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Meena Kishore Sakharkar,1 Karthic Rajamanickam,1 Ramesh Chandra,2 Haseeb A Khan,3 Abdullah S Alhomida,3 Jian Yang1 1College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada; 2Department of Chemistry, University of Delhi, Delhi, India; 3Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia Background: Bovine Respiratory Disease (BRD) is a major problem in cattle production which causes substantial economic loss. BRD has multifactorial aetiologies, is multi-microbial, and several of the causative pathogens are unknown. Consequently, primary management practices such as metaphylactic antimicrobial injections for BRD prevention are used to reduce the incidence of BRD in feedlot cattle. However, this poses a serious threat in the form of development of antimicrobial resistance and demands an urgent need to find novel interventions that could reduce the effects of BRD drastically and also delay/prevent bacterial resistance. Materials and methods: We have employed a subtractive genomics approach that helps delineate essential, host-specific, and druggable targets in pathogens responsible for BRD. We also proposed antimicrobials from FDA green and orange book that could be repositioned for BRD. Results: We have identified 107 putative targets that are essential, selective and druggable. We have also confirmed the susceptibility of two BRD pathogens to one of the proposed antimicrobials – oxytetracycline. Conclusion: This approach allows for repositioning drugs known for other infections to BRD, predicting novel druggable targets for BRD infection, and providing a new direction in developing more effective therapeutic treatments for BRD. Keywords: BRD, pathogenic bacteria, targets, drugs, prioritization, differential genome analyses, druggability

Coconut water is considered as nature's gift to mankind due to its health benefits. The steady demand for tender coconut is currently met from a local dwarf from Kerala, viz., Chowghat Orange Dwarf (COD). However, there is a need for diversification of genotypes. Based on a 20-year-old germplasm evaluation trial conducted at Coconut Research Station (CRS), Aliyarnagar, a selection from Kenthali Dwarf (KTD) has been identified as a promising genotype exclusively for tender nut purpose. It has been released as TNAU coconut ALR 3. The selection is an early flowering genotype that comes to flowering from the third year onwards. The average yield potential is 86 nuts per palm per annum from the stabilized bearing period onwards, with a maximum yield potential of 121 nuts per palm per annum. This accounts for 34.1% and 37.9 % increase in yield over COD and MYD. Tender nut water analysis revealed that the genotype possessed 5.2% soluble sugars with a high potassium level (190.21) compared to COD and MYD. The variety is recommended for irrigated belts of Tamil Nadu. [ABSTRACT FROM AUTHOR]

Following the outbreak for the first time in 2016 of a new invasive rugose spiraling whitefly (RSW), Aleurodicus rugioperculatus Martin in Pollachi, Coimbatore district, Western agro climatic zone of Tamil Nadu, India, a 3-grade damage rating scale was developed to categorize the extent of RSW infestation on different host plants when five host plants were recorded as new viz., Areca catechu L., Azadirachta indica A. Juss., Manihot esculenta Crantz., Myristica fragrans (Houtt.) and Parthenium hysterophorus L. Of the diverse array of natural enemy fauna, the aphelinid parasitoid, Encarsia guadeloupae Viggiani was observed to play a major role in bringing down RSW population. Prolonged dry spell during June to September 2016, after deficit rainfall (69 %) coupled with decreased relative humidity seem to favour the spread of the pest in coconut plantations of Pollachi tract of Tamil Nadu, India. [ABSTRACT FROM AUTHOR]

