Colloidal carbon soot templated TiO/Ag surface functionalized 3D printed metal brushes as new generation surface enhanced Raman scattering substrates.

This present work demonstrated the functional transformation of 3D printed metal substrates into a new family of Surface-enhanced Raman Scattering substrates, a promising approach in developing SERS-based Point-of-care (PoC) analytical platforms. l-Powder Bed Fusion (l-PBF, Additive manufacturing or 3D printing technique) printed metal substrates have rough surfaces, and exhibit high thermal stability and intrinsic chemical inertness, necessitating a suitable surface functionalization approach. This present work demonstrated a unique multi-stage approach to transform l-PBF printed metal structures as recyclable SERS substrates by colloidal carbon templating, chemical vapor deposition, and electroless plating methods sequentially.

Neuroprotective effects of nanogold-based Ayurveda medicine Suvarna Bhasma against rotenone-induced Parkinson's-like model.

Background: Neurodegenerative diseases have been one of the major concerns for human health. Genetic and environmental factors are believed to be responsible for neuronal diseases such as Parkinson's disease, Alzheimer's disease, and Huntington's disease. It is difficult to restore normal nervous function after neurodegeneration; hence, prevention could be the best strategy against these diseases.

Intestinal permeability and inflammatory features of juvenile age correlate with the eventual systemic autoimmunity in lupus-prone female SWR × NZB F1 (SNF1) mice.

The incidence of systemic lupus erythematosus (SLE) is about nine times higher in women than in men, and the underlying mechanisms that contribute to this gender bias are not fully understood. Previously, using lupus-prone (SWR × NZB)F1 (SNF1) mice, we have shown that the intestinal immune system could play a role in the initiation and progression of disease in SLE, and depletion of gut microbiota produces more pronounced disease protection in females than in males. Here, we show that the gut permeability features of lupus-prone female SNF1 mice at juvenile ages directly correlate with the expression levels of pro-inflammatory factors, faecal IgA abundance and nAg reactivity and the eventual systemic autoantibody levels and proteinuria onset.

Assessment of Chronic Toxicity of an Ayurvedic Herbo-Metallic Formulation Rasaraj Rasa in Wistar Rats.

Objectives: This study aimed to assess the adverse effects of Rasaraj Rasa tablets after repeated oral administration for 180 days in Wistar rats.

Methods: Wistar rats were divided into five groups, of which three were treated with 54, 162, and 270 mg/kg body weight of Rasaraj Rasa, respectively, which correspond to one, three, and five times the proposed human therapeutic dose, for 180 days consecutively. The fifth group (satellite) also received 270 mg/kg body weight of Rasaraj Rasa for 180 days.

Evaluation of chronic toxicological profile of herbo-mineral formulations: Shwaskas Chintamani Rasa and its marketed formulation namely Kas Shwas Hari Rasa.

Background: Shwaskas Chintamani Rasa (SKC) and Kas Shwas Hari Rasa (KSH) are the Ayurvedic herbo-mineral formulations. These Ayurvedic formulations contain heavy metals which is the reason of concern and might bring up the safety issue.

Objective: This research article is aimed to study chronic toxicity of SKC and KSH for safety aspect in Wistar rats.

Fecal immunoglobulin A (IgA) and its subclasses in systemic lupus erythematosus patients are nuclear antigen reactive and this feature correlates with gut permeability marker levels.

Systemic lupus erythematosus (SLE) is characterized by the production of anti-nuclear autoantibodies. Here, for the first time, we show that the abundances of gut permeability marker Zonulin and IgA1- and IgA2- subclasses are significantly higher in the fecal samples of SLE patients compared to HCs. Importantly, IgA-total, and IgA1- and IgA2-subclasses from SLE patients showed higher nAg reactivity titers.

Combination of Autophagy Selective Therapeutics With Doxil: An Assessment of Pathological Toxicity.

Combination therapy of targeted drugs in cancer treatment is a field in constant flux, with research balancing side effects with efficacy. Efficacy from combination therapy is improved either through synthetic lethality or through prevention of recurrent clones. Previous research has shown (hydroxy-)chloroquine is insufficient to disrupt autophagy in tumors.

FDA Approval Summary: Revised Indication and Dosing Regimen for Ponatinib Based on the Results of the OPTIC Trial.

On December 18, 2020, US Food and Drug Administration (FDA) approved a supplemental application for ponatinib extending the indication in patients with chronic-phase chronic myeloid leukemia (CP-CML) to patients with resistance or intolerance of at least 2 prior kinase inhibitors. Ponatinib was initially approved in December 2012 but was briefly voluntarily withdrawn due to serious safety concerns including the risk of arterial occlusive events (AOE). It returned to the market in December 2013 with an indication limited to patients with T315I mutation or for whom no other tyrosine kinase inhibitor (TKI) therapy was indicated with revised warnings and precautions.

