This article summarizes our early work with Viswanathan Natarajan in the 1980s at the University of Minnesota’s Hormel Institute, when he was at the beginning of his brilliant academic career. At that time most metabolic pathways for the biosynthesis and degradation of phospholipids were well established and known in considerable detail. Hence, it was exciting to discover a novel sequence of biochemical

Bladder cancer (Bca) is the second most common malignant tumor of the genitourinary system in Chinese male population with high potential of recurrence and progression. The overall prognosis has not been improved significantly for the past 30 years due to the lack of early theranostic technique. Currently the early theranostic technique for bladder cancer is mainly through the intravesical approach

In recent years, tankyrase inhibition has gained a great focus as an anti-cancer strategy due to their modulatory effect on WNT/β-catenin pathway implicated in many malignancies, including colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). Based on the structural homology in the catalytic domain of PARP enzymes, bis-quinazolinone 5 (Cpd 5) was designed to be a potent selective tankyrase

A comparative kinetic analysis of albino rat brain synaptic and kidney plasma membrane fraction Na,K-ATPase was performed to comprehend the different levels of sensitivity of these fractions to the neurotransmitter noradrenaline. Noradrenaline (NA) inhibits the rat brain synaptic membrane Na,K-ATPase, changes the stoichiometry of Na+ and K+ and shifts the enzyme system from an MgATP to an Mg2+ dependent

Lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P) promote vasculogenesis, angiogenesis, and wound healing by activating a plethora of overlapping signaling pathways that stimulate mitogenesis, cell survival, and migration. As such, maladaptive signaling by LPA and S1P have major effects in increasing tumor progression and producing poor patient outcomes after chemotherapy and radiotherapy.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and one of the leading causes of cancer-related death in the world. Due to the recurrence of HCC, its survival rate is still low. Therefore, it is vital to seek prognostic biomarkers for HCC. In this study, differential analysis was conducted on gene expression data in The Cancer Genome Atlas -LIHC, and 4482 differentially expressed genes

According to our previous study, fisetin (3,3’,4’,7-tetrahydroxyflavone), a bioactive phytochemical (flavonol), reportedly showed cardioprotection against ischemia-reperfusion injury (IRI) by reducing oxidative stress and inhibiting glycogen synthase kinase 3β (GSK3β) [1]. GSK3β is said to exert a non-mitochondrial mediated cardioprotection; therefore, distinct mechanisms of GSK3β on the regulatory

Our earlier in vitro and in vivo studies have revealed that the phytosterol, pentalinonsterol (cholest-4,20,24-trien-3-one) (PEN), isolated from the roots of Pentalinon andrieuxii, possesss immunomodulatory properties in macrophages and dendritic cells. Leishmaniasis, caused by the infection of Leishmania spp. (a protozoan parasite), is emerging as the second-leading cause of mortality among the tropical

Radiation-induced lung injury (RILI) is a potential complication of thoracic radiotherapy that can result in pneumonitis or pulmonary fibrosis and is associated with significant morbidity and mortality. The pathobiology of RILI is complex and includes the generation of free radicals and DNA damage that precipitate oxidative stress, endothelial cell (EC), and epithelial cell injury and inflammation

The parotid gland is the largest salivary gland. It produces watery saliva, rich in proteins (amylase, lysozymes, and antibodies). Due to the gland’s morphological cytoarchitecture composed of only serous acini, it contributes almost 50% of total salivary volume upon stimulation. It has been reported that the prevalence of saliva secretion impairments, periodontitis, delayed wound healing, and xerostomia

Lysophosphatidic acid (LPA) is a versatile lysolipid, and activates a variety of signaling cascades in many cell types. Extracellular LPA is produced from lysophosphatidylcholine (LPC) by the enzyme autotaxin (ATX), and binds to a family of G-protein coupled receptors on its target cells. Research by many groups continues to support the idea that LPA, and the ATX-LPA axis, have important roles in asthma

Background Prolonged and overlapping phases of wound healing in diabetes are mainly due to the redox imbalance resulting in the chronicity of the wound. Photobiomodulation therapy works on the principle of absorption of photon energy and its transduction into a biological response in the living tissue. It alleviates the cellular responses, thereby improving the mechanism of wound healing in diabetes

