Hemochromatosis drives acute lethal intestinal responses to hyperyersiniabactin-producing Yersinia pseudotuberculosis.

Hemachromatosis (iron-overload) increases host susceptibility to siderophilic bacterial infections that cause serious complications, but the underlying mechanisms remain elusive. The present study demonstrates that oral infection with hyperyersiniabactin (Ybt) producing Yersinia pseudotuberculosis Δfur mutant (termed Δfur) results in severe systemic infection and acute mortality to hemochromatotic mice due to rapid disruption of the intestinal barrier. Transcriptome analysis of Δfur-infected intestine revealed up-regulation in cytokine-cytokine receptor interactions, the complement and coagulation cascade, the NF-κB signaling pathway, and chemokine signaling pathways, and down-regulation in cell-adhesion molecules and Toll-like receptor signaling pathways. Further studies indicate that dysregulated interleukin (IL)-1ß signaling triggered in hemachromatotic mice infected with Δfur damages the intestinal barrier by activation of myosin light-chain kinases (MLCK) and excessive neutrophilia. Inhibiting MLCK activity or depleting neutrophil infiltration reduces barrier disruption, largely ameliorates immunopathology, and substantially rescues hemochromatotic mice from lethal Δfur infection. Moreover, early intervention of IL-1ß overproduction can completely rescue hemochromatotic mice from the lethal infection.

ER stress induces upregulation of transcription factor Tbx20 and downstream Bmp2 signaling to promote cardiomyocyte survival.

In the mammalian heart, fetal cardiomyocytes proliferate prior to birth; however, they exit the cell cycle shortly after birth. Recent studies show that adult cardiomyocytes re-enters the cell cycle postinjury to promote cardiac regeneration. The endoplasmic reticulum (ER) orchestrates the production and assembly of different types of proteins, and a disruption in this machinery leads to the generation of ER stress, which activates the unfolded protein response. There is a very fine balance between ER stress-mediated protective and proapoptotic responses. T-box transcription factor 20 (Tbx20) promotes embryonic and adult cardiomyocyte proliferation postinjury to restore cardiac homeostasis. However, the function and regulatory interactions of Tbx20 in ER stress-induced cardiomyopathy have not yet been reported. We show here that ER stress upregulates Tbx20, which activates downstream bone morphogenetic protein 2 (Bmp2)-pSmad1/5/8 signaling to induce cardiomyocyte proliferation and limit apoptosis. However, augmenting ER stress reverses this protective response. We also show that increased expression of tbx20 during ER stress is mediated by the activating transcription factor 6 arm of the unfolded protein response. Cardiomyocyte-specific loss of Tbx20 results in decreased cardiomyocyte proliferation and increased apoptosis. Administration of recombinant Bmp2 protein during ER stress upregulates Tbx20 leading to augmented proliferation, indicating a feed-forward loop mechanism. In in vivo ER stress, as well as in diabetic cardiomyopathy, the activity of Tbx20 is increased with concomitant increased cardiomyocyte proliferation and decreased apoptosis. These data support a critical role of Tbx20-Bmp2 signaling in promoting cardiomyocyte survival during ER stress-induced cardiomyopathies.

Pneumonic Plague Protection Induced by a Monophosphoryl Lipid A Decorated Yersinia Outer-Membrane-Vesicle Vaccine.

