Clinical and biological significance of miR-23b and miR-193a in human hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common cancer of the liver with a very poor prognosis. The dysregulation of microRNAs (miRs) is indeed implicated in HCC onset and progression. In this study, we have evaluated the expression of miR-23b and miR-193a in a large cohort of 59 and 67 HCC patients, respectively. miR-23b and miR-193a resulted significantly down-regulated in primary HCCs compared to their matched peritumoral counterparts. Furthermore, patients with higher miR-193a expression exhibited longer OS and DFS, suggesting that miR-193a may be a molecular prognostic factor for HCC patients. Since the regulation of miRs by DNA methylation may occur in human cancers, we verified whether the down-modulation of miR-23b and miR-193a in HCC tissues could be related to DNA methylation. An inverse trend between miR-23b expression and DNA methylation was observed, indicating that miR-23b can be epigenetically regulated. By contrast, the down-regulation of miR-193a was not mediated by DNA methylation. To verify the potential role of miR-23b and miR-193a as responsive molecular targets in vitro, we used the inhibitor of DNA methylation 5-aza-dC to restore miR-23b expression level in combination with miR-193a transfection. The combined treatment led to a significant inhibition of cellular proliferation and migration. Taken together, our findings provide evidence that miR-23b and miR-193a may be molecular diagnostic and prognostic factors for HCC; furthermore, miR-23b and miR-193a are responsive molecular targets for limiting HCC cell aggressiveness in combination with the epigenetic drug 5-aza-dC. Moreover, our results provide new advances in the epigenetic regulation of these miRs in HCC

High Density Planting in Mango cv. Alphonso

A trial was conducted to optimize spacing for high density planting in mango cv. Alphonso to obtain higher yield/ unit area at the Agriculture Research Station, Mulde, during 2006-07 to 2008-09 with four close spacings and one normal spacing as control. Highest yield (6.4 MT/ha) was recorded with a spacing of 5 m x 5 m without reduction in fruit size in 10 year old plants compared to the mean yield of 1.12 MT/ha in 10m x 10m normal spacing. High density plantation helped to get significantly higher yield per unit area compared to the normal spacing, without affecting size and quality of mango fruits. The highest cost:benefit ratio (2.33) was recorded in high density plantation of 5m x 5m, with maximum net returns of Rs.1,12,000/- per hectare. The present findings show promise for more yield and returns per unit area during the initial years of mango plantation by adopting 5m x 5m high density planting

Comparative Performance of Mango Varieties Grafted on Vellaikolamban and Mixed Rootstock

Research on rootstock in mango is very limited in our country. Kalapady was reported to be a dwarfing rootstock. Recent trend among mango growers is to high density orcharding with dwarfening nature of the varietie. Efforts were made at Agriculture Research Station, Mulde, to study comparative performance of Ratna, Alphonso and Kesar mango on Vellaikolamban and mixed rootstock i.e., heterozygous seedling stock and the effect of rootstock on a scion under high density of 5m x 5m spacing. Results indicated that use of Vellaikolamban rootstock reduced plant volume in scion cv. Alphonso by 39.1%, followed by 24.9% in Ratna and 26.5% in cv. Kesar. As volume of the canopy was reduced, it directly influenced fruit yield cvs. Alphonso and Ratna. However, reduction in canopy volume had a positive influence on yield in cv. Kesar. Net returns of Rs.38,629/- per ha were maximum for Kesar with the rootstock Vellaikolamban

Evidence for tuning adipocytes ICER levels for obesity care.

Abnormal adipokine production, along with defective uptake and metabolism of glucose within adipocytes, contributes to insulin resistance and altered glucose homeostasis. Recent research has highlighted one of the mechanisms that accounts for impaired production of adiponectin (ADIPOQ) and adipocyte glucose uptake in obesity. In adipocytes of human obese subjects and mice fed with a high fat diet, the level of the inducible cAMP early repressor (ICER) is diminished. Reduction of ICER elevates the cAMP response element binding protein (CREB) activity, which in turn increases the repressor activating transcription factor 3. In fine, the cascade triggers reduction in the ADIPOQ and GLUT4 levels, which ultimately hampers insulin-mediated glucose uptake. The c-Jun N-terminal kinase (JNK) interacting-protein 1, also called islet brain 1 (IB1), is a target of CREB/ICER that promotes JNK-mediated insulin resistance in adipocytes. A rise in IB1 and c-Jun levels accompanies the drop of ICER in white adipose tissues of obese mice when compared with mice fed with a chow diet. Other than the expression of ADIPOQ and glucose transport, decline in ICER expression might impact insulin signaling. Impairment of ICER is a critical issue that will need major consideration in future therapeutic purposes

