Cortisol affects macrophage polarization by inducing miR-143/145 cluster to reprogram glucose metabolism and by promoting TCA cycle anaplerosis.

Chronic stress can have adverse consequences on human health by disrupting the hormonal balance in our body. Earlier, we observed elevated levels of cortisol, a primary stress hormone, and some exosomal microRNAs in the serum of patients with breast cancer. Here, we investigated the role of cortisol in microRNA induction and its functional consequences. We found that cortisol induced the expression of miR-143/145 cluster in human monocyte (THP1 and U937)-derived macrophages but not in breast cancer cells. In silico analysis identified glucocorticoid-response element in the upstream CARMN promoter utilized by the miR-143/145 cluster. Enhanced binding of glucocorticoid-receptor (GR) upon cortisol exposure and its regulatory significance was confirmed by chromatin-immunoprecipitation and promoter-reporter assays. Further, cortisol inhibited IFNγ-induced M1 polarization and promoted M2 polarization, and these effects were suppressed by miR-143-3p and miR-145-5p inhibitors pretreatment. Cortisol-treated macrophages exhibited increased oxygen-consumption rate (OCR) to extracellular-acidification rate (ECAR) ratio, and this change was neutralized by functional inhibition of miR-143-3p and miR-145-5p. HK2 and ADPGK were confirmed as the direct targets of miR-143-3p and miR-145-5p, respectively. Interestingly, silencing of HK2 and ADPGK inhibited IFNγ-induced M1 polarization but failed to induce M2 polarization, since it suppressed both ECAR and OCR, while OCR was largely sustained in cortisol-treated M2-polarized macrophages. We found that cortisol treatment sustained OCR by enhancing fatty acid and glutamine metabolism through upregulation of CPT2 and GLS, respectively, to support M2 polarization. Thus, our findings unfold a novel mechanism of immune suppression by cortisol and open avenues for preventive and therapeutic interventions.

Hepatitis C virus non-structural proteins modulate cellular kinases for increased cytoplasmic abundance of host factor HuR and facilitate viral replication.

Host protein HuR translocation from nucleus to cytoplasm following infection is crucial for the life cycle of several RNA viruses including hepatitis C virus (HCV), a major causative agent of hepatocellular carcinoma. HuR assists the assembly of replication-complex on the viral-3'UTR, and its depletion hampers viral replication. Although cytoplasmic HuR is crucial for HCV replication, little is known about how the virus orchestrates the mobilization of HuR into the cytoplasm from the nucleus. We show that two viral proteins, NS3 and NS5A, act co-ordinately to alter the equilibrium of the nucleo-cytoplasmic movement of HuR. NS3 activates protein kinase C (PKC)-δ, which in-turn phosphorylates HuR on S318 residue, triggering its export to the cytoplasm. NS5A inactivates AMP-activated kinase (AMPK) resulting in diminished nuclear import of HuR through blockade of AMPK-mediated phosphorylation and acetylation of importin-α1. Cytoplasmic retention or entry of HuR can be reversed by an AMPK activator or a PKC-δ inhibitor. Our findings suggest that efforts should be made to develop inhibitors of PKC-δ and activators of AMPK, either separately or in combination, to inhibit HCV infection.

MYB sustains hypoxic survival of pancreatic cancer cells by facilitating metabolic reprogramming.

Extensive desmoplasia and poor vasculature renders pancreatic tumors severely hypoxic, contributing to their aggressiveness and therapy resistance. Here, we identify the HuR/MYB/HIF1α axis as a critical regulator of the metabolic plasticity and hypoxic survival of pancreatic cancer cells. HuR undergoes nuclear-to-cytoplasmic translocation under hypoxia and stabilizes MYB transcripts, while MYB transcriptionally upregulates HIF1α. Upon MYB silencing, pancreatic cancer cells fail to survive and adapt metabolically under hypoxia, despite forced overexpression of HIF1α. MYB induces the transcription of several HIF1α-regulated glycolytic genes by directly binding to their promoters, thus enhancing the recruitment of HIF1α to hypoxia-responsive elements through its interaction with p300-dependent histone acetylation. MYB-depleted pancreatic cancer cells exhibit a dramatic reduction in tumorigenic ability, glucose-uptake and metabolism in orthotopic mouse model, even after HIF1α restoration. Together, our findings reveal an essential role of MYB in metabolic reprogramming that supports pancreatic cancer cell survival under hypoxia.

