In recent years, carbon quantum dots (CQDs) have garnered considerable attention as a promising material for biomedical applications because of their unique optical and biological properties. In this ...study, CQDs were derived from the leaves of Hibiscus rosa-sinensis Linn. via microwave-assisted technique and characterized using different techniques such as ultraviolet-visible, Fourier transform infrared, fluorescence spectrometry, X-ray diffraction, dynamic light scattering, transmission electron microscopy and energy-dispersive X-ray spectroscopy. Subsequently, their potential for biomedical applications was investigated through in vitro assays assessing scratch healing, anti-inflammatory, antibacterial, and cytotoxicity properties. It was found that the CQDs were fluorescent, polycrystalline, quasi-spherical, ~ 12 nm in size with presence of -OH and -COOH groups on their negatively charged surfaces, and demonstrated good anti-inflammatory by inhibiting protein denaturation, cyclooxygenase-2 and regulating inflammatory cytokines. The CQDs also exhibited antimicrobial activity against Klebsiella pneumoniae and Bacillus cereus, good biocompatibility, along with excellent promotion of cell proliferation in vitro, indicating their potential as a anti-inflammatory and wound healing material. The properties were more enhanced than their precursor, H. rosa-sinensis leaf extract. Hence, the CQDs synthesized from the leaves of H. rosa-sinensis can serve as a potential biomedical agent.
Purpose
Young premenopausal women develop breast cancer (BC) within 5–10 years of the last childbirth, known as post-partum breast cancers (PPBC), often present with aggressive disease. The exact ...mechanisms that lead to poor prognosis in these patients are largely unknown.
Methods
We have evaluated the association of clinical and reproductive factors with BC in a cohort of women ≤ 45 years (
N
= 155) with long-term follow-up. Based on duration since last childbirth (LCB), grouped patients into PPBC1 (LCB ≤ 5 years), PPBC2 (LCB between 6 and 10 years), PPBC3 (LCB > 10 years), and NPBC (age-matched nulliparous BC patients). We compared disease-free survival and hazard associated with recurrence/metastasis between the groups. RNA sequencing of tumor samples was performed from three parous groups (
n
= 10), and transcriptomic data were analyzed for differentially expressed genes and altered pathways.
Results
Women in the PPBC1 group had an early menarche and late age at first and last childbirth compared to other groups. Survival analysis within lymph node-positive tumors showed that PPBC1 tumors had a worse prognosis than PPBC2 and NPBC tumors (
p
= 0.015 and
p
= 0.026, respectively). Clustering of the differentially expressed genes between the groups showed distinct expression in early PPBC (E-PPBC) tumors. Pathway analysis revealed upregulation of invasive-related pathways along with T cell exhaustion, extracellular matrix remodeling, angiogenesis, and epithelial-to-mesenchymal transition in E-PPBC tumors.
Conclusion
Early PPBC is a unique subtype with aggressive clinical features and distinct biology. Further research is needed to accurately project the risk of recurrence and optimal treatment strategies in these young patients.
Despite the established benefits of long‐term endocrine therapy, women with hormone receptor‐positive breast cancer remain at risk for late relapse. The basis of this is multi‐factorial including ...genetic, epigenetic, and host factors. In this study we have explored the epigenetic regulation of estrogen receptor (ER)‐dependent molecular and cellular phenotype by hsa‐miR‐18a‐5p using well‐established human ER‐positive (ER+) breast cancer cell lines. miR‐18a was overexpressed in MCF7 and ZR‐75‐1 and this led to an increase in the proliferative ability of the cells and concurrently resulted in decreased expression of luminal markers and higher expression of the basal marker, cytokeratin 14. The cells became more migratory with a significant repression of E‐cadherin and activation of the Wnt noncanonical pathway. We observed an activation of the planar cell polarity (PCP) pathway with increased activation of JNK pathway and eventually change in actin dynamics. There was increased F‐actin polymerization in cells with higher expression of miR‐18a. Examination of miR‐18a expression in a set of human ER+ breast cancer specimens showed a negative correlation between miR‐18a and ESR1 transcripts as well as ER protein. Kaplan‐Meier survival analysis of the cohort stratified by tumor hsa‐miR‐18a‐5p levels produced significant differences in disease‐free survival (log rank P < .05). This observation was independently validated in the METABRIC cohort. These data provide support for a role of hsa‐miR‐18a‐5p in altering the proliferative and migratory behavior of ER+ cells and its potential utility as a prognostic marker in clinical ER+ breast cancers.
Through the manuscript, we have tried to explore the epigenetic regulation of estrogen receptor (ER) dependent molecular and cellular phenotype by hsa‐miR‐18a‐5p. High levels of miR‐18a activates the epigenetic pathway of repression of the luminal phenotype through activation of Wnt pathway.
Aim
The objective was to assess respiratory efficacy of hydrochlorothiazide and spironolactone and ascertain any adverse effects.
