Perumal Subramanian

Mutation in the Drosophila melanogaster lethal giant larvae (lgl), a tumor suppressor gene with a well‐established role in cellular polarity, is known to results in massive cellular proliferation and neoplastic outgrowths. Although the tumorigenic properties of lgl mutant have been previously studied, however, little is known about its consequences on the proteome. In this study, mass spectrometry‐based label‐free quantitative proteomics was employed to investigate the changes in the head and intestinal tissues proteins of Drosophila melanogaster, due to lgl mutation and following treatment with melatonin. Additionally, to uncover the time‐influenced variations in the proteome during tumorigenesis and melatonin treatment, the rhythmic expression of proteins was also investigated at 6‐h intervals within 24‐h clock. Together, the present study has identified 434 proteins of altered expressions (p < 0.05 and fold change ±1.5) in the tissues of flies in response to lgl mutation as well as posttreatment with melatonin. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed proteins revealed that lgl mutation had significantly affected the biological functions, including metabolism, and protein synthesis and degradation, in flies' tissues. Besides, melatonin had beneficially mitigated the deleterious effects of lgl mutation by reversing the alterations in protein expression closer to baseline levels. Further, changes in protein expression in the tissues due to lgl mutation and melatonin treatment were found rhythmically orchestrated. Together, these findings provide novel insight into the pathways involved in lgl‐induced tumorigenesis as well as demonstrated the efficacy of melatonin as a potential anticancer agent. Data are available via ProteomeXchange with identifier PXD033191.

Pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignancy with a poor prognosis is usually detected at the advanced stage of the disease. The only US Food and Drug Administration-approved biomarker that is available for PDAC, CA 19-9, is most useful in monitoring treatment response among PDAC patients rather than for early detection. Moreover, when CA 19-9 is solely used for diagnostic purposes, it has only a recorded sensitivity of 79% and specificity of 82% in symptomatic individuals. Therefore, there is an urgent need to identify reliable biomarkers for diagnosis (specifically for the early diagnosis), ascertain prognosis as well as to monitor treatment response and tumour recurrence of PDAC. In recent years, proteomic technologies are growing exponentially at an accelerated rate for a wide range of applications in cancer research. In this review, we discussed the current status of biomarker research for PDAC using various proteomic technologies. This review will explore the potential perspective for understanding and identifying the unique alterations in protein expressions that could prove beneficial in discovering new robust biomarkers to detect PDAC at an early stage, ascertain prognosis of patients with the disease in addition to monitoring treatment response and tumour recurrence of patients.

A proteome is an efficient rendition of a genome, unswervingly controlling various cancer processes. Molecular mechanisms of several cancer processes have been unraveled by the proteomic approach. Thus far, numerous tumors of diverse status have been investigated by two-dimensional electrophoresis. Numerous biomarkers have been recognized and precise categorization of apparent lesions has led to the timely detection of various cancers in persons at peril. Currently used pioneering approaches and technologies in proteomics have led to highly sensitive assays of cancer biomarkers and improved the early diagnosis of various cancers. The discovery of novel and definite biomarker signatures further widened our perceptive of the disease, and novel potent drugs and aimed therapeutic outcomes in persistent cancers have emerged. However, a major limitation, even today, of proteomics is resolving and quantifying the proteins of low abundance. Despite the rapid development of proteomics technologies and their applications in cancer management, annulling the shortcomings of present proteomic technologies and the development of better methods are still desirable. The main objectives of this review are to discuss the developing aspects, merits and demerits of pharmacoproteomics, redox proteomics, novel approaches and therapies being used for various types of cancer-based on proteome studies.

A key perception of energy homeostasis is the recognition of a mutual regulation between biological clock and cell metabolism. For instance, the regular occurrences of appetite and satiety is not incessant over 24 h, but is instead organized temporally over the 24 h and the light/dark cycle. In mammals, the temporal regulation of metabolism, physiology and behaviour about 24 h is regulated by a complex system of manifold cellular clocks, synchronized via neuronal and hormonal cues by a master clock situated in the suprachiasmatic nuclei of the hypothalamus. Chronic disturbance of circadian rhythms, as seen in human shift-workers (up to 20% of the dynamic populace), has been linked with the advancement of numerous unfavourable mental and metabolic disturbances, suggesting that metabolic processes and biological clock are tightly linked with each other. Comprehension of the functional associations among circadian desynchronization and general health in animal model systems and humans, nevertheless, is still meagre. To sum up, this research topic covers a broad assortment of functional connections amid circadian rhythms and metabolism at molecular, cellular, tissue, organ and organism level.

