Tissue/Biofluid Specific Molecular Cartography of Leishmania donovani Infected BALB/c Mice: Deciphering Systemic Reprogramming

Pathophysiology of visceral leishmaniasis (VL) is not fully understood and it has been widely accepted that the parasitic components and host immune response both contribute to the perpetuation of the disease. Host alterations during leishmaniasis is a feebly touched area that needs to be explored more to better understand the VL prognosis and diagnosis, which are vital to reduce mortality and post-infection sequelae. To address this, we performed untargeted metabolomics of Leishmania donovani (Ld) infected, uninfected and treated BALB/c mice’s tissues and biofluids to elucidate the host metabolome changes using gas chromatography–mass spectrometry. Univariate and multivariate data treatments provided numerous significant differential hits in several tissues like the brain, liver, spleen and bone marrow. Differential modulations were also observed in serum, urine and fecal samples of Ld-infected mice, which could be further targeted for biomarker and diagnostic validations. Several metabolic pathways were found to be upregulated/downregulated in infected (TCA, glycolysis, fatty acids, purine and pyrimidine, etcetera) and treated (arginine, fumaric acid, orotic acid, choline succinate, etcetera) samples. Results also illustrated several metabolites with different pattern of modulations in control, infected and treated samples as well as in different tissues/biofluids; for e.g. glutamic acid identified in the serum samples of infected mice. Identified metabolites include a range of amino acids, saccharides, energy-related molecules, etcetera. Furthermore, potential biomarkers have been identified in various tissues—arginine and fumaric acid in brain, choline in liver, 9-(10) EpOME in spleen and bone marrow, N-acetyl putrescine in bone marrow, etcetera. Among biofluids, glutamic acid in serum, hydrazine and deoxyribose in urine and 3-Methyl-2-oxo pentanoic acid in feces are some of the potential biomarkers identified. These metabolites could be further looked into for their role in disease complexity or as a prognostic marker. The presented profiling approach allowed us to attain a metabolic portrait of the individual tissue/biofluid modulations during VL in the host and represent a valuable system readout for further studies. Our outcomes provide an improved understanding of perturbations of the host metabolome interface during VL, including identification of many possible potential diagnostic and therapeutic targets.

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Metabolic Profiling during Acute Myeloid Leukemia Progression Using Paired Clinical Bone Marrow Serum Samples

Metabolites ◽

10.3390/metabo11090586 ◽

2021 ◽

Vol 11 (9) ◽

pp. 586

Author(s):

Hyun Kyu Kim ◽

Su Young Son ◽

Jae Sang Oh ◽

Ye Na Song ◽

Ja Min Byun ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Complete Remission ◽

Myeloid Leukemia ◽

Genetic Variations ◽

Leukemic Cells ◽

Gas Chromatography Mass Spectrometry ◽

Healthy Individuals ◽

Serum Samples ◽

Acute Myeloid

Cellular metabolic changes reflect the characteristics of patients with acute myeloid leukemia (AML) caused by genetic variations, which are important in establishing AML treatment. However, little is known about the metabolic profile of patients with genetic variation-induced AML. Furthermore, the metabolites differ with disease progression. Here, metabolites in the bone marrow serum of ten patients with AML and healthy individuals were analyzed using gas chromatography–mass spectrometry. Compared with that in healthy individuals, expression of most metabolites decreased in patients with AML; hydroxylamine, 2-hydroxybutyric acid, monomethylphosphate, and ethylphosphate expression was unusually increased in the patients. We further examined serial metabolite changes across the initial diagnosis, postremission, and relapse phases. Patients with relapse showed increased metabolite expression compared with those in the diagnostic phase, confirming that patients with AML had aggressively modified leukemic cells. However, a clear difference in metabolite distribution was not observed between the diagnosis and complete remission phases, suggesting that the metabolic microenvironment did not change significantly despite complete remission. Interestingly, metabolite profiles differed with genetic variations in leukemic cells. Our results, which were obtained using paired samples collected during AML progression, provide valuable insights for identifying vulnerable targets in the AML metabolome and developing new treatment strategies.