A new Yersinia pseudotuberculosis mutant strain, YptbS46, carrying the lpxE insertion and pmrF-J deletion is constructed and shown to exclusively produce monophosphoryl lipid A (MPLA) having adjuvant properties. Outer membrane vesicles (OMVs) isolated from YptbS46 harboring an lcrV expression plasmid, pSMV13, are designated OMV46-LcrV, which contained MPLA and high amounts of LcrV (Low Calcium response V) and displayed low activation of Toll-like receptor 4 (TLR4). Intramuscular prime-boost immunization with 30 µg of of OMV46-LcrV exhibited substantially reduced reactogenicity than the parent OMV44-LcrV and conferred complete protection to mice against a high-dose of respiratory Y. pestis challenge. OMV46-LcrV immunization induced robust adaptive responses in both lung mucosal and systemic compartments and orchestrated innate immunity in the lung, which are correlated with rapid bacterial clearance and unremarkable lung damage during Y. pestis challenge. Additionally, OMV46-LcrV immunization conferred long-term protection. Moreover, immunization with reduced doses of OMV46-LcrV exhibited further lower reactogenicity and still provided great protection against pneumonic plague. The studies strongly demonstrate the feasibility of OMV46-LcrV as a new type of plague vaccine candidate.

Design of an Acidic pH-Activated NIR Fluorescent Convertible Rhodamine-Hemicyanine Probe-Peptide Conjugate for Living Cancer Cell Active Targeted Selective Tracking of Lysosomes.

We have synthesized an acidic pH-activatable dual targeting ratiometric fluorescent probe-peptide conjugate using the SPPS protocol on Rink amide AM resin. Living carcinoma cell specific active targeting, successive cell penetration, and selective staining of lysosomes are accomplished. Real-time monitoring of lysosomes, 3D, and multicolor cancer cell imaging are also attained. The de novo design consists of the integration of multifunctionality into a single molecular scaffold, e. g., RGDS peptide residue to target cancer cell surface overexpressed receptor αVß3 integrin, live-cell penetrating organic unsymmetrical rhodamine-hemicyanine chromophore comprising a lysosome targeting morpholine group, and an acidic pH openable spiro-lactam ring for a visible-to-NIR switchable ratiometric response. Water-soluble fluorescent probe-peptide conjugate exhibits intramolecular spirolactamization at basic pH through Arg amide N. The visible spirolactam state predominantly exists at physiological and basic pH and can be switched to the highly conjugated NIR open amide state (λem=735 nm) through spiro-lactam ring opening triggered by acidic pH with a huge bathochromic shift (Δλabs=336 nm, ΔλFL=265 nm). Moreover, pH-sensitive ratiometric optical switching is achieved. This in situ acidic cancer cell lysosome activatable multifunctional fluorophore-peptide conjugate shows augmented molar absorptivity, enhanced quantum yield, and improved fluorescence lifetime at acidic lysosomal pH; negligible cytotoxicity; and dual targeted ratiometric imaging capability of living cancer cell selective lysosomes with a pKa value of 5.1.

Degradable Polymer-Based Nanoassemblies for Precise Targeting and Drug Delivery to Breast Cancer Cells without Affecting Normal Healthy Cells.

Stimuli-responsive amphiphilic polymers are known to be precursors to forming promising nanoarchitectonics with tunable properties for application in biomedical sciences. Currently, self-immolative polymers are widely recognized as an emerging class of responsive materials with excellent degradability, which is one of the crucial criteria for designing a robust drug delivery vehicle. Here, we design an amphiphilic polyurethane endowed with a redox-responsive self-immolative linker and a pH-responsive tertiary amine on the backbone, which forms entropy-driven nanoscale supramolecular assemblies (average hydrodynamic diameter ∼110 nm) and is programmed to disassemble in a redox environment (GSH) due to the degradation of the polymer in a self-immolative fashion. The nanoassembly shows efficient drug sequestration and release in a controlled manner in response to glutathione (10 mM). The tertiary amine residing on the surface of the nanoassembly becomes protonated in the tumor microenvironment (pH ∼ 6.4-6.8) and generates positively charged nanoassembly (ζ-potential = +36 mV), which enhances the cancer cell-selective cellular uptake. The biological evaluation of the drug-loaded nanoassembly revealed triple-negative breast cancer (MDAMB-231) selective internalization and cell death while shielding normal cells (RBCs or PBMCs) from off-targeting toxicity. We envision that polyurethane with a redox-responsive self-immolative linker might open up new opportunities for a completely degradable polyurethane-based nanocarrier for drug delivery and diagnosis applications.

