DEN+2-AAF-induced multistep hepatotumorigenesis in Wistar rats: supportive evidence and insights

Diethylnitrosamine (DEN), found in many commonly consumed foods, has been reported to induce cancers in animals and humans. Several models have been developed to study multistage carcinogenesis in rat liver; these include the Solt–Farber-resistant hepatocyte model. In the Solt–Farber model, the initiation consists of either a necrogenic dose of a hepatocarcinogen or a non-necrogenic dose in conjunction with partial hepatectomy (PH). We report a novel protocol for tumor induction in liver which eliminates the need for PH. Male Wistar rats were injected with single i.p. dose of DEN (200 mg/kg body weight), controls received saline only. After 1 week of recovery, the DEN-treated animals were administered with the repeated doses of 2-acetyamino fluorine (150 mg/kg body weight) orally in 1 % carboxymethyl cellulose that served as promoting agent. Thirty days after the DEN administration, hepatocellular damage was observed as evident by histopathological analysis. The marker enzyme analysis showed elevated levels of serum AST, ALT, and alkaline phosphatase and a decrease in the levels of liver superoxide dismutase and catalase. The oxidative stress in liver was confirmed by elevated levels of lipid peroxidation and a decrease in antioxidant parameters.     

Phenolics Impart Au3+-Stress Tolerance to Cowpea by Generating Nanoparticles

While evaluating impact of Au nanoparticles on seed germination and early seedling growth of cowpea, HAuCl₄ was used as control. Seedlings of cowpea raised in HAuCl₄, even at concentration as high as 1 mM, did not show any suppression in growth. Accordingly, Au³⁺, despite being a heavy metal, did not alter levels of stress markers (viz. proline and malondialdehyde) in cowpea. Interestingly, cowpea turned clear pale yellow HAuCl₄ solutions colloidal purple during the course of seed germination and seedling growth. These purple colloidal suspensions showed Au-nanoparticle specific surface plasmon resonance band in absorption spectra. Transmission electron microscopic and powder X-ray diffraction investigations confirmed presence of crystalline Au-nanoparticles in these purple suspensions. Each germinating seed of cowpea released ∼35 nmoles of GAE of phenolics and since phenolics promote generation of Au-nanoparticles, which are less/non toxic compared to Au³⁺, it was contemplated that potential of cowpea to withstand Au³⁺ is linked to phenolics. Of the different components of germinating seed of cowpea tested, seed coat possessed immense power to generate Au-nanoparticles, as it was the key source of phenolics. To establish role of phenolics in generation of Au-nanoparticles (i) seed coat and (ii) the incubation medium in which phenolics were released by germinating seeds, were tested for their efficacy to generate Au-nanoparticles. Interestingly, incubation of either of these components with Au³⁺ triggered increase in generation of Au-nanoparticles with concomitant decrease in phenolics. Accordingly, with increase in concentration of Au³⁺, a proportionate increase in generation of Au-nanoparticles and decrease in phenolics was recorded. In summary, our findings clearly established that cowpea possessed potential to withstand Au³⁺-stress as the phenolics released by seed coat of germinating seeds possess potential to reduce toxic Au³⁺ to form non/less toxic Au-nanoparticles. Our investigations also pave a novel, simple, green and economically viable protocol for generation of Au-nanoparticles.     

Infiltrating micropapillary carcinoma of the breast. Cytologic findings

OBJECTIVE: To examine the cytologic features of infiltrating micropapillary carcinoma (IMPC). METHODS: Using the histopathology files of one of the authors (I.J.B.), we retrospectively identified 20 IMPC cases (pure, 12; partial micropapillary carcinoma differentiation, 8) with corresponding cytology. We evaluated the cases for cellularity, atypia, architecture and background. RESULTS: All cases were diagnostic of malignancy, characterized by atypical cells present predominantly in three-dimensional clusters and single cells, facilitating the diagnosis. The clusters had cell ball and papillarylike arrangements, like the morular growth pattern seen on histopathology. Apocrine cytology was present in 12 cases, focal mucin background in 5 and psamomma bodies in 2. The differential diagnosis includes primary papillary neoplasms of the breast, metastatic ovarian papillary serous carcinoma, apocrine and colloid carcinoma of the breast, and intraductal carcinoma (micropapillary type). CONCLUSION: As in histopathology, the cytologic features of IMPC are unique and should be recognized due to its aggressive behavior.     

