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Background: Exosomes are extracellular vesicles released by cells that mediate intercellular communication and actively participate in cancer progression, metastasis, and regulation of immune response within the tumour microenvironment. Inhibiting exosome release from cancer cells could be employed as a therapeutic against cancer. Methods and results: In the present study, we have studied the effects of Acorus calamus in inhibiting exosome secretion via targetting Rab27a and neutral sphingomyelinase 2 (nSMase2) in HER2-positive (MDA-MB-453), hormone receptor-positive (MCF-7) and triple-negative breast cancer (MDA-MB-231) cells. We observed that treatment with A. calamus significantly downregulated the expression of Rab27a and nSMase2 in all tested cells. NTA analysis showed that inhibition of Rab27a and nSMase2 reduced exosome secretion from breast cancer cells. We conducted metabolic profiling of A. calamus extract to reveal the phytochemicals present and docked them on Rab27a and nSMase2 to decipher the compounds responsible for protein inhibition. Molecular dynamic simulations were conducted on lead compounds, and we observed that calcitriol lactone showed the most stable binding interactions with nSMase2. Treatment of breast cancer cells with calcitriol lactone significantly downregulated nSMase2 expression. Conclusions: Our study demonstrates that A. calamus significantly inhibits exosome secretion in HER2-positive, hormone receptor-positive, and triple-negative breast cancer cells by targeting key regulatory proteins Rab27a and neutral sphingomyelinase 2 (nSMase2). These findings suggest that A. calamus holds therapeutic potential in inhibiting exosome-mediated cancer progression by targeting the exosome secretion pathway. Further investigations are warranted to explore the clinical applications of these findings in breast cancer treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: This narrative review paper highlights the multifaceted influence of dysbiotic biofilm, genetic background, host response, and environmental factors on periodontitis. It explores the roles of type I and II diabetes mellitus, gestational diabetes, and metabolic syndrome in the progression of periodontitis, drawing insights from various empirical studies and theoretical perspectives. Methods: Relevant articles were sourced using keywords in databases like PubMed/Medline, Science Direct, Scopus, and Google Scholar. Additionally, this review examines the relationship between aMMP-8 levels and increased glycemic states, as well as varying degrees of periodontitis severity. Results: The biomarker active-matrix metalloproteinase-8 (aMMP-8), produced by polymorphonuclear leukocytes (PMN), is highlighted as a reliable indicator of ongoing connective tissue degradation. Dysfunctions in PMN activity, accumulation of advanced glycation end products (AGE), and oxidative stress aggravate the periodontal inflammatory response and complications of diabetes. Traditional diagnostics of periodontitis do not provide sufficient information about the current or future disease initiation or activity of periodontitis. Conclusions: The implications of this review point to the need for monitoring periodontal health by utilizing innovative strategies like aMMP-8 point-of-care testing, using oral rinse for screening and treatment monitoring, and harnessing the potential of supportive treatments like low-dose doxycycline and light-activated mouth rinses for restoring periodontal health. Its expression in oral fluids is a promising diagnostic tool to differentiate periodontitis from gingivitis and healthy periodontium, especially when associated with systemic diseases, fostering greater collaboration among healthcare professionals. [ABSTRACT FROM AUTHOR]

Aim and background: Dengue fever (DF) is a mosquito-borne febrile illness and has a varied clinical spectrum in pregnancy. This study aims to find out the feto-maternal outcome in pregnant women with DF from July 2019 to July 2022 at a tertiary care rural institute in northern India. Materials and Methods: This cross-sectional observational study was carried out during the study period from July 2019 to July 2022. Pregnant women, irrespective of the gestational age; tested positive for dengue illness and were included in the study. Baseline socio-demographic data, obstetric data, and laboratory data were noted. Neonatal outcomes and details of any complications till the time of discharge from the hospital were noted. Statistical analysis was done using software SPSS version 22.0 (Statistical Package for Social Sciences). Results: During the study period, there were 317 pregnancies complicated with fever, a total of 32 pregnancies with dengue with a mean maternal age of 24.6 ± 3.4 years were included in the study. All women had presented with fever. Three patients presented with dengue hemorrhagic fever and one with dengue shock syndrome. Eight patients (25%) required admission to an intensive care unit for management. Platelet transfusion was required in 9 cases. Six patients had a preterm delivery; cesarean section rates were 34.4%. Around 9.4% of cases were complicated with ARDS, 15% were reported to have acute kidney injury (AKI), and 18.8% and 3.1% had a postpartum hemorrhage and hematoma formation, respectively. Around 12.5% mortality was observed among the study population. The mean birth weight of the neonates was 2375 ± 965 gms. A total of five stillbirths were reported during the study. Conclusion: With a high maternal mortality rate of 12.6%, dengue during pregnancy adversely impacts both maternal and fetal outcomes. Clinical significance: Early diagnosis, close materno-fetal monitoring, and timed interventions are essential to improve the feto-maternal outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to compare several potential mouthrinse biomarkers for periodontitis including active matrix-metalloproteinase-8 (aMMP-8), total MMP-8, and other inflammatory biomarkers in diagnosing and monitoring the effects of nonsurgical periodontal therapy. Thirteen patients with stage III/IV periodontitis were recruited, along with thirteen periodontally and systemically healthy controls. These 13 patients were representative of the number of outpatients visiting any dentist in a single day. Full-mouth clinical periodontal parameters and biomarkers (the aMMP-8 point-of-care-test [POCT], total MMP-8, tissue inhibitor of MMPs (TIMP)-1, the aMMP-8 RFU activity assay, Myeloperoxidase, PMN elastase, calprotectin, and interleukin-6) were recorded at baseline and after nonsurgical therapy at 6 weeks. The aMMP-8 POCT was the most efficient and precise discriminator, with a cut-off of 20 ng/mL found to be optimal. Myeloperoxidase, MMP-8's oxidative activator, was also efficient. Following closely in precision was the aMMP-8 RFU activity assay and PMN elastase. In contrast, the total MMP-8 assay and the other biomarkers were less efficient and precise in distinguishing patients with periodontitis from healthy controls. aMMP-8, MPO, and PMN elastase may form a proteolytic and pro-oxidative tissue destruction cascade in periodontitis, potentially representing a therapeutic target. The aMMP-8 chair-side test with a cut-off of 20 ng/mL was the most efficient and precise discriminator between periodontal health and disease. The aMMP-8 POC test can be effectively used by dental professionals in their dental practices in online and real-time diagnoses as well as in monitoring periodontal disease and educating and encouraging good oral practices among patients. [ABSTRACT FROM AUTHOR]