Role of Immune Cells and Immunotherapy in Multiple Myeloma.

The clinical signs of multiple myeloma, a plasma cell (PC) dyscrasia, include bone loss, renal damage, and paraproteinemia. It can be defined as the uncontrolled growth of malignant PCs within the bone marrow. The distinctive bone marrow milieu that regulates the progression of myeloma disease involves interactions between plasma and stromal cells, and myeloid and lymphoid cells. These cells affect the immune system independently or because of a complicated web of interconnections, which promotes disease development and immune evasion. Due to the importance of these factors in the onset of disease, various therapeutic strategies have been created that either target or improve the immunological processes that influence disease progression. The immune system has a role in the mechanism of action of multiple myeloma treatments. The main contributions of immune cells to the bone marrow microenvironment, as well as how they interact and how immune regulation might lead to therapeutic effects, are covered in this study.

Neuroprotective effects of dietary plants and phytochemicals against radiation-induced cognitive and behavioral deficits: a comprehensive review of evidence and prospects for future research.

Exposure to ionizing radiation (IR) is a common occurrence in clinical practice and incidents involving nuclear detonation or nuclear reactor accidents. IR triggers cellular events that result in oxidative stress and damage to macromolecules, rendering it harmful. While the central nervous system (CNS) was once believed to be resistant to radiation, emerging evidence suggests that even small doses of IR can adversely impact the brain. Exposure to an unsafe dose of radiation can cause increased permeability of the blood-brain barrier (BBB), neuronal apoptosis, reduced neurogenesis, impaired synaptic plasticity, and cognitive dysfunction. In recent years, the potential benefits of dietary agents and phytochemicals for mental health and radiation-induced damage have been widely investigated. Despite this, few studies have explored the protective effects of plants against radiation-induced brain damage. Here, we present a review collating evidence on the beneficial effects of dietary plants on radiation-induced brain damage based on behavioral studies. Notably, Amaranthus paniculatus, Grewia asiatica, Lycium barbarum, and phytochemicals such as vitamin E, corilagin, curcumin, resveratrol, and ursolic acid have demonstrated potential in mitigating radiation-induced damage to the CNS. Furthermore, preliminary studies have indicated that alpha-tocopherol and the micronutrient selenium have neuroprotective effects in cancer survivors previously treated with radiation to the brain. This review focuses exclusively on behavioral outcomes to assess the impact of ionizing radiation on the CNS and the effectiveness of dietary plants and phytochemicals as neuroprotective agents against radiation-induced neuronal damage.

Fruits and their phytochemicals in mitigating the ill effects of ionizing radiation: review on the existing scientific evidence and way forward.

Although helpful in treating cancer, exposure to ionizing radiation can sometimes cause severe side effects, negating its benefit. In addition to its use in clinics, a nontoxic radioprotective agent can also be beneficial in occupational settings where humans are occupationally exposed for prolonged periods to low doses of radiation. Scientific studies using laboratory animals have shown that the fruits Aegle marmelos, Capsicum annuum, Citrus aurantium, Citrullus lanatus, Crataegus microphylla, Eugenia jambolana, Emblica officinalis, Garcinia kola, Grewia asiatica, Hippophae rhamnoides, Malus baccata, Malpighia glabra or Malpighia emarginata, Mangifera indica, Prunus domestica, Prunus avium, Prunus armeniaca, Psoralea corylifolia, Punica granatum, Solanum lycopersicum, Terminalia chebula, Vaccinium macrocarpon, Vitis vinifera and Xylopia aethiopica, and the phytochemicals gallic acid, ellagic acid, quercetin, geraniin, corilagin, ascorbic acid, hesperetin, ursolic acid, lycopene, naringin, hesperidin, rutin, resveratrol, ß-sitosterol, apigenin, luteolin, chlorogenic acid, caffeic acid, mangiferin, diosmin, ferulic acid, and kaempferol are effective in preventing radiation-induced ill effects. Clinical studies with Emblica officinalis and Punica granatum have also shown that fruits help mitigate radiation-induced mucositis, dermatitis, and cystitis. For the first time, the current review summarizes the beneficial effects of fruits and phytochemicals in mitigating radiation-induced damage, the underlying mechanisms and the existing lacunae for future studies to be undertaken for the benefit of humans and the nutraceutical and agri-based industries.