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Drug-Induced Agranulocytosis: A Mini Review

Research in Pharmacy and Health Sciences ◽

10.32463/rphs.2016.v02i01.11 ◽

2016 ◽

Vol 2 (1) ◽

pp. 57-59

Author(s):

Pavithra D ◽

Praveen D ◽

Vijey Aanandhi M

Keyword(s):

Bone Marrow ◽

Complete Blood Count ◽

Genetic Manipulation ◽

White Blood Cells ◽

Deep Infection ◽

Morbidity Rate ◽

Drug Induced ◽

Serious Adverse Event ◽

Mortality And Morbidity ◽

The Individual

Agranulocytosis is also known to be granulopenia, causing neutropenia in circulating blood streams .The destruction of white blood cells takes place which leads to increase in the infection rate in an individual where immune system of the individual is suppressed. The symptoms includes fever, sore throat, mouth ulcers. These are commonly seen as adverse effects of a particular drug and are prescribed for the common diagnostic test for regular monitoring of complete blood count in an admitted patient. Drug-induced agranulocytosis remains a serious adverse event due to occurrence of severe sepsis with deep infection leading to pneumonia, septicaemia, and septic shock in two/third of the patient. Antibiotics seem to be the major causative weapon for this disorder. Certain drugs mainly anti-thyroid drugs, ticlopidine hydrochloride, spironolactone, clozapine, antileptic drugs (clozapine), non-steroidal anti-inflammatory agents, dipyrone are the potential causes. Bone marrow insufficiency followed by destruction or limited proliferative bone marrow destruction takes place. Chemotherapy is rarely seen as a causative agent for this disorder. Genetic manipulation may also include as one of the reason. Agranulocytosis can be recovered within two weeks but the mortality and morbidity rate during the acute phase seems to be high, appropriate adjuvant treatment with broad-spectrum antibiotics are prerequisites for the management of complicated neutropenia. Drugs that are treated for this are expected to change as a resistant drug to the patient. The pathogenesis of agranulocytosis is not yet known. A comprehensive literature search has been carried out in PubMed, Google Scholar and articles pertaining to drug-induced agranulocytosis were selected for review.

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Leptospirosis in Ruminants in Yogyakarta, Indonesia: A Serological Survey with Mixed Methods to Identify Risk Factors

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6020084 ◽

2021 ◽

Vol 6 (2) ◽

pp. 84

Author(s):

Dyah Ayu Widiasih ◽

Johanna Frida Lindahl ◽

Wayan T. Artama ◽

Adi Heru Sutomo ◽

Pande Made Kutanegara ◽

...

Keyword(s):

Risk Factor ◽

Management Practices ◽

Small Ruminants ◽

Case Fatality ◽

Open Water ◽

Serum Samples ◽

Public Health Importance ◽

Group Discussions ◽

The Individual ◽

And Behavior

Leptospirosis is a zoonotic disease occurring worldwide with reproductive symptoms and production losses in livestock, while humans can suffer fatal renal failure. In Yogyakarta Special Province, Indonesia, there have been several outbreaks with high case fatality, demonstrating the public health importance, but there is limited understanding of the epidemiology. This study used an EcoHealth approach to ensure transdisciplinarity and community participation. Seroprevalence of Leptospira in animals was studied between October 2011 and May 2013 in 15 villages. Serum samples from 1404 cattle and 60 small ruminants were screened by a Microscopic Agglutination Test (MAT), first in pools, and then the individual positive samples were identified. Focus group discussions including farmers, village officials, and official stakeholders were used to explore knowledge and behavior of zoonotic diseases, particularly leptospirosis. Two small ruminants were seropositive for Leptospira icterohemorrhagiae. From the cattle, 3.7% were seropositive, and the most common serovars were Leptospira hardjo, followed by L. icterohemorrhagiae. Out of all farms, 5.6% had at least one positive cattle. Risk factor analyses showed that the risk of the farm being seropositive increased if the farmer used water from an open source, or if farming was not the main occupation. This study showed the presence of Leptospira spp. in ruminants in Yogyakarta and identified use of open water as a risk factor for the livestock. We also observed that the knowledge related to leptospirosis was low, and risky farm management practices were commonly employed.