The present study aims to explore the potential biomarker application of salivary heat shock 70 kDa protein in detecting thermal stress in dairy animals noninvasively. The study spans for 45 days during the mid-summer season (April-May), involving twelve multiparous non-pregnant adult Jersey crossbred cows by randomly allocating them into groups (six animals in each group). The control animals were maintained in the shed, whereas the thermal stress group animals were exposed to environment heat between 10:00 h to 16.00 h and they were feed and watered ad libitum. During the experimental period, the hematobiochemical, physiological, behavioural, nutritional and production responses were recorded and the whole blood and saliva were collected fortnightly. Results revealed significant increase in WBC, AST, ALP, blood urea nitrogen, triglycerides, cholesterol, HDL, blood and salivary cortisol, respiratory rate, rectal temperature, skin temperature of neck, lumbar and forelimb regions, standing time, salivary and blood HSP70 mRNA expression and their protein concentrations in heat stressed animals. In addition, RBC, haemoglobin, MCV, PCV, platelet, platelet-large cell ratio (PLCR), lying time, feed intake, milk yield and rumination time were significantly decreased in thermally stress animals. Furthermore, ROC curve analysis revealed the biomarker potential of these significantly altered parameters with 100% sensitivity and specificity for predicting environmental heat stress in dairy cows with AUC and Youden's - index of 1.00 except platelet. Moreover, salivary HSP70 demonstrated significant correlation with these biomarkers. Noteworthily, salivary HSP70 also exhibited strong association with blood HSP70 and salivary cortisol. Furthermore, salivary HSP70 revealed 100% sensitivity and specificity in discriminating the dairy cattle succumbed to heat stress from healthy. In conclusion, the present study provides a newer insight into the multifaceted roles of HSP70 and identified salivary heat shock 70 kDa protein as a potential, reliable and more sensitive non-invasive biomarker for identifying environmental heat stress in dairy cattle., Competing Interests: Declarations Competing interests The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

The verification and use of the best treatment approach using 3D conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) and Rapid Arc methods for left breast radiation with dosimetric and radiobiological characteristics. The use of custom-built Python software for the estimation and comparison of volume, mean dose, maximum dose, monitor units and normal tissue integral dose along with radiobiological parameters such as NTCP, tumor control probability, equivalent uniform dose and LKB's effective volume from 3DCRT, IMRT and Rapid Arc planning with deep inspiration with breath holding (DIBH) and free breadth (FB) techniques. Volume growth of three-fourth in DIBH compared with FB causes a decrease in cardiac doses and complications because the left lung expands, pulling the heart away from the chest wall and the treatment area. A tiny area of the left lung was exposed during treatment, which reduced the mean dose. There was little difference in the treatment approaches because the spinal cord was immobile in both techniques. Rapid Arc is the unmatched modality for left-sided breast irradiation with significant patient breath-hold, as shown by the comparison of dosimetric and radiobiological parameters from treatment techniques with a deep inspiration breath-hold approach., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: The current research compared radiobiological and dosimetric results for simultaneous integrated boost (SIB) plans employing RapidArc and IMRT planning procedures in oropharyngeal cancer from head-and-neck cancer (HNC) patients., Materials and Methods: The indigenously developed Python-based software was used in this study for generation and analysis. Twelve patients with forty-eight total plans with SIB were planned using Rapid arc (2 and 3 arcs) and IMRT (7 and 9 fields) and compared with radiobiological models Lyman, Kutcher, Burman (LKB) and EUD (Equivalent Uniform Dose) along with physical index such as homogeneity index(HI), conformity index(CI) of target volumes., Results: These models' inputs are the dose-volume histograms (DVHs) calculated by the treatment planning system (TPS). The values obtained vary from one model to the other for the same technique and patient. The maximum dose to the brainstem and spinal cord and the mean dose to the parotids were analysed both dosimetrically and radiobiologically, such as the LKB model effective volume, equivalent uniform dose, EUD-based normal tissue complication probability, and normal tissue integral dose. The mean and max dose to target volume with conformity, homogeneity index, tumor control probability compared with treatment times, and monitor units., Conclusion: Rapid arc (3 arcs) resulted in significantly better OAR sparing, dose homogeneity, and conformity. The findings indicate that the rapid arc plan has improved dose distribution in the target volume compared with IMRT, but the tumor control probability obtained for the two planning methods, Rapid arc (3 arcs) and IMRT (7 fields), are similar. The treatment time and monitor units for the Rapid arc (3 arcs) were superior to other planning methods and considered to be standard in head & neck radiotherapy.

