The GC-MS Analysis of Kabasura Kudineer: A Vital Siddha Drug in COVID-19 Therapy.

Introduction: This study focuses on the gas chromatography-mass spectrometry (GC-MS) analysis of Kabasura Kudineer, a Siddha formulation renowned for its properties against cold and exclusively utilized during the coronavirus disease 2019 (COVID-19) pandemic. Methods: The medication was obtained from a reputable Siddha vendor in Chennai, India, and subsequently extracted and subjected to GC-MS analysis. Results: The GC-MS profiling revealed the presence of several molecules, including benzoic acid, eugenol, alpha-ylangeneol, trans-2,4-dimethylthiane, S, S-dioxide, humulene, methyl 4,7,10,13-hexadecatetraenoate, 17-octadecynoic acid, 1-hexadecyn-3-ol, 3,7,11,15-tetramethyl, sulfurous acid, butyl heptadecyl ester, chloroacetic acid, tetradecyl ester, n-propyl cinnamate, oleyl alcohol, trifluoroacetate, 1-heptatriacotanol, and fenretinide. These compounds exhibit expansive medicinal roles. Conclusion: Kabasura Kudineer emerges as a highly effective remedy for cold-related ailments, particularly owing to the presence of bioactive compounds such as eugenol and humulene. These constituents play pivotal roles in antimicrobial and anti-inflammatory activities. Further investigations into the individual medicinal efficacy of each identified molecule are warranted to substantiate the therapeutic potential of Kabasura Kudineer, providing valuable insights for future applications.

Manasamitra Vatakam on Scopolamine-Induced Amnesia in Female Wistar Rats.

Background: Neurodegenerative diseases induce amnesia, and effective treatment is still elusive. Aims and Objectives: The present study highlights the ameliorating effects of Manasa Mitra Vatakam (MMV) using behavioral parameters on scopolamine-induced memory loss in female Wistar rats. Materials and Methods: MMV was compared with DPZ as a standard in the present study to determine the behavioral parameters through elevated plus maze (Hebb William maze/rectangular maze)and locomotor activity in scopolamine-induced memory loss in female Wistar rats. Results and Discussion: The results of the study illustrate the effectiveness of MMV in reversing memory dysfunction and memory-enhancing effects. Conclusion: The study paves the way for exploring research in CNS disorders and its potential application in drug-induced neurotoxicity.

The GC-MS Study of the Ayurvedic Formulation "Dhanwantharam Thailam" Used for Rheumatism.

Background: The scientific validity of contemporary and alternative medicinal practices, such as Ayurveda and Siddha, holds significant importance in today's context. Aim and Objective: The present study employs gas chromatography-mass spectrometry (GC-MS) analysis to investigate a pain-relieving Ayurvedic oil, Dhanwantharam Thailam, aiming to establish correlations between its medicinal activity and the biomolecules it contains. Materials and Methods: Procured sample from a reputable Ayurvedic vendor in Chennai, Dhanwantharam Thailam underwent GC-MS analysis using standard procedures. Results and Discussion: The resulting profile revealed the presence of crucial molecules like oleic acid, dodecanoic acid, 1,2,3-propanetriyl ester, ethenyl ester, and 9,12-octadecadienoyl chloride (Z, Z), aligning with the medicinal properties attributed to Dhanwantharam Thailam. Conclusion: The identification of these biomolecules supports the role of Dhanwantharam Thailamas an effective pain-relieving oil.

Myocardial performance imaging for the early identification of cardiac dysfunction in neonates with sepsis.