Bioderived Lipoic Acid-Based Dynamic Covalent Nanonetworks of Poly(disulfide)s: Enhanced Encapsulation Stability and Cancer Cell-Selective Delivery of Drugs.

Dynamic covalent poly(disulfide)-based cross-linked nanoaggregates, termed nanonetworks (NNs), endowed with pH- and redox-responsive degradation features have been fabricated for stable noncovalent encapsulation and triggered cargo release in a controlled fashion. A bioderived lipoic acid-based Gemini surfactant-like amphiphilic molecule was synthesized for the preparation of nanoaggregates. It self-assembles by a entropy-driven self-assembly process in aqueous milieu. To further stabilize the self-assembled nanostructure, the core was cross-linked by ring-opening disulfide exchange polymerization (RODEP) of 1,2-dithiolane rings situated inside the core of the nanoaggregates. The cross-linked nanoaggregates, i.e., nanonetwork, are found to be stable in the presence of blood serum, and also, they maintain the self-assembled structure even below the critical aggregation concentration (CAC) as probed by dynamic light scattering (DLS) experiments. The nanonetwork showed almost 50% reduction in guest leakage compared to that of the nanoaggregates as shown by the release profile in the absence of stimuli, suggesting high encapsulation stability as evidenced by the fluorescence resonance energy transfer (FRET) experiment. The decross-linking of the nanonetwork occurs in response to redox and pH stimuli due to disulfide reduction and ß-thioester hydrolysis, respectively, thus empowering disassembly-mediated controlled cargo release up to ∼87% for 55 h of incubation. The biological evaluation of the doxorubicin (DOX)-loaded nanonetwork revealed environment-specific surface charge modulation-mediated cancer cell-selective cellular uptake and cytotoxicity. The benign nature of the nanonetwork toward normal cells makes the system very promising in targeted drug delivery applications. Thus, the ease of synthesis, nanonetwork fabrication reproducibility, robust stability, triggered drug release in a controlled fashion, and cell-selective cytotoxicity behavior, we believe, will make the system a potential candidate in the development of robust materials for chemotherapeutic applications.

Live-Cell Mitochondrial Targeted NIR Fluorescent Covalent Labeling of Specific Proteins Using a Dual Localization Effect.

Here, our designed water-soluble NIR fluorescent unsymmetrical Cy-5-Mal/TPP+ consists of a lipophilic cationic TPP+ subunit that can selectively target and accumulate in a live-cell inner mitochondrial matrix where a maleimide residue of the probe undergoes faster chemoselective and site-specific covalent attachment with the exposed Cys residue of mitochondrion-specific proteins. On the basis of this dual localization effect, Cy-5-Mal/TPP+ molecules remain for a longer time period even after membrane depolarization, enabling long-term live-cell mitochondrial imaging. Due to the adequate concentration of Cy-5-Mal/TPP+ reached in live-cell mitochondria, it facilitates site-selective NIR fluorescent covalent labeling with Cys-exposed proteins, which are identified by the in-gel fluorescence assay and LC-MS/MS-based proteomics and supported by a computational method. This dual targeting approach with admirable photostability, narrow NIR absorption/emission bands, bright emission, long fluorescence lifetime, and insignificant cytotoxicity has been shown to improve real-time live-cell mitochondrial tracking including dynamics and interorganelle crosstalk with multicolor imaging applications.

The Magnetism of Nonstoichiometric Sr2Cr1+xRe1-xO6 (0 < x < 0.5) Double Perovskites.

