Extracellular Caspase-1 induces hair stem cell migration in wounded and inflamed skin conditions.

The wound-healing process is a paradigm of the directed migration of various pools of stem cells from their niche to the site of injury where they replenish damaged cells. Two decades have elapsed since the observation that wounding activates multipotent hair follicle stem cells to infiltrate the epidermis, but the cues that coax these cells out of their niche remain unknown. Here, we report that Caspase-1, a protein classically known as an integral component of the cytosolic inflammasome, is secreted upon wounding and has a non-canonical role in the extracellular milieu. Through its caspase activation recruitment domain (CARD), Caspase-1 is sufficient to initiate the migration of hair follicle stem cells into the epidermis. Uncovering this novel function of Caspase-1 also facilitates a deeper understanding of the mechanistic basis of the epithelial hyperplasia found to accompany numerous inflammatory skin diseases.

Methionine uptake via the SLC43A2 transporter is essential for regulatory T-cell survival.

Cell death, survival, or growth decisions in T-cell subsets depend on interplay between cytokine-dependent and metabolic processes. The metabolic requirements of T-regulatory cells (Tregs) for their survival and how these are satisfied remain unclear. Herein, we identified a necessary requirement of methionine uptake and usage for Tregs survival upon IL-2 deprivation. Activated Tregs have high methionine uptake and usage to S-adenosyl methionine, and this uptake is essential for Tregs survival in conditions of IL-2 deprivation. We identify a solute carrier protein SLC43A2 transporter, regulated in a Notch1-dependent manner that is necessary for this methionine uptake and Tregs viability. Collectively, we uncover a specifically regulated mechanism of methionine import in Tregs that is required for cells to adapt to cytokine withdrawal. We highlight the need for methionine availability and metabolism in contextually regulating cell death in this immunosuppressive population of T cells.

Structure-Correlated Magnetic Resonance Transverse Relaxivity Enhancement in Superparamagnetic Ensembles with Complex Anisotropy Landscape.

The aim of the work is to explore structure-relaxivity relationship by observing transverse relaxivity enhancement in magnetic resonance imaging (MRI) of differently organized superparamagnetic complex ensembles of zinc ferrite isotropic/anisotropic nanosystems. We observe that superparamagnetic systems show a correlation of MRI-transverse relaxivity, r2/r1, with spatial arrangement of nanoparticles, as well as magnetic easy axes and thermal-energy-dependent anisotropy energy landscape. The presence of highly random/partially aligned easy axes with enhanced anisotropy constant leads to modulation in transverse relaxation. As a result, we achieve highest contrast efficiency in compact ensemble of isotropic nanoparticles and hollow core ensemble. Indeed, core-shell ensemble with combined effect of aligned and randomly oriented easy magnetic axes shows a reduction in MRI contrast efficiency. However, we address a hypothesis for transverse contrast efficiency where we depict the correlation among MRI-transverse contrast efficiency with structural complexity of ensembles, differently arranged primary nanoparticles/magnetic easy axes, anisotropy constant, and collective magnetic behavior. In consequence, we simplify the limitation of quantum mechanical outer-sphere diffusion model of magnetic resonance relaxivity by neglecting the contribution of magnetization and introducing an anisotropy constant contribution with complex structure landscape of easy axes.

The neuropeptide Substance P facilitates the transition from an inflammatory to proliferation phase-associated responses in dermal fibroblasts.

The wound healing process is a product of three successive and overlapping phases of inflammation, proliferation and remodelling. Considerable efforts have been invested in deconstructing the intercellular crosstalk that orchestrates tissue repair, and we investigated the role of neuropeptides released from peripheral neurons upon injury in mediating these interactions. Amongst the most abundant of these neuropeptides secreted by nerves in the skin, is Substance P (SP). Given the role of dermal fibroblasts in coordinating multiple processes in the wound healing program, the effect of SP on human dermal fibroblasts of different ages was evaluated. The use of a substrate that recapitulates the mechanical properties of the in vivo tissue revealed novel effects of SP on dermal fibroblasts, including a block in inflammatory cytokine expression. Moreover, SP can promote expression of some extracellular matrix components and generates signals that regulate angiogenesis. Interestingly, the response of fibroblasts to SP was reduced concomitant with donor age. Altogether, SP acts to inhibit the inflammatory responses and promote proliferation-associated responses in an age-dependent manner in dermal fibroblasts, suggesting a role as a molecular switch between the inflammatory and proliferative phases of the wound healing response.