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Serological Evaluation of Specific-Antibody Levels in Patients Treated for Chronic Chagas' Disease

Clinical and Vaccine Immunology ◽

10.1128/cvi.00106-07 ◽

2007 ◽

Vol 15 (2) ◽

pp. 297-302 ◽

Cited By ~ 38

Author(s):

Olga Sánchez Negrette ◽

Fernando J. Sánchez Valdéz ◽

Carlos D. Lacunza ◽

María Fernanda García Bustos ◽

María Celia Mora ◽

...

Keyword(s):

Chagas Disease ◽

Treatment Effectiveness ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Serological Tests ◽

Recombinant Antigens ◽

Antibody Titers ◽

Laboratory Procedures ◽

The Individual ◽

Antibody Levels

ABSTRACT Serological tests are the main laboratory procedures used for diagnosis during the indeterminate and chronic stages of Chagas' disease. A serological regression to negativity is the main criterion used to define parasitological cure in treated patients. The aim of this work was to monitor the individual specificities of antibody levels for 3 years posttreatment in 18 adult patients. Conventional serological techniques (hemagglutination assays and enzyme-linked immunosorbent assay [ELISA]) were modified by using recombinant antigens to detect early markers of treatment effectiveness. For this purpose, serum samples were taken before and during treatment and every 6 months after treatment for at least 3 years. When hemagglutination assays were used, a decrease in antibody levels was observed in only one patient. When ELISA with serum dilutions was used, antibody clearance became much more apparent: in 77.7% (14/18) of the patients, antibody titers became negative with time. This was observed at serum dilutions of 1/320 and occurred between the 6th and the 30th months posttreatment. The immune response and the interval for a serological regression to negativity were different for each patient. For some of the recombinant antigens, only 50% (9/18) of the patients reached the serological regression to negativity. Recombinant antigen 13 might be a good marker of treatment effectiveness, since 66.6% (six of nine) of the patients presented with an early regression to negativity for specific antibodies to this antigen (P = 0.002).

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Can the decrease of blood alcohol level be accelerated? Results of a clinical study

Orvosi Hetilap ◽

10.1556/oh.2009.28580 ◽

2009 ◽

Vol 150 (19) ◽

pp. 903-907 ◽

Cited By ~ 1

Author(s):

Mária Mátyus ◽

István Horváth ◽

János Fehér ◽

Róbert Farkas ◽

Veronika Wolf ◽

...

Keyword(s):

Solid Phase ◽

Blood Alcohol Level ◽

Gas Chromatography Mass Spectrometry ◽

Blood Alcohol ◽

Alcohol Metabolism ◽

Experimental Protocol ◽

Spectrometry Method ◽

Pure Alcohol ◽

Guardian Angel ◽

The Individual

The purpose of this study was to examine the effect of Guardian Angel powder (GA) on the blood alcohol level. According to the experimental protocol, two sets of measurement were performed: modeling the eating and drinking habit of a typical family or social meeting, alcohol containing drinks corresponding to 70 g of pure alcohol and copious amount of food were consumed first without GA powder, then with GA powder. In the latter case GA powder was dissolved in water and one dose was taken before eating, the other one was consumed during eating. Blood samples were hourly collected from the volunteers in both sets for four hours. The measurement of blood alcohol level was performed by gas chromatography-mass spectrometry method proceeding to Solid Phase Micro Extraction (SPME). Our results show that the blood alcohol level decreased significantly when two doses of GA powder were consumed. After two hours of taking GA powder, the blood alcohol level was significantly lower in each volunteers compared to their own blood alcohol level measured in the absence of GA powder. This result shows that the individual variation of the alcohol metabolism does not influence significantly the effect of GA powder. Further studies are needed to investigate the detailed mechanism of the action of GA powder to find out whether GA powder influences the absorption of alcohol or/and the metabolism of alcohol.

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Muscle and Serum Metabolomics for Different Chicken Breeds under Commercial Conditions by GC–MS

Foods ◽

10.3390/foods10092174 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2174

Author(s):

Chengkeng Tan ◽

Jinap Selamat ◽

Nuzul Noorahya Jambari ◽

Rashidah Sukor ◽

Suganya Murugesu ◽

...