This study investigated the potential genes and related pathways in burn-induced myocardial injury. Rat myocardial injury induced by third-degree burn and the histopathological structures, apoptosis, and cardiac injury markers were then identified using hematoxylin & eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and enzyme-linked immunosorbent assay

Collection of skin very top layer, called stratum corneum, by tape stripping and the analysis of stratum corneum components by mass spectrometry provides multiple advantages for clinical studies that aim to understand the origins of allergic skin diseases and food allergy. However, such a methodology has multiple challenges on the way of complex stratum corneum analysis when molecules of different

This article is intended to recognize and the life time contribution that Dr. Viswanathan Natarajan has made to the advancement of lipid metabolism and lipid signaling. In particular, his major contributions in the last three decades have been made in understanding how lipids such as phosphatidic acid, lysophosphatidic acid, sphingosine 1-phosphate and cardiolipin contribute to healthy lung functions

Asthma is a heterogeneous pulmonary disease that has constantly increased in prevalence over the past several decades. Primary symptoms include airway constriction, airway hyperresponsiveness, and airway remodeling with additional symptoms such as shortness of breath, wheezing, and difficulty breathing. Allergic asthma involves chronic inflammation of the lungs, and the rise in its yearly diagnosis

Ionizing radiation (IR) is used in a wide range of clinical applications. The study aims to evaluate various IR doses for their immunomodulatory responses, which can be used in multiple immunological conditions. Forty rats were exposed to whole-body gamma rays of 0, 0.25, 0.5, and 1 Gray (Gy). T-cell receptor (TCR) gene expression, serum transforming growth factor-beta, interleukin-10 (IL-10), and

Introduction We have earlier shown that hyperoxia (HO)-induced sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) signaling contribute to bronchopulmonary dysplasia (BPD). S1P acts through G protein-coupled receptors, S1P1 through S1P5. Further, we noted that heterozygous deletion of S1pr1 ameliorated the HO-induced BPD in the murine model. The mechanism by which S1P1 signaling contributes

Acute inflammation in the lung is essential for host defense against pathogens and other injuries but chronic or excessive inflammation can contribute to several common respiratory diseases. In health, the inflammatory response is controlled by several cellular and molecular mechanisms. In addition to anti-inflammatory processes, there are non-phlogistic pro-resolving mechanisms that are engaged to

Pulmonary hypertension (PH) is a condition when the pressure in the lung blood vessels is elevated. This leads to increase in thickness of the blood vessels and increases the workload of the heart and lungs. The incidence and prevalence of PH has been on the increase in the last decade. It is estimated that PH affects about 1% of the global population and about 10% of individuals >65 years of age.

The aberrant proliferation of pulmonary artery smooth muscle (PASMCs) cells is a defining characteristic of pulmonary arterial hypertension (PAH) and leads to increased vascular resistance, elevated pulmonary pressure, and right heart failure. The sphingosine kinase 1 (SPHK1)/sphingosine-1 phosphate/sphingosine-1 phosphate receptor 2 pathway promotes vascular remodeling and induces PAH. The aim of

Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a rare metabolic disorder caused by a deficiency in sphingosine-1-phosphate lyase (SPL), the final enzyme in the sphingolipid degradative pathway. Inactivating mutations of SGPL1—the gene encoding SPL—lead to a deficiency of its downstream products, and buildup of sphingolipid intermediates, including its bioactive substrate, sphingosine-1-phosphate

Inflammation and oxidative stress feature prominently in the secondary spinal cord injury (SCI). The present work is targeted at deciphering miR-145-5p’s role and underlying mechanism in SCI. We randomly divided Sprague-Dawley rats into SCI group and control group. Microglial BV2 cells were separated into control group and lipopolysaccharide (LPS) treatment group. Enzyme-linked immunosorbent assay

Cholesterol oxidation product, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (cholesterol 5,6-secosterol, ChSeco or Atheronal-A), formed at inflammatory sites, has been shown to promote monocyte differentiation into macrophages and cause elevated expression of macrophage scavenger receptors. Since inflammation is a key event at all stages of atherosclerotic plaque formation, the pro-inflammatory actions