Climate bond, stock, gold, and oil markets: Dynamic correlations and hedging analyses during the COVID-19 outbreak.

Adverse ecological effects have recently generated several eco-friendly investment opportunities including green and climate bonds. Although climate bonds have emerged as an appealing investment, little is known about their dynamic correlations and market linkages with US equities, crude oil, and gold markets, especially during stress times such as the COVID-19 outbreak, which are essential for asset allocation and hedging effectiveness. In this paper, we report time-varying correlations between climate bonds and each of the markets considered, which intensify during the COVID-19 pandemic. On average, climate bonds are negatively associated with US equities and have a near zero correlation with crude oil, whereas they are positively associated with gold. There is a bidirectional volatility linkage between climate bonds and the three indexes under study, whereas return linkages are marginal. The hedge ratio is positive for bond-gold, whereas it switches between positive and negative states for bond-stock and bond-oil, especially it switches more extremely during the COVID-19 outbreak. Although climate bonds provide the highest risk reduction in a portfolio containing US equities or gold as a part of a hedging strategy, their hedging effectiveness is considerably reduced during the pandemic. The findings have implications for markets participants aiming to green their portfolios and make them robust during stress times, enabling a smooth and speedy transition to a low-carbon economy.

Sting pathway - A futuristic therapeutic target for acute pancreatitis?

Acute Pancreatitis (AP) refers to the inflammatory state of the pancreatic mass caused by an abnormal release of digestive enzymes characterized by pancreatic acinar cell injury. It is mainly caused by gallstones, which primarily block sphincter of Oddi opening into the duodenum, heavyalcohol use, systemic diseases, etc. Stimulator of interferon genes known as STING uniquely senses the apoptotic and necrotic DNA fragments. Through the expression of TMEM173 (transmembrane protein 173) or STING protein in macrophages, downstream signaling pathways are activated in AP and are responsible for promoting inflammation. STING elicits a cascade of downstream signaling events such as activation of TBK1, IRF-3 phosphorylation, and IFN-ß production along with other cytokines, which result in the excessive manufacture of the type-I IFNs and different kinds of proinflammatory cytokines that take part in the immune defense system of the host. Research findings suggest that STING regulates an array of innate immunity pathways, and the absence of proper treatment measures for AP provides the opportunity of evaluating STING as a striking therapeutic target for AP associated inflammation. Although the understanding of STING hyperactivation and its association with inflammation is relative of recent interest among researchers, extensive studies are going on to identify inhibitors that can directly target STING and inhibits the downstream signaling in AP. Therefore, this review aims to collectively compile the available pieces of evidence, which could help to better understand the role of STING signaling in AP and its promising role as a therapeutic target.

Transcriptional cyclin-dependent kinases as the mediators of inflammation-a review.

