Kinetic Characterization and Partial Purification of Peroxidase in Eucalyptus F1 Hybrids

A differential pattern of peroxidase (E.C. 1.1.11.7) has been observed in reciprocal F1 hybrids of Eucalyptus (FRI-4 and FRI-5) produced using parental combination of E. tereticornis and E. camaldulensis. The hybrids were characterized for the qualitative, kinetic parameters (total and specific activity, units, Km and Vmax) and partial purification of peroxidase. The qualitative study showed the presence of high molecular weight peroxidase isoforms i.e. 260 KD, 250 KD and 110KD bands. A strong maternal inheritance was observed for 260 KD loci in FRI-5. Kinetic characterization of peroxidase revealed that F1 genotypes had efficient peroxidase system over their parental combination resulting in 8 -10 times more heterotic vigour. The FRI-5 genotypes were found to be having efficient peroxidase system with lowest Km values (0.12mM-0.17mM) and higher Vmax values ranging from 0.07-0.14mM min-1mg prot-1. The study revealed the role of maternal inheritance and was found that better genotypes are produced when superior parents are used as seed parent. The results suggest the efficient use of peroxidase marker for the identification of the better genotypes in forest tree species. &nbsp

Human T-cell lymphotropic virus (HTLV)-associated encephalopathy: an under-recognised cause of acute encephalitis? Case series and literature review

Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) is well described. Clinical features are predominantly consistent with cord pathology, though imaging and autopsy studies also demonstrate brain inflammation. In general, this is subclinical; however, six cases have previously been reported of encephalopathy in HTLV-1-infected patients, without alternative identified aetiology. We describe three further cases of encephalitis in the UK HAM cohort (n = 142), whereas the annual incidence of acute encephalitis in the general population is 0.07-12.6 per 100,000. Clinical features included reduced consciousness, fever/hypothermia, headaches, seizures, and focal neurology. Investigation showed: raised CSF protein; pleocytosis; raised CSF:peripheral blood mononuclear cell HTLV-1 proviral load ratio; and MRI either normal or showing white matter changes in brain and cord. Four of the six previous case reports of encephalopathy in HTLV-infected patients also had HAM. Histopathology, reported in three, showed perivascular predominantly CD8+ lymphocytic infiltrates in the brain. One had cerebral demyelination, and all had cord demyelination. We have reviewed the existing six cases in the literature, together with our three new cases. In all seven with HAM, the spastic paraparesis deteriorated sub-acutely preceding encephalitis. Eight of the nine were female, and four of the seven treated with steroids improved. We propose that HTLV-associated encephalopathy may be part of the spectrum of HTLV-1-induced central nervous system disease

Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer

The sesquiterpene lactones, Isodeoxyelephantopin (IDET) and Deoxyelephantopin (DET) are known to exhibit activities against some cancer types. The activities of these lactones against breast cancer and the molecular bases is not known. We examined the efficacy of lactones in breast cancer preclinical model. Although both lactones exhibited drug like properties, IDET was relatively effective in comparison to DET. IDET suppressed the proliferation of both invasive and non-invasive breast cancer cell lines. IDET also suppressed the colony formation and migration of breast cancer cells. The assays for Acridine Orange (AO)/Propidium Iodide (PI) staining, cell cycle distribution, phosphatidylserine externalization and DNA laddering suggested the apoptosis inducing potential of IDET. The treatment with IDET also induced an accumulation of cells in the sub-G1 and G2/M phases. The exposure of breast cancer cells to the lactone was associated with a depolarization in mitochondrial membrane potential, and cleavage of caspase and PARP. The lactone induced reactive oxygen species (ROS) generation in breast cancer cells. Further, the use of N-acetyl cysteine (NAC) suppressed IDET induced ROS generation and apoptosis. The NF-κB-p65 nuclear translocation induced by okadaic acid (OA) was suppressed by the sesquiterpene. IDET also suppressed the expression of NF-κB regulated tumorigenic proteins, and induced the expression of proapoptotic gene (Bax) in cancer cells. While the expression of oncogenic lncRNAs was suppressed, the tumor suppressor lncRNAs were induced by the sesquiterpene. Collectively, the modulation of multiple cell signaling molecules by IDET may contribute to its activities in breast cancer cells

