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OBJECTIVE: The purpose of this study was to explore the association between body composition in the elderly and subsequent changes in muscle strength during aging. METHODS: This was a longitudinal study with a 5-y follow-up. Eighty-seven men (n = 38) and women (n = 49) from a random sample of 75-y-old subjects in the Göteborg part of the Nordic Research on Aging study who were investigated at ages 75 and 80 y and were free from any major diseases at baseline were included. Body composition was estimated from bioelectrical impedance. The maximal isometric strengths of handgrip, arm flexion, and knee extension were measured on the side of the dominant hand while a subject was in a sitting position in an adjustable dynamometer chair. RESULTS: Fat-free mass decreased significantly (P < 0.001) in both sexes, but more in men. Percentage of body fat increased only in men (P < 0.05). Body height decreased in both sexes, but more in women (P < 0.001). Declines in muscle strengths were evident for all muscle groups in both sexes but more prominent in men. It was observed that body composition status at baseline, measured as fat-free mass and fat-free mass index, was a statistically significant predictor for decline in muscle strength, particularly in the extremities. CONCLUSION: Fat-free mass at age 75 y was associated with lower 5-y decline in muscle strength. This finding underscores the potential importance of fat-free mass for maintaining functional ability during aging. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate waist circumference (WC) and body mass index (BMI) at age 70 as risk factors for stroke. DESIGN: Cohort study of 70-year-olds with 15-year follow-up. SETTING: Geriatric Medicine Department, Goteborg University, Sweden. PARTICIPANTS: Two thousand two hundred eighty-seven (1,045 men; 1,242 women) 70-year-olds examined between 1971 and 1981 in Goteborg, Sweden. MEASUREMENTS: Cox regression model was used to calculate relative risk (RR) and 95% confidence interval (CI) for first-ever stroke (fatal and nonfatal) in reference to the lowest quartiles of WC and BMI. Tests for trend were performed fitting WC and BMI in their original continuous form. RESULTS: In men and women, RRs for stroke, in the highest WC quartile were 1.65 (95% CI = 1.08-2.51) and 1.31 (95% CI = 0.88-1.92), respectively, after adjustment for cohorts, smoking habit, coronary heart disease (CHD), diabetes mellitus, total cholesterol (TC), systolic blood pressure (SBP), and height at age 70. In men, RR for stroke in the highest BMI quartile (>/=28 kg/m2) was 1.68 (95% CI = 1.12-2.53) after adjustment for cohorts, smoking habits, CHD, diabetes mellitus, TC, and SBP at age 70. In women, adjusted RRs for stroke across the BMI quartiles were not significantly different. In men, population attributable fractions of stroke were 24.8% and 25.2% for the highest quartiles of WC and BMI, respectively. CONCLUSIONS: High WC (>/=99 cm) and BMI (>/=28 kg/m2) are risks for stroke in older men but not in older women. [ABSTRACT FROM AUTHOR]

Cisplatin, a powerful chemotherapy medication, has long been a cornerstone in the fight against cancer due to chemotherapeutic failure. The mechanism of cisplatin resistance/failure is a multifaceted and complex issue that consists mainly of apoptosis inhibition through autophagy sensitization. Currently, researchers are exploring ways to regulate autophagy in order to tip the balance in favor of effective chemotherapy. Based on this notion, the current study primarily identifies the differentially expressed genes (DEGs) in cisplatin-treated autophagic ACHN cells through the Illumina Hi-seq platform. A protein-protein interaction network was constructed using the STRING database and KEGG. GO classifiers were implicated to identify genes and their participating biological pathways. ClueGO, David, and MCODE detected ontological enrichment and sub-networking. The network topology was further examined using 12 different algorithms to identify top-ranked hub genes through the Cytoscape plugin Cytohubba to identify potential targets, which established profound drug efficacy under an autophagic environment. Considerable upregulation of genes related to autophagy and apoptosis suggests that autophagy boosts cisplatin efficacy in malignant ACHN cells with minimal harm to normal HEK-293 growth. Furthermore, the determination of cellular viability and apoptosis by AnnexinV/FITC-PI assay corroborates with in silico data, indicating the reliability of the bioinformatics method followed by qRT-PCR. Altogether, our data provide a clear molecular insight into drug efficacy under starved conditions to improve chemotherapy and will likely prompt more clinical trials on this aspect.

Spatial process models are widely used for modeling point-referenced variables arising from diverse scientific domains. Analyzing the resulting random surface provides deeper insights into the nature of latent dependence within the studied response. We develop Bayesian modeling and inference for rapid changes on the response surface to assess directional curvature along a given trajectory. Such trajectories or curves of rapid change, often referred to as wombling boundaries, occur in geographic space in the form of rivers in a flood plain, roads, mountains or plateaus or other topographic features leading to high gradients on the response surface. We demonstrate fully model based Bayesian inference on directional curvature processes to analyze differential behavior in responses along wombling boundaries. We illustrate our methodology with a number of simulated experiments followed by multiple applications featuring the Boston Housing data; Meuse river data; and temperature data from the Northeastern United States.