Keyword(s):

Principal Component ◽

Pectoralis Major ◽

Untargeted Metabolomics ◽

Gas Chromatography Mass Spectrometry ◽

Serum Samples ◽

Food Fraud ◽

Village Chicken ◽

Premium Price ◽

Chicken Breeds ◽

Serum Metabolomics

Globally, village chicken is popular and is known as a premium meat with a higher price. Food fraud can occur by selling other chicken breeds at a premium price in local markets. This study aimed to distinguish local village chicken from other chicken breeds available in the market, namely, colored broiler (Hubbard), broiler (Cobb), and spent laying hen (Dekalb) in pectoralis major and serum under commercial conditions using an untargeted metabolomics approach. Both pectoralis major and serum were analyzed using gas chromatography–mass spectrometry (GC–MS). The principal component analysis (PCA) results distinguished four different chicken breeds into three main groups for pectoralis major and serum. A total of 30 and 40 characteristic metabolites were identified for pectoralis major and serum, respectively. The four chicken breeds were characterized by the abundance of metabolites such as amino acids (L−glutamic acid, L−threonine, L−serine, L−leucine), organic acids (L−lactic acid, succinic acid, 3−hydroxybutyric acid), sugars (D−allose, D−glucose), sugar alcohols (myo−inositol), and fatty acids (linoleic acid). Our results suggest that an untargeted metabolomics approach using GC–MS and PCA could discriminate chicken breeds for pectoralis major and serum under commercial conditions. In this study, village chicken could only be distinguished from colored broiler (Hubbard) by serum samples.

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Application of green synthesized WO3-poly glutamic acid nanobiocomposite for early stage biosensing of breast cancer using electrochemical approach

Scientific Reports ◽

10.1038/s41598-021-03209-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hassan Nasrollahpour ◽

Abdolhossein Naseri ◽

Mohammad-Reza Rashidi ◽

Balal Khalilzadeh

Keyword(s):

Breast Cancer ◽

Glutamic Acid ◽

Electrochemical Biosensor ◽

Early Stage ◽

Clinical Samples ◽

Breast Cancer Patients ◽

Serum Samples ◽

Electrochemical Approach ◽

Her 2

AbstractBiopolymer films have drawn growing demand for their application in the point of care domain owing to their biocompatibility, eco-friendly, and eligibility for in vivo analyses. However, their poor conductivity restricts their sensitivity in diagnostics. For high-quality electrochemical biosensor monitoring, two vital factors to be greatly paid attention are the effective merge of amplification modifiers with transducing surface and the superior linking across the recognition interface. Here, we introduce an enzyme-free electrochemical biosensor based on electrosynthesized biocompatible WO3/poly glutamic acid nano-biocomposites to address the hardships specific to the analysis of circulating proteins clinical samples. In addition to its green synthesis route, the poor tendency of both components of the prepared nano-biocomposite to amine groups makes it excellent working in untreated biological samples with high contents of proteins. Several electrochemical and morphological investigations (SEM, EDX, and dot mapping) were fulfilled to gain a reliable and trustful standpoint of the framework. By using this nanobiosensor, the concentration of HER-2 was detectable as low as 1 fg mL−1 with a wide linear response between 1 ng mL−1 and 1 fg mL−1. Meanwhile, the protocol depicted ideal specificity, stability, and reproducibility for the detection of HER-2 protein in untreated serum samples of breast cancer patients.

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Determination of Mycoplasma bovis specific antibodies in blood sera of asymptomatic carriers-calves in three farms in the Republic of Serbia by using indirect ELISA assay

Journal of the Hellenic Veterinary Medical Society ◽

10.12681/jhvms.15518 ◽

2017 ◽

Vol 65 (2) ◽

pp. 79

Author(s):

D. VOJINOVIĆ ◽

A. VASIĆ ◽

J. ŽUTIĆ ◽

B. DURIČIĆ ◽

Z. ILIĆ ◽

...

Keyword(s):

Indirect Elisa ◽

Mycoplasma Bovis ◽

Elisa Assay ◽

Serum Samples ◽

Asymptomatic Carriers ◽

Elisa Kit ◽

Cattle Blood ◽

The Republic ◽

The Individual

Blood serum samples of asymptomatic carriers-calves were collected from three farms in the territory of the Republic of Serbia during 2011 and 2012. Commercial Mycoplasma bovis ELISA kit (Bio-X Diagnostics, Belgique) for serological diagnosis from cattle blood sera and milk was used in this research. Calves’ blood sera were tested using immunoenzymatic indirect ELISA assay as described by manufacturer’s instructions. From 5603 blood sera of asymptomatic carriers-calves 144 (2,57%) samples were tested positive for the presence of specific Mycoplasma bovis antibodies. In three different farms proportions of seropositive samples varied from 0,32% to 10,6% in regard to total number of tested samples from the individual farms. In this paper we present the results of Mycoplasma bovis prevalence in asymptomatic carriers-calves.