Quantitative Determination and Source Variation of Rutin in Fagopyrum Tataricum

Buckwheat (Fagopyrum sp.) is a traditional crop of Uttarakhand (India) known for its high Rutin content, a bioflavonoid with significant medicinal properties. This study explores the quantitative measurement of Rutin in various buckwheat varieties grown in different regions of Uttarakhand using Thin Layer Chromatography (TLC) and High-Performance Thin Layer Chromatography (HPTLC). Twelve seed sources of Fagopyrum tataricum from the Garhwal and Kumaon regions, along with Fagopyrum esculentum seeds for comparison, were collected. Preliminary phytochemical screening of the extracts revealed the presence of flavonoids, alkaloids, tannins, and carbohydrates, with methanolic extracts showing higher concentrations. TLC analysis was employed to determine the most effective solvent system for Rutin separation, leading to the identification of three samples with substantial Rutin content. HPTLC was then used for quantitative Rutin assessment, with a calibration curve established using standard Rutin solutions. The three selected samples, along with the standard, were applied to HPTLC plates, and the Rutin content was measured based on peak areas and peak heights. The sample collected from Joshimath, Uttarakhand, known as "JOG," exhibited the highest Rutin content. This study provides valuable insights into the phytochemical composition of buckwheat varieties in Uttarakhand, which can inform the development of high-quality functional foods. Rutin, a potent antioxidant with various health benefits, underscores the significance of buckwheat as a naturally occurring functional food source. The results contribute to understanding the Rutin-rich potential of buckwheat grown in Uttarakhand and its applications in functional foods and nutraceuticals. Further research in this field can promote the cultivation and utilization of buckwheat as a source of this valuable bioactive compound with numerous health benefits

Phytochemical Analysis And Evaluation Of Antioxidant Activity In Fagopyrum Esculentum

Herbal nutraceutical products have become increasingly popular in recent years, particularly in the dermatology and cosmetics fields, because of their potential to prevent skin photodamage and their photoprotective qualities against UV radiation. Standardized herbal extracts are necessary for modern phytopharmaceutics and phytocosmetics, and buckwheat herb, which is high in flavonoids, has shown promise as an antioxidant source. The objective of the research is to ascertain the existence of various nutraceutical components in buckwheat, such as proteins, carbohydrates, sterols, alkaloids, saponins, and tannins, both quantitatively and qualitatively. The study assesses possible interactions between these components, food, and prescribed medications as the body of research on their health benefits grows. Through a variety of phytochemical tests, the results show the high antioxidant and nutraceutical qualities of Fagopyrum esculentum, with methanolic extracts showing greater activity than water extracts. Notably, the study highlights the high antioxidant activity, alkaloids, flavonoids, tannins, and phenolic compounds of F. esculentum as potential major food supplement. This study offers a biochemical justification for its application in ethnopharmacology and as a nutraceutical to improve health and prevent a variety of ailment

Molecular Docking of Known Carcinogen 4- (Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with Cyclin Dependent Kinases towards Its Potential Role in Cell Cycle Perturbation

Cell cycle is maintained almost all the times and is controlled by various regulatory proteins and their complexes (Cdk+Cyclin) in different phases of interphase (G1, S and G2) and mitosis of cell cycle. A number of mechanisms have been proposed for the initiation and progression of carcinogenesis by abruption in cell cycle process. One of the important features of cancer/carcinogenesis is functional loss of these cell cycle regulatory proteins particularly in CDKs and cyclins. We hypothesize that there is a direct involvement of these cell cycle regulatory proteins not only at the genetic level but also proteins level, during the initiation of carcinogenesis. Therefore, it becomes significant to determine inconsistency in the functioning of regulatory proteins due to interaction with carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Hence, we investigated the interaction efficiency of NNK, against cell cycle regulatory proteins. We found a different value of ΔG (free energy of binding) among the studied proteins ranging between -3.29 to -7.25 kcal/mol was observed. To validate the results, we considered Human Oxy-Hemoglobin at 1.25 Å Resolution, [PDB_ID:1HHO] as a +ve control, (binding energy -6.06 kcal/mol). Finally, the CDK8 (PDB_ID:3RGF) and CDK2 (PDB_ID:3DDP) regulatory proteins showing significantly strong molecular interaction with NNK -7.25 kcal/mol, -6.19 kcal/mol respectively were analyzed in details. In this study we predicted that CDK8 protein fails to form functional complex with its complementary partner cyclin C in presence of NNK. Consequently, inconsistency of functioning in regulatory proteins might lead to the abruption in cell cycle progression; contribute to the loss of cell cycle control and subsequently increasing the possibility of carcinogenesis

Nanotechnology Synergised Immunoengineering for Cancer

Novel strategies modulating the immune system yielded enhanced anticancer responses and improved cancer survival. Nevertheless, the success rate of immunotherapy in cancer treatment has been below expectation(s) due to unpredictable efficacy and off-target effects from systemic dosing of immunotherapeutic. As a result, there is an unmet clinical need for improving conventional immunotherapy. Nanotechnology offers several new strategies, multimodality, and multiplex biological targeting advantage to overcome many of these challenges. These efforts enable programming the pharmacodynamics, pharmacokinetics, delivery of immunomodulatory agents/co-delivery of compounds to prime at the tumor sites for improved therapeutic benefits. This review provides an overview of the design and clinical principles of biomaterials driven nanotechnology and their potential use in personalized nanomedicines, vaccines, localized tumor modulation, and delivery strategies for cancer immunotherapy. In this review, we also summarize the latest highlights and recent advances in combinatorial therapies avail in the treatment of cold and complicated tumors. It also presents key steps and parameters implemented for clinical success. Finally, we analyse, discuss, and provide clinical perspectives on the integrated opportunities of nanotechnology and immunology to achieve synergistic and durable responses in cancer treatment

