Papers by Partha Ramasastry
J Life Sci ((Westlake Village, CA), 2019
Vaccination has been one of the most successful medical interventions to date, reducing the morbi... more Vaccination has been one of the most successful medical interventions to date, reducing the morbidity and mortality of vaccine-preventable infectious disease by over 90% in countries where vaccines are readily available. Despite its success, the uptake of vaccines worldwide is declining; so much so that in 2019 the World Health Organisation declared that vaccine hesitancy, the reluctance or refusal to vaccinate despite the availability of vaccines, is one of the top ten threats to Global Health in 2019. The reasons for decreased vaccination uptake are complex, but it is becoming increasingly clear that solutions to counter this trend are required as vaccine-preventable illness and death are increasing worldwide
J Life Sci (Westlake Village, CA), 2019
Mitochondria fulfill the high metabolic energy demands of the kidney and are regularly exposed to... more Mitochondria fulfill the high metabolic energy demands of the kidney and are regularly exposed to oxidative stress causing mitochondrial damage. The selective removal of damaged and dysfunctional mitochondria through a process known as mitophagy is essential in maintaining cellular homeostasis and physiological function. Mitochondrial quality control by mitophagy is particularly crucial for an organ such as the kidney, which is rich in mitochondria. The role of mitophagy in the pathogenesis of kidney diseases has lately gained significant attention. In this review, we summarize the current understanding of the implications of mitophagy during pathological conditions of the kidney, including acute and chronic kidney diseases.
J Life Sci (Westlake Vilage, CA), 2019
Breast cancer classifications are based on the presence or absence of estrogen receptor and proge... more Breast cancer classifications are based on the presence or absence of estrogen receptor and progesterone receptor along with the overexpression or amplification of the Her2 receptor. Although the overall 5-year survival rate of breast cancer patients has increased due to the use of targeted therapies, a subset of patients can acquire resistance over time or are unresponsive when presented in the clinic. Novel therapies focusing on molecular pathways and cell cycle regulation currently being used in the clinic may lead to increased response in this subset of patients.
J Life Sci (Westlake Village, California), 2019
Aberrant EGFR family signaling pathways are well known as oncogenic drivers and account for sever... more Aberrant EGFR family signaling pathways are well known as oncogenic drivers and account for several types of cancer with their functions in abnormally promoting cell proliferation and preventing cell apoptosis. Accumulating evidence has indicated that EGFR family signaling could facilitate tumor cells to escape from immunological surveillance by reducing tumor mutation burden and inducing immunosuppressive tumor microenvironment. Therefore, ErbB driven cancers are sensitive to ErbB targeted therapies and resistant to immune checkpoint blockade (ICB). Whether combining ErbB targeted therapies and ICB can actually benefit cancer patients is still controversial. Here, we review the correlation between EGFR family signaling and cancer, summarize the recent findings in the immune related mechanisms of ErbB targeted therapies and the potential reasons why ErbB driven cancers are resistant to ICB, and further discuss the potential strategies of combining ErbB targeted therapies and ICB.
Epigenetic control mechanisms play critical roles in organ development and tissue homeostasis. In... more Epigenetic control mechanisms play critical roles in organ development and tissue homeostasis. Increasing evidence suggests that cardiac lineage commitment and cardiovascular disease are tightly regulated by epigenetic mechanisms, controlling changes in DNA methylation, histone modifications, ATP-dependent chromatin remodeling, and expression levels for non-coding RNAs. This review summarizes our current understanding of epigenetic control mechanisms regulating cardiac development and disease, particularly focuses on the function of DNA methylation and demethylation through families of DNA methyltransferases and dioxygenases.
JoLS, Journal of Life Sciences, 2019
Pancreatic ductal adenocarcinoma (PDAC), a poorly vascularized malignancy, is one of the most let... more Pancreatic ductal adenocarcinoma (PDAC), a poorly vascularized malignancy, is one of the most lethal human cancers. Despite using chemotherapy, radiation, and surgery in the treatment of pancreatic cancer, the survival rate remains largely dismal. Several in vivo and patient-based metabolomics analyses revealed that, compared to normal tissues, PDAC tumors are depleted of glutamine, a major metabolic substrate. Yet the mechanisms by which PDAC cells adapt to low glutamine levels are still unclear. Thus, it is imperative to understand the differential metabolic mechanisms in pancreatic cancer. Here, we review the current understanding of metabolic rewiring in pancreatic cancer in response to glutamine deprivation. The elucidation of these adaptive strategies may highlight new opportunities to improve PDAC diagnosis, as well as, shed insight towards novel therapeutic developments.
