Functional Significance of miR-4693-5p in Targeting HIF1α and Its Link to Rheumatoid Arthritis Pathogenesis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes joint inflammation and destruction with an unknown origin. Our study aims to elucidate the molecular mechanism behind HIF1α overexpression in RA. Dysregulated miRNA expressions are known to influence gene behavior, thereby enhancing cell proliferation, inflammation, and resistance to apoptosis, contributing to RA development. Our earlier finding indicated that exogenous miRNA similar to miR-4693-5p may modulate RA-related targets. However, the specific role of miR-4693-5p and its targets in RA remain unexplored. In this study, we found that miR-4693-5p was significantly reduced in PBMCs of RA patients, with evidence suggesting it targets the 3' UTR of HIF1α, thereby potentially contributing to its overexpression in RA. In vitro overexpression of miR-4693-5p leads to the knockdown of HIF1α, resulting in inhibited expression of Survivin to disrupt apoptosis resistance, inflammation suppression, and a reduction in the total cellular ROS response in SW982 and RAFLS cells. The results were validated using the CIA Rat model. In conclusion, this study provides a crucial foundation for understanding the functional role of miR-4693-5p. These findings improve our understanding and provide novel insights into the molecular mechanisms underlying RA pathogenesis.

Antitumor Activity of Choerospondias axillaris Fruit Extract by Regulating the Expression of SNCAIP and SNCA on MDA-MB-231 Cells.

OBJECTIVE: Cancer is a huge problem of disease globally. Today, the percentage of people die from cancer is more than a combination of various diseases. In females, most common types of malignancies that occur are breast and cervical. The present focus has been shifted on medicinal plants as a form of therapy and there is a constant need to identify new therapeutic agents. Choerospondias axillaris (C. axillaris), an underutilized fruit, has been used in the remedy of various diseases. In the present communication, we evaluated the molecular mechanism of C. axillaris methanol extract in regulating cell death in human breast cancer cells (MDA-MB-231). METHODS: Methanol extract of C. axillaris was prepared and compounds were screened by Gas chromatography-mass spectrometry. The effect of fruit extract was determined on MDA-MB-231 cells by MTT ((3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and to analyse the molecular mechanism of human breast cancer cells after treating with fruit extract, protein profiling study was performed by two-dimensional gel electrophoresis. RESULTS: A total 9 differentially expressed proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS/MS) analysis. Among 9 identified proteins, synphilin-1 protein was found to be significantly downregulated, validated by western blot and RT-qPCR analysis. Possible interacting partners of synphilin-1 (SNCAIP) were analyzed for their possible role in cancer by the in-silico method. CONCLUSION: Our data implicate that the presence of bioactive compound(s) in C. axillaris fruits might play an important role in inhibiting the proliferation of breast carcinoma cells and Synphilin-1 protein may play a role of apoptotic function.

Estrogen-mediated differential protein regulation and signal transduction in rheumatoid arthritis.

Exploration of the dual and opposing facets of estrogen necessitates a clear understanding to diminish the controversy of estrogen regulation in averting the systemic, autoimmune, joint degrading disorder, and rheumatoid arthritis (RA). Experimental evidences consider estrogen as a pivotal enzyme to modulate the disease progression via managing several cellular mechanisms targeting inflammatory markers such as TNF, ILs, nuclear factor kappa B, and other regulatory proteins like matrix metalloproteinases impeding joint erosion and cartilage degradation. Estrogen modulates cellular signaling associated with inflammation, oxidative stress, related cardiovascular risk, and miRNA regulation during RA progression. Studies determining estrogen regulation in RA complicate the resemblance of the outcome as they represent both hyper and hypo level of estrogen is linked to the disease. Although some reports deliver estrogen as malign, there is now increasing evidence of rendering protection dose dependently. Variation in estrogen level causes differential expression of certain proteins and their related signaling which is directly or indirectly linked to RA pathogenesis. This review summarizes the variations in protein expression levels by focusing on the in vitro, in vivo,and clinical studies of estrogen deficiency and treatment. Construction of protein-protein interaction network, GO, and KEGG pathway enrichment analysis of the differentially expressed proteins assist in hypothesizing a potential molecular mechanism of estrogen in RA via in silico studies. Targeting these differential proteins can emerge a new path for developing advanced therapeutic strategies.

Evaluation of Anti-inflammatory Effects of Choerospondias axillaris Fruit's Methanolic Extract in Synoviocytes and CIA Rat Model.

BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune, systemic disease mainly affecting joints. Presently, there is no specific treatment/ drug available for curing RA except few supportive medicines. Therefore, the focus has been shifted to medicinal plants for the treatment of such diseases. Choerospondias axillaris commonly known as Lupsi/Lapsi and has been reported to have several properties for the treatment of various diseases. OBJECTIVE: The present study has been conducted to explore the anti-inflammatory effects of Choerospondias axillaris fruit extract on Synoviocytes (FLS) and Collagen-Induced Arthritis (CIA) rat model. METHODS: Methanolic extract of the Choerospondias axillaris fruit was used for determining phytochemical, antioxidant and anti-inflammatory properties. Antioxidant activity of Choerospondias axillaris fruit was determined by free radicals scavenging assays and bioactive compounds were identified via LC-MS/MS analysis. Anti-inflammatory effect was investigated in RA and Osteo Arthritis (OA) primary cells and also in Collagen Induced Arthritis (CIA) rat models. Further, the medicinal properties of anti-inflammatory bioactive compounds were supported by docking studies. RESULTS: In-vitro and in-vivo studies showed significant decrease in the levels of inflammatory cytokines. Docking analysis revealed that quercetin inhibits TNF-α having -9.1 kcal/mol binding energy and 10.13 µM inhibitory constant. Quercetin also inhibits IL-6 having -6.6 kcal/mol binding energy and 21.9 µM inhibitory constant. CONCLUSION: Observed results suggest that the underutilized fruit Choerospondias axillaris can be used to reduce the inflammation of inflammatory diseases like RA.

Racism and Oral Health Outcomes among Pregnant Canadian Aboriginal Women.

This study assessed links between racism and oral health outcomes among pregnant Canadian Aboriginal women. Baseline data were analyzed for 541 First Nations (94.6%) and Métis (5.4%) women in an early childhood caries preventive trial conducted in urban and on-reserve communities in Ontario and Manitoba. One-third of participants experienced racism in the past year determined by the Measure of Indigenous Racism Experience. In logistic regressions, outcomes significantly associated with incidents of racism included: wearing dentures, off-reserve dental care, asked to pay for dental services, perceived need for preventive care, flossing more than once daily, having fewer than 21 natural teeth, fear of going to dentist, never received orthodontic treatment and perceived impact of oral conditions on quality of life. In the context of dental care, racism experienced by Aboriginal women can be a barrier to accessing services. Programs and policies should address racism's insidious effects on both mothers' and children's oral health outcomes.

Racism and Oral Health Outcomes among Pregnant Canadian Aboriginal Women.

This study assessed links between racism and oral health outcomes among pregnant Canadian Aboriginal women. Baseline data were analyzed for 541 First Nations (94.6%) and Métis (5.4%) women in an early childhood caries preventive trial conducted in urban and on-reserve communities in Ontario and Manitoba. One-third of participants experienced racism in the past year determined by the Measure of Indigenous Racism Experience. In logistic regressions, outcomes significantly associated with incidents of racism included: wearing dentures, off-reserve dental care, asked to pay for dental services, perceived need for preventive care, flossing more than once daily, having fewer than 21 natural teeth, fear of going to dentist, never received orthodontic treatment and perceived impact of oral conditions on quality of life. In the context of dental care, racism experienced by Aboriginal women can be a barrier to accessing services. Programs and policies should address racism's insidious effects on both mothers' and children's oral health outcomes.

Identification and molecular docking analysis of active ingredients with medicinal properties from edible Baccaurea sapida.

Underutilized plant species has started changing the conception of plants by expanding the use well beyond from foods and fibers to rich source of medicinally important secondary metabolites. Bioactive compounds from natural sources are gaining importance as potential drug candidates towards many inflammatory conditions like Rheumatoid Arthritis (RA). The focus of the present study has been centred to reveal the anti-inflammatory potential of an underutilized fruits of B. sapida. Further efforts towards its medicinal significance may provide relieve from symptoms of RA by reducing the side effects that are observed in available medications. Total 10 compounds in fruit crude methanol extract were identified and quantified by LC-MS/MS analysis followed by the agar well diffusion method for their anti microbial activity. Among all studied micro organism S. aureus was found to surmount the inflammation in RA through domain B of surface protein A (Staphylococcal surface protein A). Identified compounds (having anti-inflammatory properties) were scrutinized for their toxicity and quantitative structure-activity relationship (QSAR) using lazer toxicity and Molinspiration servers respectively. Further, docking studies have been carried out between domain B and studied compounds using AutoDock. Out of 6 anti-inflammtory compounds, quercetin has been identified as the most potent compound in reference to its inhibitory constant (47.01) and binding energy (-5.90 kcal/mol) to bacterial protein. Our data suggest that methanol extract of B. sapida fruit posses medicinally significant anti-inflammatory compounds and thus justifies the use of this fruit as folklore medicine for preventing inflammation related diseases.

Financial stress, attitudes toward money, and scores on a Dream Inventory.

During stock market losses in 2009 and high unemployment, ratings on the KJP Dream Inventory were correlated with factors of the Money Attitude Scale and items on the Contemporary Financial Stress Inventory for 71 graduate students in Counseling Psychology and Education. Correlations were significant for Retention on the Money Attitude Scale with Dissociative Avoidance (-.31), Dreams of falling (.26), Risk-taking in dreams (.24), and Dreaming of being chased (.28). Also, ratings for the Money Attitude Scale of Distrust correlated with Discontentedness in dreams (.33) and Dreams of being chased (.26), Repetitive trauma (.33), Nightmares (.30), and Recurring nightmares (.35). Concern about retention in graduate school due to finances correlated with recalled frequencies of nightmares (.27) and dreams of flying (.25).