Dextran sodium sulfate alters antioxidant status in the gut affecting the survival of Drosophila melanogaster.

Inflammatory bowel disease (IBD) is a group of disorders characterized by chronic inflammation in the intestine. Several studies confirmed that oxidative stress induced by an enormous amount of reactive free radicals triggers the onset of IBD. Currently, there is an increasing trend in the global incidence of IBD and it is coupled with a lack of adequate long-term therapeutic options. At the same time, progress in research to understand the pathogenesis of IBD has been hampered due to the absence of adequate animal models. Currently, the toxic chemical Dextran Sulfate Sodium (DSS) induced gut inflammation in rodents is widely perceived as a good model of experimental colitis or IBD. Drosophila melanogaster, a genetic animal model, shares ~ 75% sequence similarity to genes causing different diseases in humans and also has conserved digestion and absorption features. Therefore, in the current study, we used Drosophila as a model system to induce and investigate DSS-induced colitis. Anatomical, biochemical, and molecular analyses were performed to measure the levels of inflammation and cellular disturbances in the gastrointestinal (GI) tract of Drosophila. Our study shows that DSS-induced inflammation lowers the levels of antioxidant molecules, affects the life span, reduces physiological activity and induces cellular damage in the GI tract mimicking pathophysiological features of IBD in Drosophila. Such a DSS-induced Drosophila colitis model can be further used for understanding the molecular pathology of IBD and screening novel drugs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03349-2.

Medicinal plants in mitigating electromagnetic radiation-induced neuronal damage: a concise review.

Although the evidence is inconclusive, epidemiological studies strongly suggest that increased exposure to electromagnetic radiation (EMR) increases the risk of brain tumors, parotid gland tumors, and seminoma. The International Agency for Research on Cancer (IARC) has classified mobile phone radiofrequency radiation as possibly carcinogenic to humans (Group 2B). Humans being are inadvertently being exposed to EMR as its prevalence increases, mainly through mobile phones. Radiation exposure is unavoidable in the current context, with mobile phones being an inevitable necessity. Prudent usage of medicinal plants with a long history of mention in traditional and folklore medicine and, more importantly, are safe, inexpensive, and easily acceptable for long-term human use would be an appealing and viable option for mitigating the deleterious effects of EMR. Plants with free radical scavenging, anti-oxidant and immunomodulatory properties are beneficial in maintaining salubrious health. Green tea polyphenols, Ginkgo biloba, lotus seedpod procyanidins, garlic extract, Loranthus longiflorus, Curcuma amada, and Rosmarinus officinalis have all been shown to confer neuroprotective effects in validated experimental models of study. The purpose of this review is to compile for the first time the protective effects of these plants against mobile phone-induced neuronal damage, as well as to highlight the various mechanisms of action that are elicited to invoke the beneficial effects.

Indian Indigenous Fruits as Radioprotective Agents: Past, Present and Future.

