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Authors = Rajaraman D. Eri

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17 pages, 768 KiB  
Review
Synbiotics as Supplemental Therapy for the Alleviation of Chemotherapy-Associated Symptoms in Patients with Solid Tumours
by Neeraj K. Singh, Jeffrey M. Beckett, Krishnakumar Kalpurath, Muhammad Ishaq, Tauseef Ahmad and Rajaraman D. Eri
Nutrients 2023, 15(7), 1759; https://doi.org/10.3390/nu15071759 - 4 Apr 2023
Cited by 23 | Viewed by 5061
Abstract
Chemotherapy is still the first line of treatment for most cancer patients. Patients receiving chemotherapy are generally prone to infections, which result in complications, such as sepsis, mucositis, colitis, and diarrhoea. Several nutritional approaches have been trialled to counter the chemotherapy-associated side effects [...] Read more.
Chemotherapy is still the first line of treatment for most cancer patients. Patients receiving chemotherapy are generally prone to infections, which result in complications, such as sepsis, mucositis, colitis, and diarrhoea. Several nutritional approaches have been trialled to counter the chemotherapy-associated side effects in cancer patients, but none have yet been approved for routine clinical use. One of the approaches to reduce or avoid chemotherapy-associated complications is to restore the gut microbiota. Gut microbiota is essential for the healthy functioning of the immune system, metabolism, and the regulation of other molecular responses in the body. Chemotherapy erodes the mucosal layer of the gastrointestinal tract and results in the loss of gut microbiota. One of the ways to restore the gut microbiota is through the use of probiotics. Probiotics are the ‘good’ bacteria that may provide health benefits if consumed in appropriate amounts. Some studies have highlighted that the consumption of probiotics in combination with prebiotics, known as synbiotics, may provide better health benefits when compared to probiotics alone. This review discusses the different nutritional approaches that have been studied in an attempt to combat chemotherapy-associated side effects in cancer patients with a particular focus on the use of pre-, pro- and synbiotics. Full article
(This article belongs to the Special Issue Cancer and Nutrition: From Epidemiology to Medical Nutrition Therapy)
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32 pages, 4853 KiB  
Review
Biosimilars in Oncology: Latest Trends and Regulatory Status
by Deeksha Joshi, Rubiya Khursheed, Saurabh Gupta, Diksha Wadhwa, Thakur Gurjeet Singh, Sumit Sharma, Sejal Porwal, Swati Gauniyal, Sukriti Vishwas, Sanjay Goyal, Gaurav Gupta, Rajaraman D. Eri, Kylie A. Williams, Kamal Dua and Sachin Kumar Singh
Pharmaceutics 2022, 14(12), 2721; https://doi.org/10.3390/pharmaceutics14122721 - 5 Dec 2022
Cited by 27 | Viewed by 5062
Abstract
Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) [...] Read more.
Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe’s worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars. Full article
(This article belongs to the Section Biologics and Biosimilars)
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26 pages, 762 KiB  
Review
Gut Dysbiosis and Diabetic Foot Ulcer: Role of Probiotics
by Ankit Awasthi, Leander Corrie, Sukriti Vishwas, Monica Gulati, Bimlesh Kumar, Dinesh Kumar Chellappan, Gaurav Gupta, Rajaraman D. Eri, Kamal Dua and Sachin Kumar Singh
Pharmaceutics 2022, 14(11), 2543; https://doi.org/10.3390/pharmaceutics14112543 - 21 Nov 2022
Cited by 15 | Viewed by 4534
Abstract
Diabetic foot ulcer (DFU) is a multifactorial disease and one of the complications of diabetes. The global burden of DFU in the health sector is increasing at a tremendous rate due to its cost management related to hospitalization, medical costs and foot amputation. [...] Read more.