High Level Activity of Recombinant Lysostaphin After Computer Simulation and Additive-Based Refolding

International Journal of Peptide Research and Therapeutics - Lysostaphin is a peptidoglycan hydrolase, produced by Staphylococcus simulans, which has illustrated significant bactericidal activities...     

Measuring biological aging in humans: A quest

The global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of well‐established clinical guidelines. Physicians are often forced to engage in cycles of “trial and error” that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are “aging faster” to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine.     

Protective effect of Nasturtium officinale R. Br and quercetin against cyclophosphamide-induced hepatotoxicity in rats

Molecular Biology Reports - Cyclophosphamide (CPA) is used in the management of autoimmune conditions and malignant illnesses. However, its therapeutic use is limited because of its severe side...     

Evaluating the bone regeneration in calvarial defect using osteoblasts differentiated from adipose-derived mesenchymal stem cells on three different scaffolds: an animal study

The aim of this study was to investigate the effect of three different scaffolds on the viability and differentiation of adipose-derived mesenchymal stem cells (ADMSCs) to osteoblast for bone regeneration of calvarial defect in rabbit model. Adipose was harvested from the nape of 12 rabbits by direct surgery or hollow-tip cannula. Two standardized circular calvarial defects (case and control), 8 mm in diameter each, were created in all the animals. The animals were divided into 3 different groups. In group 1 (G1), the defect was filled with polyamide + ADMSC. In group 2, poly lactic-co-glycolic acid + ADMSC was used. In group 3, decellularized amniotic membrane + ADMSC was applied. In the control defect, the non-seeded scaffolds were applied for filling the defect. Decellularized pericardial scaffolds were used as a membrane on the scaffolds. The animals were euthanized 2, 4, and 8 weeks of operation and new bone formation was assessed by different analyses. Immunohistochemical (IHC) staining with osteopontin and osteocalcin antibodies was also performed. After 2 weeks of wound healing, minimal bone regeneration was detected in all groups. Almost complete defect closure was observed in all experimental groups after 8 weeks of operation, with the greatest defect closure in the animals treated with polyamide scaffolds as compared to biopsies obtained from control defects and other experimental groups. The maximal tensile load was higher in G1, 4 and 8 weeks postoperatively, suggesting the usefulness of polyamide + ADMSC for bone regeneration in calvarial defects. Results of the IHC staining demonstrated a significant difference between seeded and non-seeded scaffold in both short- and long-term follow-ups (P < 0.05). In addition, a significant difference was observed in enhancement of IHC staining of both markers in polyamide group (seeded or non-seeded) 4 and 8 weeks postoperatively in comparison with other scaffolds. It was concluded that bone regeneration in critical calvarial defect was more successful in seeded polyamide.     

Outcomes of deliveries by family physicians or obstetricians: a population-based cohort study using an instrumental variable

Background:

Previous research has suggested that obstetric outcomes are similar for deliveries by family physicians and obstetricians, but many of these studies were small, and none of them adjusted for unmeasured selection bias. We compared obstetric outcomes between these provider types using an econometric method designed to adjust for unobserved confounding.

Methods:

We performed a retrospective population-based cohort study of all Canadian (except Quebec) hospital births with delivery by family physicians and obstetricians at more than 20 weeks gestational age, with birth weight greater than 500 g, between Apr. 1, 2006, and Mar. 31, 2009. The primary outcomes were the relative risks of in-hospital perinatal death and a composite of maternal mortality and major morbidity assessed with multivariable logistic regression and instrumental variable–adjusted multivariable regression.

Results:

After exclusions, there were 3600 perinatal deaths and 14 394 cases of maternal morbidity among 799 823 infants and 793 053 mothers at 390 hospitals. For deliveries by family physicians v. obstetricians, the relative risk of perinatal mortality was 0.98 (95% confidence interval [CI] 0.85–1.14) and of maternal morbidity was 0.81 (95% CI 0.70–0.94) according to logistic regression. The respective relative risks were 0.97 (95% CI 0.58–1.64) and 1.13 (95% CI 0.65–1.95) according to instrumental variable methods.