Immunopathology of herpes simplex virus-associated neuroinflammation: Unveiling the mysteries.

The immunopathology of herpes simplex virus (HSV)-associated neuroinflammation is a captivating and intricate field of study within the scientific community. HSV, renowned for its latent infection capability, gives rise to a spectrum of neurological expressions, ranging from mild symptoms to severe encephalitis. The enigmatic interplay between the virus and the host's immune responses profoundly shapes the outcome of these infections. This review delves into the multifaceted immune reactions triggered by HSV within neural tissues, intricately encompassing the interplay between innate and adaptive immunity. Furthermore, this analysis delves into the delicate equilibrium between immune defence and the potential for immunopathology-induced neural damage. It meticulously dissects the roles of diverse immune cells, cytokines, and chemokines, unravelling the intricacies of neuroinflammation modulation and its subsequent effects. By exploring HSV's immune manipulation and exploitation mechanisms, this review endeavours to unveil the enigmas surrounding the immunopathology of HSV-associated neuroinflammation. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of HSV infections.

Revamped Role for Approved Drug: Integrative Computational and Biophysical Analysis of Saquinavir's PAD4 Inhibition for Rheumatoid Arthritis.

The pursuit of novel therapeutics is a complex and resource-intensive endeavour marked by significant challenges, including high costs and low success rates. In response, drug repositioning strategies leverage existing FDA-approved compounds to predict their efficacy across diverse diseases. Peptidyl arginine deiminase 4 (PAD4) plays a pivotal role in protein citrullination, a process implicated in the autoimmune pathogenesis of rheumatoid arthritis (RA). Targeting PAD4 has thus emerged as a promising therapeutic approach. This study employs computational and enzyme inhibition strategies to identify potential PAD4-targeting compounds from a library of FDA-approved drugs. In-silico docking analyses validated the binding interactions and orientations of screened compounds within PAD4's active site, with key residues such as ASP350, HIS471, ASP473, and CYS645 participating in crucial hydrogen bonding and van der Waals interactions. Molecular dynamics simulations further assessed the stability of top compounds exhibiting high binding affinities. Among these compounds, Saquinavir (SQV) emerged as a potent PAD4 inhibitor, demonstrating competitive inhibition with a low IC50 value of 1.21 ± 0.04 µM. In-vitro assays, including enzyme kinetics and biophysical analyses, highlighted significant changes in PAD4 conformation upon SQV binding, as confirmed by circular dichroism spectroscopy. SQV induced localized alterations in PAD4 structure, effectively occupying the catalytic pocket and inhibiting enzymatic activity. These findings underscore SQV's potential as a therapeutic candidate for RA through PAD4 inhibition. Further validation through in-vitro and in-vivo studies is essential to confirm SQV's therapeutic benefits in autoimmune diseases associated with dysregulated citrullination.

Transcriptome-wide association mapping provides insights into the genetic basis and candidate genes governing flowering, maturity and seed weight in rice bean (Vigna umbellata).