Background Objectives: There is limited evidence studying the relationship of liver segmental dose and segmental volume changes. The segmental dose thresholds could potentially allow for segmental regeneration after liver stereotactic body radiation therapy (SBRT). Given improved survival in hepatocellular cancer (HCC) and liver metastases and more salvage therapy options, this has become an important clinical question to explore. This study assesses the impact of liver segmental dose on segmental volume changes (gain or loss) after SBRT., Methods: Liver segmental contours were delineated on baseline and serial follow up triphasic computed tomography scans. The volumes of total liver and doses to total liver, uninvolved liver and individual segments were noted. A correlation was evaluated between liver/segmental volume and dose using Pearson's correlation. Furthermore, receiver operator's curve (ROC) analysis was performed to find the segmental dose, i.e . predictive for liver volume loss., Results: A total of 140 non-tumour liver segments were available for analysis in 21 participants. Overall, 13 participants showed loss of overall liver volume and eight showed gain of overall liver volume. The median dose in segments reporting an increase in volume was 9.1 Gy (7-36 Gy). The median dose in segments losing volume was 15.5 Gy (1-49 Gy). On ROC analysis, segmental dose >11 Gy was associated with volume loss. On univariate analysis, only liver segmental dose contributed to a significant segmental volume loss., Interpretation Conclusions: We propose from the findings of this study that in SBRT for large hepatocellular cancer or liver metastases, liver segments should be individually delineated. Furthermore, 3-5 liver segments may be preferentially subjected to <9 Gy to facilitate hepatocyte regeneration. Preferential sparing of uninvolved liver segments may improve outcomes in liver stereotaxyas lower segmental doses were associated with liver regeneration. This may have implications on future liver SBRT planning where segmental doses may be as important as the mean dose., (Copyright © 2024 Copyright: © 2024 Indian Journal of Medical Research.)

Aim  To compare the bacterial reduction in single-rooted teeth with pulpal necrosis after laser-activated irrigation technique (LAI) and conventional needle irrigation (CNI). Methodology In this clinical trial (CTRI/2021/09/047767), 32 patients with pulpal necrosis were enrolled. Under complete aseptic conditions, access cavity preparation was done and the baseline sample S1 was collected from the root canal using paper points. After chemo-mechanical preparation they were allocated into two groups, following block randomization; Group A - CNI with 27 gauge side-vented needle, Group B - LAI with pulsed Er,Cr:YSGG (erbium, chromium:yttrium-scandium-gallium-garnet) (2780 nm) laser. After irrigant activation, canals were dried and a second sample S2 was taken using paper points. Microbial analysis using quantitative polymerase chain reaction (qPCR) was done to quantify the bacterial reduction among the two groups. Inter-group and intra-group analysis was done using the independent student t-test and Bonferroni test, respectively. The data was represented in terms of quantification cycle (Cq) values, which are inversely proportional to the microbial count.  Results There was no significant difference in S1 between the two groups (mean difference=0.0205; p=0.912). There was a significant difference in S2 between the two groups for the organisms (mean difference=0.8042; p=0.000). The mean percentage of bacterial reduction in CNI was 10.82% and in LAI it was 25.92%.  There was a significant difference in S1 through S2 within the two groups for the organisms (p=0.000). The mean difference of Cq value is high for LAI compared to CNI (1.3494).  The fold change was calculated by taking the ΔCq value and ΔΔCq value after the logarithmic transformation of the Cq value. LAI showed lower levels of DNA at S2 similar to CNI. There is no significant difference in mean fold change between CNI and LAI (p=0.564).  Conclusion This clinical trial concluded that both LAI and CNI were effective in bacterial reduction. There was greater bacterial reduction with LAI (25.92%) than with the CNI (10.82%) in single-rooted teeth with pulpal necrosis using qPCR analysis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rajamanickam et al.)

Human corona viral infection leads to acute breathing disease and death if not diagnosed and treated properly in time. The disease can be treated with the help of simple natural compounds, which we use in day-to-day life. These natural compounds act against several diseases but their drug targeting mechanism needs to be improved for more efficient and promising applications. In the present study five compounds (gingerol, thymol, thymohydroquinone, cyclocurcumin, hydrazinocurcumin) from three Indian medicinal plants (ginger, black cumin, turmeric) and its hyaluronic acid (HA) conjugates were docked against initially deposited spike structural proteins (PDB ID 6WPT) and its mutant variant D-614G (PDB ID 6XS6). Docking study result reveals that all the HA conjugates showed the most effective inhibitor of S-protein of initially deposited and D-614G variant forms of SARS-CoV-2. The compounds like Gingerol, Thymol, Thymohydroquinone, Cyclocurcumin, Hydrazinocurcumin, Hydroxychloroquinone, and hyaluronic acid conjugates inhibit the viral protein of both wild-type and mutated S-protein of SARS-CoV-2. The molecular docking studies of phytocompounds with initial deposited and variant spike protein targets show superior binding affinity than with the commercial repurposed viral entry inhibitor hydroxychloroquine. Further, the docking result was modeled using MD simulation study shows excellent simulation trajectories between spike proteins and HA conjugates spices constituents than its free form. DFT analysis was carried out to affirm the reason behind the highest binding affinity of HA conjugates over its free form towards SARS-CoV-2 spike protein targets. Further HA conjugates synthesis and its evaluation against SARS-CoV-2 in vitro studies are needed to prove our novel idea for an anti-viral drug.Communicated by Ramaswamy H. Sarma.