The effect of nonstoichiometry on the cation distribution, crystal structure, and magnetic properties of a series of Cr-rich Sr2Cr1+xRe1-xO6 samples has been investigated. The double perovskite structure is maintained over a wide solid solution range that extends from x = 0 to approximately x = 0.5. For most of the solid solution range, the Cr-rich octahedral site maintains a nearly constant occupancy, 87% Cr and 13% Re, that is comparable to prior studies of Sr2CrReO6, while Cr steadily replaces Re on the other octahedral site. As x approaches 0.5, long-range Cr/Re ordering drops precipitously. Analysis of X-ray powder diffraction peak shapes reveals antiphase boundaries, associated with Cr/Re ordering, the concentration of which increases steadily with increasing x. Neutron powder diffraction studies confirm antiferromagnetic coupling between antisite Cr3+ ions and Cr3+ ions that occupy the normal sites, leading to site-dependent ferrimagnetic ordering. Density functional theory calculations indicate that chromium maintains a +3 oxidation state across the series, while the oxidation state of rhenium increases with increasing x. Calculations are also used to explore the energies of competing magnetic ground states. Except for the most chromium-rich compositions (x ≈ 0.5), site-dependent ferrimagnetism is retained with only a modest reduction in TC. The saturation magnetization steadily decreases as the chromium content increases due to a combination of Cr/Re antisite disorder and antiphase boundaries.

A state-of-the-art review on cadmium uptake, toxicity, and tolerance in rice: From physiological response to remediation process.

Cadmium (Cd), a major contaminant of concern, has been extensively reviewed and debated for its anthropogenic global shifts. Cadmium levels in rice grains raise wide food safety concerns. The aim of this review is therefore to capture the dynamics of Cd in paddy soil, translocation pathways of Cd from soil to consumption rice, and assess its bio-accessibility in human consumption. In crop plants, Cd reduces absorption of nutrients and water, triggers oxidative stress, and inhibits plant metabolism. Understanding the mechanisms and behaviour of Cd in paddy soil and rice allows to explain, predict and intervene in Cd transferability from soil to grains and human exposure. Factors affecting Cd movement in soil, and further to rice grain, are elucidated. Recently, physiological and molecular understanding of Cd transport in rice plants have been advanced. Morphological-biochemical characteristics and Cd transporters of plants in such a movement were also highlighted. Ecologically viable remediation approaches, including low input cost agronomic methods, phytoremediation and microbial bioremediation methods, are emerging.

3D ultrasound strain imaging of puborectal muscle with and without unilateral avulsion.

INTRODUCTION AND HYPOTHESIS: The puborectal muscle (PRM), one of the female pelvic floor (PF) muscles, can get damaged during vaginal delivery, leading to disorders such as pelvic organ prolapse. Current diagnosis involves ultrasound (US) imaging of the female PF muscles, but functional information is limited. Previously, we developed a method for strain imaging of the PRM from US images in order to obtain functional information. In this article, we hypothesize that strain in the PRM would differ from intact to the avulsed end. METHODS: We calculated strain in PRMs at maximum contraction, along their muscle fiber direction, from US images of two groups of women, which consisted of women with intact (n1 = 8) and avulsed PRMs (unilateral) (n2 = 10). Normalized strain ratios between both ends of the PRM (avulsed or intact) and the mid region were calculated. Subsequently, the difference in ratio between the avulsed and intact PRMs was determined. RESULTS: We observe from the obtained results that the contraction/strain pattern of intact and undamaged PRMs is different from PRMs with unilateral avulsion. Normalized strain ratios between avulsed and intact PRMs were statistically significant (p = 0.04). CONCLUSION: In this pilot study, we were able to show that US strain imaging of PRMs can show differences between intact PRMs and PRMs with unilateral avulsion.

YAP1 induces hyperglycemic stress-mediated cardiac hypertrophy and fibrosis in an AKT-FOXM1 dependent signaling pathway.