PURPOSE: The assessment of cardiac performance in septic new-borns is crucial for detecting hemodynamic instability and predicting outcome. The aim of the study is to assess myocardial performance in neonates with sepsis for the early identification of cardiac dysfunction. PATIENTS AND METHODS: A case control study was carried out from September 2022 to May 2023 at the Neonatal Intensive care unit, Kasturba Medical College, Manipal. A total of 68 neonates were included in the study, with 33 females and 35 males. The study population was further subdivided into 3 groups namely preterm septic neonates (n = 21), term septic neonates (n = 10) and non-septic healthy controls (n = 37). The cardiac structure and function were assessed using conventional method, Tissue Doppler imaging (Sm) and speckle tracking echocardiography (GLS). The study was approved by the Institutional Ethics Committee at Kasturba Medical College, Manipal (approval number IEC: 90/2022). The CTRI registration number for the study is CTRI/2022/09/045437 and was approved on September 12, 2022. Prior to the neonate's enrolment, informed consent was obtained from their mothers or legal guardians. RESULTS: Out of the total 68 neonates, 31 were cases and 37 were controls which included 33 females and 35 males. LV systolic function was not statistically significant between cases and controls. E/A ratio of the mitral valve was significantly lower in septic newborns than in healthy neonates. (1.01 ± 0.35 vs 1.18 ± 0.31, p < 0.05) preterm neonates showed significantly lower Lateral E' and RV E' velocities than term neonates. TAPSE was significantly lower in septic preterm neonates. (8.61 ± 1.28 vs. 10.7 ± 2.11, p < 0.05) No significant difference was noted in the Myocardial Performance Index between septic neonates and healthy neonates. LV Global Longitudinal Strain was slightly lower in preterm septic neonates than in term neonates with sepsis. CONCLUSION: Septic newborns are associated with LV diastolic dysfunction, RV systolic dysfunction and substantially higher pulmonary systolic pressures.

Robot-assisted Foley Tie Ureteric Tapering and Reimplantation.

Objective: This study aimed to introduce and evaluate the feasibility and outcomes of a novel surgical technique, robot-assisted Foley tie ureteric tapering (RAFUT) and reimplantation, specifically designed for intravesical ureteral tapering during pediatric robotic-assisted ureteric reimplantation. Materials and Methods: A retrospective analysis was conducted on pediatric patients diagnosed with primary vesicoureteric reflux (VUR), who underwent RAFUT between January 2019 and July 2021. Patient records were reviewed to assess preoperative characteristics, operative details, and postoperative outcomes. RAFUT involved meticulous patient positioning, precise port placement with a 6 mm separation, and bladder anchoring to maintain pneumovesicum. Ureteric tapering was performed with the Foley tie technique to enhance surgical precision. The primary outcome measures included operative time, complications, and postoperative VUR resolution. Results: All four patients underwent successful intravesical RAFUT without any intraoperative or postoperative complications. The age of the patients ranged from 3 to 12 years, with varying bladder capacities (range: 210-550 mL). The operating times ranged from 180 to 210 min, and the estimated blood loss was 35-50 mL. None of the patients required conversion to open surgery. Patients demonstrated resolution of VUR on postoperative imaging, and none experienced recurrent urinary tract infections during follow-up, which ranged from 1.5 to nearly 4 years. Conclusion: RAFUT represents a safe and effective surgical technique for intravesical ureteral tapering during pediatric robotic-assisted ureteric reimplantation. This innovative approach addresses the challenges posed by intravesical surgery for dilated ureters, maintains anatomical orientation, and offers precise excision and suturing capabilities.

Plasma neurological biomarkers as a measure of neurotoxicity in pediatric dental general anesthesia: a prospective observational feasibility study.