Diabetic foot ulcer (DFU) is a multifactorial disease and one of the complications of diabetes. The global burden of DFU in the health sector is increasing at a tremendous rate due to its cost management related to hospitalization, medical costs and foot amputation. Hence, to manage DFU/DWs, various attempts have been made, including treating wounds systematically/topically using synthetic drugs, herbal drugs, or tissue engineering based surgical dressings. However, less attention has been paid to the intrinsic factors that are also the leading cause of diabetes mellitus (DM) and its complications. One such factor is gut dysbiosis, which is one of the major causes of enhancing the counts of Gram-negative bacteria. These bacteria produce lipopolysaccharides, which are a major contributing factor toward insulin resistance and inflammation due to the generation of oxidative stress and immunopathy. These all lead to DM and DFU. Probiotics are the commercial form of beneficial gut microbes that are taken as nutraceuticals by people of all ages to improve gut immunity and prevent gut dysbiosis. However, the role of probiotics has been less explored in the management of DFU. Hence, the therapeutic potential of probiotics in managing DFU is fully described in the current review. This report covers the linkage between gut dysbiosis and DFU, sources of probiotics, the mechanisms of probiotics in DW healing, and the impact of probiotic supplementation in treating DFU. In addition, techniques for the stabilization of probiotics, market status, and patents related to probiotics have been also covered. The relevant data were gathered from PubMed, Scopus, Taylor and Francis, Science Direct, and Google Scholar. Our systematic review discusses the utilization of probiotic supplementation as a nutraceutical for the management of DFU. Full article
(This article belongs to the Special Issue Targeted Therapies in Diabetes and Its Complications)
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18 pages, 807 KiB  
Review
An Appraisal of the Current Scenario in Vaccine Research for COVID-19
by Wai Chin Chong, Dinesh K. Chellappan, Shakti D. Shukla, Gregory M. Peterson, Rahul P. Patel, Niraj Kumar Jha, Rajaraman D. Eri, Kamal Dua, Murtaza M. Tambuwala and Madhur D. Shastri
Viruses 2021, 13(7), 1397; https://doi.org/10.3390/v13071397 - 18 Jul 2021
Cited by 5 | Viewed by 4928
Abstract
The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still [...] Read more.
The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still remains obscure, ongoing genomic studies have been successful in identifying its genomic sequence and the presenting antigen. These may serve as promising, potential therapeutic targets in the effective management of COVID-19. In an attempt to establish herd immunity, massive efforts have been directed and driven toward developing vaccines against the SARS-CoV-2 pathogen. This review, in this direction, is aimed at providing the current scenario and future perspectives in the development of vaccines against SARS-CoV-2. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
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15 pages, 8227 KiB  
Article
Streptococcus Thermophilus UASt-09 Upregulates Goblet Cell Activity in Colonic Epithelial Cells to a Greater Degree than other Probiotic Strains
by Madhur D. Shastri, Wai Chin Chong, Ravichandra Vemuri, Christopher J. Martoni, Santosh Adhikari, Harinder Bhullar, Dale Kunde, Stephen G. Tristram and Rajaraman D. Eri
Microorganisms 2020, 8(11), 1758; https://doi.org/10.3390/microorganisms8111758 - 9 Nov 2020
Cited by 11 | Viewed by 3315
Abstract
Probiotics have been widely used in maintaining gastrointestinal health, despite their actual mechanism remaining obscure. There are several hypotheses behind the beneficial effects of probiotics including the regulation of intestinal barrier function and improvement in immune responses in the gastrointestinal system. Multiple probiotics [...] Read more.
Probiotics have been widely used in maintaining gastrointestinal health, despite their actual mechanism remaining obscure. There are several hypotheses behind the beneficial effects of probiotics including the regulation of intestinal barrier function and improvement in immune responses in the gastrointestinal system. Multiple probiotics have been introduced in the market as effective dietary supplements in improving gastrointestinal integrity, but there are no or few studies that demonstrate their underlying mechanism. In the current study, we investigated and compared the efficacy of four probiotics (based on different bacterial species) in refining gastrointestinal health by improving mucus biosynthesis and intestinal immune response under in-vitro conditions. By analyzing the gene expression of mucus biosynthesis and intestinal immune response markers, we found that probiotic Streptococcus thermophilus UASt-09 showed promising potential in refining mucosal barrier and gastrointestinal health in human colonic epithelial cells, as compared to other commercial probiotics. Full article
(This article belongs to the Section Gut Microbiota)
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9 pages, 692 KiB  
Article
Anti-Heartburn Effects of Sugar Cane Flour: A Double-Blind, Randomized, Placebo-Controlled Study
by Jeffrey M. Beckett, Neeraj K. Singh, Jehan Phillips, Krishnakumar Kalpurath, Kent Taylor, Roger A. Stanley and Rajaraman D. Eri
Nutrients 2020, 12(6), 1813; https://doi.org/10.3390/nu12061813 - 18 Jun 2020
Cited by 7 | Viewed by 7383
Abstract
Gastroesophageal reflux disease (GERD) affects approximately 20% of Australians. Patients suffer a burning sensation known as heartburn due to the movement of acidic stomach content into the esophagus. There is anecdotal evidence of the effectiveness of prebiotic sugarcane flour in controlling symptoms of [...] Read more.