The present study was undertaken for the production of encapsulated zinc and its evaluation in broiler chicken diet. The process of microencapsulation involved the use of polymers, gum arabic and maltodextrin with a maximum encapsulation of efficiency of 66%. Encapsulated material contained about 20% zinc oxide (ZnO) as core material following the freeze-drying process. One hundred and ninety-two-day-old broiler chicks were distributed in four groups in six replications having eight birds in each. The four groups comprised control (inorganic source of zinc), En-Zn-100 (encapsulated zinc at 100% of control), En-Zn-50 (encapsulated zinc at 50% of control), and Org-Zn-50 (Zn-methionine at 50% of control). The experiment was carried out for 35 days following standard management practices. The live weight gain, feed intake and FCR were comparable among groups. Plasma and muscle zinc (ppm) content was unaffected by the level or source of zinc supplementation. The zinc apparent ileal digestibility coefficient was significantly (P < 0.05) higher in En-Zn-50 fed groups, while crude protein digestibility was not affected by the level or form of Zn supplementation. Bone weight, length, and zinc content were comparable, and bone ash content was significantly different among the groups. Relative expression of ZnT2 was significantly upregulated in encapsulated zinc-fed groups. From the study, it could be concluded that supplementation of zinc either as encapsulated or organic form at 50% of inorganic source (ZnO) could be sufficient to maintain the growth performance, serum, tissue and bone mineral content in broiler chicken., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Human immunodeficiency virus (HIV) dynamics have been the focus of epidemiological and biostatistical research during the past decades to understand the progression of acquired immunodeficiency syndrome (AIDS) in the population. Although there are several approaches for modeling HIV dynamics, one of the most popular is based on Gaussian mixed-effects models because of its simplicity from the implementation and interpretation viewpoints. However, in some situations, Gaussian mixed-effects models cannot (a) capture serial correlation existing in longitudinal data, (b) deal with missing observations properly, and (c) accommodate skewness and heavy tails frequently presented in patients' profiles. For those cases, mixed-effects state-space models (MESSM) become a powerful tool for modeling correlated observations, including HIV dynamics, because of their flexibility in modeling the unobserved states and the observations in a simple way. Consequently, our proposal considers an MESSM where the observations' error distribution is a skew-t. This new approach is more flexible and can accommodate data sets exhibiting skewness and heavy tails. Under the Bayesian paradigm, an efficient Markov chain Monte Carlo algorithm is implemented. To evaluate the properties of the proposed models, we carried out some exciting simulation studies, including missing data in the generated data sets. Finally, we illustrate our approach with an application in the AIDS Clinical Trial Group Study 315 (ACTG-315) clinical trial data set., (© 2023 Wiley-VCH GmbH.)

The tumor microenvironment is surrounded by blood vessels and consists of malignant, non-malignant, and immune cells, as well as signalling molecules, which primarily affect the therapeutic response and curative effects of drugs in clinical studies. Tumor-infiltrating immune cells participate in tumor progression, impact anticancer therapy, and eventually lead to the development of immune tolerance. Immunotherapy is evolving as a promising therapeutic intervention to stimulate and activate the immune system to suppress cancer cell growth. Endometrial cancer (EC) is an immunogenic disease, and in recent years, immunotherapy has shown benefit in the treatment of recurrent and advanced EC. This review discusses the key molecular pathways associated with the intra-tumoral immune response and the involvement of circulatory signalling molecules. Specific immunologic signatures in EC which offer targets for immunomodulating agents, are also discussed. We have summarized the available literature in support of using immunotherapy in EC. Lastly, we have also discussed ongoing clinical trials that may offer additional promising immunotherapy options in the future. The manuscript also explored innovative approaches for screening and identifying effective drugs, and to reduce the financial burdens for the development of personalized treatment strategies. Collectively, we aim to provide a comprehensive review of the role of immune cells and the tumor microenvironment in the development, progression, and treatment of EC., Competing Interests: Declaration of Competing Interest The authors of the manuscript have no known competing conflicts of interest, neither in terms of finance nor data., (Copyright © 2023. Published by Elsevier Inc.)

Complex urbanisation dynamics, on the one hand, create a high demand for animal products, and on the other hand put enormous pressure on arable land with negative consequences for animal feed production. To explore the impact of accelerated urbanisation on dairy cattle health in urban farming systems, 151 farmers from different parts of the Greater Bengaluru metropolitan area in India were individually interviewed on aspects addressing cattle management and cattle health. In addition, 97 samples of forages from the shores of 10 different lakes, and vegetable leftovers used in cattle feeding were collected for nutritional analysis. Along with the use of cultivated forages, crop residues, and concentrate feed, 47% and 77% of the farmers occasionally or frequently used lake fodder and food leftovers, respectively. Nutritionally, lake fodder corresponded to high-quality pasture vegetation, but 43% of the samples contained toxic heavy metals such as arsenic, cadmium, chromium, and lead above official critical threshold levels. Therefore, lake fodder may affect cows' health if consumed regularly; however, heavy metal concentrations varied between lakes (P < 0.05), but not between fodder types (P > 0.05). Although 60% of the interviewed farmers believed that their cows were in good health, logit model applications revealed that insufficient drinking water supply and the use of lake fodder negatively impacted cattle health (P < 0.05). While it remains unknown if regular feeding of lake fodder results in heavy metal accumulation in animal products, farmers and farm advisors must address this and other urbanization-related challenges to protect cattle health., (© 2023. The Author(s).)

The major reason for multidrug resistance is the failure of chemotherapy in many tumors, including colon cancer. Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor that simulates multiple cellular response to hypoxia. HIF-1α has been known to play a vital role towards tumor resistance; however, its mechanism of action is still not fully elucidated. N this study, we found that HIF-1α remarkably modulated drug resistance-associated proteins upon CopA3 peptide treatment against colon cancer cells. Abnormal rates of tumor growth along with high metastatic potential lacks the susceptibility towards cellular signals is a key characteristic in many tumor types. Moreover, in growing tumors, cells are exposed to insufficient nutrient supply and low oxygen availability. These stress force them to switch into adaptable and aggressive phenotypes. Our study investigated the interaction of HIF-1α and MDR gene association upon CopA3 treatment in the tumor microenvironment. We demonstrate that the multidrug resistance gene is associated with tumor resistance to chemotherapeutics, which upon CopA3 treatment promotes p53 activation and proteasomal degradation of HIF-1α, effecting the angiogenesis response to hypoxia. p53 downregulation augments HIF-1-dependent transcriptional activation of VEGF in response to oxygen deprivation., Competing Interests: Declaration of competing interest I, Prof., Sun Chul Kang, would like to state that, the authors of the manuscript do not have any conflict of interest neither in terms of data nor money., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endometrial cancer is the most common female cancer showing continuous rise in its incidence and mortality rate. Despite the extensive research efforts in cancer therapeutics, still there is a lack of effective treatment options and the outcome is poor for patients with advanced and recurrent endometrial cancers. In this study, we aimed to evaluate the efficacy of niclosamide (NIC) against endometrial cancer. NIC is an FDA-approved anti-helminthic drug, which has been recently extensively studied as a potent anti-cancerous agent in several cancers. The anti-cancerous activity of NIC was analyzed in-vitro (ANC3A, Hec1B, and Ishikawa endometrial cancer cell lines) by cell viability-, soft agar-, invasion- and migration- assay. The action mechanism of NIC was demonstrated by western blot analysis and immune-fluorescence imaging and validated by specific inhibitors. The in-vivo efficacy of NIC was studied in the Ishikawa xenograft animal model. NIC effectively suppressed the viability (IC 50< 1 μM), colony formation ability, migration, and invasion of all endometrial cancer cells tested. We demonstrated that NIC inhibited AKT/mTOR signaling pathway and induced apoptosis and autophagy in endometrial cancer cells. Further study demonstrated that although NIC induced autophagosome formation, it inhibits autolysosome formation. In addition, we observed that NIC induced BAX co-localization with lysosome and inhibited Cathepsin B maturation from pro-cathepsin B, thereby inducing the lysosomal membrane permeability and release of hydrolytic enzymes from the lysosome to cytosol, which eventually contributed cell death. NIC also inhibited tumor weight and volume in the Ishikawa xenograft animal model without having any evidence of toxicity. Due to its potent anti-cancerous activity and safety profile, NIC seems to be a promising agent for human endometrial cancer therapeutics., Competing Interests: Conflict of interest statement The authors of the manuscript do not have any conflict of interest neither in terms of data nor money., (Published by Elsevier Masson SAS.)