Cardiac disease is one of the most common complications associated with diabetes. Cardiac hypertrophy and fibrosis often lead to structural and functional abnormalities leading to risks of heart failure. Several regulatory molecules related to major signaling pathways have been found to overexpress in different tissues during diabetes which show very low level of expression in non-diabetic condition. YAP1 and FOXM1 are recently being reported to play important role in various hypertrophic and fibrotic disorders. But, very limited information is still known regarding their roles in cardiomyopathies especially in the context of diabetes and hyperglycemic stress. YAP1 is known to be associated with AKT- GSK3ß signaling that is one of the important regulatory pathways in glucose and lipid metabolism. On the other hand, the expression of FOXM1 has been found to be significantly upregulated in adult lung tissue with induction of fibrosis but little is known about their role in cardiac diseases. In our study, YAP1 and FOXM1 have been found to overexpress in cardiac tissue under hyperglycemic condition leading to cardiomyocyte hypertrophy and increased fibrotic response. Further YAP1 inhibition has resulted in a reduced expression of FOXM1 pointing to a possible association of YAP1 and FOXM1 in high glucose-stressed cardiomyocyte. As mechanism we have found that YAP1 undergoes reduced ser127 phosphorylation as well as extensive O-GlcNAcylation mediated activation under hyperglycemia. Upregulated YAP1 further acts through increased AKT phosphorylation causing inhibition of GSK3ß that in turn results in increased FOXM1 expression, leading to cardiomyocyte hypertrophy and fibrosis.

Tale of Viruses in Male Infertility.

Male infertility is a condition where the males either become sterile or critically infertile. The World Health Organisation assessed that approximately 9% of the couple have fertility issues where the contribution of the male partner was estimated to be 50%. There are several factors that can amalgamate to give rise to male infertility. Among them are lifestyle factors, genetic factors and as well as several environmental factors. The causes of male infertility may be acquired, congenital or sometimes idiopathic. All these factors adversely affect the spermatogenesis process as well as they impart serious threats to male genital organs thus resulting in infertility. Viruses are submicroscopic pathogenic agents that rely on host for their replication and survival. They enter the host cell, hijack the host cell machinery to aid their own replication and exit the cell for a new round of infection. With the growing abundance of different types of viruses and the havoc they have stirred in the form of pandemics, it is very essential to decipher their route of entry inside the human body and understand their diverse functional roles in order to combat them. In this chapter, we will review how viruses invade the male genital system thus in turn leading to detrimental consequence on male fertility. We will discuss the tropism of various viruses in the male genital organs and explore their sexual transmissibility. This chapter will summarise the functional and mechanistic approaches employed by the viruses in inducing oxidative stress inside spermatozoa thus leading to male infertility. Moreover, we will also highlight the various antiviral therapies that have been studied so far in order to ameliorate viral infection in order to combat the harmful consequences leading to male infertility.

Mechanism of interaction between autophagy and apoptosis in cancer.

The mechanisms of two programmed cell death pathways, autophagy, and apoptosis, are extensively focused areas of research in the context of cancer. Both the catabolic pathways play a significant role in maintaining cellular as well as organismal homeostasis. Autophagy facilitates this by degradation and elimination of misfolded proteins and damaged organelles, while apoptosis induces canonical cell death in response to various stimuli. Ideally, both autophagy and apoptosis have a role in tumor suppression, as autophagy helps in eliminating the tumor cells, and apoptosis prevents their survival. However, as cancer proceeds, autophagy exhibits a dual role by enhancing cancer cell survival in response to stress conditions like hypoxia, thereby promoting chemoresistance to the tumor cells. Thus, any inadequacy in either of their levels can lead to tumor progression. A complex array of biomarkers is involved in maintaining coordination between the two by acting as either positive or negative regulators of one or both of these pathways of cell death. The resulting crosstalk between the two and its role in influencing the survival or death of malignant cells makes it quintessential, among other challenges facing chemotherapeutic treatment of cancer. In view of this, the present review aims to highlight some of the factors involved in maintaining their diaphony and stresses the importance of inhibition of cytoprotective autophagy and deletion of the intermediate pathways involved to facilitate tumor cell death. This will pave the way for future prospects in designing drug combinations facilitating the synergistic effect of autophagy and apoptosis in achieving cancer cell death.

Unfolded protein response during cardiovascular disorders: a tilt towards pro-survival and cellular homeostasis.