Cyclin-dependent kinases (CDKs) belong to the serine/threonine kinase family, and their unique interactions with a variety of cyclin complexes influence its catalytic activity to ensure unimpaired cell cycle progression. In addition to their cell cycle regulatory roles, it is becoming increasingly clear that the CDKs can have multiple functional roles like transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions, and in spermatogenesis. Further in addition, recent reports suggest that CDKs have a remarkable regulatory role in influencing the pro-inflammatory functions of various cytokines during the clinical inflammatory responses. CDKs initiate the inflammatory responses by triggering the activity of prominent pro-inflammatory transcription factors such as nuclear factor kappa B (NF-kB), signal transducer and activator of transcription 3 (STAT3), and activator protein 1 (AP-1). The transcriptional CDKs (tCDKs) is crucial for organizing various transcription events and associated processes such as RNA capping, splicing, 3' end formation, and chromatin remodeling. Although the in-depth mechanism of certain mammalian CDKs is explored with respect to inflammation, the role of other tCDKs or any synergistic play among the members still remains unexplored. Until today, there is only supportive and palliative care available most of the inflammatory disorders, and thus it is the right time to explore novel pharmacological targets. In this regard, we focus on the pathophysiological role of CDK7, CDK8 and CDK9 and their impact on the development of inflammatory disorders within the mammals. Additionally, we discuss the potential trends of having tCDKs as a therapeutic target for fine-tuning inflammatory disorders.

COVID-19 and oil market crash: Revisiting the safe haven property of gold and Bitcoin.

The global crude oil market has experienced a significant downturn following the novel coronavirus outbreak (COVID-19) in December 2019. Thereafter, all the major oil markets have become extremely volatile, and investments in these markets could lead to substantial losses. This paper empirically investigates the time-varying correlations between gold and oil markets to examine whether gold is a safe haven asset for the international crude oil markets during the COVID-19 period. For the purpose of comparison, the safe haven property of Bitcoin is tested as well. The results of the time-varying correlations obtained through the DCC-GARCH model suggest that gold is a safe haven asset for global crude oil markets. Bitcoin, on the other hand, acts only as a diversifier for crude oil. The results further show that the portfolio risk is minimized when investors include oil and gold in their portfolio rather than holding assets in oil and Bitcoin markets. Given that financial downturn, terrorist attacks, pandemics and similar global events often play a crucial role in portfolio risk analysis, our results could be of interest to those who invest in oil, gold and Bitcoin markets.

Short communication: Effect of carbon emission trading on European Union butter prices.

Since its inception, the European Union (EU) carbon emission market has been vastly successful in reducing greenhouse gas emissions. Accordingly, the usage of environmentally friendly fuels (e.g., ethanol, biodiesel) has increased significantly over the last few years. Given that EU biodiesel is mainly produced from rapeseed oil and soybean oil, higher carbon taxes are likely to increase the demand of these important vegetable oils, which further affects the prices of its close substitute such as butter. Nevertheless, the association between the EU emission trading scheme and butter prices remains understudied. In this paper, we aim to fill this vacuum in the existing literature. Applying the autoregressive distributed lag bound testing procedure, we show that emission market seems to have a long-term effect on EU butter prices, implying that changes in the levels of carbon taxes will lead to changes in the price level of butter. These results are of vital importance to policymakers and investors.

Profile of Acute Liver Failure from North-east India and Its Differences from other Parts of the Country.

BACKGROUND: Acute liver failure (ALF) is a critical illness with a large number of viral and nonviral causes. Clinical course and etiologies in the Asian countries are different from those reported from the Western world and mortality is high. There may even be intracountry variations in large countries like India, which have differing culture, ethnicity, and environment. Data from North-east part of India is lacking. MATERIALS AND METHODS: Acute liver failure cases (>14 years of age) seen over a period of 8 years (n = 255) were studied at a Government Medical College in Assam for their etiological and other demographic profile. Viral serology was carried out and revalidated at a laboratory in New Delhi. RESULTS: Majority of cases were <30 years of age. Commonest etiology was nonviral (non-ABCE). Amongst viral causes, hepatitis A and E were common, while hepatitis B virus (HBV) was rare. Unknown herbal medication use was very frequent in our cases with a significantly higher mortality. Mortality was highest in cases in 3rd decade of life. Statistically, international normalized ratio (INR) was the strongest predictor of death. CONCLUSION: Unlike the rest of India, hepatitis virus is not the major cause of ALF in our part; hepatitis A being commoner than hepatitis E, and B is rare. Unknown herbal medications are major cause of mortality and is important medicosocial issue. Our study highlights the differences in the profile of ALF from other Indian and western studies, possibly due to sociocultural factors prevalent in this part. HOW TO CITE THIS ARTICLE: Das AK, Begum T, Kar P, Dutta A. Profile of Acute Liver Failure from North-east India and Its Differences from other Parts of the Country. Euroasian J Hepato-Gastroenterol 2016;6(2):111-115.