The global COVID-19 pandemic continues with continued cases worldwide and the emergence of new SARS-CoV-2 variants. In our study, we have developed novel tools with applications for screening antivirals, identifying virus-host dependencies, and characterizing viral variants. Using reverse genetics, we rescued SARS-CoV-2 Wuhan1 (D614G variant) wild type (WTFL) and reporter virus (NLucFL) using molecular BAC clones. The replication kinetics, plaque morphology, and titers were comparable between viruses rescued from molecular clones and a clinical isolate (VIDO-01 strain). Furthermore, the reporter SARS-CoV-2 NLucFL virus exhibited robust luciferase values over the time course of infection and was used to develop a rapid antiviral assay using remdesivir as proof-of-principle. In addition, as a tool to study lung-relevant virus-host interactions, we established novel human lung cell lines that support SARS-CoV-2 infection with high virus-induced cytopathology. Six lung cell lines (NCI-H23, A549, NCI-H1703, NCI-H520, NCI-H226, and HCC827) and HEK293T cells were transduced to stably express ACE2 and tested for their ability to support virus infection. A549ACE2 B1 and HEK293TACE2 A2 cell lines exhibited more than 70% virus-induced cell death, and a novel lung cell line, NCI-H23ACE2 A3, showed about ~99% cell death post-infection. These cell lines are ideal for assays relying on live-dead selection, such as CRISPR knockout and activation screens.

Background: The aim was to develop in-house software that is able to calculate and generate the biological plan evaluation of the esophagus treatment plan using the Niemierko model for normal tissue complication probability and tumor control probability. The Niemierko model can be applied for esophagus cancer treatment plan to estimate the tumor control probability (TCP) and the normal tissue complication probability (NTCP) using different planning techniques. The equivalent uniform dose (EUD) and effective volume parameters were compared with organ at risk. Subsequently, EUD and TCP parameter were compared with tumor volume for all five different planning techniques., Materials and Methods: Ten cases for esophageal cancer were included in this study. For each patient, five treatment plans were generated. The Anisotropic analytical algorithms (AAA) were used for dose calculation for the three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques. The in-house developed radiobiological plan evaluation software using python programming is used for this study which takes a dose volume histogram (DVH) text file as an input file for biological plan evaluation., Results and Conclusion: EUD, NTCP, TCP and effective volume were calculated from the Niemierko model using the in-house developed python based software and compared with treatment monitor units (MU) with all five different treatment plan. The best technique is quantified as benchmarked out of other different qualities of treatment. The four field 3D-CRT treatment plan is found to be the best suited from the perspective of biological plan index evaluation among the other planning techniques., Competing Interests: Conflict of interest None declared., (© 2023 Greater Poland Cancer Centre.)

Coronaviruses have caused enough devastation in the last two decades. These viruses have some rare features while sharing some common features. Novel coronavirus disease (nCoV-19) caused an outbreak with a fatality rate of 5%. It emerged from China and spread into many countries. The present research focused on genome analysis of Indian nCoV-19 Isolate and its translational product subjected to homology modeling and its subsequent molecular simulations to find out potent FDA approved drug for treating COVID-19. Phylogenetic analysis of SARS-CoV-2 Indian isolate shows close resemblance with 17 countries SARS-CoV-2 isolates. Homology modeling of four non-structural proteins translational product of Indian SARS-CoV-2 genome shows high similarity and allowed regions with the existing PDB deposited SARS-CoV-2 target proteins. Finally, these four generated proteins show more affinity with cobicistat, remdesivir and indinavir out of 14 screened FDA approved drugs in molecular docking which is further proven by molecular dynamics simulation and MMGBSA analysis of target ligand complex with best simulation trajectories. Overall our present research findings is that three proposed drugs namely cobicistat, remdesivir and indinavir showed higher interaction with the model SARS-CoV-2 viral target proteins from the Indian nCoV-19 isolate. These compounds could be used as a starting point for the creation of active antiviral drugs to combat the deadly COVID-19 virus during global pandemic and its subsequent viral infection waves across the globe.Communicated by Ramaswamy H. Sarma.