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A STUDY ON THE "IN VITRO" SYNTHESIS OF CITRULLINE: PART II. EFFECT OF GLUTAMIC ACID AND DERIVATIVES IN THE PRESENCE OF FUMARIC ACID

Canadian Journal of Biochemistry ◽

10.1139/o64-142 ◽

1964 ◽

Vol 42 (9) ◽

pp. 1325-1330 ◽

Cited By ~ 2

Author(s):

René Charbonneau ◽

Louis Berlinguet

Keyword(s):

Glutamic Acid ◽

Rat Liver ◽

Fumaric Acid ◽

Liver Homogenate ◽

Particulate Fraction ◽

In Vitro Synthesis ◽

System L ◽

Acyl Derivatives

The role of N-carbamyl, N-acetyl, and L-glutamic acids with and without fumaric acid on the "in vitro" synthesis of citrulline was studied by using a particulate fraction obtained from a rat liver homogenate and a partially purified citrulline-synthesizing enzyme system. In the presence of a particulate fraction of rat liver homogenate, N-carbamyl and N-acetyl-L-glutamic acids are unable to replace L-glutamic acid, which is essential for citrulline biosynthesis. However, in the presence of fumaric acid, they both give a better synthesis of citrulline than L-glutamic acid alone. It is postulated that the acyl derivatives serve only in the transport of "activated CO2" whereas fumaric acid enters the citric acid to furnish the essential ATP molecules. Glutamic acid would be able to perform both functions. However, in the presence of a system containing partially purified citrulline-synthesizing enzymes, L-glutamic acid is unable to replace N-carbamyl and N-acetyl-L-glutamic acids with or without fumaric acid. In such a system, L-glutamic acid cannot serve in the transport of "activated CO2". It is postulated that L-glutamic acid must be acetylated prior to its utilization in this respect.With the particulate fraction of rat liver homogenate, N-allyl aspartic acid inhibits totally the synthesis of citrulline both in the presence and absence of fumaric acid with or without glutamic or N-acetyl glutamic acids. It probably interferes with the transport of "activated CO2".

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Differential Expression of MicroRNA-3148 in Patients with Osteoporosis and Its Impacts on the Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2635 ◽

2021 ◽

Vol 11 (5) ◽

pp. 957-962

Author(s):

Ainiwaerjiang Damaola ◽

Maerdan Aierken ◽

Mieralimu Muertizha ◽

Abudouaini Abudoureheman ◽

Haishan Lin ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Serum Samples ◽

Alizarin Red ◽

Differentiation Potential ◽

Qrt Pcr ◽

Marrow Mesenchymal Stem Cells ◽

Rat Bone

We aimed to explore the effects of rat bone marrow mesenchymal stem cells (BMSCs) on osteogenic differentiation via analyzing miR-3148 expression in patients with osteoporosis. Realtime quantitative PCR was conducted for assessing microRNA-3148 expression. BMSCs from SD rats were transfected with microRNA-3148 mimics and microRNA-3148 inhibitor via liposomal trans-fection method utilizing Lipo2000, followed by analysis of microRNA-3148 level. After 10-days of osteogenic differentiation induction, alkaline phosphatase (ALP) staining and alizarin red (ARS) staining were done to investigate the osteogenic differentiation potential. Simultaneously, qRT-PCR measured the expression of osteogenesis marker genes (BMP and Runx2) in each group. qRT-PCR analysis revealed a high expression of miR-3148 in the bone tissue and the serum samples from patients with osteoporosis in comparison with healthy individuals. In addition, miRNA-3148 mimics could retard the osteogenic differentiation of BMSCs, while microRNA-3148 inhibitor could prompt the procedure. MicroRNA-3148 was highly expressed in the skeletal tissues and the serum samples from patients with osteoporosis and it could restrain the differentiation of BMSCs into osteoblasts, suggesting that it might be a novel therapeutic target for treating osteoporosis.

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