The diverse expression patterns of the tumor suppressor p53 in cancer cells reflect the regulatory efficiency of multiple cellular pathways. By contrast, many human tumors are reported to develop in the presence of wild-type p53. Recently, several oncogene inhibitors have been used clinically to suppress tumor development by functionally reactivating other oncoproteins. On the other hand, p53 reactivation therapies have not been well established, as few of the p53-MDM2 complex inhibitors such as Nutlin-3 induces mutation in p53 gene upon prolonged usage. Therefore, in this study CopA3, a 9-mer dimeric D-type peptide with anticancer activity against the human colorectal cancer cells, was used to explore the efficacy of p53 reactivation in-vitro and in-vivo. The anticancer activity of CopA3 was more selective towards the wild-type p53 expressing cells than the p53 deficient or mutant colorectal cancer cells. In response to this, this study investigated the signaling pathway in vitro and validated its anti-tumor activity in-vivo. The protein-peptide interaction and molecular docking efficiently provided insight into the specific binding affinity of CopA3 to the p53-binding pocket of the MDM2 protein, which efficiently blocked the p53 and MDM2 interaction. CopA3 plays a crucial role in the binding with MDM2 and enhanced the nuclear translocation of the p53 protein, which sequentially activated the downstream targets to trigger the autophagic mediated cell death machinery through the JNK/Beclin-1 mediated pathway. Collectively, CopA3 affected the MDM2-p53 interaction, which suppressed tumor development. This study may provide a novel inhibitor candidate for the MDM2-p53 complex, which could ultimately suppress the growth of colorectal cancer cells without being cytotoxic to the healthy neighboring cells present around the tumor microenvironment., Competing Interests: Declaration of competing interest We would like to state that, the authors of the manuscript do not have any conflict of interest neither in terms of data nor money., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mycotoxins are produced primarily as secondary fungal metabolites. Mycotoxins are toxic in nature and naturally produced by various species of fungi, which usually contaminate food and feed ingredients. The growth of these harmful fungi depends on several environmental factors, such as pH, humidity, and temperature; therefore, the mycotoxin distribution also varies among global geographical areas. Various rules and regulations regarding mycotoxins are imposed by the government bodies of each country, which are responsible for addressing global food and health security concerns. Despite this legislation, the incidence of mycotoxin contamination is continuously increasing. In this review, we discuss the geographical regulatory guidelines and recommendations that are implemented around the world to control mycotoxin contamination of food and feed products. Researchers and inventors from various parts of the world have reported several innovations for controlling mycotoxin-associated health consequences. Unfortunately, most of these techniques are restricted to laboratory scales and cannot reach users. Consequently, to date, no single device has been commercialized that can detect all mycotoxins that are naturally available in the environment. Therefore, in this study, we describe severe health hazards that are associated with mycotoxin exposure, their molecular signaling pathways and processes of toxicity, and their genotoxic and cytotoxic effects toward humans and animals. We also discuss recent developments in the construction of a sensitive and specific device that effectively implements mycotoxin identification and detection methods. In addition, our study comprehensively examines the recent advancements in the field for mitigating the health consequences and links them with the molecular and signaling pathways that are activated upon mycotoxin exposure.

Rhabdomyolysis induced acute kidney injury (RIAKI) is a life-threatening condition responsible for approximately 19-58% of AKI cases worldwide. We performed an intramuscular injection of glycerol (10 mL/kg) in male wistar rats to induce AKI. Epigallocatechin gallate (EGCG) was administered for 3 consecutive days to evaluate its protective effects. We observed significant downregulation in serum creatinine, blood urea nitrogen (BUN) and LDH at different time points on EGCG treatment groups in a dose-dependent manner. Similarly, H&E staining also revealed that EGCG was able to reduce the formation of damaged tubules and tubular necrosis which was prominently spread throughout the kidney tissue of glycerol treatment group. Concomitantly, we observed upregulated inflammation, ER stress and elevated oxidative stress in the glycerol treated group only, which was significantly normalized upon EGCG treatment in both in vitro and in vivo studies. The occurrence of apoptosis in kidney tubules was found to be relatively higher in glycerol treated group and H 2 O 2 treated HEK-293 cells. The results obtained after EGCG treatment revealed a significant decrease in apoptotic cell population, which was further validated by immunofluorescence staining against p53 and comet assay in HEK-293 cells and p53 IHC in kidney tissues. Western blotting also revealed a systemic downregulation of intrinsic mitochondrial apoptotic pathway markers such as bax, bcl-2, pro and cleaved caspase 3, caspase 9 and PARP1. Additionally, the results for flow cytometry analysis and TUNEL assay corroborated apoptotic equilibrium. Conclusively, we reckon EGCG as a multi-therapeutic natural product that can be used the for treatment of AKI., Competing Interests: Conflict of interest The authors declare that they have no competing financial and/or non-financial competing interests or other interests that might be perceived to influence the results and/or discussion reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The present study was undertaken to investigate the ability of a drug curcumin-loaded polymer to inhibit the growth of cervical cancer cells by enhancing the anti-cancer efficiency of curcumin. We synthesized poly(methacryloyl beta-alanine) (PMBA) as a nanocarrier by radical polymerization in supercritical CO 2 . The results showed that the curcumin encapsulated and folic acid (FA)-treated PMBA (Poly@Cur-FA) for 24 h activated the reactive oxygen species-mediated programmed cell death machinery in HeLa cells. This remarkable effect of Poly@Cur-FA treatment was visualized using different fluorescent probes, which demonstrated that the Poly@Cur-FA treatment disrupted the cell membrane, as also supported by scanning electron microscopy observations. The effect of Poly@Cur-FA dispersion on the cells was observed under a transmission electron microscope. Further, the HeLa cells were treated with the polymer encapsulated curcumin and Bcl2 siRNA (Pol-Cur-siRNA) for 24 h, which effectively suppressed the Bcl2 and simulated the autophagic pathway. This co-delivery system was designed to inhibit curcumin efflux and can enhance the treatment efficacy by targeting multiple signaling pathways, including cell cycle, apoptotic, and autophagic pathways. Collectively, the Pol-Cur-siRNA system appears to offer an efficient combinational therapeutic strategy that might overcome the problems associated with the chemosensitivity against the standard synthetic anti-cancer drugs. To support the experimental data, an artificial neural network model was developed to foresee the drug and gene release behaviors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Spatio-temporal Poisson models are commonly used for disease mapping. However, after incorporating the spatial and temporal variation, the data do not necessarily have equal mean and variance, suggesting either over- or under-dispersion. In this paper, we propose the Spatio-temporal Conway Maxwell Poisson model. The advantage of Conway Maxwell Poisson distribution is its ability to handle both under- and over-dispersion through controlling one special parameter in the distribution, which makes it more flexible than Poisson distribution. We consider data from the pandemic caused by the SARS-CoV-2 virus in 2019 (COVID-19) that has threatened people all over the world. Understanding the spatio-temporal pattern of the disease is of great importance. We apply a spatio-temporal Conway Maxwell Poisson model to data on the COVID-19 deaths and find that this model achieves better performance than commonly used spatio-temporal Poisson model., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V.)