Burden of SARS-CoV-2 infection in healthcare workers during second wave in England and impact of vaccines : prospective multicentre cohort study (SIREN) and mathematical model

Funding: The study is funded by the Department of Health and Social Care (DHSC) and UK Health Security Agency (UKHSA; formally Public Health England), with contributions from the governments of Northern Ireland, Scotland, and Wales. Funding was also provided by the National Institute for Health Research (NIHR) as an Urgent Public Health Priority Study and through the Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (NIHR200915), a partnership between UKHSA and the University of Oxford.OBJECTIVE: To describe the incidence of, risk factors for, and impact of vaccines on primary SARS-CoV-2 infection during the second wave of the covid-19 pandemic in susceptible hospital healthcare workers in England. DESIGN: Multicentre prospective cohort study. SETTING: National Health Service secondary care health organisations (trusts) in England between 1 September 2020 and 30 April 2021. PARTICIPANTS: Clinical, support, and administrative staff enrolled in the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study with no evidence of previous infection. Vaccination status was obtained from national covid-19 vaccination registries and self-reported. MAIN OUTCOME MEASURE: SARS-CoV-2 infection confirmed by polymerase chain reaction. Mixed effects logistic regression was conducted to determine demographic and occupational risk factors for infection, and an individual based mathematical model was used to predict how large the burden could have been if vaccines had not been available from 8 December 2020 . RESULTS: During England's second wave, 12.9% (2353/18 284) of susceptible SIREN participants became infected with SARS-CoV-2. Infections peaked in late December 2020 and decreased from January 2021, concurrent with the cohort's rapid vaccination coverage and a national lockdown. In multivariable analysis, factors increasing the likelihood of infection in the second wave were being under 25 years old (20.3% (132/651); adjusted odds ratio 1.35, 95% confidence interval 1.07 to 1.69), living in a large household (15.8% (282/1781); 1.54, 1.23 to 1.94, for participants from households of five or more people), having frequent exposure to patients with covid-19 (19.2% (723/3762); 1.79, 1.56 to 2.06, for participants with exposure every shift), working in an emergency department or inpatient ward setting (20.8% (386/1855); 1.76, 1.45 to 2.14), and being a healthcare assistant (18.1% (267/1479); 1.43, 1.16 to 1.77). Time to first vaccination emerged as being strongly associated with infection (P<0.001), with each additional day multiplying a participant's adjusted odds ratio by 1.02. Mathematical model simulations indicated that an additional 9.9% of all patient facing hospital healthcare workers would have been infected were it not for the rapid vaccination coverage. CONCLUSIONS: The rapid covid-19 vaccine rollout from December 2020 averted infection in a large proportion of hospital healthcare workers in England: without vaccines, second wave infections could have been 69% higher. With booster vaccinations being needed for adequate protection from the omicron variant, and perhaps the need for further boosters for future variants, ensuring equitable delivery to healthcare workers is essential. The findings also highlight occupational risk factors that persisted in healthcare workers despite vaccine rollout; a greater understanding of the transmission dynamics responsible for these is needed to help to optimise the infection prevention and control policies that protect healthcare workers from infection and therefore to support staffing levels and maintain healthcare provision. TRIAL REGISTRATION: ISRCTN registry ISRCTN11041050.Publisher PDFPeer reviewe

SEASONAL COMPARISON OF ERA-INTERIM PRECIPITATION DATASET FOR ENTIRE INDIAN REGION

Era-Interim (ECMWF Re- analysis) is a global reanalysis atmospheric product which is being continuously updated in real time since 1979. It is also termed as third generation reanalysis product. The Era–Interim gives meteorological products like precipitation, temperature, etc. In the present work, 3-hourly Era–Interim product for the entire India is compared with gridded data provided by IMD for period 1979&ndash;2013 and APHRODITE data for period 1979&ndash;2007, respectively. The comparison is done on seasonal basis and the seasons are taken based on the pattern of rainfall, hence, the four seasons selected are DJF (December, January & February), MAM (March, April & May), JJAS (June, July, August & September) and ON (October & November). In the methodology the Era-Interim 3-hourly products are converted into the daily products and then it is used to form seasonal images for each year. All the images are then taken to form four images as outcome for the entire study period which represents the average rainfall (mm/day) for the entire region. This is being done for the IMD and for the APHRODITE Data. All the four images are then taken for the comparison with the reference images of the IMD 0.5º&thinsp;&times;&thinsp;0.5º gridded rainfall data and with the APHRODITE 0.5º&thinsp;&times;&thinsp;0.5º gridded rainfall data. The correlation coefficient and the RMSE for each season is calculated. The mean value is compared with the mean of IMD and APHRODITE rainfall products, respectively and a bias in mean is also calculated along with the scatter plots of Era-Interim with the reference datasets. The Era &ndash; Interim data came out with suitable comparative parameters with high correlation coefficient and low RMSE value in certain regions and in specific seasons. Scatter plots have also given good correlation in all the seasons. Bias maps have also shown very less bias in specific seasons for certain regions. The suitability maps prepared for the study region also shows that most of the region lies in most suitable range and very less in unsuitable range