Due to its potential impact on food safety and human health, commercial species that have been contaminated with microplastics (MPs) are drawing more attention on a global scale. This study investigated the possibility of MPs contamination in different marine fish species with substantial commercial value that was captured off the south coast of India, from Adyar and Ennore regions. Over the course of six months, from October 2019 to March 2020, 220 fish were examined. It was discovered that the gills and guts had accumulated more numbers of MPs (1115 MPs) of which 68% were fibres and fragments. The commercial fish samples contained an average of 3.2-7.6 MPs per fish. Greater MPs pollution is seen in the Ennore regions. The prevalence of MPs was observed in carnivorous and planktivorous fish collected from both the sites. Fish guts contained the most MPs, according to the data. Pelagic fish accounted for the least amount of MPs, followed by mid- and demersal fish. Four different types of polymers were also identified in the present study: polyethylene, polypropylene, polystyrene, and polyamide. These results clearly showed the degree of microplastic contamination in fish tissues from the south Indian coastal regions of Adyar and Ennore. These results we hope will create a baseline data for MPs contamination in commercial fish species. The presence of MPs in the fish could have detrimental effects both on the environment and human health and thus comprehensive steps are required to prevent plastic pollution of the environment in south India's coastal region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cancer burden in India is increasing. Cancer treatment today is multi-disciplinary requiring the coordination of many specialists for best outcomes. Bringing such expertise together to the district level is the greatest challenge for cancer care in any country, moreover in India. This article focuses on the step-wise journey to make comprehensive cancer care center in a small city., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2022.)

The success of endodontic treatment relies on both apical and coronal sealing. To achieve a good three-dimensional seal, the removal of the smear layer becomes mandatory. This study aims to assess the difference in debris accumulation and smear layer formation while using automated root canal irrigation and conventional syringe needle irrigation. Single-rooted human mandibular premolar teeth (n = 30) which were indicated for orthodontic extractions were selected. An endodontic access cavity was prepared, and a glide path was created. Based on the irrigation protocol decided upon for the study, the teeth were randomly allocated into three study groups, namely Group 1, where the manual syringe needle irrigation method was adopted; Group 2, in which automated root canal irrigation was undertaken; and Group 3, in which teeth remained un-instrumented as it was considered the Control group. The teeth were decoronated at the cement-enamel junction (CEJ) and were subjected for scanning electron microscopy (SEM) examination. Debris and smear layers were viewed in 1000× magnification and scored. A statistically significant (p < 0.05) lower mean debris and smear layer score (p < 0.05) was observed in both study groups when compared with the control group. However, no significant difference (p > 0.05) in the debris and smear layer was observed between the manual syringe needle irrigation and automated irrigation, although automated irrigation devices can be a potential alternative. The present study concluded that the efficacy of smear layer removal remained the same with both automated irrigation and manual syringe irrigation.

Macrophages are considered to be key players in innate immunity and inflammatory responses. Domestic cattle with standard body size quickly reach their heat tolerance limit and are prone to heat stress. The combined effects of high temperature and endotoxemia on bovine monocyte-derived macrophages remain almost undisclosed. This study aims to unravel the molecular and functional responses of bovine monocyte-derived macrophages to thermal cum lipopolysaccharide induced stress challenge in vitro. The cells were incubated at 37 °C or 40 °C with lipopolysaccharide (1.0 μg/mL) for 24 h and 48 h. At the end of each treatment, cell viability, apoptotic rate, mitochondrial membrane potential, oxidative activity, phagocytosis, and autophagy functions were assessed and mRNA abundance of genes related to heat shock (HSP 70), inflammation (IL1β, IL6, IL 12, TNF, INF γ), cell signalling (TLR4), cell viability (Bax, Bcl2), nitric oxide synthesis (NOS2) and natural resistant associated macrophage protein were quantified by quantitative polymerase chain reaction (qPCR). The results revealed the increased apoptosis, reduced mitochondrial membrane potential, and cell viability, decreased oxidative and phagocytosis ability in cells co-stimulated with LPS and thermal stimuli. Upregulation of HSP 70 gene and downregulation of natural resistant associated macrophage protein, cell signalling, and inflammation related genes mRNA expressions were also identified due to these stressors. In conclusion, the observed thermal cum LPS stress induced dysregulation in macrophage functionality may be one facet of the increased disease susceptibility in dairy cattle during thermal stress., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

(1) Background: There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2) Methods: In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3) Results: Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4) Conclusions: Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.