The present study aimed to modulate the oxidative status-mediated polarity of the oocytes for sex-specific sperm fertilization to generate desired sex embryos. In vitro embryos were produced at different oxidative status, varying O 2 concentrations, and without/with L-carnitine in maturation and culture media. The majority of the embryos produced at high oxidative stress were males whereas; low oxidative status favoured female embryos production. Low O 2 doubled the proportion of female embryos (10.59 vs 21.95%); however, L-carnitine supplementation in media increased approximately seven-folds of the female embryos (12.26 vs. 77.62%) production. Oocytes matured at high oxidative status were in the repolarized state favouring positively charged Y sperm fertilization to produce significantly more male embryos. Low oxidative status favoured negatively charged X sperm fertilization to the oocytes in the depolarized state to produce more female embryos. Intracellular ROS was significantly low in female embryos than in males; however, female embryos were more stressful than males. The study concluded that the oxidative status-mediated alteration in pH of the medium to modulate the intracellular positive ions is the main critical factor to influence the sex of embryos through sex-specific sperms fertilization to the oocytes as per their polarity., (© 2022. The Author(s).)

Helicobacter pylori (H. pylori) is a major causative agent of chronic gastritis, gastric ulcer and gastric carcinoma. H. pylori cytotoxin associated antigen A (CagA) plays a crucial role in the development of gastric cancer. Gastric cancer is associated with glycosylation alterations in glycoproteins and glycolipids on the cell surface. H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer through post-translation modification of fucosylation to develop gastric cancer. The involvement of a variety of sugar antigens in the progression and development of gastric cancer has been investigated, including type II blood group antigens. Lewis Y (LeY) is overexpressed on the tumor cell surface either as a glycoprotein or glycolipid. LeY is a difucosylated oligosaccharide, which is catalyzed by fucosyltransferases such as FUT4 (α1,3). FUT4/LeY overexpression may serve as potential correlative biomarkers for the prognosis of gastric cancer. We discuss the various aspects of H. pylori in relation to fucosyltransferases (FUT1-FUT9) and its fucosylated Lewis antigens (LeY, LeX, LeA, and LeB) and gastric cancer. In this review, we summarize the carcinogenic effect of H. pylori CagA in association with Le Y and its synthesis enzyme FUT4 in the development of gastric cancer as well as discuss its importance in the prognosis and its inhibition by combination therapy of anti-Le Y antibody and celecoxib through MAPK signaling pathway preventing gastric carcinogenesis., Competing Interests: Declaration of Competing Interest All the authors declare no conflict of interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The gamma distribution has been extensively used in many areas of applications. In this paper, considering a Bayesian analysis we provide necessary and sufficient conditions to check whether or not improper priors lead to proper posterior distributions. Further, we also discuss sufficient conditions to verify if the obtained posterior moments are finite. An interesting aspect of our findings are that one can check if the posterior is proper or improper and also if its posterior moments are finite by looking directly in the behavior of the proposed improper prior. To illustrate our proposed methodology these results are applied in different objective priors.

Sasa coreana Nakai (SCN) is a medicinal plant commonly used against inflammation. However, the underlined mechanisms against skin inflammation is poorly understood. The present study investigated the effects of SCN leave extract on ear inflammation. To this aim, six-week-old male ICR mice was subjected to 12-O-tetradecanoyl-phorbol-13-acetate induce ear edema, which were then topically treated with the leave extract of SCN. Ear thickness, weight, and morphological changes were recorded to ensure the induction of ear edema. Further, histological analysis and protein expression for inflammatory markers were also recorded to validate the study. Topical treatment with SCN repressed TPA-induced ear edema in a dose-dependent manner. Further, SCN treatment significantly antagonized the protein expression of MAP kinase signaling pathway and reduced the effect of TPA-induced NF-κB activation, sequentially, deactivated its transcriptional targets in a dose-dependent manner. Collectively, the study suggested that SCN could be a useful therapeutic agent against skin inflammation.