Lysophosphatidylserine (LysoPS) is an emerging lysophospholipid (LPL) mediator, which acts through G protein-coupled receptors, like lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). LysoPS is detected in various tissues and cells and thought to be produced mainly by the deacylation of phosphatidylserine. LysoPS has been known to stimulate degranulation of mast cells. Recently, four LysoPS-specific

NOS–NO system activity is closely correlated with ischemia–reperfusion injury (IRI) and NOS subtypes were suggested to play different roles in IRI. In this work, the activity of serum NOS, NO levels, and ischemic necrosis after reperfusion in rabbit with AMI at different time was studied. We also explored the NOS–NO system activity changes and its correlation with myocardial ischemia and necrosis.

This study aimed to investigate the underlying molecular pathogenic mechanism of Sec62 in hepatocellular carcinoma (HCC). Microarray analysis was conducted to profile the global gene expression in the HCC cell line Huh7 cells transfected with Sec62high vs. NC and Sec62low vs. NC. Ingenuity pathway analysis and gene set enrichment analysis were used to perform Sec62-related signaling pathway analysis

Our aim was to clarify the regulations of lncRNA HOXA11-AS (HOXA11-AS) played on the progression of glioma as well as to investigate the mechanisms by which HOXA11-AS modulated development of glioma. This study confirmed the regulations of miR-124 and HOXA11-AS on the progression of glioma. Here, HOXA11-AS was overexpressed and miR-124 was underexpressed in glioma. Expression of miR-124 was negatively

The bio-active lipid, lysophosphatidic acid (LPA) interacts with various lysophosphatidic acid receptors (LPARs) to affect a variety of cellular functions, including proliferation, differentiation, survival, migration, morphogenesis and others. The Rho family of small GTPases, is well-known downstream signaling pathways activated by LPA. Among the Rho GTPases, RhoA, Rac1, and Cdc42 are best characterized

Alpha-amylase (α-amylase) not long ago has acquire recognition as a possible drug target for the management of diabetes. Here, we have investigated the binding and enzyme activity of α-amylase by hesperidin; a naturally occurring flavanone having wide therapeutic potential. Hesperidin exerted an inhibitory influence on α-amylase activity with an IC50 value of 16.6 µM. Hesperidin shows a significant

In the present study, HFD/STZ-mediated type 2 diabetic rodent model was used to comparatively evaluate coconut oil (CO) and thermally oxidized CO (TCO) as fat sources for the development of NAFLD. Female Wistar rats (six in each group; average bwt 200 g) fed HFD containing either CO or TCO for 2 months along with an intraperitoneal injection of streptozotocin (30 mg/kg bwt) at the end of 1-month feeding

The secretory phospholipase A2 (sPLA2) group of secreted enzymes hydrolyze phospholipids and lead to the production of multiple biologically active lipid mediators. sPLA2s and their products (e.g., eicosanoids) play a significant role in the pathophysiology of various inflammatory diseases, including life-threatening lung disorders such as acute lung injury (ALI) and the Acute Respiratory Distress

Sphingosine-1-phosphate (S1P), a bioactive lipid mediator, is generated from sphingosine by sphingosine kinases (SPHKs) 1 and 2 and is metabolized to ∆2-hexadecenal (∆2-HDE) and ethanolamine phosphate by S1P lyase (S1PL) in mammalian cells. We have recently demonstrated the activation of nuclear SPHK2 and the generation of S1P in the nucleus of lung epithelial cells exposed to Pseudomonas aeruginosa

An overview of Prof. Viswanathan Natarajan's journey in academia as a mentor, teacher, and lipid scientist for nearly 50 years is presented. As a graduate student, Dr. Natarajan interrogated biosynthesis and catabolism of phospholipids in the developing brain; however, in the last five decades, he has been investigating the role of sphingolipids and sphingolipid-metabolizing enzymes in pulmonary endothelial