Gastroesophageal reflux disease (GERD) affects approximately 20% of Australians. Patients suffer a burning sensation known as heartburn due to the movement of acidic stomach content into the esophagus. There is anecdotal evidence of the effectiveness of prebiotic sugarcane flour in controlling symptoms of GERD. This pilot study aimed to investigate the effectiveness of a prebiotic sugarcane flour in alleviating symptoms in medically-diagnosed GERD patients. This pilot study was a single center, double-blinded, placebo-controlled randomized trial conducted on 43 eligible participants. The intervention group (n = 22) were randomized to receive 3 g of sugarcane flour per day, and the control group (n = 21) received 3 g of cellulose placebo per day. Symptoms of gastroesophageal reflux disease were assessed before and after three weeks treatment using the validated Gastroesophageal Reflux Disease-Health Related Quality of Life questionnaire (GERD-HRQL). After three weeks there were significant differences in symptoms for heartburn, regurgitation, and total symptoms scores (p < 0.05) between the sugarcane flour and placebo. Mean GERD-HRQL scores increased in the placebo group for regurgitation (mean increase 1.7; 95% CI 0.23 to 3.2; p = 0.015) and total symptom scores (2.9; 95% CI 0.26 to 5.7; p = 0.033). In contrast, there were significant reductions in heartburn (mean decrease −2.2; 95% CI −4.2 to −0.14; p = 0.037) and total symptom scores (−3.7; 95% CI −7.2 to −0.11; p = 0.044) in the intervention group. This pilot study has shown significant positive effects of sugarcane flour in the reduction of GERD symptoms, and a larger randomized controlled trial is warranted. Full article
(This article belongs to the Special Issue Role of Prebiotics and Probiotics in Health and Disease)
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23 pages, 3657 KiB  
Article
Lactobacillus acidophilus DDS-1 Modulates Intestinal-Specific Microbiota, Short-Chain Fatty Acid and Immunological Profiles in Aging Mice
by Ravichandra Vemuri, Rohit Gundamaraju, Tanvi Shinde, Agampodi Promoda Perera, Waheedha Basheer, Benjamin Southam, Shakuntla V. Gondalia, Avinash V. Karpe, David J. Beale, Stephen Tristram, Kiran D. K. Ahuja, Madeleine Ball, Christopher J. Martoni and Rajaraman Eri
Nutrients 2019, 11(6), 1297; https://doi.org/10.3390/nu11061297 - 7 Jun 2019
Cited by 66 | Viewed by 8485
Abstract
Distribution of the microbiota varies according to the location in the gastrointestinal (GI) tract. Thus, dysbiosis during aging may not be limited to faecal microbiota and extend to the other parts of the GI tract, especially the cecum and colon. Lactobacillus acidophilus DDS-1, [...] Read more.
Distribution of the microbiota varies according to the location in the gastrointestinal (GI) tract. Thus, dysbiosis during aging may not be limited to faecal microbiota and extend to the other parts of the GI tract, especially the cecum and colon. Lactobacillus acidophilus DDS-1, a probiotic strain, has been shown to modulate faecal microbiota and its associated metabolic phenotype in aging mice. In the present study, we investigated the effect of L. acidophilus DDS-1 supplementation on caecal- and mucosal-associated microbiota, short-chain fatty acids (SCFAs) and immunological profiles in young and aging C57BL/6J mice. Besides differences in the young and aging control groups, we observed microbial shifts in caecal and mucosal samples, leading to an alteration in SCFA levels and immune response. DDS-1 treatment increased the abundances of beneficial bacteria such as Akkermansia spp. and Lactobacillus spp. more effectively in caecal samples than in mucosal samples. DDS-1 also enhanced the levels of butyrate, while downregulating the production of inflammatory cytokines (IL-6, IL-1β, IL-1α, MCP-1, MIP-1α, MIP-1β, IL-12 and IFN-γ) in serum and colonic explants. Our findings suggest distinct patterns of intestinal microbiota, improvements in SCFA and immunological profiles with DDS-1 supplementation in aging mice. Full article
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21 pages, 3928 KiB  
Article
Interplay between Endoplasmic Reticular Stress and Survivin in Colonic Epithelial Cells
by Rohit Gundamaraju, Ravichandra Vemuri, Wai Chin Chong, Stephen Myers, Shaghayegh Norouzi, Madhur D. Shastri and Rajaraman Eri
Cells 2018, 7(10), 171; https://doi.org/10.3390/cells7100171 - 15 Oct 2018
Cited by 20 | Viewed by 6086
Abstract
Sustained endoplasmic reticular stress (ERS) is implicated in aggressive metastasis of cancer cells and increased tumor cell proliferation. Cancer cells activate the unfolded protein response (UPR), which aids in cellular survival and adaptation to harsh conditions. Inhibition of apoptosis, in contrast, is a [...] Read more.