Cell-cycle arrest reflects an accumulation of responses to DNA damage that sequentially affects cell growth and division. Herein, we analyzed the effect of the 9-mer dimer defensin-like peptide, CopA3, against colorectal cancer cell growth and proliferation in a dose-dependent manner upon 96 h of treatment. As observed, CopA3 treatment significantly affected cancer cell growth, reduced colony formation ability, increased the number of SA-β-Gal positive cells, and remarkably reduced Ki67 protein expression. Notably, in HCT-116 cells, CopA3 (5 μM) treatment effectively increased oxidative stress and, as a result, amplified the endogenous ROS, mitochondrial ROS, and NO content in the cells, which further activated the DNA damage response and caused cell-cycle arrest at the G1 phase. The prolonged cell-cycle arrest elevated the release of inflammatory cytokines in the cell supernatant. Nevertheless, mechanistically, NAC treatment effectively reversed the CopA3 effect and significantly reduced the oxidative stress; subsequently rescuing the cells from G1 phase arrest. Overall, CopA3 treatment can inhibit the growth and proliferation of colorectal cancer cells by inducing cell-cycle arrest through the ROS-mediated pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The harmful effects of excessive ultraviolet (UV) exposure are well known. However, moderate exposure to UV radiation is beneficial and required for active vitamin D synthesis in our body. People living in the coldest regions on the earth are unable to expose their skin to the solar UV radiation and, therefore, additional supplementation of Vitamin D2 is recommended. Mushrooms are one such consumable macrofungi, which has high vitamin content and therefore used in various traditional medicines. Particularly, UVB-irradiated mushrooms are rich in active vitamin D content and that is why recommended to include in the daily diets for the patients suffering from the problems associated with bone mineralization. In the present study, we evaluated the cytotoxic effect of mushroom extract (UVB-ME) (Lentinus edodes) treatment against MG-63 cells, HepG2 cells, and CCD 841 CoN cells. Furthermore, we elucidated the potential of UVB-ME on Ca ++ uptake in osteoblast-like MG-63 cells. Next, we validated the response of Ca ++ uptake on the growth and development of zebrafish larvae. In addition, the anti-inflammatory and immunomodulatory potential of UVB-ME treatment against lipopolysaccharide-induced inflammatory response was also analyzed in vivo. Collectively, the study suggested that dietary supplementation of UVB-irradiated mushroom is beneficial for bone calcification and could modulate the host immune system., (© 2021 Wiley Periodicals LLC.)

The two-part model and the Tweedie model are two essential methods to analyze the positive continuous and zero-augmented responses. Compared with other continuous zero-augmented models, the zero-augmented gamma model (ZAG) demonstrates its performance on the mass zeros data. In this article, we compare the Bayesian model for continuous data of excess zeros by considering the ZAG and Tweedie model. We model the mean of both models in a logarithmic scale and the probability of zero within the zero-augmented model in a logit scale. As previous researchers employed different priors in Bayesian settings for the Tweedie model, by conducting a sensitivity analysis, we select the optimal priors for Tweedie model. Furthermore, we present a simulation study to evaluate the performance of two models in the comparison and apply them to a dataset about the daily fish intake and blood mercury levels from National Health and Nutrition Examination Survey. According to the Watanabe-Akaike information criterion and leave-one-out cross-validation criterion, the Tweedie model provides higher predictive accuracy for the positive continuous and zero-augmented data., (© 2020 John Wiley & Sons, Ltd.)

Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl 4 ). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl 4 through the intraperitoneal injection of 1 mL/kg CCl 4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl 4 -induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl 4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl 4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl 4 treatment. Furthermore, the apoptotic response induced by CCl 4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl 4 .

The inability to distinguish aggressive from indolent prostate cancer is a longstanding clinical problem. Prostate specific antigen (PSA) tests and digital rectal exams cannot differentiate these forms. Because only ∼10% of diagnosed prostate cancer cases are aggressive, existing practice often results in overtreatment including unnecessary surgeries that degrade patients' quality of life. Here, we describe a fast microfluidic immunoarray optimized to determine 8-proteins simultaneously in 5 μL of blood serum for prostate cancer diagnostics. Using polymeric horseradish peroxidase (poly-HRP, 400 HRPs) labels to provide large signal amplification and limits of detection in the sub-fg mL -1 range, a protocol was devised for the optimization of the fast, accurate assays of 100-fold diluted serum samples. Analysis of 130 prostate cancer patient serum samples revealed that some members of the protein panel can distinguish aggressive from indolent cancers. Logistic regression was used to identify a subset of the panel, combining biomarker proteins ETS-related gene protein (ERG), insulin-like growth factor-1 (IGF-1), pigment epithelial-derived factor (PEDF), and serum monocyte differentiation antigen (CD-14) to predict whether a given patient should be referred for biopsy, which gave a much better predictive accuracy than PSA alone. This represents the first prostate cancer blood test that can predict which patients will have a high biopsy Gleason score, a standard pathology score used to grade tumors.

This study was undertaken to investigate the anticancer effects of organic extracts derived from the floral cones of Metasequoia glyptostroboides. Dried powder of M. glyptostroboides floral cones was subjected to methanol extraction, and the resulting extract was further partitioned by liquid-liquid extraction using the organic solvents n-hexane, dichloromethane (DME), chloroform, and ethyl acetate in addition to deionized water. HeLa cervical and COS-7 cells were used as a cancer cell model and normal cell control, respectively. The anticancer effect was evaluated by using the Cell Counting Kit-8 assay. The viability of COS-7 cells was found to be 12-fold higher than that of the HeLa cells under the administration of 50 µg/ml of the DME extract. Further, the sub-G1 population was determined by FACS analysis. The number of cells at the sub-G1 phase, which indicates apoptotic cells, was increased approximately fourfold upon treatment with the DME and CE extracts compared with that in the negative control. Furthermore, RT-qPCR and western blotting were used to quantitate the relative RNA and protein levels of the cell death pathway components, respectively. Our results suggest that the extracts of M. glyptostroboides floral cones, especially the DME extract, which possesses several anticancer components, as determined by GC-MS analysis, could a potential natural anticancer agent.