PURPOSE: Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children. The secondary aim was to compare changes in motor manipulative skills pre- and post-anesthetic exposure. METHODS: This single-center prospective observational study included 22 healthy children aged between 3 and 6 years old who underwent DGA. Subclinical neurotoxicity was measured with a panel of four plasma biomarkers: Caspase-3, neuron-specific enolase (NSE), neurofilament light chain, and S100B at three time points (1; at start, 2; end and 3; on recovery from DGA). The Skillings-Mack test was used to identify the difference in the biomarker levels at three time points. Motor manipulative score assessment, prior and two weeks after DGA was also performed. RESULTS: A total of 22 study participants (mean age = 5 ± 1 years) were included with a median DGA duration of 106 ± 28 min. A reduction in Caspase-3 levels was recorded, with pairwise comparison over three time points, reporting a statistical significance between time point 2 vs. 1 and time point 3 vs. 1. Although fluctuations in NSE levels were recorded, no significant changes were found following pairwise comparison analysis. Among other biomarkers, no significant changes over the three periods were recorded. Furthermore, no significant changes in manipulative motor scores were reported. CONCLUSION: Caspase-3 reduced significantly in the short time frames during day-care DGA; this might be due to the relatively short anesthesia duration associated with dental treatment as compared with more extensive medical-related treatments. Therefore, further studies on Caspase-3 as a potential biomarker in pediatric DGA neurotoxicity are required to further ascertain results of this study.

Acute Myeloid Leukemia Causes T Cell Exhaustion and Depletion in a Humanized Graft-versus-Leukemia Model.

Allogeneic hematopoietic stem cell transplantation (alloSCT) is, in many clinical settings, the only curative treatment for acute myeloid leukemia (AML). The clinical benefit of alloSCT greatly relies on the graft-versus-leukemia (GVL) effect. However, AML relapse remains the top cause of posttransplant death; this highlights the urgent need to enhance GVL. Studies of human GVL have been hindered by the lack of optimal clinically relevant models. In this article, we report, the successful establishment of a novel (to our knowledge) humanized GVL model system by transplanting clinically paired donor PBMCs and patient AML into MHC class I/II knockout NSG mice. We observed significantly reduced leukemia growth in humanized mice compared with mice that received AML alone, demonstrating a functional GVL effect. Using this model system, we studied human GVL responses against human AML cells in vivo and discovered that AML induced T cell depletion, likely because of increased T cell apoptosis. In addition, AML caused T cell exhaustion manifested by upregulation of inhibitory receptors, increased expression of exhaustion-related transcription factors, and decreased T cell function. Importantly, combined blockade of human T cell-inhibitory pathways effectively reduced leukemia burden and reinvigorated CD8 T cell function in this model system. These data, generated in a highly clinically relevant humanized GVL model, not only demonstrate AML-induced inhibition of alloreactive T cells but also identify promising therapeutic strategies targeting T cell depletion and exhaustion for overcoming GVL failure and treating AML relapse after alloSCT.

Activation of GPR44 decreases severity of myeloid leukemia via specific targeting of leukemia initiating stem cells.

Relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia-initiating stem cells (LICs) that are typically not targeted by most existing therapies. Using a murine AML model, human AML cell lines, and patient samples, we show that AML LICs are sensitive to endogenous and exogenous cyclopentenone prostaglandin-J (CyPG), Δ12-PGJ2, and 15d-PGJ2, which are increased upon dietary selenium supplementation via the cyclooxygenase-hematopoietic PGD synthase pathway. CyPGs are endogenous ligands for peroxisome proliferator-activated receptor gamma and GPR44 (CRTH2; PTGDR2). Deletion of GPR44 in a mouse model of AML exacerbated the disease suggesting that GPR44 activation mediates selenium-mediated apoptosis of LICs. Transcriptomic analysis of GPR44-/- LICs indicated that GPR44 activation by CyPGs suppressed KRAS-mediated MAPK and PI3K/AKT/mTOR signaling pathways, to enhance apoptosis. Our studies show the role of GPR44, providing mechanistic underpinnings of the chemopreventive and chemotherapeutic properties of selenium and CyPGs in AML.

Refined fiber inulin promotes inflammation-associated colon tumorigenesis by modulating microbial succinate production.