Sustained endoplasmic reticular stress (ERS) is implicated in aggressive metastasis of cancer cells and increased tumor cell proliferation. Cancer cells activate the unfolded protein response (UPR), which aids in cellular survival and adaptation to harsh conditions. Inhibition of apoptosis, in contrast, is a mechanism adopted by cancer cells with the help of the inhibitor of an apoptosis (IAP) class of proteins such as Survivin to evade cell death and gain a proliferative advantage. In this study, we aimed to reveal the interrelation between ERS and Survivin. We initially verified the expression of Survivin in Winnie (a mouse model of chronic ERS) colon tissues by using immunohistochemistry (IHC) and immunofluorescence (IF) in comparison with wild type Blk6 mice. Additionally, we isolated the goblet cells and determined the expression of Survivin by IF and protein validation. Tunicamycin was utilized at a concentration of 10 µg/mL to induce ERS in the LS174T cell line and the gene expression of the ERS markers was measured. This was followed by determination of inflammatory cytokines. Inhibition of ERS was carried out by 4Phenyl Butyric acid (4PBA) at a concentration of 10 mM to assess whether there was a reciprocation effect. The downstream cell death assays including caspase 3/7, Annexin V, and poly(ADP-ribose) polymerase (PARP) cleavage were evaluated in the presence of ERS and absence of ERS, which was followed by a proliferative assay (EdU click) with and without ERS. Correspondingly, we inhibited Survivin by YM155 at a concentration of 100 nM and observed the succeeding ERS markers and inflammatory markers. We also verified the caspase 3/7 assay. Our results demonstrate that ERS inhibition not only significantly reduced the UPR genes (Grp78, ATF6, PERK and XBP1) along with Survivin but also downregulated the inflammatory markers such as IL8, IL4, and IL6, which suggests a positive correlation between ERS and the inhibition of apoptosis. Furthermore, we provided evidence that ERS inhibition promoted apoptosis in LS174T cells and shortened the proliferation rate. Moreover, Survivin inhibition by YM155 led to a comparable effect as that of ERS inhibition, which includes attenuation of ERS genes and inflammatory markers as well as the promotion of programmed cell death via the caspase 3/7 pathway. Together, our results propose the interrelation between ERS and inhibition of apoptosis assigning a molecular and therapeutic target for cancer treatment. Full article
(This article belongs to the Special Issue Cellular Stress Response in Health and Disease)
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Graphical abstract

19 pages, 1097 KiB  
Review
Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Nexus Implicated in Bowel Disease Pathophysiology
by Wai Chin Chong, Madhur D. Shastri and Rajaraman Eri
Int. J. Mol. Sci. 2017, 18(4), 771; https://doi.org/10.3390/ijms18040771 - 5 Apr 2017
Cited by 255 | Viewed by 12156
Abstract
The endoplasmic reticulum (ER) is a complex protein folding and trafficking organelle. Alteration and discrepancy in the endoplasmic reticulum environment can affect the protein folding process and hence, can result in the production of misfolded proteins. The accumulation of misfolded proteins causes cellular [...] Read more.
The endoplasmic reticulum (ER) is a complex protein folding and trafficking organelle. Alteration and discrepancy in the endoplasmic reticulum environment can affect the protein folding process and hence, can result in the production of misfolded proteins. The accumulation of misfolded proteins causes cellular damage and elicits endoplasmic reticulum stress. Under such stress conditions, cells exhibit reduced functional synthesis, and will undergo apoptosis if the stress is prolonged. To resolve the ER stress, cells trigger an intrinsic mechanism called an unfolded protein response (UPR). UPR is an adaptive signaling process that triggers multiple pathways through the endoplasmic reticulum transmembrane transducers, to reduce and remove misfolded proteins and improve the protein folding mechanism, in order to improve and maintain endoplasmic reticulum homeostasis. An increasing number of studies support the view that oxidative stress has a strong connection with ER stress. During the protein folding process, reactive oxygen species are produced as by-products, leading to impaired reduction-oxidation (redox) balance conferring oxidative stress. As the protein folding process is dependent on redox homeostasis, the oxidative stress can disrupt the protein folding mechanism and enhance the production of misfolded proteins, causing further ER stress. It is proposed that endoplasmic reticulum stress and oxidative stress together play significant roles in the pathophysiology of bowel diseases. Full article
(This article belongs to the Special Issue Modulators of Endoplasmic Reticulum Stress 2016)
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