The endoplasmic reticulum (ER) is an organelle that orchestrates the production and proper assembly of an extensive types of secretory and membrane proteins. Endoplasmic reticulum stress is conventionally related to prolonged disruption in the protein folding machinery resulting in the accumulation of unfolded proteins in the ER. This disruption is often manifested due to oxidative stress, Ca2+ leakage, iron imbalance, disease conditions which in turn hampers the cellular homeostasis and induces cellular apoptosis. A mild ER stress is often reverted back to normal. However, cells retaliate to acute ER stress by activating the unfolded protein response (UPR) which comprises three signaling pathways, Activating transcription factor 6 (ATF6), inositol requiring enzyme 1 alpha (IRE1α), and protein kinase RNA-activated-like ER kinase (PERK). The UPR response participates in both protective and pro-apoptotic responses and not much is known about the mechanistic aspects of the switch from pro-survival to pro-apoptosis. When ER stress outpaces UPR response then cell apoptosis prevails which often leads to the development of various diseases including cardiomyopathies. Therefore, it is important to identify molecules that modulate the UPR that may serve as promising tools towards effective treatment of cardiovascular diseases. In this review, we elucidated the latest advances in construing the contribution imparted by the three arms of UPR to combat the adverse environment in the ER to restore cellular homeostasis during cardiomyopathies. We also summarized the various therapeutic agents that plays crucial role in tilting the UPR response towards pro-survival.

Functional characterization and evaluation of protective efficacy of EA752-862 monoclonal antibody against B. anthracis vegetative cell and spores.

The most promising means of controlling anthrax, a lethal zoonotic disease during the early infection stages, entail restricting the resilient infectious form, i.e., the spores from proliferating to replicating bacilli in the host. The extractible antigen (EA1), a major S-layer protein present on the vegetative cells and spores of Bacillus anthracis, is highly immunogenic and protects mice against lethal challenge upon immunization. In the present study, mice were immunized with r-EA1C, the C terminal crystallization domain of EA1, to generate a neutralizing monoclonal antibody EA752-862, that was evaluated for its anti-spore and anti-bacterial properties. The monoclonal antibody EA752-862 had a minimum inhibitory concentration of 0.08 mg/ml, was bactericidal at a concentration of 0.1 mg/ml and resulted in 100% survival of mice against challenge with B. anthracis vegetative cells. Bacterial cell lysis as observed by scanning electron microscopy and nucleic acid leakage assay could be attributed as a possible mechanism for the bactericidal property. The association of mAb EA752-862 with spores inhibits their subsequent germination to vegetative cells in vitro, enhances phagocytosis of the spores and killing of the vegetative cells within the macrophage, and subsequently resulted in 90% survival of mice upon B. anthracis Ames spore challenge. Therefore, owing to its anti-spore and bactericidal properties, the present study demonstrates mAb EA752-862 as an efficient neutralizing antibody that hinders the establishment of early infection before massive multiplication and toxin release takes place.

A sandwich duplex immuno PCR for rapid and sensitive identification of Clostridium perfringens alpha and enterotoxin.

The prevalence and lethality associated with C. perfringens alpha (CPA) and enterotoxin (CPE) toxaemia necessitate the need for rapid and definitive detection systems to initiate management measures. In the present study, a sandwich duplex immuno-capture PCR (SD-IPCR) was developed by employing IgY antibodies against a bivalent protein r-Cpae derived from CPA and CPE for antigen capture and reporter antibodies against truncated CPA or CPE conjugated to oligomers of distinguishable size for antigen revealing and signal amplification. The avian immunoglobulin's (IgY) were devoid of reactivity with S. aureus protein A (SpA), a commensal that often co-exists with C. perfringens. The assay was specific, had a detection limit (LOD) of 1 pg/ml for both CPA and CPE in PBS and improved the LOD by 104 folds compared to an analogous sandwich ELISA with same set of antibodies. In spiking studies, a ten-fold reduction in LOD was observed in case of intestinal tissue samples (10 pg/ml) however, no change in LOD was observed when SD-IPCR was applied on to faecal, serum or muscle tissue samples. Of the 136 natural samples examined, the SD-IPCR could detect CPA and CPE in 29.4% and 35.3% samples, while the sandwich ELISAs could detect the same in 25.7% and 25% samples respectively owing to the relatively lesser sensitivity. The LOD and specificity of the SD-IPCR demonstrates its applicability as an efficient and rapid platform for direct detection CPA and CPE from diverse samples matrices in clinical microbiological and meat testing laboratories.