Ionising radiation has been an important modality in cancer treatment and its value is immense when surgical intervention is risky or might debilitate/adversely affect the patient. However, the beneficial effect of radiation modality is negated by the damage to the adjacent healthy tissue in the field of radiation. Under these situations, the use of radioprotective compounds that can selectively protect normal tissues against radiation injury is considered very useful. However, research spanning over half a century has shown that there are no ideal radioprotectors available. The United States Food and Drug Administration (FDA or USFDA) approved amifostine, or WR-2721 (Walter Reed-2721) [chemically S-2-(3-aminopropyl-amino) ethyl phosphorothioic acid] is toxic at their optimal concentrations. This has necessitated the need for agents that are safe and easily acceptable to humans. BACKGROUND: Dietary agents with beneficial effects like free radical scavenging, antioxidant and immunomodulatory effects are being recognized as useful and have been investigated for their radioprotective properties. Studies in these lines have shown that the fruits of Aegle marmelos (stone apple or bael), Emblica officinalis or Phyllanthus emblica (Indian gooseberry/amla), Eugenia jambolana or Syzygium jambolana (black plum/jamun), Mangifera indica (mango) and Grewia asiatica (phalsa or falsa) that are originally reported to be indigenous to India have been investigated for their usefulness as radioprotective agents. OBJECTIVE: The objective of this review is to summarize the beneficial effects of the Indian indigenous fruits, stone apple, mango, Indian gooseberry, black plum, and phalsa, in mitigating radiation-induced side effects, emphasize the underlying mechanism of action for the beneficial effects and address aspects that merit detail investigations for these fruits to move towards clinical application in the near future. METHODS: The authors data-mined Google Scholar, PubMed, Embase, and the Cochrane Library for publications in the field from 1981 up to July 2020. The focus was on the radioprotection and the mechanism responsible for the beneficial effects, and accordingly, the articles were collated and analyzed. RESULTS: This article emphasizes the usefulness of stone apple, mango, Indian gooseberry, black plum, and phalsa as radioprotective agents. From a mechanistic view, reports are suggestive that the beneficial effects are mediated by triggering free radical scavenging, antioxidant, anti-mutagenic and anti-inflammatory effects. CONCLUSION: For the first time, this review addresses the beneficial effects of mango, Indian gooseberry, black plum, stone apple and phalsa as radioprotective agents. The authors suggest that future studies should be directed at understanding the selective radioprotective effects with tumor-bearing laboratory animals to understand their usefulness as radioprotective drug/s during radiotherapy and as a food supplement to protect people from getting exposed to low doses of radiation in occupational settings. Phase I clinical trial studies are also required to ascertain the optimal dose and the schedule to be followed with the standardized extract of these fruits. The most important aspect is that these fruits, being a part of the diet, have been consumed since the beginning of mankind, are non-toxic, possess diverse medicinal properties, have easy acceptability, all of which will help take research forward and be of benefit to patients, occupational workers, agro-based sectors and pharma industries.

Study of Serum Zinc and Copper Levels and Tumor Pathology: A Pilot Study in People Affected with Head and Neck Cancers.

This study aimed to determine understanding the role of serum copper, zinc and copper/zinc ratio with tumor staging in people newly diagnosed to be affected with Head and Neck cancer and by comparing with age matched health individuals devoid of any orodental maladies. The study included patients confirmed to be affected with HN cancer with histological diagnosis of Head and Neck cancer (60) and age matched healthy volunteers (N = 23). The demographic details like age, domicile, menopausal status and pathological details (like tumor stage, number of lymph node involvement, tumor size) were collected from the patient's hospital data file. The serum levels of zinc and copper assayed as per standard procedures and the zinc/copper was calculated for the cancer patients and controls. The data were subjected to unpaired "t" test and ANOVA with Bonferroni's multiple comparisons. The association between zinc and copper levels with pathological details between the variables was ascertained using the Pearson correlation coefficient(r). A statistical value of p < 0.05 was considered to be significant in agreeance to the accepted norms. Results: This result of the study indicates that when compared to the healthy individuals, the serum levels of copper, and zinc, and copper/zinc ratio were high in patients with H&N cancer. Also when compared with controls, the levels of zinc decreased, while that of copper and copper/zinc ratio increased in people affected with H&N cancer (p = 0.017 to 0.0001) and with the stage of the tumor (p = 0.03 to 0.001). The results of the study suggest that levels of serum zinc were significantly lower and that of copper higher in H&N cancer patients than that in controls and also that it was dependent on the tumor stage. When analyzed cumulatively the results hint that zinc and copper, due to their role in free radical generation and prevention have an important role in cancer progression and possible prevention by judicious intervention.

Dietary agents in mitigating chemotherapy-related cognitive impairment (chemobrain or chemofog): first review addressing the benefits, gaps, challenges and ways forward.

