve, with a focus on medicinal and food plants. Data on NTFPs use were gathered through an ethnobotanical inventory with semistructured, free-listing, and household socioeconomic interviews. Interviews were supplemented with voucher collections. Bamboo shoots were analyzed further as proxy NTPF. It was hypothesized that there is no significant difference between collection amounts of bamboo shoots and their contribution to the household income between the villages studied. A rapid vulnerability assessment (RVA) was conducted to identify vulnerable and threatened species. A total of 480 plant species (25% of recorded flora) from 117 families and 334 genera are used as NTFPs by the local people. Results revealed that there is a significant difference in the collection and contribution of bamboo shoots to household income among the villages. However, their contribution to per-capita income is very low, and they are mainly used in households. Vulnerability assessment showed that most of the medicinal species have moderate vulnerable status and that most of the food species have less vulnerable status. Some medicinal plants, such as Paris polyphylla var. yunnanensis, are overexploited and getting scarce. Sustainable harvest and management strategies should be implemented to prevent overexploitation of these species.     

Targeted drug delivery of magnetic microbubble for abdominal aortic aneurysm: an in silico study

Biomechanics and Modeling in Mechanobiology - Targeted drug delivery (TDD) to abdominal aortic aneurysm (AAA) using a controlled and efficient approach has recently been a significant challenge. In...     

Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes

Background

Although obesity and cardiometabolic traits commonly overlap, underlying pathways remain incompletely defined. The association of metabolite profiles across multiple cardiometabolic traits may lend insights into the interaction of obesity and metabolic health. We sought to investigate metabolic signatures of obesity and related cardiometabolic traits in the community using broad-based metabolomic profiling.

Methods and Results

We evaluated the association of 217 assayed metabolites and cross-sectional as well as longitudinal changes in cardiometabolic traits among 2,383 Framingham Offspring cohort participants. Body mass index (BMI) was associated with 69 of 217 metabolites (P<0.00023 for all), including aromatic (tyrosine, phenylalanine) and branched chain amino acids (valine, isoleucine, leucine). Additional metabolic pathways associated with BMI included the citric acid cycle (isocitrate, alpha-ketoglutarate, aconitate), the tryptophan pathway (kynurenine, kynurenic acid), and the urea cycle. There was considerable overlap in metabolite profiles between BMI, abdominal adiposity, insulin resistance [IR] and dyslipidemia, modest overlap of metabolite profiles between BMI and hyperglycemia, and little overlap with fasting glucose or elevated blood pressure. Metabolite profiles were associated with longitudinal changes in fasting glucose, but the involved metabolites (ornithine, 5-HIAA, aminoadipic acid, isoleucine, cotinine) were distinct from those associated with baseline glucose or other traits. Obesity status appeared to “modify” the association of 9 metabolites with IR. For example, bile acid metabolites were strongly associated with IR among obese but not lean individuals, whereas isoleucine had a stronger association with IR in lean individuals.

Conclusions

In this large-scale metabolite profiling study, body mass index was associated with a broad range of metabolic alterations. Metabolite profiling highlighted considerable overlap with abdominal adiposity, insulin resistance, and dyslipidemia, but not with fasting glucose or blood pressure traits.     

A new aqueous biphasic system containing polypropylene glycol and a water-miscible ionic liquid

In this work, we proposed a novel aqueous biphasic system (ABS) composed of polypropylene glycol P400 (PPG P400) and hydrophilic ionic liquids (IL), 1-alkyl-3-methylimidazolium bromide (alkyl = ethyl or butyl), forming an upper polymer-rich phase and a lower IL-rich phase at ambient temperature. This new ABS can present interesting characteristics shared by ILs and polymers such as low volatility, good solvation ability, tunable physical properties, and high design capacity for achieving task-specific phase components to enhance the partitioning of target species. Ternary phase diagram of the novel ABS formed by PPG 400 and [C(2) mim]Br in water was measured at T = 298.15 K. Factors affecting the binodal curves such as the cation side alkyl chain length and the temperature were also evaluated. The results were successfully interpreted in terms of the kosmotropic/chaotropic nature of ILs. Furthermore, the phase behavior of the PPG-[C(2) mim]Br ABS is described by the NRTL model. Finally, the extraction potential of the proposed ABS was evaluated through its application to the extraction of the essential amino acids such as L-tryptophan and L-tyrosine. The partition coefficients here obtained demonstrated the fine potential of the proposed ABS for biomolecules separation.     