BACKGROUND: Rice bean (Vigna umbellata), an underrated legume, adapts to diverse climatic conditions with the potential to support food and nutritional security worldwide. It is used as a vegetable, minor food crop and a fodder crop, being a rich source of proteins, minerals, and essential fatty acids. However, little effort has been made to decipher the genetic and molecular basis of various useful traits in this crop. Therefore, we considered three economically important traits i.e., flowering, maturity and seed weight of rice bean and identified the associated candidate genes employing an associative transcriptomics approach on 100 diverse genotypes out of 1800 evaluated rice bean accessions from the Indian National Genebank. RESULTS: The transcriptomics-based genotyping of one-hundred diverse rice bean cultivars followed by pre-processing of genotypic data resulted in 49,271 filtered markers. The STRUCTURE, PCA and Neighbor-Joining clustering of 100 genotypes revealed three putative sub-populations. The marker-trait association analysis involving various genome-wide association study (GWAS) models revealed significant association of 82 markers on 48 transcripts for flowering, 26 markers on 22 transcripts for maturity and 22 markers on 21 transcripts for seed weight. The transcript annotation provided information on the putative candidate genes for the considered traits. The candidate genes identified for flowering include HSC80, P-II PsbX, phospholipid-transporting-ATPase-9, pectin-acetylesterase-8 and E3-ubiquitin-protein-ligase-RHG1A. Further, the WRKY1 and DEAD-box-RH27 were found to be associated with seed weight. Furthermore, the associations of PIF3 and pentatricopeptide-repeat-containing-gene with maturity and seed weight, and aldo-keto-reductase with flowering and maturity were revealed. CONCLUSION: This study offers insights into the genetic basis of key agronomic traits in rice bean, including flowering, maturity, and seed weight. The identified markers and associated candidate genes provide valuable resources for future exploration and targeted breeding, aiming to enhance the agronomic performance of rice bean cultivars. Notably, this research represents the first transcriptome-wide association study in pulse crop, uncovering the candidate genes for agronomically useful traits.

Experimental demonstration of Ge2Sb2Te5 loaded 1-D plasmonic metasurface perfect absorber for near-IR wavelength regime.

Inclusion of a phase change material such as germanium-antimony-telluride (Ge2Sb2Te5 or GST) enhances the performance of plasmonic metasurface absorbers (PMAs). One-dimensional (1-D) plasmonic metasurfaces (PMs) support the excitation of surface plasmon modes for the normal incidence of transverse magnetically (TM) polarized light. The 1-D PMAs absorb incident light because of their confinement in the groove region, which is possible because of the surface plasmon modes excited at the metal-dielectric interface. A thin layer of the phase change material enhances the absorption of incident light because of the increasing strength of the confined electromagnetic field in the vicinity of the PMA. We developed a GST loaded, low cost, 1-D PMA for the absorption of near-infrared (NIR) light (740-920 nm). The PMA was fabricated using an Ag coated 1-D patterned polycarbonate, which was obtained from a commercial digital versatile disk (DVD). A 1-D PMA of 1 cm2 in size obtained from a DVD was coated with a GST layer of 8 nm in thickness to achieve the maximum absorption of 99.56% for the hexagonal closed packed (h.c.p.) crystalline state of the GST loaded layer. Control experiments were performed for different temperatures and different thicknesses of the GST layer for achieving an optimal performance nearing perfect absorption. Electric and magnetic field profiles were simulated for the normal incidence of TM-polarized light to understand the underlying physics of the light-matter interaction with the PMA. Such a PMA can be used to develop various cost-effective optical devices, such as optical sensors, optical filters, photodetectors, and heat absorbing photonic windows in the NIR wavelength regime.

Unraveling the role of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.

RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells.

Oncogenic fusion genes as the result of chromosomal rearrangements are important for understanding genome instability in cancer cells and developing useful cancer therapies. To date, the mechanisms that create such oncogenic fusion genes are poorly understood. Previously we reported an unappreciated RNA-driven mechanism in human prostate cells in which the expression of chimeric RNA induces specified gene fusions in a sequence-dependent manner. One fundamental question yet to be addressed is whether such RNA-driven gene fusion mechanism is generalizable, or rather, a special case restricted to prostate cells. In this report, we demonstrated that the expression of designed chimeric RNAs in human endometrial stromal cells leads to the formation of JAZF1-SUZ12, a cancer fusion gene commonly found in low-grade endometrial stromal sarcomas. The process is specified by the sequence of chimeric RNA involved and inhibited by estrogen or progesterone. Furthermore, it is the antisense rather than sense chimeric RNAs that effectively drive JAZF1-SUZ12 gene fusion. The induced fusion gene is validated both at the RNA and the genomic DNA level. The ability of designed chimeric RNAs to drive and recapitulate the formation of JAZF1-SUZ12 gene fusion in endometrial cells represents another independent case of RNA-driven gene fusion, suggesting that RNA-driven genomic recombination is a permissible mechanism in mammalian cells. The results could have fundamental implications in the role of RNA in genome stability, and provide important insight in early disease mechanisms related to the formation of cancer fusion genes.