Chemobrain or chemofog is one of the important but less investigated side effects, where the cancer survivors treated with chemotherapy develop long-term cognitive impairments, affecting their quality of life. The biological mechanisms triggering the development of chemobrain are largely unknown. However, a literature study suggests the generation of free radicals, oxidative stress, inflammatory cytokines, epigenetic chromatin remodeling, decreased neurogenesis, secretion of brain-derived neurotropic factor (BDNF), dendritic branching, and neurotransmitter release to be the cumulative contributions to the ailment. Unfortunately, there is no means to prevent/mitigate the development and intensity of chemobrain. Given the lack of effective prevention strategies or treatments, preclinical studies have been underway to ascertain the usefulness of natural products in mitigating chemobrain in the recent past. Natural products used in diets have been shown to provide beneficial effects by inhibition of free radicals, oxidative stress, inflammatory processes, and/or concomitant upregulation of various cell survival proteins. For the first time, this review focuses on the published effects of astaxanthin, omega-3 fatty acids, ginsenoside, cotinine, resveratrol, polydatin, catechin, rutin, naringin, curcumin, dehydrozingerone, berberine, C-phycocyanin, the higher fungi Cordyceps militaris, thyme (Thymus vulgaris) and polyherbal formulation Mulmina™ in mitigating cognitive impairments in preclinical models of study, and also addresses their potential neuro-therapeutic mechanisms and applications in preventing/ameliorating chemobrain.

Radioprotective role of uric acid: evidence from studies in Drosophila and human dermal fibroblast cells.

Exposure to ionizing radiation (IR) is a common phenomenon during medical diagnosis and treatment. IRs are deleterious because cellular exposure to IR can cause a series of molecular events that may lead to oxidative stress and macromolecular damage. Radiation protection is therefore essential and significant for improving safety during these procedures. Over decades several antioxidant molecules have been screened to explore their potential as radio-protectors with little success. Therefore, the current study was carried out to confirm the role of uric acid (UA)-a putative antioxidant molecule in radioprotection using radio-resistant insect Drosophila and human dermal fibroblast (HDF) cells. Here, we demonstrate the depleted levels of UA in the mutant flies of Drosophila melanogaster-rosy and by targeting xanthine oxidase (XO an enzyme involved in UA metabolism), through maintaining flies on an allopurinol mixed diet. Allopurinol is a drug that reduces UA levels by inhibiting XO; it reduces the survival percentage in D. melanogaster compared to wild type flies following gamma irradiation at a dose of 1000 Gy. Enzymatic antioxidants such as superoxide dismutase (SOD), catalase, D. melanogaster glutathione peroxidase (DmGPx) and levels of non-enzymatic antioxidants were measured to evaluate the importance of UA. The results indicate that lack of UA reduces the total antioxidant capacity. The activity of SOD was lowered in male flies. Furthermore, we show that supplementation of UA to HDFs cells in media improved their survival rate following gamma irradiation (2 Gy). From the present study we conclude that UA is a potent antioxidant molecule present in high levels among insects. Also, it appears that UA contributes to the radiation resistance of Drosophila flies. Hence, UA emerges as a promising molecule for mitigating radiation-induced oxidative damage in higher organisms.

Escherichia coli Braun Lipoprotein (BLP) exhibits endotoxemia - like pathology in Swiss albino mice.

The endotoxin lipopolysaccharide (LPS) promotes sepsis, but bacterial peptides also promote inflammation leading to sepsis. We found, intraperitoneal administration of live or heat inactivated E. coli JE5505 lacking the abundant outer membrane protein, Braun lipoprotein (BLP), was less toxic than E. coli DH5α possessing BLP in Swiss albino mice. Injection of BLP free of LPS purified from E. coli DH5α induced massive infiltration of leukocytes in lungs and liver. BLP activated human polymorphonuclear cells (PMNs) ex vivo to adhere to denatured collagen in serum and polymyxin B independent fashion, a property distinct from LPS. Both LPS and BLP stimulated the synthesis of platelet activating factor (PAF), a potent lipid mediator, in human PMNs. In mouse macrophage cell line, RAW264.7, while both BLP and LPS similarly upregulated TNF-α and IL-1ß mRNA; BLP was more potent in inducing cyclooxygenase-2 (COX-2) mRNA and protein expression. Peritoneal macrophages from TLR2-/- mice significantly reduced the production of TNF-α in response to BLP in contrast to macrophages from wild type mice. We conclude, BLP acting through TLR2, is a potent inducer of inflammation with a response profile both common and distinct from LPS. Hence, BLP mediated pathway may also be considered as an effective target against sepsis.