A detailed insight into macrophages' role in shaping lung carcinogenesis.

Despite significant advancements in cancer treatment in recent decades, the high mortality rate associated with lung cancer remains a significant concern. The development and proper execution of new targeted therapies needs more deep knowledge regarding the lung cancer associated tumour microenvironment. One of the key component of that tumour microenvironment is the lung resident macrophages. Although in normal physiological condition the lung resident macrophages are believed to maintain lung homeostasis, but they may also initiate a vicious inflammatory response in abnormal conditions which is linked to lung cancer development. Depending on the activation pathway, the lung resident macrophages are either of M1 or M2 sub-type. The M1 and M2 sub-types differ significantly in various prospectuses, from phenotypic markers to metabolic pathways. In addition to this generalized classification, the recent advancement of the multiomics technology is able to identify some other sub-types of lung resident macrophages. Researchers have also observed that these different sub-types can manipulate the pathogenesis of lung carcinogenesis in a context dependent manner and can either promote or inhibit the development of lung carcinogenesis upon receiving proper activation. As proper knowledge about the role played by the lung resident macrophages' in shaping the lung carcinogenesis is limited, so the main purpose of this review is to bring all the available information under the same roof. We also elaborated the different mechanisms involved in maintenance of the plasticity of M1/M2 sub-type, as this plasticity can be a good target for lung cancer treatment.

Immunotherapeutic potential of ethanolic olive leaves extract (EOLE) and IL-28B combination therapy in ENU induced animal model of leukemia.

Cytokine therapies have shown promising results against cancers. Cytokines are secreted naturally from different bodily cells. These have fewer side effects but higher specificity than chemotherapy and radiation therapy. In leukemia, changes in normal hematopoiesis and defective leukocyte production limit the efficacy of immunotherapy by reducing the count of functional immune cells. Therefore, the treatment of leukemia needs advanced therapeutics that can target multiple cancer sustaining mechanisms. In combination therapy, using two different therapeutic agents affect cancer growth in many ways and sometimes gives synergistic effects. Here, we examined the effect of the ethanolic olive leaf extract (EOLE) and IL-28B in combination. N-N' Ethyl-nitrosourea (ENU) induced leukemia in Swiss albino mice was treated with EOLE for four weeks and IL-28B for one week after confirming the development of leukemia. The combination of EOLE and IL-28B significantly reduced the blast cell and total WBC counts in the peripheral blood, altered the levels of various cytokines in plasma, and induced the functional activity of NK cells in leukemic mice. The induced NK activity correlates with increased expression of perforin and granzyme studied at the gene level through real-time (RT)-PCR. The treatment of leukemic mice with combined EOLE and IL-28B has also caused an increased serum IL-10 and IFN-γ level, and reduced serum TGF-ß indicates improved overall immunity. Altogether, the combination of EOLE and IL-28B has given substantial therapeutic activity against leukemia.

Mechanistic insight into the synergism of IL-27 and IL-28B in regulation of benzo(a)pyrene-induced lung carcinogenesis associated ROS/NF-κB/NLRP3 crosstalk.

AIM: Our previous work depicted that benzo(a)pyrene (BaP)-induced lung cancer associated pulmonary redox imbalance and inflammation were effectively regulated by the combinatorial treatment of IL-27 and IL-28B. So in continuation of that finding the present study was designed to reveal the inflammation regulating signaling network modulated by IL-27 and IL-28B treatment related to BaP-induced lung cancer. METHODS: Male Swiss albino mice were treated with BaP to induce lung tumor. Then they received individual as well as combinatorial treatment of IL-27 and IL-28B. At the end of the experimental schedule, the expression of NF-κB signaling proteins, the formation of NLRP3 inflammasome complex and IL-18; IL-17A expression in the lung were observed using Western blot and RT-PCR. The tissue and serum levels of some proinflammatory cytokines were also studied using ELISA. Mast cell density was also studied using toluidine blue staining procedure. RESULTS: Treatment with IL-27 or IL-28B alone was successful to regulate the expression of NF-κB signaling proteins and NLRP3 complex in some cases but best attenuation was observed in animals who received both IL-27 and IL-28B in combination. In combination, it was successful in down-regulating the expression of p-ERK1/2 and in reducing the accumulation of mast cells in the lung tissue associated with BaP-induced lung carcinogenesis. The impaired PPARγ expression was also reinstated upon combination treatment. CONCLUSION: Altogether, the treatment in combination with IL-27 and IL-28B is an effective regimen to attenuate the ROS/NF-κB/NLRP3 axis associated with BaP-induced lung carcinogenesis.