Activation of T cell checkpoint pathways during β-cell antigen presentation by engineered dendritic cells promotes protection from type 1 diabetes.

Defective immune regulation has been recognized in type 1 diabetes (T1D). Immune regulatory T cell check-point receptors, which are generally upregulated on activated T cells, have been the molecules of attention as therapeutic targets for enhancing immune response in tumour therapy. Here, we show that pancreatic β-cell antigen (BcAg) presentation by engineered tolerogenic dendritic cells (tDCs) that express CTLA4 selective ligand (B7.

Preclinical stage abundance and nuclear antigen reactivity of faecal Immunoglobulin A vary among males and females of lupus-prone mouse models.

Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies with nuclear antigen (nAg) specificity. Using (SWRxNZB)F1 (SNF1) mice, we showed higher levels of Immunoglobulin A (IgA) production in the intestine and the nAg reactivity of faecal IgA under lupus susceptibility. Here, we determined whether the faecal IgA abundance and nAg reactivity are higher in, different among, various lupus-prone preclinical models (MRL/lpr, NZBxNZW-F1, SNF1, NZM2410 and NZM2328).

FDA Approval Summary: Belumosudil for Adult and Pediatric Patients 12 Years and Older with Chronic GvHD after Two or More Prior Lines of Systemic Therapy.

On July 16, 2021, the FDA approved belumosudil, a kinase inhibitor, for adult and pediatric patients 12 years and older with chronic GvHD (cGvHD) after failure of at least two prior lines of systemic therapy. Approval was based on the results of Study KD025-213, which included 65 patients with cGvHD treated with belumosudil 200 mg daily in an open-label, single-arm cohort. Efficacy was determined by the overall response rate (ORR) through Cycle 7 Day 1, which included complete response (CR) or partial response (PR) according to the 2014 NIH consensus criteria, and durability of response.

Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes.

Progressive destruction of pancreatic islet β-cells by immune cells is a primary feature of type 1 diabetes (T1D) and therapies that can restore the functional β-cell mass are needed to alleviate disease progression. Here, we report the use of mesenchymal stromal/stem cells (MSCs) for the production and delivery of Gastrin, a peptide hormone that is produced by intestinal cells and foetal islets and can increase β-Cell mass, to promote protection from T1D. A single injection of syngeneic MSCs that were engineered to express Gastrin (Gastrin-MSCs) caused a significant delay in hyperglycaemia in non-obese diabetic (NOD) mice compared to engineered control-MSCs.

Nanostructured gold in ancient Ayurvedic calcined drug 'swarnabhasma'.

Background: Swarnabhasma (calcined gold) is a famous ancient Ayurvedic medicine. However, its detail characteristic investigations are very limited.

Objective: Herein, investigation of swarnabhasma is demonstrated using ancient and ultramodern techniques to understand the physicochemical nature of this drug, and to understand whether the mercury [Parada] used during preparation method marks its presence in swarnabhasma.

Centrosomal P4.1-associated protein (CPAP) positively regulates endocytic vesicular transport and lysosome targeting of EGFR.

Centrosomal P4.1-associated protein (CPAP) plays a critical role in restricting the centriole length in human cells. Here, we report a novel, positive regulatory influence for CPAP on endocytic vesicular transport (EVT) and lysosome targeting of internalized-cell surface receptor EGFR.

Physicochemical Variation in Nanogold-Based Ayurved Medicine Suvarna Bhasma Produced by Various Manufacturers Lead to Different In Vivo Bioaccumulation Profiles.

(SB) is a gold particle-based medicine that is used in to treat tuberculosis, arthritis and nervous diseases. Traditionally, the preparation processes of SB do exist, but they are all long, tedious and involve several steps. Due to this, there is a possibility of bypassing the necessary processes or non-adherence to all steps or use of synthetic gold particles.

Loss of CPAP causes sustained EGFR signaling and epithelial-mesenchymal transition in oral cancer.

Higher epidermal growth factor receptor (EGFR) signaling can contribute to tumor metastasis and resistance to therapies in oral squamous cell carcinoma (OSCC). EGFR signaling can promote epithelial-mesenchymal transition (EMT) in OSCC. EMT is a process by which epithelial cells acquire invasive properties and it can contribute to tumor metastasis.

FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with a Mutation.

On November 28, 2018, the FDA approved gilteritinib (Xospata; Astellas), a small-molecule FMS-like tyrosine kinase 3 (FLT3) inhibitor, for treatment of relapsed or refractory acute myeloid leukemia with a mutation as detected by an FDA-approved test. In the ADMIRAL study, patients were randomized 2:1 to receive gilteritinib or standard chemotherapy and stratified by response to first-line treatment and intensity of prespecified chemotherapy. Efficacy was established on interim analysis on the basis of complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion from transfusion dependence to transfusion independence in 138 patients in the gilteritinib arm.