Vagally Mediated Heart Rate Variability and Mood States in Patients with Chronic Pain Receiving Prolonged Expiration Regulated Breathing: A Randomized Controlled Trial.

Reduced vagally mediated heart rate variability (VmHRV) has been reported in patients with chronic pain. In healthy persons, breathing with longer expiration relative to inspiration increases VmHRV at 12 breaths per minute. The present study aimed to determine the immediate effect of breathing with longer expiration relative to inspiration on VmHRV and mood states in patients with chronic pain. Fifty patients with chronic pain aged between 20 and 67 years were prospectively randomized as two groups with an allocation ratio of 1:1. The interventional group practiced breathing with metronome based visual cues, maintaining an inspiration to expiration ratio of 28:72 (i/e ratio, 0.38) at a breath rate of 12 breaths per minute. The average i/e ratio they attained based on strain gauge respiration recording was 0.685 (SD 0.48). The control group, which looked at the metronome without conscious breath modification had an average i/e ratio of 0.745 (SD 0.69). The VmHRV, respiration and self-reported mood states (using the Brief Mood Introspection Scale (BMIS)) were assessed. There was a significant increase in HF-HRV and RMSSD during low i/e breathing (repeated measures ANCOVA, Bonferroni adjusted post-hoc test, p < 0.05; in all cases). Self-reported mood states changed as follows: (i) following low i/e breathing positive-mood states increased while the aroused mood state decreased whereas (ii) following the control intervention the aroused mood state increased (repeated measure ANOVA, p < 0.05; in all cases). Hence breathing with prolonged expiration is possibly useful to increase VmHRV and improve self- reported mood states in patients with chronic pain.

Allergic contact dermatitis to lip care cosmetic products - a systematic review.

Aim: Lip care cosmetics products are any external preparation used by people to prevent drying, chapping, dullness, and beautification of lips. This study aimed to review the literature on allergic reactions induced by different types of lip care cosmetic products. Methods: A literature search was performed in PubMed from inception to June 2022. The study included articles published in English and available in full text. References of illegible articles were searched. Studies describing any patient who developed allergic contact dermatitis after the application of lip care cosmetic products were included. Results: A total of 47 reports consisting of 58 individuals experienced allergic reactions to lip care products. Several lip care cosmetics products, such as lipsticks, lip balms, lip salve, lip gloss, lip liner, and lip plumper, were found to be associated with allergic reactions. The most common ingredients that caused the allergic contact dermatitis were castor oil, benzophenone-3, gallate, wax, and colophony. Conclusions: Lip care cosmetics products contain several components that have been associated with allergic reactions. Awareness needs to be created among the general public and dermatologists regarding the presence of possible allergens in lip care cosmetic products.

Enhancing drug bioavailability for Parkinson's disease: The promise of chitosan delivery mechanisms.

Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD.

Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling.

Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.

De-glutathionylases: The resilient underdogs to keep neurodegeneration at bay.

Proteins become S-glutathionylated as a result of the derivatization of their cysteine thiols with the thiolate anion derivative of glutathione; this process is frequently linked to diseases and protein misbehavior. Along with the other well-known oxidative modifications like S-nitrosylation, S-glutathionylation has quickly emerged as a major contributor to a number of diseases, with a focus on neurodegeneration. The immense clinical significance of S-glutathionylation in cell signaling and the genesis of diseases are progressively coming to light with advanced research, which is also creating new opportunities for prompt diagnostics that utilize this phenomenon. In-depth investigation in recent years has revealed other significant deglutathionylases in addition to glutaredoxin, necessitating the hunt for their specific substrates. The precise catalytic mechanisms of these enzymes must also be understood, along with how the intracellular environment affects their impact on protein conformation and function. These insights must then be extrapolated to the understanding of neurodegeneration and the introduction of novel and clever therapeutic approaches to clinics. Clarifying the importance of the functional overlap of glutaredoxin and other deglutathionylases and examining their complementary functions as defense systems in the face of stress are essential prerequisites for predicting and promoting cell survival under high oxidative/nitrosative stress.