Breast cancer is the most common cancer in women. Despite advances in screening women for genetic predisposition to breast cancer and risk stratification, a majority of women carriers remain undetected until they become affected. Thus, there is a need to develop a cost-effective, rapid, sensitive and non-invasive early-stage diagnostic method. Kinases are involved in all fundamental cellular processes and mutations in kinases have been reported as drivers of cancer. PPARγ is a ligand-activated transcription factor that plays important roles in cell proliferation and metabolism. However, the complete set of kinases modulated by PPARγ is still unknown. In this study, we identified human kinases that are potential PPARγ targets and evaluated their differential expression and gene pair correlations in human breast cancer patient dataset TCGA-BRCA. We further confirmed the findings in human breast cancer cell lines MCF7 and SK-BR-3 using a kinome array. We observed that gene pair correlations are lost in tumours as compared to healthy controls and could be used as a supplement strategy for diagnosis and prognosis of breast cancer.

Cancer is a highly malignant disease, killing approximately 10 million people worldwide in 2020. Cancer patient survival substantially relies on early diagnosis. In this study, we evaluated whether genes involved in glucose metabolism could be used as potential diagnostic markers for cancer. In total, 127 genes were examined for their gene expression levels and pairwise gene correlations. Genes ADH1B and PDHA2 were differentially expressed in most of the 12 types of cancer and five pairs of genes exhibited consistent correlation changes (from strong correlations in normal controls to weak correlations in cancer patients) across all types of cancer. Thus, the two differentially expressed genes and five gene pairs could be potential diagnostic markers for cancer. Further preclinical and clinical studies are warranted to prove whether these genes and/or gene pairs would indeed aid in early diagnosis of cancer., Competing Interests: CONFLICT OF INTEREST The authors declare no potential conflicts of interest., (Copyright: © 2021 Sakharkar et al.)

Tryptophan metabolism plays essential roles in both immunomodulation and cancer development. Indoleamine 2,3-dioxygenase, a rate-limiting enzyme in the metabolic pathway, is overexpressed in different types of cancer. To get a better understanding of the involvement of tryptophan metabolism in cancer development, we evaluated the expression and pairwise correlation of 62 genes in the metabolic pathway across 12 types of cancer. Only gene AOX1 , encoding aldehyde oxidase 1, was ubiquitously downregulated, Furthermore, we observed that the 62 genes were widely and strongly correlated in normal controls, however, the gene pair correlations were significantly lost in tumor patients for all 12 types of cancer. This implicated that gene pair correlation coefficients of the tryptophan metabolic pathway could be applied as a prognostic and/or diagnostic biomarker for cancer., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Bovine mastitis is one of the major infectious diseases in dairy cattle, resulting in large economic loss due to decreased milk production and increased production cost to the dairy industry. Antibiotics are commonly used to prevent/treat bovine mastitis infections. However, increased antibiotic resistance and consumers' concern regarding antibiotic overuse make it prudent and urgent to develop novel therapeutic protocols for this disease., Materials and Methods: Potential druggable targets were found in 20 mastitis-causing pathogens and conserved and unique targets were identified. Bacterial strains Staphylococcus aureus (ATCC 29213, and two clinical isolates CI 1 and CI 2) and Staphylococcus epidermidis (ATCC 12228, and two clinical isolates CI 1 and CI 2) were used in the present study for validation of an effective drug combination., Results: In the current study, we identified the common and the unique druggable targets for twenty mastitis-causing pathogens using an integrative approach. Furthermore, we showed that phosphorylcholine, a drug for a unique target gamma-hemolysin component B in Staphylococcus aureus , and ceftiofur, the mostly used veterinary antibiotic that is FDA approved for treating mastitis infections, exhibit a synergistic effect against S. aureus and a strong additive effect against Staphylococcus epidermidis in vitro., Conclusion: Based on the data generated in this study, we propose that combination therapy with drugs that work synergistically against conserved and unique targets can help increase efficacy and lower the usage of antibiotics for treating bacterial infections. However, these data need further validations in animal models of infection.