Methods
Data from 2014 to 2018 was analysed for infants <28 weeks' ...gestational age (GA) administered oral diuretics. Impact on respiratory support, weight gain and electrolyte status was assessed as a pre‐post intervention study.
Results
Of 491 infants, 117 (24%) were administered diuretics for evolving or established bronchopulmonary dysplasia. GA and birthweight of the cohort were 25.7 ± 1.1 weeks and 779 ± 172 g, respectively. Median (interquartile range) chronological age and GA at the start of diuretics was 45 (22, 62) days and 32.1 (30.1, 35.1) weeks, respectively. In 71/117 (61%) infants, diuretics were started at <36 weeks GA. Of them 63 (88.7%) went on to develop bronchopulmonary dysplasia. Median duration of diuretics was 38 (18–52) days. Modest improvement was noted in respiratory parameters (ventilator pressure (cm of H2O), 8.8 ± 0.4 vs. 8.8 ± 0.5, P = 0.39, oxygen requirement (%), 32 ± 1 vs. 30 ± 1, P = 0.07 and pO2 (mm Hg) 34.5 ± 1.3 vs. 36.6 ± 1, P = 0.04. Ninety‐eight (84%) infants developed hyponatraemia (<135 mmol/L); sodium supplements were administered in 58/98 (59%) infants. In one third infants, phosphate levels dropped below 1.8 mmol/L, needing supplementation. Weight gain (g/kg/day) slowed down significantly (18.2 ± 2.1 to 10 ± 2.9, P = <0.001).
Conclusions
Use of diuretics was associated with modest improvements in respiratory support requirements but was associated with significant electrolyte abnormalities and slowdown in weight gain (or weight loss).
Apart from germ-line BRCA1-mutated breast cancers, a significant proportion of women with sporadic triple negative breast cancer (TNBC) sub-type are known to harbour varying levels of ...BRCA1-dysfuction. There is currently no established diagnostic method to identify these patients.
The analysis was performed on 183 primary breast cancer tumor specimens from our longitudinal case-series archived as formalin-fixed-paraffin-embedded (FFPE) blocks comprising 71 TNBCs and 112 Hormone receptor positive HER2 negative (HR+HER2-) tumors. Transcript levels of BRCA1 and two of its repressors ID4 and microRNA182 were determined by TaqMan quantitative PCR. BRCA1 protein was detected immunohistochemically with the MS110 antibody.
The representation of BRCA1 and its repressor ID4 as a ratio led to improved separation of TNBCs from HR+HER2- compared to either measure by itself. We then dichotomised the continuous distribution of each of the three measurements (Protein, MIRNA and transcript:repressor ratio) into categories of deficient (0) and adequate (1). A composite BRCA1 Deficiency Score (BDS) was computed by the addition of the score for all three measures. Samples deficient on 2 or more measures were deemed to be BRCA1 deficient; and 40% of all TNBCs met this criterion.
We propose here a simple multi-level assay of BRCA1 deficiency using the BRCA1:ID4 ratio as a critical parameter that can be performed on FFPE samples in clinical laboratories by the estimation of only 3 bio-markers. The ease of testing will hopefully encourage adoption and clinical validation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Breast cancer (BC) among premenopausal women is an aggressive disease associated with poor outcome despite intensive treatment. Higher burden is observed in southeast Asian countries attributed to ...younger population structure. We compared the reproductive and clinicopathological characteristics, distribution of subtypes and survival between pre and postmenopausal women from a retrospective cohort of BC patients with median follow up over 6 years to examine the differences. In our cohort of 446 BC patients, 162/446 (36.3%) were premenopausal. Parity and age at last childbirth were significantly different between pre and postmenopausal women. Premenopausal BC had a higher proportion of HER2 amplified and triple negative breast cancer (TNBC) tumors (p = 0.012). Stratified analysis by molecular subtypes showed TNBC had significantly better disease free (DFS) and overall survival (OS) among premenopausal group (mean survival, pre vs. post, DFS = 79.2 vs. 54.0 months, OS = 72.5 vs. 49.5 months, p = 0.002 for both). Analysis on external datasets (SCAN-B, METABRIC) confirmed this finding for overall survival. Our data confirmed the previously observed association of clinical and pathological features between pre and postmenopausal BC. Exploration of better survival among premenopausal TNBC tumors is warranted in larger cohorts with long term follow up.
Purpose: To understand the role played by the immediate family in treatment decision and support in patients diagnosed with breast cancer, the influence of demographic factors on psychosocial roles ...of women within the family. Methods: A mixed method design used for data collection on family support, financial arrangement and psychosocial impact of cancer from 378 women with breast cancer recruited at first diagnosis between 2008 and 2012, during multiple counseling sessions. The median follow-up is 7 years with only 2% lost to follow-up. Results: Most patients (99%) had support from family members. 57% of patients met the costs of treatment through personal savings and health insurance. The rest (43%) had difficulty and had to resort to desperate measures such as selling their property or taking on high-interest personal loans. Patients with higher education and urban settings had better financial management. A male member of the family (husband or son) was the main decision maker in half of the cases. Concerns over women's responsibilities within the family varied by the age of the patient. The vast majority of women (90%) experienced social embarrassment in dealing with the disease and its aftermath. Conclusion: In India, it is the family that provides crucial support to a woman with breast cancer during her ordeal with the disease and its treatment. This study has implications on the psychosocial support beyond the cancer patients alone, to include the immediate family and consider aspects of finance and social adjustments as critical in addition to the routine medical aspects of the disease.