The ability to achieve spatial and temporal control over biological processes and drug activation... more The ability to achieve spatial and temporal control over biological processes and drug activation has led to many applications of "photocages". By definition, photocages are chemical structures that are light-sensitive and is used to "cage" or restrict the activity of any molecule. Upon illumination of light at appropriate wavelength, the protecting group of the molecule is cleaved releasing the active entity. Many recent reports in research areas including molecular biology, neurosciences and drug delivery have demonstrated the applications of photocages. In this write-up, we provide a brief overview on commonly used photocages, ortho-Nitrobenzyl (o-NB) derivatives that are relevant to cancer-biology, and emphasize upon the usefulness and advantages of using these photosensitive molecules.
Recent exponential growth of investors in stock markets brings the idea to develop a predictive m... more Recent exponential growth of investors in stock markets brings the idea to develop a predictive model to forecast the total risk of investment in stock markets. In this paper, an evolutionary approach was proposed to predict the total risk in stock investment based on an S&P 500 database in a time period of 1991-2010 employing a multi-objective genetic programming along with an adaptive regression by mixing algorithm. The reasonable results suggest that the proposed model can be applied to various stock databases to assess the total risk of investment. The proposed model along with stock selection decision support systems can overcome the disadvantages of weighted scoring stock selection. K E Y W O R D S Stock Market, Risk Assessment, Multi-Objective Genetic Programming, Adaptive Regression
Cell transfection is an essential step for gene editing and intracellular delivery of cargoes suc... more Cell transfection is an essential step for gene editing and intracellular delivery of cargoes such as mRNA and proteins. Significant improvements have been made to reduce the cytotoxicity and to improve efficiency associated with transfection over the few decades. Nevertheless, with new, exciting biological questions, the demand for the ideal transfection technique with high throughput, single cell transfection ability and control of cargo dosage has increased. This review focuses on recent innovations in cell transfection techniques, and discusses the pros and cons of each method.
For 20 years it has been known that concentrations of leptin, a hormone produced by the white adi... more For 20 years it has been known that concentrations of leptin, a hormone produced by the white adipose tissue (WAT) largely in proportion to body fat, drops precipitously with starvation, particularly in lean humans and animals. The role of leptin to suppress the thyroid and reproductive axes during a prolonged fast has been well defined; however, the impact of leptin on metabolic regulation has been incompletely understood. However emerging evidence suggests that, in starvation, hypoleptinemia increases activity of the hypothalamic-pituitary-adrenal axis, promoting WAT lipolysis, increasing hepatic acetyl-CoA concentrations, and maintaining euglycemia. In addition, leptin may be largely responsible for mediating a shift from a reliance upon glucose metabolism (absorption and glycogenolysis) to fat metabolism (lipolysis increasing gluconeogenesis) which preserves substrates for the brain, heart, and other critical organs. In this way a leptin-mediated glucose-fatty acid cycle appears to maintain glycemia and permit survival in starvation.
Molecular gold compounds have shown intermittent promise as human pharmaceuticals, mostly in in v... more Molecular gold compounds have shown intermittent promise as human pharmaceuticals, mostly in in vitro assays. Rational approaches to gold prodrugs are essential for desired cytotoxicity. This work describes non-natural nu-cleosides of 6-mercaptopurine. Binding to (organophosphine)-and (N-heterocyclic carbene)gold(I) proceeds in high-yield reactions at room temperature. Three such metallonucleosides were prepared. They differ in the phos-phine or carbene ligand on gold. New compounds are characterized by multinuclear NMR spectroscopy, mass spectrometry, and elemental analysis. One complex is crystallographically characterized; gold(I) is bound to the sulfur atom of the mercaptopurine moiety, and aurophilic interactions are absent. Experiments in human cell lines showed evidence of mitochondrial swelling, programmed cell death, and inhibition of rat liver thioredoxin reduc-tase.
Postdoc Journal, 2013
Periodontal disease is characterized by chronic inflammation of the gingiva (gum tissues) caused ... more Periodontal disease is characterized by chronic inflammation of the gingiva (gum tissues) caused by infection with anaerobic bacteria. In older adults, progression of disease can lead to tooth loss, inadequate nutritional intake, and a higher risk of other chronic conditions such as cardiovascular disease and diabetes mellitus. As the proportion of older adults continues to grow over time and rates of tooth loss decline, prevalence and severity of periodontal disease will increase. While much is known about risk factors for disease onset, gaps remain in our understanding of factors that could influence disease progression. Over the past few decades, stress has been implicated as a contributory factor. This review critically examines the epidemiological and laboratory evidence and describes a conceptual framework that could help move the research forward.
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Papers by Partha Ramasastry