Negative regulation of natural killer cell in tumor tissue and peripheral blood of oral squamous cell carcinoma.

Natural killer (NK) cells are the key lymphocytes in solid tumors. Its activity is regulated by both germline encoded receptors and cytokine microenvironment. We conducted a case-control study to investigate the activation status of NK cell in oral squamous cell carcinoma (OSCC). NK cell activation was assessed in context of NK cell cytotoxicity and transcript expression of NK cell receptors (NKp46 and KIRs) and NK cell associated cytokines (IL-1ß, IL-2, IL-10, IL-12ß, IL-15, IL-18, IL-21, IFN-γ, TNF-α and TGF-ß). The results revealed possible mechanisms involved in reduced NK cell activation in peripheral circulation: quantitative deficiency of NK cell number and lowered cytotoxicity together with qualitative NK impairments caused by--(1) decreased expression of NK activating receptor NKp46, (2) increased expression of NK suppressive cytokines--IL-10 and TGF-ß and (3) induction of FOXP3(+)CTLA4(+) suppressor cells. On the other hand, in the tumor tissue, escape of NK immune surveillance appeared to be modulated by upregulation of TGF-ß and IL-10 together with downregulation of NK cell activating cytokines (IL-2, IL-12ß, IL-15, IL-18, IL-21 and IFN-γ) and NK receptors (NKp46 and KIRs). In addition, our study supported the earlier contention that TNF-α and IL-1ß expression levels may be used as markers of malignant transformation in oral leukoplakia. In conclusion, the study provided an insight into the negative regulation of NK cell in tumor tissue and peripheral blood of OSCC patients, which can be exploited to boost the current NK cell and cytokine based immunotherapy for the treatment of oral cancer.

Association of killer cell immunoglobulin-like receptor gene 2DL1 and its HLA-C2 ligand with family history of cancer in oral squamous cell carcinoma.

Killer cell immunoglobulin-like receptors (KIR) are involved in regulating natural killer cell activation through recognition of their human leukocyte antigen (HLA) class I ligands. We conducted a case-control study with 169 oral squamous cell carcinoma (OSCC) patients and 177 healthy participants to study the genomic diversity of KIR and HLA loci and KIR gene expression in context of family history of cancer (FHC) in OSCC. Polymerase chain reaction (PCR) sequence-specific priming approach was used to type 16 KIR genes in individuals. SSP-real-time PCR was used for HLA class I ligand genotyping and real-time quantitative reverse transcriptase PCR was used to determine the expression of KIR gene. KIR2DL1(+)-HLA-C2(+) genotype was higher and positively associated with OSCC. Notably, all KIR2DL1(+)-HLA-C2(+) genotypes occurred exclusively in patients with FHC, showing a strong positive association of KIR2DL1(+)-HLA-C2(+) genotype with FHC. In addition, all younger age group patients (<55 years) with FHC were positive for KIR2DL1(+)-HLA-C2(+) genotype suggesting association of the genotype with early onset of disease. RNA transcript abundance of inhibitory KIR2DL1 in FHC patients, particularly of lower age groups (<45 and 45-54 years), supports the contention. Further, KIR2DL3(+)-HLA-C(+) genotype was negatively associated with OSCC. Our findings suggest KIR2DL1(+)-HLA-C2(+) genotype as heritable risk factor in OSCC predisposing to OSCC at younger age. Interestingly, KIR2DL3(+)-HLA-C(+) genotype was seen to be protective in OSCC. This study may be useful towards cancer surveillance and early detection of oral cancer in patients with FHC.