While normal functioning neutrophils contribute in various, critical ways to the maintenance of a stable immune system, their hypo- or hyper-activation has been implicated in the onset or exacerbation of multiple inflammatory conditions often affecting the vulnerable, aging population. As such, many would benefit from interventions capable of targeting neutrophils in disease-specific ways without disrupting

Although pectin oligosaccharide (POS) can inhibit the growth and proliferation of gastric, colon, prostate, breast, melanoma, and leukemia cells, its effect on bladder cancer remains unknown. Therefore, screening and identification of factors associated with the sensitivity of bladder cancer to drugs and elucidation of their molecular mechanisms will help provide a theoretical basis for establishing

Alveolar enlargement is a pathological feature of emphysema. Long-term exposure to cigarette smoke (CS) is a high-risk factor for the development of emphysema. Abnormal protein ubiquitination has been implicated to regulate the development of human disorders, however, the role of protein ubiquitination in emphysema has not been well-studied. In this study, we attempted to investigate if a deubiquitinase

Lysophosphatidic acid receptor 1 (LPA1) belongs to the G protein-coupled receptor family. The ligand for LPA1 is LPA, the simplest lysophospholipid. LPA is considered a growth factor and induces cell proliferation, anti-apoptosis, and cell migration. The pro-inflammatory and pro-fibrotic roles of LPA have also been well-demonstrated. Most of the biological functions of LPA are mostly executed through

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel shows only weak selectivity between different small monovalent anions, however, little is known about its ability to discriminate between monovalent and divalent anions. The present study uses patch clamp recording to investigate the interaction between the small divalent anions S2O32- and SO42- and wild-type and pore-mutant

In addition to nucleic acids, a variety of other biomolecules have also been found on the plasma membrane. Although researchers have realized that RNA has the ability to bind to membrane vesicles in vitro, little is known about whether and how RNA connects to the plasma membrane of the cell. The combination of high-throughput sequencing and in situ labeling methods provides an innovative approach for

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and the primary cause of cancer-related mortality in China. micoRNA plays a vital role during tumor initiation and malignant progression. miR-4306 has been reported to negatively regulate aggressive cell phenotypes in triple-negative breast cancer (TNBC). Nevertheless, the function of miR-4306 in ESCC was still not clear

Dihydroceramide desaturase (Degs1) catalyses the introduction of a 4,5-trans double bond into dihydroceramide to form ceramide. We show here that Degs1 is polyubiquitinated in response to retinol derivatives, phenolic compounds or anti-oxidants in HEK293T cells. The functional predominance of native versus polyubiquitinated forms of Degs1 appears to govern cytotoxicity. Therefore, 4-HPR or celecoxib

Under normal physiological conditions, IGF-1 (insulin-like growth factor-1) has important biological effects. However, many studies have found that IGF-1 is closely related to the occurrence and development of breast cancer. But up to now, the cellular properties of IGF-1 have not been systematically explored in breast cancer cell. It is well-known that the cellular properties and behaviors of IGF-1/IGF-1R

Abdominal massage (AM), a traditional Chinese medicine-based treatment method, has received considerable attention in the recent years. The aim of the present study was to investigate the effect of AM on high-fat diet (HFD)-induced insulin resistance (IR) in comparison with resveratrol (RSV) treatment. Forty-eight male Sprague-Dawley rats were randomly divided into the following four groups: standard

Breast cancer resistance protein (ABCG2) is a human ATP-binding cassette (ABC) that plays a paramount role in multidrug resistance (MDR) in cancer therapy. The discovery of ABCG2 inhibitors could assist in designing unprecedented therapeutic strategies for cancer treatment. There is as yet no approved drug targeting ABCG2, although a large number of drug candidates have been clinically investigated

HNO (nitroxyl, IUPAC name azanone) is an electrophilic reactive nitrogen species of growing pharmacological and biological significance. Here, we present data on the pH-dependent kinetics of azanone reactions with the low molecular thiols glutathione and N-acetylcysteine, as well as with important serum proteins: bovine serum albumin and human serum albumin. The competition kinetics method used is

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, which was caused by a complex interplay of inflammatory responses and chronic damage. miR-21 is increased in patients with IPF, but its function in the embryonic lung-derived diploid fibroblasts cells subjected to LPS is elusive. miRNA expression profile was obtained from GEO database and target genes of miRNAs were forecasted by TargetScan

