Targeting CERS6-AS1/FGFR1 axis as synthetic vulnerability to constrain stromal cells supported proliferation in Mantle cell lymphoma.

The interaction between stromal and tumor cells in tumor microenvironment is a crucial factor in Mantle cell lymphoma (MCL) progression and therapy resistance. We have identified a long non-coding RNA, CERS6-AS1, upregulated in MCL and associated with poor overall survival. CERS6-AS1 expression was elevated in primary MCL within stromal microenvironment and in a subset of MCL cells adhered to stromal layer. These stromal-adhered MCL-subsets exhibited cancer stem cell signatures than suspension counterparts. Mechanistically, we found that downregulating CERS6-AS1 in MCL reduced Fibroblast Growth Factor Receptor-1 (FGFR1), expression attributed to loss of its interaction with RNA-binding protein nucleolin. In addition, using in-silico approach, we have discovered a direct interaction between nucleolin and 5'UTR of FGFR1, thereby regulating FGFR1 transcript stability. We discovered a positive association of CERS6-AS1 with cancer stem cell signatures, and Wnt signaling. Building on these, we explored potential therapeutic strategies where combining nucleolin-targeting agent with FGFR1 inhibition significantly contributed to reversing cancer stem cell signatures and abrogated primary MCL cell growth on stromal layer. These findings provide mechanistic insights into regulatory network involving CERS6-AS1, nucleolin, and FGFR1 axis-associated crosstalk between tumor cells and stromal cell interaction and highlights therapeutic potential of targeting a non-coding RNA in MCL.

Evaluation of different regression models for detection of adulteration of mustard and canola oil with argemone oil using fluorescence spectroscopy coupled with chemometrics.

Mustard and canola oils are commonly used cooking oils in Asian countries such as India, Nepal, and Bangladesh, making them prone to adulteration. Argemone is a well-known adulterant of mustard oil, and its alkaloid sanguinarine has been linked with health conditions such as glaucoma and dropsy. Utilising a non-destructive spectroscopic method coupled with a chemometric approach can serve better for the detection of adulterants. This work aimed to evaluate the performance of various regression algorithms for the detection of argemone in mustard and canola oils. The spectral dataset was acquired from fluorescence spectrometer analysis of pure as well as adulterated mustard and canola oils with some local and commercial samples also. The prediction performance of the eight regression algorithms for the detection of adulterants was evaluated. Extreme gradient boosting regressor (XGBR), Category gradient boosting regressor (CBR), and Random Forest (RF) demonstrate potential for predicting adulteration levels in both oils with high R2 values.

Correlation of Serum Cancer Antigen-125 (CA-125) Levels with Severity of Pre-eclampsia.

Background: Pre-eclampsia is often associated with unfavourable feto-maternal outcomes. There is a lacuna in its pathophysiology, which emphasizes the need to research for tests, which can predict or correlate with the severity of pre-eclampsia. Cancer antigen-125 (CA-125) is a simple, readily available biomarker with evidence of its secretion at the choriodecidual unit and may have a possible role. This study compared serum CA-125 levels between normal pregnant and pre-eclamptic women and determined its clinical usefulness in correlating with the severity of pre-eclampsia. Methods: A case-control study was conducted enrolling 58 women with pre-eclampsia further divided into severe and non-severe groups and 62 gestational age-matched healthy, pregnant controls. Serum CA-125 levels were compared between the two groups. Results: The mean serum CA-125 in the controls was 16.44 ± 8.28 IU/ml, 13.82 ± 9.18 IU/ml in the non-severe and 23.55 ± 30.55 IU/ml in the severe pre-eclampsia group (p = 0.134). Serum CA-125 had a significant association with systolic blood pressure (SBP) p = 0.002), diastolic blood pressure (DBP) (p = 0.026), foetal growth restriction (p = 0.025), pre-term birth (p = 0.039) and a highly significant association with 24-h urinary protein, liver enzymes, placental abruption, need of maternal intensive care as well as with poor neonatal outcome including stillbirth and neonatal mortality (p < 0.001). Conclusion: Serum CA-125 levels were found to be higher in the severe pre-eclampsia group as compared to non-severe pre-eclampsia and normotensive group, but the difference was not statistically significant. More studies on a larger scale are required to prove the usefulness of this marker with respect to maternal and perinatal outcome as well as its association with pre-eclampsia and its severity.

Does leukocyte-platelet-rich fibrin (L-PRF) cause long term acceleration in the rate of canine retraction? A split-mouth, two-arm parallel group, randomized control trial

ABSTRACT Objective: The present study was conducted to investigate the effects of leukocyte-platelet-rich fibrin (L-PRF) on the rate of maxillary canine retraction for a period of 5 months. Methods: A split-mouth study was conducted on 16 subjects (9 males and 7 females; age range 17-25 years; mean age, 21.85±2.45 years) who required therapeutic extraction of bilateral maxillary first premolars. After the initial leveling and alignment, L-PRF plugs were placed in a randomly selected extraction socket (Experimental Group), and the other side served as a control (Control Group). Canine retraction was carried out by the activation of nickel-titanium (NiTi) closed-coil springs delivering 150 g of force. The rates of canine movement, canine rotation, tipping, root resorption, and molar movement were assessed at monthly intervals for five months (T0-T5). Pain, swelling and discomfort accompanying the procedure were assessed using a Likert scale. Results: The study revealed a significant increase in the rate of canine movement on the experimental side in the first two months, and significant molar anchorage loss was observed only in the first month for control side. There were no statistically significant differences between the groups regarding canine rotation, tipping, probing depth, root resorption, and pain perception. Conclusions: The use of L-PRF plugs in extraction sockets considerably enhanced the rate of canine movement only in the first two months, and long-term efficacy was not observed in this study.

RESUMO Objetivo: O presente estudo foi realizado para investigar os efeitos da fibrina rica em leucócitos e plaquetas (L-PRF) na taxa de retração do canino superior, durante um período de cinco meses. Métodos: Um estudo de boca dividida foi realizado em 16 indivíduos (9 homens e 7 mulheres; faixa etária de 17 a 25 anos; idade média de 21,85 ± 2,45 anos) que precisavam de extração terapêutica dos primeiros pré-molares superiores de ambos os lados. Após o nivelamento e o alinhamento iniciais, os plugs de L-PRF foram colocados em um alvéolo pós-extração, selecionado aleatoriamente (Grupo Experimental), e o outro lado serviu como controle (Grupo Controle). A retração do canino foi realizada pela ativação de molas fechadas de níquel-titânio (NiTi) com 150 g de força. As taxas de movimentação do canino, rotação, inclinação e reabsorção radicular do canino e movimentação do molar foram avaliadas em intervalos mensais durante cinco meses (T0-T5). A dor, o inchaço e o desconforto após o procedimento foram avaliados por meio de uma escala de Likert. Resultados: O estudo revelou um aumento significativo na taxa de movimentação do canino no lado experimental nos dois primeiros meses, e uma perda significativa de ancoragem do molar foi observada apenas no primeiro mês no lado controle. Não houve diferenças estatisticamente significativas entre os grupos, com relação à percepção da dor e rotação, inclinação, profundidade de sondagem e reabsorção radicular do canino. Conclusões: O uso de plugs de L-PRF em alvéolos pós-extração aumentou consideravelmente a taxa de movimentação do canino apenas nos dois primeiros meses, não sendo observada uma eficácia em longo prazo.