Gastric Black Fungus: A Rare Case Report Srinath, BM; Vasugi, Gramani Arumugam; Ganesh, P ...
Journal of clinical and diagnostic research,
08/2024, Letnik:
18, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Mucormycosis is an opportunistic fungal infection that typically affects patients with diabetes mellitus or immunosuppression. The fungus invades nearby blood vessels, leading to thrombosis and organ ...necrosis. While Mucorales can infiltrate any organ in the body, the gastrointestinal system is an uncommon site for infection. Gastric mucormycosis is a rare but potentially lethal fungal infection resulting from the invasion of Mucorales into the gastric mucosa, exhibiting angioinvasive characteristics. It can lead to high mortality rates due to the increased risk of complications in immunocompromised patients. Common predisposing factors include diabetes mellitus, neutropenia, iron overload states, malnourishment, and other immunocompromised conditions. Mucormycosis is a fatal infection, necessitating prompt intervention to ensure survival. In this case report, authors present a 42-year-old man with a history of chronic alcoholism and chronic kidney disease who presented with complaints of abdominal pain and vomiting for six months, significant weight loss, and loss of appetite for one month. Initially suspected clinically and radiologically as a malignant gastric ulcer, an endoscopy was performed, and a gastric biopsy was sent for Histopathological Examination (HPE). Histological analysis of the gastric biopsy revealed multiple fragments of gastric mucosa with areas of ulceration, neutrophilic abscess, and numerous broad aseptate obtuse-angle fungal hyphae resembling Mucorales. The presence of the organisms was confirmed through special stains for fungus. Very few cases of invasive gastric mucormycosis associated with uncontrolled diabetes, alcoholism, and chronic kidney disease have been reported in the literature.
The biosynthesis of nanoparticles is a cost effective, eco-friendly and non toxic alternative to physical and chemical methods. In the present study, we report a rapid and eco-friendly method for ...extracellular biosynthesis of gold nanoparticles (GNPs) using cell free extract of Staphylococcus epidermidis. In this method, the formation of GNPs is rapid as the reaction process completes within few minutes. The synthesis of GNPs was preliminary observed by colour change from pale yellow to pink red and confirmed by peaks at 545–550nm using a UV–visible spectroscopy. Transmission electron microscopy (TEM) showed formation of well dispersed GNPs in the range of 20–25nm. Fourier transform-infrared spectroscopy (FT-IR) was used to characterise the functional groups which might have played an important role in reduction and stabilisation of GNPs. The synthesised GNPs showed good catalytic activity for methylene blue degradation. This is the first to report on the rapid and ecofriendly method for the biosynthesis of GNPs by S. epidermidis.
•First report on biosynthesis of gold nanoparticles from S. epidermidis.•Gold nanoparticles were synthesised within few minutes at optimised incubation temperature.•The gold nanoparticles formed are 20–25nm of size at 100°C.•The synthesised gold nanoparticles show good catalytic activity.
Epigenetic alterations that lead to differential expression of microRNAs (miRNAs/miR) are known to regulate tumour cell states, epithelial-mesenchymal transition (EMT) and the progression to ...metastasis in breast cancer. This study explores the key contribution of miRNA-18a in mediating a hybrid E/M cell state that is pivotal to the malignant transformation and tumour progression in the aggressive ER-negative subtype of breast cancer. The expression status and associated effects of miR-18a were evaluated in patient-derived breast tumour samples in combination with gene expression data from public datasets, and further validated in in vitro and in vivo breast cancer model systems. The clinical relevance of the study findings was corroborated against human breast tumour specimens (n = 446 patients). The down-regulated expression of miR-18a observed in ER-negative tumours was found to drive the enrichment of hybrid epithelial/mesenchymal (E/M) cells with luminal attributes, enhanced traits of migration, stemness, drug-resistance and immunosuppression. Further analysis of the miR-18a targets highlighted possible hypoxia-inducible factor 1-alpha (HIF-1α)-mediated signalling in these tumours. This is a foremost report that validates the dual role of miR-18a in breast cancer that is subtype-specific based on hormone receptor expression. The study also features a novel association of low miR-18a levels and subsequent enrichment of hybrid E/M cells, increased migration and stemness in a subgroup of ER-negative tumours that may be attributed to HIF-1α mediated signalling. The results highlight the possibility of stratifying the ER-negative disease into clinically relevant groups by analysing miRNA signatures.
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