BACKGROUND AND AIM: There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health remain unclear. Therefore, we elucidated the impact of the refined DF inulin on colonic inflammation and tumorigenesis. METHODS: Four-week-old wild-type (WT) mice were fed diets containing insoluble DF cellulose (control) or refined DF inulin for 4 weeks. A subgroup of mice was then switched to drinking water containing dextran sulfate sodium (DSS, 1.4% wt/vol) for colitis induction. In another subgroup of mice, colitis-associated colorectal cancer (CRC) was initiated with three 7-day alternate cycles of DSS following an initial dose of mutagenic substance azoxymethane (AOM; 7.5 mg/kg body weight; i.p.). Post 7 weeks of AOM treatment, mice were euthanized and examined for CRC development. RESULTS: Mice consuming inulin-containing diet exhibited severe colitis upon DSS administration, as evidenced by more body weight loss, rectal bleeding, and increased colonic inflammation than the DSS-treated control group. Correspondingly, histological analysis revealed extensive disruption of colon architecture and massive infiltration of immune cells in the inulin-fed group. We next examined the effect of inulin on CRC development. Surprisingly, significant mortality (~50%) was observed in the inulin-fed but not in the control group during the DSS cycle. Consequently, the remaining inulin-fed mice, which completed the study exhibited extensive colon tumorigenesis. Immunohistochemical characterization showed comparatively high expression of the cell proliferation marker Ki67 and activation of the Wnt signaling in tumor sections obtained from the inulin-fed group. Gut microbiota and metabolite analysis revealed expansion of succinate producers and elevated cecal succinate in inulin-fed mice. Human colorectal carcinoma cells (HCT116) proliferated more rapidly when supplemented with succinate in an inflamed environment, suggesting that elevated luminal succinate may contribute to tumorigenesis. CONCLUSIONS: Our study uncovers that supplementation of diet with refined inulin induces abnormal succinate accumulation in the intestinal lumen, which in part contributes to promoting colon inflammation and tumorigenesis.

The selenoprotein P-LRP5/6-WNT3A complex promotes tumorigenesis in sporadic colorectal cancer.

Some studies suggest that the trace element selenium protects against colorectal cancer (CRC). However, the contribution of selenoprotein P (SELENOP), a unique selenocysteine-containing protein, to sporadic colorectal carcinogenesis challenges this paradigm. SELENOP is predominately secreted by the liver but is also expressed in various cells of the small intestine and colon in mice and humans. In this issue of the JCI, Pilat et al. demonstrate that increased SELENOP expression promoted the progression of conventional adenomas to carcinoma. SELENOP functioned as a modulator of canonical WNT signaling activity through interactions with WNT3A and its coreceptor LDL receptor-related protein 5/6 (LRP5/6). Secreted SELENOP formed a concentration gradient along the gut crypt axis, which might amplify WNT signaling activity by binding to LRPL5/6. The mechanism for WNT control via SELENOP may affect colorectal tumorigenesis and provide therapeutic targets for CRC.

Abundance, spatial distribution, and chemical characterization of face masks on the beaches of SE Kanyakumari, India.

Personal Protective Equipment (PPE) is a new world of waste during the COVID-19 pandemic. In this baseline study, the occurrence of PPE faces masks were assessed on the eleven beaches of Kanyakumari, India concerning the abundance, spatial distribution, and chemical characterization (ATR-FTIR spectroscopy). A total of 1593 items/m2 of PPE face masks and their mean density of 0.16 PPE/m2, ranging from 0.02 to 0.54 PPE/m2 were determined in the study area. Kanyakumari beach (n = 430 items/m2) has the highest concentration of masks (26.99 %), with a mean density of 0.54 m2 due to recreational, sewage disposal, and tourism activities. This is perhaps the most important study describing the scientific data that focuses on the significant effects of communal activities and accessibility on COVID-19 PPE face mask pollution. It also highlights the need for sufficient management facilities to optimize PPE disposal.

Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair.