Genome-wide, integrative analysis of circular RNA dysregulation and the corresponding circular RNA-microRNA-mRNA regulatory axes in autism.

Circular RNAs (circRNAs), a class of long noncoding RNAs, are known to be enriched in mammalian neural tissues. Although a wide range of dysregulation of gene expression in autism spectrum disorder (ASD) have been reported, the role of circRNAs in ASD remains largely unknown. Here, we performed genome-wide circRNA expression profiling in postmortem brains from individuals with ASD and controls and identified 60 circRNAs and three coregulated modules that were perturbed in ASD. By integrating circRNA, microRNA, and mRNA dysregulation data derived from the same cortex samples, we identified 8170 ASD-associated circRNA-microRNA-mRNA interactions. Putative targets of the axes were enriched for ASD risk genes and genes encoding inhibitory postsynaptic density (PSD) proteins, but not for genes implicated in monogenetic forms of other brain disorders or genes encoding excitatory PSD proteins. This reflects the previous observation that ASD-derived organoids show overproduction of inhibitory neurons. We further confirmed that some ASD risk genes (NLGN1, STAG1, HSD11B1, VIP, and UBA6) were regulated by an up-regulated circRNA (circARID1A) via sponging a down-regulated microRNA (miR-204-3p) in human neuronal cells. Particularly, alteration of NLGN1 expression is known to affect the dynamic processes of memory consolidation and strengthening. To the best of our knowledge, this is the first systems-level view of circRNA regulatory networks in ASD cortex samples. We provided a rich set of ASD-associated circRNA candidates and the corresponding circRNA-microRNA-mRNA axes, particularly those involving ASD risk genes. Our findings thus support a role for circRNA dysregulation and the corresponding circRNA-microRNA-mRNA axes in ASD pathophysiology.

Modulation of terpenoid indole alkaloid pathway via elicitation with phytosynthesized silver nanoparticles for the enhancement of ajmalicine, a pharmaceutically important alkaloid.

MAIN CONCLUSION: The use of silver nanoparticles as elicitors in cell cultures of Rauwolfia serpentina resulted in increased levels of ajmalicine, upregulated structural and regulatory genes, elevated MDA content, and reduced activity of antioxidant enzymes. These findings hold potential for developing a cost-effective method for commercial ajmalicine production. Plants possess an intrinsic ability to detect various stress signals, prompting the activation of defense mechanisms through the reprogramming of metabolites to counter adverse conditions. The current study aims to propose an optimized bioprocess for enhancing the content of ajmalicine in Rauwolfia serpentina callus through elicitation with phytosynthesized silver nanoparticles. Initially, callus lines exhibiting elevated ajmalicine content were established. Following this, a protocol for the phytosynthesis of silver nanoparticles using seed extract from Rauwolfia serpentina was successfully standardized. The physicochemical attributes of the silver nanoparticles were identified, including their spherical shape, size ranging from 6.7 to 28.8 nm in diameter, and the presence of reducing-capping groups such as amino, carbonyl, and amide. Further, the findings indicated that the presence of 2.5 mg L-1 phytosynthesized silver nanoparticles in the culture medium increased the ajmalicine content. Concurrently, structural genes (TDC, SLS, STR, SGD, G10H) and regulatory gene (ORCA3) associated with the ajmalicine biosynthetic pathway were observed to be upregulated. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were observed. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were also observed. Our results strongly recommend the augmentation of ajmalicine content in the callus culture of R. serpentina through supplementation with silver nanoparticles, a potential avenue for developing a cost-effective process for the commercial production of ajmalicine.

COVID-19-induced autoimmune thyroiditis: Exploring molecular mechanisms.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin-converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS-CoV-2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID-19 infection. This phenomenon may be attributed to aberrant responses of T-cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)-6, IL-1ß, interferon-γ, and tumor necrosis factor-α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID-19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms.

From nature to therapy: Luteolin's potential as an immune system modulator in inflammatory disorders.