This study focused on the possible chemo-preventive effects of insect peptide CopA3 on normal human colon cells against the inflammation induced by the toxic environmental pollutant aflatoxin B1 (AFB1). In the study, we used CCD 841 CoN normal human colon cells to investigate the cytotoxic effect induced by AFB1 and elucidated the negative impact of AFB1 exposure on the cell cycle progression. Further, we also carried out the in-vivo experiment, where male BALB/c mice were administrated with AFB1 to induce inflammation associated cancer like phenotype and the dietary effect of CopA3 was evaluated on the early stages of AFB1-induced hepatotoxicity and inflammation in colon tissues. At the initiation stage, CopA3 was given along with water, which significantly decreased the inflammation in the liver and colon of AFB1 exposed mice model. Mice that received CopA3 alone showed enhanced activity of several antioxidant enzymes. In the post treatment stage, the CopA3 dosage remarkably increased the Ki-67 protein expression, indicating the enhancement in cell proliferation event and increased the number of apoptotic cells in colonic crypts, suggesting the capability of CopA3 treatment towards the epithelial cell turnover. Thus, CopA3 treatment shows its potential to inhibit the development of the early stages of AFB1-induced colon inflammation and hepatotoxicity in mice by inhibiting the DNA synthesis of the damaged and inflammatory cell and induced apoptosis for the clearance of damaged cells. Collectively, the results of this study suggest that CopA3 treatment may play a protective role against the mycotoxin induced inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Understanding how the natural products structural diversity interacts with cellular metabolism and infectious disease targets remains a challenge. Inflammation is an important process in the human healing response in which the tissues respond to injuries induced by many agents, including pathogens. In recent years, several drugs derived from plant products have been developed, and current drug research is actively investigating the pharmacotherapeutic role of natural products in advanced multimodal inflammatory disease targeting. Sugiol, a diterpenoid, can act as an antimicrobial, antioxidant, anti-inflammatory, anti-carcinoma, antiviral, and cardiovascular agent. Until now, there have been no updates on the pharmacotherapeutic advancement of sugiol. Herein, we correlate the diverse molecular pathways in disease prevention involving sugiol. We also discuss the origins of its structural diversity and summarize new research directions toward exploring its novel effective future uses. Despite much evidence of its efficacy and safety, the sugiol has not yet been approved as a therapeutic agent due to its low bioavailability, and insolubility in an aqueous environment. The aim of this review is to renew and update noteworthy information on the pharmacotherapeutic characteristics of sugiol to approach different advanced strategies employed in the context of natural nurturing-based biomedicine., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 μg) caused chromosomal aberrations on the Allium cepa root tip and induced mitotic dysfunction. Similarly, PMA caused embryonic and larval deformities and a plummeted survivability rate on zebrafish embryo in a dose-dependent manner. Persistently, PMA treatment on immortalized human keratinocyte human keratinocyte (HaCaT) cells caused massive inflammatory rush at 4 h and a drop in cell survivability at 24 h. Concomitantly, we replicated a cutaneous inflammation similar to human psoriasis induced by PMA. Herein, we used tangeretin (TAN), as an antagonist to counteract the inflammatory response. Results from an in vivo experiment indicated that TAN (10 and 30 mg/kg) significantly inhibited PMA stimulated epidermal hyperplasia and intra-epidermal neutrophilic abscesses. In addition, its treatment effectively neutralized PMA induced elevated reactive oxygen species (ROS) generation on in vitro and in vivo systems, promoting antioxidant response. The association of hypoxia-inducible factor 1-alpha (HIF-1α)-nuclear factor kappa-light-chain-enhancer of activated b cells (NF-κB) crosstalk triggered by PMA enhanced PKCα-ERK1/2-NF-κB pathway; its activation was also significantly counteracted after TAN treatment. Conclusively, we demonstrated TAN inhibited the nuclear translocation of HIF-1α and NF-κB p65. Collectively, TAN treatment ameliorated PMA incited malignant inflammatory response by remodeling the cutaneous microenvironment.

Most of the human gene homologs are found in Caenorhabditis elegans. As a wide variety of micro-organisms present in the environment is pathogens, so, C. elegans could be a useful model to track future infectious disease. With this knowledge, in this study, we isolated Acinetobacter courvalinii from the soil and characterized its pathogenicity for the first time. For the isolation, we used Glucose-Yeast extract-Ethanol-Calcium carbonate medium. To this aim, we evaluated the resistivity of bacteria against several stressful microenvironments. As we observed, A. courvalinii JP&#95;A1001 shown highly tolerance against the acidic environment (pH 3-7), resistant against up to 0.2% of phenol content, and survived in the medium supplemented with 0.3% of bile salt. In addition, the bacteria were also resistant against several antibiotics showing the property of multidrug-resistant bacteria. Moreover, the isolated bacteria have shown the biofilm formation ability within 60 h. Further, we found that incubation of C. elegans with A. courvalinii JP&#95;A1001 decreased the body movement and increased the free radical generation which remarkably influenced the life expectancy of C. elegans compared to E. coli OP50. Therefore, we concluded that A. courvalinii JP&#95;A1001 found in the soil could be a future threat as a pathogen to public health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Mycotoxin contamination of food and water is a serious global concern. Aflatoxin B1 (AFB1) is a deadly mycotoxin that contaminates both food and water bodies in the environment. AFB1 is reported to cause severe health issues, including hepatotoxicity, teratogenicity, and immunotoxicity in humans; however, the mechanistic effects on plant and aquatic animals are not fully understood. To obtain a clear understanding of the effects of AFB1 on the ecosystem, we examined the influence of AFB1 exposure on different model systems corresponding to various habitats. In the current study, AFB1 contamination consequences were studied on a human normal cell lines (HaCaT, CCD 841 CoN), meristematic Allium cepa (onion) root cells, and zebrafish embryonic development. Our results clearly indicate that concentrations of AFB1 >10 μM are toxic to HaCaT cells. Morphological changes of HaCaT and CCD 841 CoN cells were clearly observed after exposure to AFB1. Particularly in HaCaT cells, treatment with 50 μM and 100 μM AFB1induces oxidative stress by excessive endogenous free-radical production such as ROS and NO generation. These consequences accelerate the ROS-dependent DNA damage events, which subsequently result in caspase mediated programmed cell death. Exposure of A. cepa root cells to AFB1 for 24 h resulted in abnormal cell division. A. cepa root cells subjected to AFB1 treatment showed a significant concentration-dependent increase in metaphase arrest. Exposure of zebrafish embryos to AFB1 also revealed that AFB1 contamination restricts the larval growth and development, resulting in a remarkably increased zebrafish mortality rate. Collectively, results of the current study indicate that AFB1 contamination triggers the programmed cell death machinery, subsequently affecting the ecosystem., Competing Interests: Declaration of competing interest The authors of the paper declare that they do not have any known competing financial or personal interests which could influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Synergistic therapy is emerging as a promising strategy for improving the chemotherapeutic efficacy of anticancer drugs. Addition of adjuvants with standard anticancer drugs has shown successful reduction of adverse side effects. The synthetic drug 5-Fluorouracil (5-FU) shows several side effects upon prolonged chemotherapy, thereby restricting its long-term clinical application. Several studies have reported anticancer potential and anti-inflammatory activity of tangeretin (TAN) towards mammalian cells. Therefore, we investigate whether the combination of TAN with 5-FU increases their anticancer potential against colorectal cancer. In this study, we examined the synergistic activity of TAN and 5-FU on the viability of several human cancer and normal cells. Several possible mechanistic pathways were screened, and found that co-exposure of TAN and 5-FU accelerates oxidative-stress and increases endogenous-ROS generation, which sequentially triggers the DNA damage response and activates the apoptotic pathway, by down-regulating autophagy and DNA repair system in HCT-116 cells. TAN and 5-FU co-treatment also remarkably reduces the mitochondrial membrane potential, and sequentially decreases ATPase activity. Collectively, results indicate that combination of TAN and 5-FU significantly accelerates apoptosis via JNK mediated pathway. To our knowledge gained from literature, this study is the first to describe synergistic activity of TAN and 5-FU against colorectal cancer cells., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Increasing multidrug-resistant pathogenic bacterial contamination in the environment has become the leading cause of food poisoning, resulting in life-threatening conditions due to late detection and limited therapeutic options. Escherichia coli O157:H7 is one such pathogen which is severely affecting the environmental livestock and ultimately leads to human infection. In this context, probiotics could be a useful strategy to minimize the growth of pathogens, as they produce several antimicrobial compounds and shows an exclusive competitive behavior against the pathogens. Therefore, supplementation of probiotics is wieldy accepted in the field of agriculture for the maintenance of animal's health. Previously, we reported that W. confusa DD&#95;A7 possesses anti-bacterial and immune-stimulatory activity in-vitro. Therefore, in the present study, we investigated the impact of oral-administration of DD&#95;A7 powder against E. coli O157:H7. The 6 days post-fertilized zebrafish larvae were used to evaluate the pathogenicity of the microbe. 1 × 10 8 CFU/ml of E. coli O157:H7 effectively induced the inflammatory response in zebrafish larvae. Where 1 × 10 8 CFU/ml DD&#95;A7 pre-treatment prolonged the survivability of zebrafish larvae and improved the immune response of zebrafish larvae against pathogenic infection. The antibacterial property of DD&#95;A7 against the pathogen correlated with the significant reduction of oxidative stress and host inflammatory response, by inhibiting NF-κB and its downstream signaling pathway. The findings demonstrated the prophylactic activity of DD&#95;A7 suggesting that its supplementation improved the host defense mechanism by reducing oxidative stress. The growth of pathogen was effectively suppressed in the DD&#95;A7 pre-treated larvae and maintained a healthy gastrointestinal environment in the zebrafish model., Competing Interests: Declaration of Competing Interest We would like to state that, the authors of the manuscript do not have any conflict of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Response variables in medical sciences are often bounded, e.g. proportions, rates or fractions of incidence of some disease. In this work, we are interested to study if some characteristics of the population, e.g. sex and race which can explain the incidence rate of colorectal cancer cases. To accommodate such responses, we propose a new class of regression models for bounded response by considering a new distribution in the open unit interval which includes a new parameter to make a more flexible distribution. The proposal is to obtain compound power normal distribution as a base distribution with a quantile transformation of another family of distributions with the same support and then is to study some properties of the new family. In addition, the new family is extended to regression models as an alternative to the regression model with a unit interval response. We also present inferential procedures based on the Bayesian methodology, specifically a Metropolis-Hastings algorithm is used to obtain the Bayesian estimates of parameters. An application to real data to illustrate the use of the new family is considered.