Selenoprotein W (Selenow) is a ~9 kDa selenoprotein suggested to play a beneficial role in resolving inflammation. However, the underlying mechanisms are poorly understood. SELENOW expression in the human GI tract using ScRNAseq Gut Cell Atlas and Gene Expression Omnibus (GEO) databases revealed its expression in the small intestine and colonic epithelial, endothelial, mesenchymal, and stem cells and correlated with a protective effect in ulcerative colitis patients. Selenow KO mice treated with 4% dextran sodium sulfate (DSS) showed exacerbated acute colitis, with greater weight loss, shorter colons, and increased fecal occult blood compared to the WT counterparts. Selenow KO mice expressed higher colonic Tnfα, increased Tnfα+ macrophages in the colonic lamina propria, and exhibited loss in epithelial barrier integrity and decreased zonula occludens 1 (Zo-1) expression following DSS treatment. Expression of epithelial cellular adhesion marker (EpCam), yes-associated protein 1 (Yap1), and epidermal growth factor receptor (Egfr) were decreased along with CD24lo cycling epithelial cells in Selenow KO mice. Colonic lysates and organoids confirmed a crosstalk between Egfr and Yap1 that was regulated by Selenow. Overall, our findings suggest Selenow expression is key for efficient resolution of inflammation in experimental colitis that is mediated through the regulation of Egfr and Yap1.

Nitric oxide regulates metabolism in murine stress erythroid progenitors to promote recovery during inflammatory anemia.

Inflammation skews bone marrow hematopoiesis increasing the production of myeloid effector cells at the expense of steady-state erythropoiesis. A compensatory stress erythropoiesis response is induced to maintain homeostasis until inflammation is resolved. In contrast to steady-state erythroid progenitors, stress erythroid progenitors (SEPs) utilize signals induced by inflammatory stimuli. However, the mechanistic basis for this is not clear. Here we reveal a nitric oxide (NO)-dependent regulatory network underlying two stages of stress erythropoiesis, namely proliferation, and the transition to differentiation. In the proliferative stage, immature SEPs and cells in the niche increased expression of inducible nitric oxide synthase ( Nos2 or iNOS ) to generate NO. Increased NO rewires SEP metabolism to increase anabolic pathways, which drive the biosynthesis of nucleotides, amino acids and other intermediates needed for cell division. This NO-dependent metabolism promotes cell proliferation while also inhibiting erythroid differentiation leading to the amplification of a large population of non-committed progenitors. The transition of these progenitors to differentiation is mediated by the activation of nuclear factor erythroid 2-related factor 2 (Nfe2l2 or Nrf2). Nrf2 acts as an anti-inflammatory regulator that decreases NO production, which removes the NO-dependent erythroid inhibition and allows for differentiation. These data provide a paradigm for how alterations in metabolism allow inflammatory signals to amplify immature progenitors prior to differentiation. Key points: Nitric-oxide (NO) dependent signaling favors an anabolic metabolism that promotes proliferation and inhibits differentiation.Activation of Nfe2l2 (Nrf2) decreases NO production allowing erythroid differentiation.

Intra-Peritoneal Transplantation for Generating Acute Myeloid Leukemia in Mice.

There is an unmet need for novel therapies to treat acute myeloid leukemia (AML) and the associated relapse that involves persistent leukemia stem cells (LSCs). An experimental AML rodent model to test therapies based on successfully transplanting these cells via retro-orbital injections in recipient mice is fraught with challenges. The aim of this study was to develop an easy, reliable, and consistent method to generate a robust murine model of AML using an intra-peritoneal route. In the present protocol, bone marrow cells were transduced with a retrovirus expressing human MLL-AF9 fusion oncoprotein. The efficiency of lineage negative (Lin-) and Lin-Sca-1+c-Kit+ (LSK) populations as donor LSCs in the development of primary AML was tested, and intra-peritoneal injection was adopted as a new method to generate AML. Comparison between intra-peritoneal and retro-orbital injections was done in serial transplantations to compare and contrast the two methods. Both Lin- and LSK cells transduced with human MLL-AF9 virus engrafted well in the bone marrow and spleen of recipients, leading to a full-blown AML. The intra-peritoneal injection of donor cells established AML in recipients upon serial transplantation, and the infiltration of AML cells was detected in the blood, bone marrow, spleen, and liver of recipients by flow cytometry, qPCR, and histological analyses. Thus, intra-peritoneal injection is an efficient method of AML induction using serial transplantation of donor leukemic cells.

Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation.

Macrophages play a pivotal role in mediating inflammation and subsequent resolution of inflammation. The availability of selenium as a micronutrient and the subsequent biosynthesis of selenoproteins, containing the 21st amino acid selenocysteine (Sec), are important for the physiological functions of macrophages. Selenoproteins regulate the redox tone in macrophages during inflammation, the early onset of which involves oxidative burst of reactive oxygen and nitrogen species. SELENOW is a highly expressed selenoprotein in bone marrow-derived macrophages (BMDMs). Beyond its described general role as a thiol and peroxide reductase and as an interacting partner for 14-3-3 proteins, its cellular functions, particularly in macrophages, remain largely unknown. In this study, we utilized Selenow knock-out (KO) murine bone marrow-derived macrophages (BMDMs) to address the role of SELENOW in inflammation following stimulation with bacterial endotoxin lipopolysaccharide (LPS). RNAseq-based temporal analyses of expression of selenoproteins and the Sec incorporation machinery genes suggested no major differences in the selenium utilization pathway in the Selenow KO BMDMs compared to their wild-type counterparts. However, selective enrichment of oxidative stress-related selenoproteins and increased ROS in Selenow-/- BMDMs indicated anomalies in redox homeostasis associated with hierarchical expression of selenoproteins. Selenow-/- BMDMs also exhibited reduced expression of arginase-1, a key enzyme associated with anti-inflammatory (M2) phenotype necessary to resolve inflammation, along with a significant decrease in efferocytosis of neutrophils that triggers pathways of resolution. Parallel targeted metabolomics analysis also confirmed an impairment in arginine metabolism in Selenow-/- BMDMs. Furthermore, Selenow-/- BMDMs lacked the ability to enhance characteristic glycolytic metabolism during inflammation. Instead, these macrophages atypically relied on oxidative phosphorylation for energy production when glucose was used as an energy source. These findings suggest that SELENOW expression in macrophages may have important implications on cellular redox processes and bioenergetics during inflammation and its resolution.

Ventricular strain patterns in multivalvular heart disease: a cross-sectional study.

Multivalvular heart disease (MVD) is an aggregate of regurgitant and/or stenotic lesions of at least two cardiac valves. Ventricular tissue deformation imaging is a powerful predictor of subclinical myocardial dysfunction in patients with MVD.The aim of this study was to examine the left and right ventricular strain patterns in MVD as well as observe any association between right-sided valvular involvement (tricuspid or pulmonary valve lesion) with that of aortic and/or mitral valve lesion. Patients with at least moderate forms of MVD were included in the present study. 72 patients with mean age of 56.69 ± 14.59 years and various presentations of MVD were finally enrolled in this study. The commonest cause for MVD was rheumatic heart disease in these patients. Conventional 2-dimensional parameters as well as tissue deformation imaging parameters were assessed in offline mode for these patients. The Mean ± SD values for various quantitative 2D echocardiographic conventional and tissue deformation imaging were assessed. It was observed that LV strain parameters including the global longitudinal strain (GLS) were preserved whereas the RV strain parameters were mildly reduced (RV GLS total is - 19.49 ± 6.08%). Also, when conventional echocardiographic parameters were assessed to see any association between aortic and/or mitral valve disease with that of right-sided valvular lesions (tricuspid or pulmonary); 2D conventional echocardiographic parameters like left atrial dimension (p = 0.034), TAPSE (tricuspid annular plane systolic excursion) (p < 0.001), RVSP (right ventricular systolic pressure) (p < 0.001) and IVC (inferior vena cava) dimensions (p < 0.001) showed a statistically significant result; whereas, when strain parameters for LV and RV were assessed, they did not show any statistical difference for the same. In this series of patients with significant MVD, our findings suggest that ventricular strain parameters may be reliable markers of myocardial dysfunction, but may alter depending on the underlying combination of MVD, and right ventricular strain should also be an important parameter while assessing different combinations of MVD.