Optimization of disinfectant dosage for simultaneous control of lead and disinfection-byproducts in water distribution networks.

Drinking water utilities are increasingly facing the challenges of maintaining water quality, and simultaneously complying with conflicting regulatory standards. One such challenge is the dosage of chlorine-based disinfectants which is typically regulated to prevent microbial growth in the water distribution systems, while limiting disinfection by-products (DBPs). On the other hand, chlorine residuals also influence the dissolution of lead into drinking water from corrosion scales in the pipe internals, as has been shown by previous studies.

Abundance and nuclear antigen reactivity of intestinal and fecal Immunoglobulin A in lupus-prone mice at younger ages correlate with the onset of eventual systemic autoimmunity.

Our recent studies, using (SWRxNZB)F1 (SNF1) mice, showed a potential contribution of the gut microbiota and pro-inflammatory immune responses of the gut mucosa to systemic autoimmunity in lupus. Here, using this mouse model, we determined the abundance and the nAg reactivity of IgA antibody produced in the intestine under lupus susceptibility. Intestinal lymphoid tissues from SNF1 mice, females particularly, showed significantly higher frequencies of nAg (dsDNA and nucleohistone) reactive IgA producing B cells compared to B6 females.

Dynamics of Structural and Functional Changes in Gut Microbiota during Treatment with a Microalgal β-Glucan, Paramylon and the Impact on Gut Inflammation.

Previously, we have shown that oral administration of yeast derived β-1,3/1,6-d-glucan enhances immune regulation and alters the composition of the gut microbiota. However, it is not known if other structurally distinct β-glucans have similar properties. Here, using C57BL/6 mice, we show the potential of a microalgae derived β-1,3-d-glucan, paramylon (PM), in shaping the gut microbiota and modulating the susceptibility to colitis.

FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease.

On May 24, 2019, the Food and Drug Administration approved ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-271 (REACH-1; NCT02953678), an open-label, single-arm, multicenter trial that included 49 patients with grades 2-4 SR-aGVHD occurring after allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered at 5 mg twice daily, with dose increases to 10 mg twice daily permitted after 3 days in the absence of toxicity.

Gut microbiota differently contributes to intestinal immune phenotype and systemic autoimmune progression in female and male lupus-prone mice.

The risk of developing systemic lupus erythematosus (SLE) is about 9 times higher in women as compared to men. Our recent report, which used (SWRxNZB) F1 (SNF1) mouse model of spontaneous lupus, showed a potential link between immune response initiated in the gut mucosa at juvenile age (sex hormone independent) and SLE susceptibility. Here, using this mouse model, we show that gut microbiota contributes differently to pro-inflammatory immune response in the intestine and autoimmune progression in lupus-prone males and females.

Pretreatment with Yeast-Derived Complex Dietary Polysaccharides Suppresses Gut Inflammation, Alters the Microbiota Composition, and Increases Immune Regulatory Short-Chain Fatty Acid Production in C57BL/6 Mice.

Background: β-Glucans (BGs), a group of complex dietary polysaccharides (CDPs), are available as dietary supplements. However, the effects of orally administered highly purified BGs on gut inflammation are largely unknown.

Objectives: The aim of this study was to investigate the impact of orally administering highly purified, yeast-derived BG (YBG; β-1,3/1,6-d-glucan) on susceptibility to colitis.

Physicochemical characterization of Suvarna Bhasma, its toxicity profiling in rat and behavioural assessment in zebrafish model.

Ethnopharmacological Relevance: Suvarna Bhasma is a gold-based Ayurved medicine that has a wide range of therapeutic indications like tuberculosis, diabetes mellitus, rheumatoid arthritis and nervous diseases. Suvarna Bhasma is also used in Suvarnaprashana, an Ayurved advocated therapy being practised to improve immunity in children.

Aim Of The Study: To augment traditional understanding, here we present an evidence-based study on Suvarna Bhasma regarding its physicochemical properties, toxicity and efficacy.

Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance.

Inhibitory/repressor-receptors are upregulated significantly on activated T cells, and have been the molecules of attention as targets for inducing immune tolerance. Induction of effective antigen specific tolerance depends on concurrent engagement of the TCR and one or more of these inhibitory receptors. Here, we show, for the first time that dendritic cells (DCs) can be efficiently engineered to express multiple T cell inhibitory ligands, and enhanced engagement of T cell inhibitory receptors, upon antigen presentation, by these DCs can induce effective CD4+ T cell tolerance and suppress autoimmunity.