Spatial modeling of consumer response data has gained increased interest recently in the marketing literature. In this paper, we extend the (spatial) multi-scale model by incorporating both spatial and temporal dimensions in the dynamic multi-scale spatiotemporal modeling approach. Our empirical application with a US company's catalog purchase data for the period 1997-2001 reveals a nested geographic market structure that spans geopolitical boundaries such as state borders. This structure identifies spatial clusters of consumers who exhibit similar spatiotemporal behavior, thus pointing to the importance of emergent geographic structure, emergent nested structure and dynamic patterns in multi-resolution methods. The multi-scale model also has better performance in estimation and prediction compared with several spatial and spatiotemporal models and uses a scalable and computationally efficient Markov chain Monte Carlo method that makes it suitable for analyzing large spatiotemporal consumer purchase datasets., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 Informa UK Limited, trading as Taylor & Francis Group.)

RNA binding proteins (RBPs) associate with nascent and mature RNAs to perform biological functions such as alternative splicing and RNA stability. Having unique RNA recognition binding motifs, RBPs form complexes with RNA in a sequence- and structure-based manner. Aberrant expressions of several RBPs have been identified in tumorigenesis and cancer progression. These uncontrolled RBPs affect several mechanisms, including cell proliferation, tumor growth, invasion, metastasis and chemoresistance. Epithelial splicing regulatory protein 1 (ESRP1) is a member of the hnRNP family of proteins that play a crucial role in regulating numerous cellular processes, including alternative splicing and translation of multiple genes during organogenesis. Abnormal expression of ESRP1 alters the cell morphology, and leads to cell proliferation and tumor growth during cancer progression. ESRP1 mediated alternative splicing of target genes, including CD44, FGFR, PTBP1, LYN, ENAH, SPAG1 and ZMYND8, results in cancer progression. In addition, ESRP1 also regulates circularization and biogenesis of circular RNAs such as circUHRF1, circNOL10 and circANKS1B, whose expressions have been identified as key factors in various cancers. This multi-functional protein is also involved in imposing stability of target mRNAs such as cyclin A2, and thereby cell cycle regulation. The scope of this review is to examine recent scientific data, outcomes of the up- and down-regulated proteins, and the role of ESRP1 in various cancers. We conclude by summarizing ESRP1 dysregulation and its consequences on target genes in various human cancers. Collectively, the consequences of ESRP1 mediated splicing in cancer cells suggest the role of ESRP1 in cell proliferation and chemoresistance via apoptosis and autophagy modulation, which could, therefore, be potential targets for cancer therapeutics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Decursinol angelate (DA) is a pyranocoumarin purified from the roots of Angelica gigas. Here, we synthesized DA and determined its anti-inflammatory potential on TPA-induced mice ear inflammation. First, we evaluated the non-toxic behaviour of DA on HaCaT cells. Additionally, we observed the free radical scavenging potential of DA at 60 μM to be 50%. This finding was further supported by nitric oxide assay, malondialdehyde assay, H2DCFDA staining and western blotting analysis of antioxidant enzymes. DA also suppressed the activation and polarization of macrophage phagocytic activity on RAW 264.7 cells. We further evaluated the expression of ICAM-1, MCP-1, MIP-2 and MIP-1β on in-vivo model system. Consequently, DA significantly reduced the production of NF-κB and COX-2 induced proinflammatory cytokine levels on TPA induced ear edema. Inhibition of MAPK and transcriptional factor NF-κB was also validated by western blotting analysis of p-ERK, p-p38, IKKα, IKKγ, IκBα, NF-κB-p65. Immunohistochemistry and immunofluorescence staining of NFκB-p65, TNF-α and IL-1β were also performed to support the findings. Conclusively, these results suggest that topical administration of DA significantly inhibited the expression of pro-inflammatory cytokines by blocking the canonical NF-κB and MAPK pathway. Therefore, we suggest DA as a potent therapeutic compound against skin inflammation related diseases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In this paper, we introduce a new approach to generate flexible parametric families of distributions. These models arise on competitive and complementary risks scenario, in which the lifetime associated with a particular risk is not observable; rather, we observe only the minimum/maximum lifetime value among all risks. The latent variables have a zero-truncated Poisson distribution. For the proposed family of distribution, the extra shape parameter has an important physical interpretation in the competing and complementary risks scenario. The mathematical properties and inferential procedures are discussed. The proposed approach is applied in some existing distributions in which it is fully illustrated by an important data set., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 Informa UK Limited, trading as Taylor & Francis Group.)