Olive Oil Consumption can Prevent Non-communicable Diseases and COVID-19: A Review.

The Mediterranean diet is appraised as the premier dietary regimen, and its espousal is correlated with the prevention of degenerative diseases and extended longevity. The consumption of olive oil stands out as the most peculiar feature of the Mediterranean diet. Olive oil rich in various bioactive compounds like oleanolic acid, oleuropein, oleocanthal, and hydroxytyrosol is known for its antiinflammatory as well as cardioprotective property. Recently in silico studies have indicated that phytochemicals present in olive oil are a potential candidate to act against SARS-CoV-2. Although there are many extensive studies on olive oil and its phytochemical composition, however, some lacunas persist in understanding how the phytochemical composition of olive oil is dependent on upstream processing. The signaling pathways regulated by olive oil in the restriction of various diseases are also not clear. For answering these queries, a detailed search of research and review articles published between 1990 to 2019 were reviewed. Olive oil consumption was found to be advantageous for various chronic non-communicable diseases. Olive oil's constituents are having potent anti-inflammatory activities and thus restrict the progression of various inflammation-linked diseases ranging from arthritis to cancer. But it is also notable that the amount and nature of the phytochemical composition of household olive oil are regulated by its upstream processing, and the physicochemical properties of this oil can give a hint regarding the manufacturing method as well as its therapeutic effect. Moreover, daily uptake of olive oil should be monitored as excessive intake can cause body weight gain and a change in the basal metabolic index. So, it can be concluded that the olive oil consumption is beneficial for human health, and particularly for the prevention of cardiovascular diseases, breast cancer, and inflammation. The simple way of processing olive oil is to maintain the polyphenol constituents, whichprovide the protection against noncommunicable diseases and SARS-CoV-2.

Bromelain and Olea europaea (L.) leaf extract mediated alleviation of benzo(a)pyrene induced lung cancer through Nrf2 and NFκB pathway.

Lung cancer is the most aggressive as well as deadly form of cancer and most of the lung cancer cases are involved in direct smoking or passive smoking. Oxidative stress and pulmonary inflammation regulated by some transcription factors like Nrf2, NF-κB etc. play important roles in lung cancer. Various combinations of therapies are currently attributed to lung cancer treatment. A plethora of evidence supports that the consumption of plant-derived foods can prevent chronic diseases like cancer. Leaves of olive (Olea europaea L.) are rich in phenolic compounds which are having antioxidant and anti-inflammatory property. Also, bromelain from pineapple juice and from pineapple stem is a potent anti-inflammatory agent. We took a pragmatic approach to prevent carcinogenesis by supplementing the combination of these two extracts. In this study, we have tried to evaluate the amelioration of various hallmarks associated with benzo(a)pyrene-induced lung carcinogenesis upon the combinatorial treatment of ethanolic olive leaf extract (EOLE) and bromelain. We have studied the role of EOLE in amelioration of BaP-induced oxidative stress in the lung. As several reports of anticancer activity of bromelain are available, we have combined EOLE with bromelain to study their protective role against BaP-mediated lung damage. Changes in DNA integrity, LPO level in lung after EOLE-treated animal were examined. Then, we have evaluated the synergistic role of EOLE and bromelain. We have found that EOLE in combination with bromelain was able to increase the translocation of Nrf2 from cytoplasm to nucleus and decrease the translocation of NF-κB from cytoplasm to nucleus. Combination of treatment also reduced the expression of TNFα, IL-6, and some matrix metalloproteinases in lung tissue. Our findings suggest that EOLE and bromelain can synergistically reduce the BaP-induced lung carcinogenesis associated with inflammation and oxidative stress via regulating the expression of various inflammatory markers and also modulating the activity of pulmonary antioxidant armories.

Understanding the complicated relationship between antioxidants and carcinogenesis.

Reactive oxygen species (ROS) are generated as by-product of cellular respiration and also due to the exposure of various xenobiotics, whereas mitochondrial electron transport chain is considered as the main source of ROS generation. The sequential addition to molecular oxygen gives rise to various forms of ROS like superoxide anion, peroxide, hydroxyl radical, hydroxyl ion, and so forth. However, the uncontrolled level of ROS generation and accumulation alters the body homeostasis. Excessive generation of ROS leads to oxidative stress and various kinds of diseases including cancer. To counteract ROS, enzymatic and nonenzymatic antioxidants' armory is available in our body. Apart from endogenous antioxidants, we are also consuming various exogenous antioxidants. Antioxidants protect us from ROS-mediated damages and inhibit ROS-induced carcinogenesis. Recent studies have revealed that antioxidants could also act as tumor-promoting agents. Various anticancer drugs are used to kill the cancer cells through the generation of oxidative stress in them, but the cancer cells can counteract the effect with the help of various endogenous as well as exogenous antioxidants. Our review will summarize the multifaceted relationship between antioxidants and carcinogenesis, and it will help to create new directions in antioxidant-based chemotherapy.

