Bioactive nanotherapeutic trends to combat triple negative breast cancer

The management of aggressive breast cancer, particularly, triple negative breast cancer (TNBC) remains a formidable challenge, despite treatment advancement. Although newer therapies such as atezolizumab, olaparib, and sacituzumab can tackle the breast cancer prognosis and/or progression, but achieved limited survival benefit(s). The current research efforts are aimed to develop and implement strategies for improved bioavailability, targetability, reduce systemic toxicity, and enhance therapeutic outcome of FDA-approved treatment regimen. This review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s) for breast cancer treatment. This article also documents novel strategies to employ cellular and cell membrane cloaked (biomimetic) nanoparticles for effective clinical translation. These technologies offer a safe and active targeting nanomedicine for effective management of breast cancer, especially TNBC

Bioactive nanotherapeutic trends to combat triple negative breast cancer

The management of aggressive breast cancer, particularly, triple negative breast cancer (TNBC) remains a formidable challenge, despite treatment advancement. Although newer therapies such as atezolizumab, olaparib, and sacituzumab can tackle the breast cancer prognosis and/or progression, but achieved limited survival benefit(s). The current research efforts are aimed to develop and implement strategies for improved bioavailability, targetability, reduce systemic toxicity, and enhance therapeutic outcome of FDA-approved treatment regimen. This review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s) for breast cancer treatment. This article also documents novel strategies to employ cellular and cell membrane cloaked (biomimetic) nanoparticles for effective clinical translation. These technologies offer a safe and active targeting nanomedicine for effective management of breast cancer, especially TNBC

Chemistry of enediynyl azides: activation through a novel pathway

The spontaneous activation of a nonaromatic enediynyl azide under ambient conditions has been demonstrated. The aromatic enediyne followed the expected cycloaddition with the alkene in the neighbouring arm to form a stable bridged bicyclic enediyne

Extracellular Vesicles in Triple–Negative Breast Cancer: Immune Regulation, Biomarkers, and Immunotherapeutic Potential

Triple–negative breast cancer (TNBC) is an aggressive subtype accounting for ~10–20% of all human BC and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) amplification. Owing to its unique molecular profile and limited targeted therapies, TNBC treatment poses significant challenges. Unlike other BC subtypes, TNBC lacks specific molecular targets, rendering endocrine therapies and HER2–targeted treatments ineffective. The chemotherapeutic regimen is the predominant systemic treatment modality for TNBC in current clinical practice. However, the efficacy of chemotherapy in TNBC is variable, with response rates varying between a wide range of patients, and the emerging resistance further adds to the difficulties. Furthermore, TNBC exhibits a higher mutational burden and is acknowledged as the most immunogenic of all BC subtypes. Consequently, the application of immune checkpoint inhibition has been investigated in TNBC, yielding promising outcomes. Recent evidence identified extracellular vesicles (EVs) as an important contributor in the context of TNBC immunotherapy. In view of the extraordinary ability of EVs to transfer bioactive molecules, such as proteins, lipids, DNA, mRNAs, and small miRNAs, between the cells, EVs are considered a promising diagnostic biomarker and novel drug delivery system among the prospects for immunotherapy. The present review provides an in–depth understanding of how EVs influence TNBC progression, its immune regulation, and their contribution as a predictive biomarker for TNBC. The final part of the review focuses on the recent key advances in immunotherapeutic strategies for better understanding the complex interplay between EVs and the immune system in TNBC and further developing EV–based targeted immunotherapies

Ketorolak-dekstran konjugati: sinteza, in vitro i in vivo vrednovanje

Ketorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. In vitro hydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. In vivo biological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.U radu je opisana sinteza konjugata dektrana i protuupalnog lijeka ketorolaka (KD). Konjugati su pripravljeni da bi se povećala topljivost ketorolaka u vodi i smanjila njegova nusdjelovanja u gastrointestinanom traktu. Ketorak je prvo preveden u N-acilimidazolni derivat (KAI) koji je kondenziran s polimernim nosačem, dekstranom različitih molekulskih masa (40000, 60000, 110000 i 200000). IR-spektri potvrdili su nastajanje esterske veze. Udio ketorolaka u konjugatu određen je UV-spektrofotometrijskom analizom. Molekulske mase određene su mjerenjem viskoznosti koristeći Mark-Howink-Sakurada jednadžbu. Hidroliza in vitro praćena je u puferskim otopinama (pH 1,2, 7,4 i 9) i u 80% V/V humanoj plazmi (pH 7,4). Pri pH 9 primjećeno je značajno brže oslobađanje ketorolaka iz KD nego u puferskoj otopini pH 7,4 i krvnoj plazmi. Oslobađanje je prati kinetiku prvog reda. In vivo biološka ispitivanja na miševima i štakorima ukazuju da konjugati imaju analgetsko i protuupalno djelovanje, a značajno smanjeno ulcerogeno djelovanje

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Allelopathy in two species of Chenopodium -inhibition of germination and seedling growth of certain weeds

The activity of washed leaf and inflorescence material of Chenopodium ambrosioides and C. murale, decaying leaves and inflorescences, and field soils collected beneath Chenopodium plants were examined in terms of the inhibition of seed germination and seedling growth of five weeds, viz. Abutilon indicum, Cassia sophera var. purpurea, C. tora, Evolvulus numularius and Tephrosia hamiltonii. The allelopathic pattern varied in each of the two test species and this depended on the type of test matter. However, the germination as well as the root and hypocotyl growth of A. indicum and E. nummularius were more hampered by phytotoxins or inhibitors from Chenopodium than were the other weeds. Since the leaf and inflorescence of Chenopodium formed the source of inhibitors, the respective plant-parts from the two species were chemically analysed and the presence of three terpenes (p-cymene, ascaridole and aritazone) from C. ambrosioides and an organic acid (oxalic acid) from C. murale were implicated in the allelopathic effect

A novel azetidinyl γ-lactam based peptide with a preference for β-turn conformation

Novel azetidinyl γ-lactam based peptides 1-3 have been synthesized with only compound 1 showing a preference for the β-turn conformation