Adverse Events in Italian Nursing Homes During the COVID-19 Epidemic. A National Survey

Older people living in nursing homes (NHs) are particularly vulnerable in the ongoing COVID-19 pandemic, due to the high prevalence of chronic diseases and disabilities (e.g., dementia). The phenomenon of adverse events (AEs), intended as any harm or injury resulting from medical care or to the failure to provide care, has not yet been investigated in NHs during the pandemic. We performed a national survey on 3,292 NHs, either public or providing services both privately and within the national health system, out of the 3,417 NHs covering the whole Italian territory. An online questionnaire was addressed to the directors of each facility between March 24 and April 27, 2020. The list of NHs was provided by the Dementia Observatory, an online map of Italian services for people with dementia, which was one of the objectives of the implementation of the Italian National Dementia Plan. About 26% of residents in the Italian NHs for older people listed within the Dementia Observatory site had dementia. The objective of our study was to report the frequency of AEs that occurred during the months when SARS-CoV-2 spreading rate was at its highest in the Italian NHs and to identify which conditions and attributes were most associated with the occurrence of AEs by means of multivariate regression logistic analysis. Data are referred to 1,356 NHs that participated in the survey. The overall response rate was 41.2% over a time-period of six weeks (from March 24 to May 5). About one third of the facilities (444 out of 1,334) (33.3%) reported at least 1 adverse event, with a total of 2,000 events. Among the included NHs, having a bed capacity higher than the median of 60 beds (OR=1.57, CI95% 1.17–2.09; p=0.002), an observed increased in the use of psychiatric drugs (OR=1.80, CI95% 1.05–3.07; p=0.032), adopting physical restraint measures (OR=1.97, CI95% 1.47–2.64; p<0.001), residents hospitalized due to flu-like symptoms (OR =1.73, CI95% 1.28–2.32; p<0.001), and being located in specific geographic areas (OR=3.59, CI95% 1.81–7.08; OR = 2.90, CI95% 1.45–5.81 and OR = 4.02, CI05% 2.01–8.04 for, respectively, North-West, North-East and Centre vs South, p<0.001) were all factors positively associated to the occurrence of adverse events in the facility. Future recommendations for the management and care of residents in NHs during the COVID-19 pandemic should include specific statements for the most vulnerable populations, such as people with dementia

HYPOTHETICAL HUMAN IMMUNE GENOME COMPLEX GRADIENT MAY HELP TO EXPLAIN THE CONGENITAL ZIKA SYMDROME CATASTROPHE IN BRAZIL: A NEW THEORY

There are few data considering human genetics as an important risk factor for birth abnormalities related to ZIKV infection during pregnancy, even though sub-Saharan African populations are apparently more resistant to CZS as compared to populations in the Americas. We hypothesized that single nucleotide variants (SNVs), especially in innate immune genes, could make some populations more susceptible to Zika congenital complications than others. Differences in the SNV frequencies among continental populations provide great potential for Machine Learning techniques. We explored a key immune genomic gradient between individuals from Africa, Asia and Latin America, working with complex signatures, using 297 SNVs. We employed a two-step approach. In the first step, decision trees (DTs) were used to extract the most discriminating SNVs among populations. In the second step, machine learning algorithms were used to evaluate the quality of the SNV pool identified in step one for discriminating between individuals from sub-Saharan African and Latin-American populations. Our results suggest that 10 SNVs from 10 genes (CLEC4M, CD58, OAS2, CD80, VEPH1, CTLA4, CD274, CD209, PLAAT4, CREB3L1) were able to discriminate sub-Saharan Africans from Latin American populations using only immune genome data, with an accuracy close to 100%. Moreover, we found that these SNVs form a genome gradient across the three main continental populations. These SNVs are important elements of the innate immune system and in the response against viruses. Our data support the Human Immune Genome Complex Gradient hypothesis as a new theory that may help to explain the CZS catastrophe in Brazil