The role of selenoproteins in neutrophils during inflammation.

Polymorphonuclear neutrophils (PMNs)-derived ROS are involved in the regulation of multiple functions of PMNs critical in both inflammation and its timely resolution. Selenium is an essential trace element that functions as a gatekeeper of cellular redox homeostasis in the form of selenoproteins. Despite their well-studied involvement in regulating functions of various immune cells, limited studies have focused on the regulation of selenoproteins in PMN and their associated functions. Ex-vivo treatment of murine primary bone marrow derived PMNs with bacterial endotoxin lipopolysaccharide (LPS) indicated temporal regulation of several selenoprotein genes at the mRNA level. However, only glutathione peroxidase 4 (Gpx4) was significantly upregulated, while Selenof, Selenow, and Gpx1 were significantly downregulated in a temporal manner at the protein level. Exposure of PMNs isolated from tRNASec (Trsp)fl/fl S100A8Cre (TrspN) PMN-specific selenoprotein knockout mice, to the Gram-negative bacterium, Citrobacter rodentium, showed decreased bacterial growth, reduced phagocytosis, as well as impaired neutrophil extracellular trap (NET) formation ability, when compared to the wild-type PMNs. Increased extracellular ROS production upon LPS stimulation was also observed in TrspN PMNs that was associated with upregulation of Alox12, Cox2, and iNOS, as well as proinflammatory cytokines such as TNFα and IL-1ß. Our data indicate that the inhibition of selenoproteome expression results in alteration of PMN proinflammatory functions, suggesting a potential role of selenoproteins in the continuum of inflammation and resolution.

Randomized Controlled Study on Effect of Concentrated Growth Factors on Crestal Bone Levels and Peri-implant Bone Density in Dental Implants.

Introduction: Modern dentistry aims to restore the comfort and health of the stomatognathic system. Dental implants have emerged as a promising option for this purpose. Concentrated growth factors (CGFs) have been suggested to enhance the healing of bone grafts and enhance the integration of implants into the bone. Growth factors are proteins which regulate the complex process of wound healing. They play an important role in cell migration, cell proliferation, and angiogenesis in the tissue regeneration phase. CGF was first developed by Sacco in 2006. It can be used as a barrier membrane to accelerate soft-tissue healing. CGF does not require any chemical or anticoagulants, and hence, it is free from viral transmission diseases. Crestal bone levels, peri-implant bone density, bleeding, probing depth, mobility, occlusion factors, restoration adequacy, radiographic images, oral hygiene, and patient health status are some of the important parameters for determining longevity of success rates in implant dentistry. This study will assess the peri-implant bone density and crestal bone levels with and without the use of CGF. Aim: To evaluate the effect of CGFs on peri-implant bone density and in the preservation of crestal bone levels around dental implants. Materials and Methods: Sampling procedure: Random selection of population (Sealed envelope method)Number of groups: Two-Control group (Group 1) and Experimental group (Group 2)Sample size: 20 For Group 2, implants were placed with CGF. For Group 1, implants were placed without CGF. The peri-implant bone density and bone levels were measured by Digora and signora software. Results: The mean crestal bone loss on the mesial aspect of implants placed in Group 2 is 0.294 mm and Group 1 is 0.345 mm, and the mean crestal bone loss on the distal aspect of implants placed in Group 2 is 0.320 mm and in Group 1 is 0.331 mm. There are no many significant differences on mesial and distal aspects around implants between the two groups Intragroup comparison of bone density values in Group 1 shows the mean difference from baseline to 1 month is 0.6, and after three and 6 months periods are 1.1 and 1.1, respectively, which indicates not much significant improvement in bone density values in Group 1. Intergroup comparison shows a significant difference between both the groups starting from as early as the 1st month. Conclusion: The results of this study indicate that CGF is significantly better in the regeneration of bone around the implants when comparing with nonCGF groups. Although CGF showed improvement in bone formation, there are no many differences in crestal bone level changes on mesial and distal sides of the implants between the two groups.

