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Background and Aim: Rheumatoid arthritis (RA) is a prevalent and debilitating disease that affects the joints. The study was intended to evaluate the anti-arthritic activity of aerial parts of Heliotropium zeylanicum (EEHZ). EEHZ constituting phytoconstituents to treat adjuvant induced arthritic rats to minimize the side effects. Materials and Methods: The anti-arthritic activity study was carried out by using adjuvant induced model of Wistar albino strain rats. EEHZ was injected at different doses such as 100 and 300 mg/kg/i.p., and the study was compared with standard drug dexamethazone (5 g/kg). The results obtained from the above methods were subjected to statistical analysis. Results: The study was conducted various hematological parameters and histopathological sections were carried out. The plant has various phytoconstituents such as reducing sugars, saponins, starch, steroids and terpenoids. Significantly one among those phytoconstituent lessens to oedema and arthritis of the rodents. The EEHZ showed the maximum inhibitory activity at (300 mg/kg/i.p.) by dose dependent manner. These inhibitions were statistically significant (P < 0.01-0.001). Conclusion: From these results indicate that EEHZ is a bioactive agent and having significant results in anti-inflammatory and anti-arthritic action by inhibition of the exudation, and leukocytes recruitment into the inflamed tissues and bone regeneration calcium deposition.

The main aims in the development of a novel drug delivery vehicle is to efficiently carry therapeutic drugs in the body’s circulatory system and successfully deliver them to the targeted site as needed to safely achieve the desired therapeutic effect. In the present study, a passive targeted functionalised nanocarrier was fabricated or wrapped the hollow mesoporous silica nanoparticles with 3-aminopropyl triethoxysilane (APTES) to prepare APTES-coated hollow mesoporous silica nanoparticles (HMSNAP). A nitrogen sorption analysis confirmed that the shape of hysteresis loops is altered, and subsequently the pore volume and pore diameters of GaC-HMSNAP was reduced by around 56 and 37%, respectively, when compared with HMSNAP. The physico-chemical characterisation studies of fabricated HMSNAP, Ga-HMSNAP and GaC-HMSNAP have confirmed their stability. The drug release capacity of the fabricated Ga-HMSNAP and GaC-HMSNAP for delivery of gallium and curcumin was evaluated in the phosphate buffered saline (pH 3.0, 6.0 and 7.4). In an in silico molecular docking study of the gallium-curcumin complex in PDI, calnexin, HSP60, PDK, caspase 9, Akt1 and PTEN were found to be strong binding. In vitro antitumor activity of both Ga-HMSNAP and GaC-HMSNAP treated MCF-7 cells was investigated in a dose and time-dependent manner. The IC50 values of GaC-HMSNAP (25 µM) were significantly reduced when compared with free gallium concentration (40 µM). The mechanism of gallium-mediated apoptosis was analyzed through western blotting and GaC-HMSNAP has increased caspases 9, 6, cleaved caspase 6, PARP, and GSK 3β(S9) in MCF-7 cells. Similarly, GaC-HMSNAP is reduced mitochondrial proteins such as prohibitin1, HSP60, and SOD1. The phosphorylation of oncogenic proteins such as Akt (S473), c-Raf (S249) PDK1 (S241) and induced cell death in MCF-7 cells. Furthermore, the findings revealed that Ga-HMSNAP and GaC-HMSNAP provide a controlled release of loaded gallium, curcumin and their complex. Altogether, our results depicted that GaC-HMNSAP induced cell death through the mitochondrial intrinsic cell death pathway, which could lead to novel therapeutic strategies for breast adenocarcinoma therapy.

An analysis is made of 223 cases of mammography seen in the Outram Road General Hospital, Singapore, from October 1967 to May 1971. All cases had histological confirmation., There were 90 (40-36%) cases of carcinoma. The mammographic diagnosis, when combined with clinical examination, was 93% correct. The diagnosis based on the reading of mammograms alone was 71 % correct. Calcification in carcinoma occurred in 27% of cases, but only 11 % showed fine sand-like calcifications. The skin was thickened in 22% of cases., There were 56 cases (25-11%) of fibroadenoma. The accuracy of mammography taken in conjunction with clinical findings was 32%; mammography alone gave a 30% accuracy. Calcification was seen in 11 % of cases., Forty cases (17-94%) of mammary dysplasia were seen. Mammography in association with clinical examination was 32% correct; mammography alone was 30% correct. Thus the accuracy rates for both fibroadenoma and for mammary dysplasia were much lower than for carcinoma., An assortment of other non-malignant conditions numbered 37 cases (16-59%). The accuracy rate was the lowest for this group, coming to 16% when mammography was combined with clinical examination, and only 8% when mammograms alone were read., Approximately 20% of all non-malignant conditions were incorrectly interpreted as carcinoma from mammograms., Mammography is found to be a useful procedure in the detection of cancer of the breast in Asian women. Unpublished data from the Singapore Cancer Registry shows that cancer of the breast is the commonest malignant tumour in the female. It is therefore anticipated that mammography will be increasingly employed in the developing countries of South-East Asia in the years to come. [ABSTRACT FROM AUTHOR]

Dually targeting the epigenetic proteins lysine specific demethylase 1 (LSD1) and histone deacetylases (HDACs) that play a key role in cancer cells by modulating gene repressor complexes including CoREST will have a profound effect in inhibiting tumour growth. Here, we evaluated JBI-097 a dual LSD1/HDAC6 inhibitor, for its in vitro and in vivo activities in various tumor models. In vitro, JBI-097 showed a strong potency in inhibiting LSD1 and HDAC6 enzymatic activities with the isoform selectivity over other HDACs. Cell-based experiments demonstrated a superior anti-proliferative profile against haematological and solid tumor cell lines. JBI-097 also showed strong modulation of HDAC6 and LSD1 specific biomarkers, alpha-tubulin, CD86, CD11b, and GFi1b. In vivo, JBI-097 showed a stronger effect in erythroleukemia, multiple myeloma xenograft models, and in CT-26 syngeneic model. JBI-097 also showed efficacy as monotherapy and additive or synergistic efficacy in combination with the standard of care or with immune checkpoint inhibitors. These and other findings suggest that JBI-097 could be a promising molecule for targeting the LSD1 and HDAC6. Further studies are warranted to elucidate the mechanism of action., Competing Interests: D.S, C.G, NS.M, Z.M, S.R are employees of Jubilant Therapeutics India Ltd. SJ. T, P.D, M.H, S.N, K.V, B.N are employees of Jubilant Biosys Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Gajendran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lysine specific demethylase 1 (LSD1) and HDAC6 are epigenetic proteins associated with several diseases, including cancer and combined inhibition of these proteins could be highly beneficial in treating some cancers such as AML, MM and solid tumors. Multiple myeloma (MM) is a challenging cancer with fast relapse rate where novel treatment options are the need of the hour. We have designed and developed novel, LSD1 and HDAC6 selective dual inhibitors to target MM. Our dual inhibitor compound 1 shows superior potency in multiple MM cell lines. In MM.1S xenograft model compound 1 shows superior efficacy compared to single agent LSD1 and HDAC6 inhibitors by oral administration and is well tolerated. Further evaluation of the molecule in other cancers is in progress., (Copyright © 2020 Elsevier Ltd. All rights reserved.)