IL-27 along with IL-28B ameliorates the pulmonary redox impairment, inflammation and immunosuppression in benzo(a)pyrene induced lung cancer bearing mice.

AIMS: The major cause behind lung cancer development is exposure to various polycyclic aromatic hydrocarbons like benzo(a)pyrene (BaP) present in tobacco smoke, motor vehicle, and industrial exhaust. BaP is reported to induce the expression of various pro-inflammatory cytokines and matrix remodeling proteins. It is also responsible for dysfunction and exhaustion of the killing capacity of CD8+ T lymphocytes, one of the important components of the immune system which can kill tumor cells. We tried to evaluate the synergistic role of IL-27 and IL-28B in modulation of BaP-induced lung carcinogenesis associated with various hallmarks like pulmonary redox imbalance, angiogenesis, inflammation and cell proliferation in lung tissue. MAIN METHOD: BaP was treated to Swiss albino mice to develop lung tumor. After the confirmation of lung tumor development Swiss albino mice were treated with IL-27 and IL-28B alone or in combination intraperitoneally. Histological analysis, immunohistochemistry, biochemical assay, western blot analysis, cell cytotoxicity assay, real-time PCR assay etc. were performed to evaluate the modulatory role of IL-27 and IL-28B. KEY FINDINGS: We observed that IL-27 and IL-28B were able to suppress the expression of lung cancer-associated NFkB, COX-2, and iNOS. The expression of TNF-α, PCNA and some matrix remodeling enzymes were also modulated upon IL-27 and IL-28B treatment. Although the population of lung residing CD8+ T cells in tumor bearing lung tissue were unresponsive but the activity of systemic CD8+ cells was increased. SIGNIFICANCE: Results hinted that IL-27 along with IL-28B were able to ameliorate various hallmarks ranging from angiogenesis to inflammation associated with the BaP-induced lung carcinogenesis. From this study, we propose that IL-27 and IL28B can be used as immunotherapeutic agent to regulate lung cancer.

IL-15 and GM-CSF stimulated macrophages enhances phagocytic activity in ENU induced leukemic mice.

Murine splenic macrophage plays a decisive role in host immunity through phagocytosis against pathogens. It was reported that, macrophages also involves in phagocytosis of some tumour cells upon its activation initiated by certain cytokines produced by other immune cell or by indigenously treated. In this study, we have investigated the killing of leukemic blast cells by macrophages upon stimulated with IL-15 and GM-CSF alone or in combination in ENU challenged leukemic murine model. Along with, the release of TNF-α, IL-12 and IFN-γ by macrophages were assayed by ELISA. NO production by macrophages was also investigated. The molecular expressions like GM-CSF and TLRs were investigated for better understand of macrophage-leukemic cell interaction. Result shows that in disease condition macrophages have poor phagocytic activities which may be due to less release of TNF-α, IL-12 and IFN-γ by macrophages. This impaired phagocytic activity in leukemic mice was increase upon stimulation with IL-15 and GM-CSF.

Bromelain plus peroxidase reduces non-Hodgkin lymphoma progression in invivo via up-regulation of antioxidant enzymes and modulating apoptotic protein expression.

Aim: Pineapple (Ananas comosus (L.) Merr.) is a good source of bromelain (B) and also contain peroxidase. The objective of this study is isoaltion of bromelain plus peroxidase (BP) from the pineapple fruit to evaluate the anticancer activity of BP from the pineapple fruit of Tripura, compared to commercial bromelain against ascitic Dalton's lymphoma cells (DLA) in mice. Methods: By acetone precipitation BP was isolated from the pineapple. Animals bearing DLA, receive B and BP orally for 15 alternative days. Apoptotic proteins are assayed using western blot. Results: BP treated mice showed recover of hemoglobin and WBC count compared to control lymphoma animal. The animal showed significant reduction of body weight due to reduced tunor load and elevated reactive oxygen species (ROS) production, elevated levels of vitamin C and vitamin E and other antioxidants in blood after BP treatment. Histology of liver and kidney also shows restored architecture in BP treated animal compared to only B treated group. BP treatment upregulates the cytochrome C, BAD, and BAX protein and downregulates the Bcl-2 and NF-kß occuring upon BP treatment in the DLA cells collected from lymphoma animal. This induce the apoptosis of DLA cells in lymphoma animal and reduce the tumor load. Conclusion: The present findings suggest that BP from pineapple improves the survival of the induced lymphoma animal compared to only B which may be used as therapeutic target.