Mylohyoid Ridge as a Predictor of Available Bone for Implant Placement: A Cone-Beam Computed Tomography (CBCT) Retrospective Observational Study.

INTRODUCTION: The posterior mandibular region, due to the presence of vital structures, poses a high risk during implant placement because of its susceptibility to neurovascular injury and perforation of the lingual cortex. A breach in implant length and available bone height may lead to serious intraoperative and postoperative complications. Prediction of the exact location of the inferior alveolar nerve and submandibular fossa anatomy is a prerequisite for ideal implant placement, which is always not possible with conventional radiographic and clinical techniques. MATERIALS AND METHODS: One hundred ten cone-beam computed tomographies (CBCTs) of patients were acquired from the radiological archives of a radiological center in Chennai. DICOM files from CBCT were exported to Bly Sky Plan software. Cross-sections of the second molar and first molar were extracted following the inclusion criteria. The linear dimension between the mandibular canal and mylohyoid ridge and anatomic variables of the submandibular fossa were measured digitally on the left and right sides using software measuring tools. Descriptive statistics were done. The unilateral and bilateral site and gender differences were evaluated. Bone height superior to the mandibular canal was correlated with the submandibular fossa parameters; depth of undercut in the vertical and horizontal directions; and angle of the undercut. RESULTS: The mandibular canal was on average 5.5 mm and 4 mm inferior to the Mylohyoid ridge in the second molar region and first molar region, respectively, with the right and left sides showing no statistically significant difference. The depth of fossa undercut in vertical and horizontal dimensions was higher in the second molar region compared to the first molar region. The height of the deepest point of the undercut in the vertical dimensions showed a positive correlation with the bone available between the mandibular canal and the mylohyoid ridge. CONCLUSION: Keeping 2 mm of safety factor in consideration, implants can be safely placed up to the mylohyoid ridge in 100% of cases and 2 mm below the mylohyoid ridge in 78.9% of cases in the mandibular second molar region. In keeping with a safety factor of 2 mm, implants can be safely placed up to the mylohyoid ridge in 82.6% of cases and 2 mm below the mylohyoid ridge in 43.1% of cases in the first molar region. A more pronounced undercut was seen in the second molar region than in the first molar region. Deeper fossa undercuts in vertical dimension are associated with more inferior positioning of the mandibular canal.

Interleukin-4 treatment reduces leukemia burden in acute myeloid leukemia.

Interleukin-4 (IL-4) is a signature cytokine pivotal in Type 2 helper T cell (Th2) immune response, particularly in allergy and hypersensitivity. Interestingly, IL-4 increases endogenous levels of prostaglandin D2 (PGD2 ) and its metabolites, Δ12 -prostaglandin J2 (Δ12 -PGJ2 ) and 15-deoxy-Δ12,14 -prostaglandin J2 (15d-PGJ2 ), collectively called cyclopentenone PGs (CyPGs). However, the therapeutic role of IL-4 in hematologic malignancies remains unclear. Here, we employed a murine model of acute myeloid leukemia (AML), where human MLL-AF9 fusion oncoprotein was expressed in hematopoietic progenitor cells, to test the effect of IL-4 treatment in vivo. Daily intraperitoneal treatment with IL-4 at 60 µg/kg/d significantly alleviated the severity of AML, as seen by decreased leukemia-initiating cells (LICs). The effect of IL-4 was mediated, in part, by the enhanced expression of hematopoietic- PGD2  synthase (H-PGDS) to effect endogenous production of CyPGs, through autocrine and paracrine signaling mechanisms. Similar results were seen with patient-derived AML cells cultured ex vivo with IL-4. Use of GW9662, a peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, suggested endogenous CyPGs-PPARγ axis mediated p53-dependent apoptosis of LICs by IL-4. Taken together, our results reveal a beneficial role of IL-4 treatment in AML suggesting a potential therapeutic regimen worthy of clinical trials in patients with AML.