Copper ions play various roles in mammalian cells. Some investigations indicated that copper correlates with liver fibrosis and changes in bone marrow cells. Here, we explored the role of bone marrow cell parameters in copper liver fibrosis development and possible underlying mechanisms. The age-related features of biochemical indicators, bone marrow cell parameters, and electrical conductivity of

Hanging drop represents a simple approach designed for the generation of 3D models that have potential to be used for the study of solid tumors characteristics. The aim of the study was to develop and characterize the breast cancer 3D cellular models obtained through hanging drop technique using MDA-MB-231 cells. The biological characteristics such as: morphology, cellular viability, proliferation

Metastatic colorectal cancer (mCRC) patients are treated with standard chemotherapeutic drugs in the form of FOLFOX and FOLFIRI regimens. There are no reliable markers that could predict response to chemotherapy for mCRC. TGF-β signaling which interacts with microRNA (miRNA) network has important roles in tumor progression and chemotherapy resistance, thus the interplay between TGF-β signaling and

The present study aimed to investigate the impacts and underlying mechanisms of 14,15-DHETs on eNOS and vascular endothelial functions. Bovine aortic endothelial cells (BAECs) were treated with various concentrations of 14, 15-DHET. The expressions of eNOS protein and mRNA were observed at different time points. The eNOS expression and phosphorylation were subsequently detected administered with 8

Temperature is a fundamental thermodynamic property that can serve as a probe of biochemical reactions. Extracellular thermometry has previously been used to probe cancer metabolism and thermoregulation, with measured temperature changes of ~1–2 K in tissues, consistent with theoretical predictions. In contrast, previous intracellular thermometry studies remain disputed due to reports of >1 K intracellular

The recently emerged SARS-like coronavirus (SARS-CoV-2) has continued to spread rapidly among humans with alarming upsurges in global mortality rates. A major key to tackling this virus is to disrupt its RNA replication process as previously reported for Remdesivir (Rem-P3). In this study, we theorize, using computational simulations, novel mechanisms that may underlie the binding of Rem-P3 to SARS-CoV-2

Background B7 homolog 3 (B7-H3), a member of the immunoregulatory ligand B7 family, is pivotal in T-cell-mediated immune response. It is widely expressed in diverse human tumors and its high expression indicates the poor prognosis of the patients. Nonetheless, B7-H3’s role in colorectal cancer (CRC) needs to be further explored. Methods Western blot and immunohistochemistry were employed for detecting

Defects in inosine monophosphate dehydrogenase-1 (IMPDH1) lead to insufficient biosyntheses of purine nucleotides. In eyes, these defects are believed to cause retinitis pigmentosa (RP). Major retinal isoforms of IMPDH1 are structurally distinct from those in other tissues, by bearing terminal extensions. Using recombinant mouse IMPDH1 (mH1), we evaluated the kinetics and oligomerization states of

Colorectal cancer (CRC) belongs to one of gastric cancers that half of cases will develop metastasis, causing higher mortality or chemotherapy resistance. In the present study, the long noncoding RNA zinc finger antisense 1 (ZFAS1) was proved to have high expression level in CRC samples and in advanced stages. Additionally, it also indicated that p53 status is associated with ZFAS1 expression. Silencing

Hepatic fibrosis is known as the accumulation of connective tissue secondary to chronic damage to the liver. Epithelial–mesenchymal transition (EMT) corresponding increase in liver fibrogenesis was shown with immunohistochemistry and PCR-based studies. Suberoylanilide hydroxamic acid (SAHA), a synthetic compound approved as a histone deacetylase inhibitor (HDAC) by the FDA to treat cutaneous T-cell

The proliferation of fetal alveolar type II cells (FATIICs) was impaired in bronchopulmonary dysplasia (BPD), which is modulated by hyperoxia and inflammatory response. Interleukin 24 (IL-24), a cytokine produced by certain cell types, plays an essential role in inflammation and host protection against infection. However, the ability of FATIICs to produce IL-24 remains unclear, and the role of IL-24