Interpretation:

After adjusting for both observed and unobserved confounders, we found a similar risk of perinatal mortality and adverse maternal outcome for obstetric deliveries by family physicians and obstetricians. Whether there are differences between these groups for other outcomes remains to be seen.Over the past several decades in Canada, obstetric deliveries have increasingly been attended by specialist obstetricians rather than family physicians.¹ Although specialized care is beneficial for high-risk mothers and their infants,^2–4 there are concerns that it might increase risk for women whose deliveries could be safely managed without a specialized approach. Most prior studies have concluded that obstetric outcomes between family physicians and obstetricians are similar, but many of these studies were small, and none of them adjusted for unmeasured factors that might affect both the choice of delivery provider and outcomes.^5–8Obstetric risk is typically divided between providers, with family physicians and obstetricians sharing the lowest-risk patients, obstetricians caring for moderate-risk patients, and sub-specialized perinatologists caring for the highest-risk individuals. Although traditional statistical methods can be used to adjust for observed differences between these groups, they cannot be used to adjust for unobserved differences. For example, the presence of gestational diabetes mellitus is usually noted, but its severity is often not coded in administrative databases. Women with mild diabetes mellitus are usually eligible for delivery by family physicians, but those with severe diabetes (and the attendant increased risk of adverse outcome) are not. There are many prominent examples where traditional analyses of observational data produced results that were subsequently refuted by randomized trials, presumably because of these unmeasured or unknown factors that also affect treatment decisions or outcomes.^4,9–11The instrumental variable method from the field of econometrics is a technique designed to control for unmeasured covariates in regression analyses. Results from instrumental variable–controlled observational analyses of the effect of angiography after myocardial infarction⁹ and of long-acting bronchodilators on asthma control¹² closely approximated those of randomized controlled trials, whereas analyses using traditional statistical methods differed substantially. Instrumental variable analyses of obstetric data have shown that traditional statistical approaches significantly underestimate the mortality benefit of high-volume hospitals for high-risk neonates.⁴ The objective of the current study was to compare perinatal mortality and maternal morbidity and mortality for deliveries by family physicians and obstetricians using instrumental variable methodology.     

Impact of Rice Husk Biochar on Drought Stress Tolerance in Perennial Ryegrass (Lolium perenne L.)

Journal of Plant Growth Regulation - In a water shortage crisis, the landscape management of perennial ryegrass, a common lawn grass, is a major challenge. An organic material that can help to...     

Nitric oxide generation from heme/copper assembly mediated nitrite reductase activity

Nitric oxide (NO) as a cellular signaling molecule and vasodilator regulates a range of physiological and pathological processes. Nitrite (NO₂ ^?) is recycled in vivo to generate nitric oxide, particularly in physiologic hypoxia and ischemia. The cytochrome c oxidase binuclear heme a ₃/Cu_B active site is one entity known to be responsible for conversion of cellular nitrite to nitric oxide. We recently reported that a partially reduced heme/copper assembly reduces nitrite ion, producing nitric oxide; the heme serves as the reductant and the cupric ion provides a Lewis acid interaction with nitrite, facilitating nitrite (N–O) bond cleavage (Hematian et al., J. Am. Chem. Soc. 134:18912–18915, 2012). To further investigate this nitrite reductase chemistry, copper(II)–nitrito complexes with tridentate and tetradentate ligands were used in this study, where either O,O′-bidentate or O-unidentate modes of nitrite binding to the cupric center are present. To study the role of the reducing ability of the ferrous heme center, two different tetraarylporphyrinate–iron(II) complexes, one with electron-donating para-methoxy peripheral substituents and the other with electron-withdrawing 2,6-difluorophenyl substituents, were used. The results show that differing modes of nitrite coordination to the copper(II) ion lead to differing kinetic behavior. Here, also, the ferrous heme is in all cases the source of the reducing equivalent required to convert nitrite to nitric oxide, but the reduction ability of the heme center does not play a key role in the observed overall reaction rate. On the basis of our observations, reaction mechanisms are proposed and discussed in terms of heme/copper heterobinuclear structures.