The prevalence of bullying and cyberbullying in high school: a 2011 survey.

BACKGROUND: Bullying is common among young students, and cyberbullying has increased due to the use of technology. This study investigates the prevalence of bullying and cyberbullying among high school students and the emotional effects of bullying on students. METHODS: Students at East Chapel Hill High School, Chapel Hill, North Carolina completed the Gatehouse Bullying Scale and the Peer Relations Questionnaire. They answered questions regarding how often they had experienced certain types of bullying in school and the emotional effects the bullying had on them. RESULTS: The combined results from both surveys indicated that the prevalence of bullying was 55% with 18% of respondents reporting cyberbullying. Teasing and name-calling were the most common types of bullying, as 40% of students reported having been teased or called names. The most serious type of bullying, being threatened with harm, hit, or kicked, occurred in 20% of boys and 8% of girls, with 25% of respondents reported "quite upset" by the experience. The majority (79%) of students who had been bullied did not share with anyone about being bullied, and of those who did, only 50% were taken seriously. CONCLUSIONS: Bullying is still prevalent among high school students, and cyberbullying is becoming more widespread. Most victims do not share their bullying experience, and if they did, only half believe they are taken seriously. Both bullying among students in school and cyberbullying deserve attention due to their potentially devastating effects on victims.

Limestone and yellow gypsum can reduce cadmium accumulation in groundnut (Arachis hypogaea): A study from a three-decade old landfill site.

Cadmium (Cd) toxicity has cropped up as an important menace in the soil-plant system. The use of industrial by-products to immobilise Cd in situ in polluted soils is an interesting remediation strategy. In the current investigation, two immobilizing amendments of Cd viz., Limestone (traditionally used) and Yellow gypsum (industrial by-product) have been used through a green-house pot culture experiment. Soil samples were collected from four locations based on four graded levels of DTPA extractable Cd as Site 1 (0.43 mg kg-1), Site 2 (0.92 mg kg-1), Site 3 (1.77 mg kg-1) and Site 4 (4.48 mg kg-1). The experiment was laid out in a thrice replicated Factorial Complete Randomized Design, with one factor as limestone (0, 250, 500 mg kg-1) and the other being yellow gypsum (0, 250, 500 mg kg-1) on the collected soils and groundnut was grown as a test crop. Results revealed that the DTPA-extractable Cd content in soil and Cd concentration in plants decreased significantly with the increasing doses of amendments irrespective of initial soil available Cd and types of amendment used. The effect of amendment was soil specific and in case of Site 1 (low initial Cd) the effect was more prominent. The reduction in DTPA-extractable Cd in combined application of limestone and yellow gypsum @500 mg kg-1 over the absolute control in soil under groundnut for the sites was by far the highest with the values of 83.72%, 77.17%, 48.59% and 40.63% respectively. With the combined application, Target Cancer Risk (TCR) of Cd was also reduced. Hence, combined application of limestone and yellow gypsum can be beneficial in the long run for mitigating Cd pollution.

Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management.

Sarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting enzyme inhibitors (ACEIs), and butyrate precursors lead to the production of anti-inflammatory fatty acids and regulate appetite, gut motility, and microbial impact on gut health. Further research is warranted to deepen our understanding of the interaction between gut microbiota and muscle health for developing therapeutic strategies for ameliorating sarcopenic muscle loss.