This paper proposes a Bayesian hierarchical cure rate survival model for spatially clustered time to event data. We consider a mixture cure rate model with covariates and a flexible (semi)parametric baseline survival distribution for uncured individuals. The spatial correlation structure is introduced in the form of frailties which follow a Multivariate Conditionally Autoregressive distribution on a pre-specified map. We obtain the usual posterior estimates, smoothed by regional level maps of spatial frailties and cure rates. A simulation study demonstrates that the parameters of the models with spatially correlated frailties have smaller relative biases and MSE than the ones obtained using simple frailty models. We apply our methodology to Hodgkin lymphoma cancer survival times for patients diagnosed in the state of Connecticut., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Extended-spectrum β-lactamase (ESBL) positive bacteria are emerging pathogens causing disease like sepsis. Diseases caused by these organisms have become a challenge; because these organisms are getting resistance against almost all the recommended antibiotics used for its treatment. In the present study, in vitro antimicrobial effects of kimchi isolate Weissella confusa (DD&#95;A7) has shown the ability to trigger an oxidative attack and limits the growth of multidrug-resistant (MDR) ESBL positive E. coli bacteria. The dose-dependent and time-dependent potential of cell-free culture supernatant (CFCS) were evaluated on the exposure of targeted pathogenic bacteria and has shown the maximum cell death upon treatment. Fluorescence and scanning electron microscopic analysis have confirmed the potential of CFCS to damage the cell membrane of the pathogenic bacteria. Moreover, in the study, we have also shown the capability of DD-A7 to reduce inflammatory cytokines in the host cells. Nevertheless, our study has revealed the prophylactic activity of DD&#95;A7 against the invasion of pathogenic bacteria ex-vivo and possesses the non-hemolytic activity on mouse blood cells. Taken together, the present study successfully describes DD&#95;A7 as a natural and alternative prophylactic agent against the ESBL-positive E. coli bacteria., (Copyright © 2018. Published by Elsevier Ltd.)

Interest in probiotics has grown significantly in the last decades due to their reported nutritional and health promoting effects. The aim of this study is to investigate the therapeutic potential of probiotic fermented milk (PFM) prepared using three different probiotic strains i.e. Lactobacillus rhamnosus MTCC: 5957, Lactobacillus rhamnosus MTCC: 5897 and Lactobacillus fermentum MTCC: 5898; independently or in combination, for treating streptozotocin induced type-1 diabetes in male Wistar rats. Diabetic rats were fed with PFM preparations for 6 weeks and then analyzed for the various biochemical parameters associated. The results indicated that feeding of PFM significantly improved glucose metabolism (fasting blood glucose, glycated hemoglobin, serum insulin), serum inflammation status (tumor necrosis factor-α, and serum interleukin-6), oxidative stress (thiobarbituric acid reactive substance, catalase, superoxide dismutase and glutathione peroxidase activities in liver and kidney), serum lipid profile (total cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, triglycerides) in diabetic rats. In addition, feeding of PFM has significantly reduced mRNA expression of pepck and g6pase genes that code the key enzymes of gluconeogenesis pathway. The results of this study showed that daily consumption of PFM can be effective in combating of type -1 diabetes and its complications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We developed a Bayes factor based approach for the design of non-inferiority clinical trials with a focus on controlling type I error and power. Historical data are incorporated in the Bayesian design via the power prior discussed in Ibrahim and Chen (2000). The properties of the proposed method are examined in detail. An efficient simulation-based computational algorithm is developed to calculate the Bayes factor, type I error and power. The proposed methodology is applied to the design of a non-inferiority medical device clinical trial.

In this paper, we present a Weibull link (skewed) model for categorical response data arising from binomial as well as multinomial model. We show that, for such types of categorical data, the most commonly used models (logit, probit and complementary log-log) can be obtained as limiting cases. We further compare the proposed model with some other asymmetrical models. The Bayesian as well as frequentist estimation procedures for binomial and multinomial data responses are presented in detail. The analysis of two datasets to show the efficiency of the proposed model is performed., Competing Interests: The authors declare no conflict of interest.

Many modern statistical problems can be cast in the framework of multivariate regression, where the main task is to make statistical inference for a possibly sparse and low-rank coefficient matrix. The low-rank structure in the coefficient matrix is of intrinsic multivariate nature, which, when combined with sparsity, can further lift dimension reduction, conduct variable selection, and facilitate model interpretation. Using a Bayesian approach, we develop a unified sparse and low-rank multivariate regression method to both estimate the coefficient matrix and obtain its credible region for making inference. The newly developed sparse and low-rank prior for the coefficient matrix enables rank reduction, predictor selection and response selection simultaneously. We utilize the marginal likelihood to determine the regularization hyperparameter, so our method maximizes its posterior probability given the data. For theoretical aspect, the posterior consistency is established to discuss an asymptotic behavior of the proposed method. The efficacy of the proposed approach is demonstrated via simulation studies and a real application on yeast cell cycle data.