Mutant lethal giant larvae (lgl) flies (Drosophila melanogaster) are known to develop epithelial tumors with invasive characteristics. The present study has been conducted to investigate the influence of melatonin (0.025 mM) on behavioral responses of lgl mutant flies as well as on biochemical indices (redox homeostasis, carbohydrate and lipid metabolism, transaminases, and minerals) in hemolymph, and head and intestinal tissues. Behavioral abnormalities were quantitatively observed in lgl flies but were found normalized among melatonin‐treated lgl flies. Significantly decreased levels of lipid peroxidation products and antioxidants involved in redox homeostasis were observed in hemolymph and tissues of lgl flies, but had restored close to normalcy in melatonin‐treated flies. Carbohydrates including glucose, trehalose, and glycogen were decreased and increased in the hemolymph and tissues of lgl and melatonin‐treated lgl flies, respectively. Key enzymes of carbohydrate metabolism showed a significant increment in their levels in lgl mutants but had restored close to wild‐type baseline levels in melatonin‐treated flies. Variables of lipid metabolism showed significantly inverse levels in hemolymph and tissues of lgl flies, while normalization of most of these variables was observed in melatonin‐treated mutants. Lipase, chitinase, transaminases, and alkaline phosphatase showed an increment in their activities and minerals exhibited decrement in lgl flies; reversal of changes was observed under melatonin treatment. The impairment of cognition, disturbance of redox homeostasis and metabolic reprogramming in lgl flies, and restoration of normalcy in all these cellular and behavioral processes indicate that melatonin could act as oncostatic and cytoprotective agents in Drosophila.

The circadian clock regulates vital aspects of physiology including protein synthesis and oxidative stress response. In this investigation, we performed a proteome‐wide scrutiny of rhythmic protein accrual in Drosophila melanogaster on exposure to rotenone, rotenone + hesperidin and hesperidin in D. melanogaster. Total protein from fly samples collected at 6 h intervals over the 24 h period was subjected to two‐dimensional gel electrophoresis and mass spectrometry. Bioinformatics tool, Protein ANalysis THrough Evolutionary Relationships classification system was used to the determine the biological processes of the proteins of altered abundance. Conspicuous variations in the proteome (151 proteins) of the flies exposed to oxidative stress (by rotenone treatment) and after alleviating oxidative stress (by hesperidin treatment) were observed during the 24 h cycle. Significantly altered levels of abundance of a wide variety of proteins under oxidative stress (rotenone treatment) and under alleviation of oxidative stress (rotenone + hesperidin treatment) and hesperidin (alone) treatment were observed. These proteins are involved in metabolism, muscle activity, heat shock response, redox homeostasis, protein synthesis/folding/degradation, development, ion‐channel/cellular transport, and gustatory and olfactory function of the flies. Our data indicates that numerous cellular processes are involved in the temporal regulation of proteins and widespread modulations happen under rotenone treatment and, action of hesperidin could also be seen on these categories of proteins.

Rhythmicity is observed in transcriptional expression of a wide range of clock-controlled genes which regulate a variety of normal cell functions like cell division and proliferation. The human circadian timing system functions to co-ordinate humoral, physiological, and behavioral mechanism to promote sleep and waking behavior. The rhythms are generated by neural structures in the hypothalamus that function as a biological clock. Modern lifestyle is also turning to be a relevant factor promoting desynchrony, especially in individuals staying for long hours awake during the night and with disturbed sleep patterns. Chronotherapeutics is relatively new concept in medicine. The main goal of chronotherapeutics is the enhancement of the desired effects of medications and control of their adverse effects. This review addresses the role of circadian rhythms in tumorigenesis.

This review describes the characteristics of a number of pathologies, which are considered from the point of view of chronobiology, that is, the way in which biological processes are expressed throughout the 24-hour day. This perspective is a relatively new way of thinking about disease and additionally about how to treat diseases. It has called attention to the importance of not only the quantity of a drug that is administered but also when it is administered. In addition, the review presents an overview of the emerging clinical strategies known as chronotherapeutics, that is, the effects of the daily scheduling of drug administration and the consequences of the activity and efficacy of therapies that are applied in this manner. This article also reviews innovative ways in which physicians are applying time-specified drug treatment (chronopharmacology) for sleep disorders. Here, we present a systematic description of chronopharmacology as well as definitions of key terms that, we believe, will be helpful for newcomers to the field. It is hoped that greater awareness of this new perspective on pharmacology will promote its adoption by researchers and clinicians.

Cancer is still one of the major causes of mortality in both developing and developed countries. At present, in spite of intensive interventions, a large number of patients suffer from poor prognosis. Also, regarding some phytochemicals, only beneficial effects on cancer-related symptoms or on quality of life have been reported and no positive results exist for their antitumor actions. This review was focused on the phytochemicals whole beneficial effects on various types of cancer have been supported by clinical trials. This review discusses how a disruption of the “biological clock” or circadian rhythms could be involved in the development of these diseases as circadian rhythms control multiple physiological processes such as wake/sleep cycles, hormonal levels, body temperature, metabolism, and immune system.