Induction of broad cross-subtype-specific HIV-1 immune responses by a novel multivalent HIV-1 peptide vaccine in cynomolgus macaques

One of the major obstacles in the design of an effective vaccine against HIV-1 is its antigenic variation, which results in viral escape from the immune system. Through a bioinformatics approach, we developed an innovative multivalent HIV-1 vaccine comprised of a pool of 176 lipidated and nonlipidated peptides representing variable regions of Env and Gag proteins. The potency and breadth of the candidate vaccine against a panel of HIV-1 subtypes was evaluated in nonhuman primate (cynomolgus macaques) and humanized mouse (HLA-A2.1) models. The results demonstrate strong immunogenicity with both breadth (humoral and cellular immunity) and depth (immune recognition of widely divergent viral sequences) against heterologous HIV-1 subtypes A-F.     

Regenerative potential of Wharton's jelly-derived mesenchymal stem cells: A new horizon of stem cell therapy

Umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have recently gained considerable attention in the field of regenerative medicine. Their high proliferation rate, differentiation ability into various cell lineages, easy collection procedure, immuno-privileged status, nontumorigenic properties along with minor ethical issues make them an ideal approach for tissue repair. Besides, the number of WJ-MSCs in the umbilical cord samples is high as compared to other sources. Because of these properties, WJ-MSCs have rapidly advanced into clinical trials for the treatment of a wide range of disorders. Therefore, this paper summarized the current preclinical and clinical studies performed to investigate the regenerative potential of WJ-MSCs in neural, myocardial, skin, liver, kidney, cartilage, bone, muscle, and other tissue injuries.     

Phytochemicals,Essential Oils Composition and Antioxidant Activity of Astragalus spp., Phlomis olivieri and Daphne mucronata in Habitats of Central Iran

This study evaluated several secondary metabolites, essential oils (EOs) compositions, and antioxidant activity in four medicinal plants that originated in Isfahan rangelands. The species were Astragalus verus, Astragalus adscendens, Daphne mucronata, and Phlomis olivieri. Thirty-two genotypes of these species were evaluated for different biochemical traits. Based on the evaluation of EOs compounds, GC/MS analysis revealed the total number of identified compounds. These compounds were 25, 22, 12, and 22 for A. adscendens, A. verus, D. mucronata, and P. olivieri, respectively. The dominant compounds were phthalate (59.88 %) in A. adscendens, phytol (38.02 %) in A. verus, hexanoic acid (32.05 %) in D. mucronata and β-cubebene (30.94 %) in P. olivieri. Phytochemical analysis showed that D. mucronata, A. adscendens, and P. olivieri had the highest total phenolics content (TPC) (18.24 mg gallic acid equivalent/g dry weight), total flavonoids content (5.57 mg QE/g DW), and total anthocyanins content (0.23 mg/g DW), respectively. The highest total chlorophyll (0.27 mg/g DW), total carotenoids (0.03 mg/g DW), and antioxidant activity (71.36 %) were observed in A. adscendens, A. adscendens and A. verus, respectively. Among all genotypes, the highest TPC (20.1 mg GAE/g DW) was observed in genotype 5 of D. mucronata. This study provided new information on the chemical compounds within the distribution range of these ecologically dominant rangeland species in Isfahan province, Iran. The data revealed that superior genotypes from these species are rich in natural antioxidants and bioactive compounds. Thus, they can be used in ethno pharmacological fields, food, and industrial applications.     

Cinnamon: does it hold its promises in cows? Using non-targeted blood serum metabolomics profiling to test the effects of feeding cinnamon to dairy cows undergoing lactation-induced insulin resistance

Introduction

Cinnamon exerts insulin-enhancing activity in vitro and was demonstrated to improve blood glucose and lipid profiles in several human studies. Such effects may have an impact on metabolically stressed cows.

Objective

To study the effects of cinnamon supplementation during the transition from late pregnancy to early lactation on the metabolism in dairy cows.

Methods

Twenty-four Holstein cows (n?=?8/group) were assigned to either the control group (CTR; without supplementation) or the supplementation groups [supplemental cinnamon at 20 (LCIN) or 40 (HCIN) g/cow per day (d)] from 28 d before calving until 21 d thereafter. Blood samples were assayed for glucose, nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and insulin; an index estimating insulin sensitivity (RQUICKI) was calculated. The serum metabolome was characterized in the samples collected from d 14 using a non-targeted approach.

Results

The serum concentrations of glucose and insulin did not differ among groups and followed a similar pattern over time. The serum NEFA concentrations were greater in LCIN (d 2, 7, and 14) and HCIN (d 14) than in CTR. On d 14 and 21, LCIN and HCIN had greater serum BHBA concentrations than CTR cows. The top 10 metabolites identified with significantly higher levels in the supplemented than the CTR cows were related to fatty acid metabolism.

Conclusion

The data suggest lipolytic and ketogenic effects of cinnamon supplementation in dairy cows during the transition from late gestation to early lactation. The fatty acid metabolites found elevated in the supplemented cows point towards impaired mitochondrial fatty acid β-oxidation.