Development of Objective Evidence in Rorschach Ink Blot Test: An Eye Tracking Study.

The Rorschach inkblot test (RIBT) is a standardized projective technique. It uses a subjective way of collecting and mapping responses of different regions like large (D) and small details (d). In this paper, eye tracking parameters like Initial Fixation Location, SF Ratio, Mean Fixation Duration and Mean Return are used to develop some objective measures which would be helpful in the assessment of the Rorschach responses. The study was conducted on 25 normal subjects who were administered RIBT cards I, II and X. The result shows an initial tendency to fixate in the central regions of the Rorschach cards. Computation of SF ratio helps in understanding most frequently fixated regions leading to popular response. Certain locations of each card have high attentional value where most shifts and fixations occur. The study supplements to the information obtained by the subjective scoring of RIBT and also indicates that specific eye tracking parameters could be an objective marker for personality assessment with RIBT.

A Study of Depression in Adult Patients with Bronchial Asthma Presenting to a Tertiary Care Hospital in Eastern India.

BACKGROUND: Bronchial asthma is a serious global health problem. Depression, the most common mood disorder, is often found to be higher among people with chronic health conditions like bronchial asthma. METHODS: Patients with newly diagnosed to have bronchial asthma (n = 100) who fulfilled the study criteria were evaluated for depression with Beck Depression Inventory (BDI) score. Severity and level of bronchial asthma control were determined as per Global Initiative for Asthma (GINA) guidelines. Subjective asthma severity was assessed by Perceived Control of Asthma Questionnaire. Follow-up evaluation was done after three months of asthma management with the same study tools. RESULTS: In our study population, 65% asthma patients showed depression on first visit (95% Confidence interval [CI] 55.65-74.35). Correlation coefficient between subjective asthma severity and severity of depression was -0.945 (p < 0.001) while correlation coefficient between objective asthma severity and depression severity was 0.066 (p = 0.515). In follow-up visit after asthma management 63% patients still had depression (95% CI 53.54-72.46). Correlation coefficient between objective asthma control and depression severity was 0.1 (p = 0.320). Correlation coefficient between subjective asthma severity and severity of depression was -0.979 (p < 0.001). CONCLUSIONS: Our observational study suggests that depression is highly prevalent in asthma patients. There is a high inverse correlation between depression and patient's perception of asthma control. However, no significant correlation could be observed between objective measures of asthma severity and depression.

Acute stress-related psychological impact in children following devastating natural disaster, the Sikkim earthquake (2011), India.

BACKGROUND: Psychological stress following natural disaster is common. Despite several earthquakes in India, data on evaluation of acute stress among the child victims in the early postdisaster period is scarce. Immediately following a devastating earthquake (6.9 Richter) at Sikkim on September, 18 2011, many children attended North Bengal Medical College, the nearest government tertiary care institution, with unusual stress symptoms. OBJECTIVE: Evaluation of acute stress symptoms in children in the immediate postearthquake period. MATERIALS AND METHODS: This was a cross-sectional study done over 4 weeks and includes all the children from 1 to 12 years presenting with unusual physical or behavioral symptoms. Those with major injuries requiring admission were excluded. They were divided into two age groups. For older children (8-12 years) the 8-item Children Impact of Event Scale (CIES) was used for screening of stress. Unusual symptoms were recorded in younger children (1-8 years) as CIES is not validated < 8 years. RESULT: A total of 84 children (2.66%) out of 3154 had stress symptoms. Maximum attendance was noted in first 3 days (65.47%) and declined gradually. In children ≥ 8 years, 48.78% had psychological stress, which was statistically significant on CIES scores without any gender predilection. Static posturing (41.86%), sleeplessness (32.55%), anorexia (9.30%), recurrent vomiting (13.95%), excessive crying (13.95%), or night-awakenings (4.65%) were found in younger children (n = 43) and three required admission. CONCLUSION: This study represent the first Indian data showing statistically significant psychological impact in older children (8-12 years) and various forms of physical stress symptoms in young children (1-8 years) following earthquake.