Inflammation is an essential immune response that helps fight infections and heal tissues. However, chronic inflammation has been linked to several diseases, including cancer, autoimmune disorders, cardiovascular diseases, and neurological disorders. This has increased interest in finding natural substances that can modulate the immune system inflammatory signaling pathways to prevent or treat these diseases. Luteolin is a flavonoid found in many fruits, vegetables, and herbs. It has been shown to have anti-inflammatory effects by altering signaling pathways in immune cells. This review article discusses the current research on luteolin's role as a natural immune system modulator of inflammatory signaling mechanisms, such as its effects on nuclear factor-kappa B, mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and inflammasome signaling processes. The safety profile of luteolin and its potential therapeutic uses in conditions linked to inflammation are also discussed. Overall, the data point to Luteolin's intriguing potential as a natural regulator of immune system inflammatory signaling processes. More research is needed to fully understand its mechanisms of action and possible therapeutic applications.

Magnetically recoverable sol-gel auto-combustion developed Ni1-xCuxDyyFe2-yO4 magnetic nanoparticles for photocatalytic, electrocatalytic, and antibacterial applications.

Copper and dysprosium doped NiFe2O4 magnetic nanomaterials, Ni1-xCuxDyyFe2-yO4 (x = y = 0.00, 0.01, 0.02, 0.03), was prepared by utilizing sol-gel auto-combustion approach to inspect the photodegradation of methylene blue (MB) pollutant and also, to perform the electrocatalytic water splitting and antibacterial studies. The XRD analysis reveal the growth of a single-phase spinel cubic structure for produced nanomaterials. The magnetic traits show an increasing trend in saturation magnetization (Ms) from 40.71 to 47.90 emu/g along with a decreasing behaviour of coercivity from 158.09 to 156.34 Oe at lower and higher Cu and Dy doping content (x = 0.0-0.01). The study of optical band gap values of copper and dysprosium-doped nickel nanomaterials decreased from 1.71 to 1.52 eV. This will increase the photocatalytic degradation of methylene blue pollutant from 88.57% to 93.67% under natural sunlight, respectively. These findings clearly show that under natural sunlight irradiation for 60 min, the produced N4 photocatalyst displays the greatest photocatalytic activity with a maximum removal percentage of 93.67%. The electrocatalytic characteristics of produced magnetic nanomaterials for both HER and OER were examined with a Calomel electrode taking as a reference in a 0.5 N H2SO4 and 0.1 N KOH electrolyte. The N4 electrode demonstrated considerable 10 and 0.024 mA/cm2 of current density, with onset potentials of 0.99 and 1.5 V for HER and OER and also, have tafel slopes of 58.04 and 295 mV/dec, respectively. The antibacterial activity for produced magnetic nanomaterials was examined against various bacteria (Bacillus subtilis, Staphylococcus aureus, S. typhi, and P. aeruginosa) in which N3 sample produced significant inhibition zone against gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) but no zone of inhibition against gram-negative bacteria (S. typhi and P. aeruginosa). With all these superior traits, the produced magnetic nanomaterials are highly valuable for the wastewater remediation, hydrogen evolution, and biological applications.

Effect of Kangen and reverse osmosis water on dental plaque, salivary pH and salivary Streptococcus mutans counts: a randomized-controlled trial (A preliminary study).

PURPOSE: The present randomized-controlled trial was conducted to assess the effect of Kangen water and reverse osmosis (RO) water on dental plaque, salivary pH and salivary Streptococcus mutans count. MATERIALS AND METHODS: This randomized control trial was conducted for 14 days on 24 randomly selected participants from the pool of undergraduate dental students. Participants were randomly divided into two groups of 12 each: the Kangen water (pH 9) group and the RO water group. Participants in each group were asked to drink allocated water for 7 days. Dental plaque, salivary pH and microbial colony-forming units (CFUs) were assessed after 7 and 14 days. RESULTS: Intragroup comparison showed that all three outcomes showed a significant improvement in the Kangen water group after 14 days, whereas no difference was seen in the RO water group. Intergroup comparison showed a significant difference in plaque score and CFU among the two groups after 7 and 14 days, whereas pH between the two groups did not show a significant difference. CONCLUSIONS: Regular drinking of alkaline Kangen water with pH 9 was found to be effective in reducing plaque and salivary Streptococcus mutans count when compared to RO water.