Mechanistic insight into human milk extracellular vesicle-intestinal barrier interactions.

Human milk extracellular vesicles (EVs) are crucial mother-to-baby messengers that transfer biological signals. These EVs are reported to survive digestion and transport across the intestine. The mechanisms of interaction between human milk EVs and the intestinal mucosa, including epithelial uptake remain unclear.

The difficulty of studying the association between pathway delays and survival in cancer - an example from bladder cancer.

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Ethnic Differences in Response to Oral Vitamin D Supplementation: A Systematic Review and Meta-analysis.

Context: Individual variability in oral vitamin D supplement response hinders the understanding of its clinical impact, and while ethnicity has been implicated in this variability it has not been well described.

Objective: The aim was to systematically assess the impact of ethnicity on response to oral vitamin D supplementation.

Data Source: The Web of Science and PubMed databases were searched for articles published from 1960 to the end of 2020.

Navigating fluoroquinolone resistance in Gram-negative bacteria: a comprehensive evaluation.

Since the introduction of quinolone and fluoroquinolone antibiotics to treat bacterial infections in the 1960s, there has been a pronounced increase in the number of bacterial species that have developed resistance to fluoroquinolone treatment. In 2017, the World Health Organization established a priority list of the most critical Gram-negative resistant pathogens. These included , , , and .

Isolation of a new iso-quinoline alkaloid and cytotoxicity studies of pure compounds and crude extracts of engl.

A new 2-quinolone alkaloid, iso-oligophyline (), and two very unusual C terpenoids, proposed names ravespanol () and ravespanone (), along with two known compounds, β-sitosterol (), and methyl linoleate (), were isolated from the leaf extract of . Methyl linoleate constitutes the first report of isolation from this species. We have already reported the isolation of atanine (), oligophyline (), ravenoline (8), and arborinine ) from the plant.

Unified Language for Knowledge Dissemination: The Vascular Ageing Glossary, an Initiative by VascAgeNet.

Objectives: In general, a terminology shared and agreed by different stakeholders is important to facilitate communication and cooperation. This holds true in the field of vascular ageing for the benefit of global cardiovascular health. The need to promote a common language and understanding across this area was recognised by VascAgeNet, a collaborative network with relevant and diverse expertise in the vascular ageing field, supported by the European Cooperation in Science and Technology.

Cyclosporin A-Based PROTACs Can Deplete Abundant Cellular Cyclophilin A without Suppressing T Cell Activation.

Cyclophilin A (CypA), the cellular receptor of the immunosuppressant cyclosporin A (CsA), is an abundant cytosolic protein and is involved in a variety of diseases. For example, CypA supports cancer proliferation and mediates viral infections, such as the human immunodeficiency virus 1 (HIV-1). Here, we present the design of PROTAC (proteolysis targeting chimera) compounds against CypA to induce its intracellular proteolysis and to investigate their effect on immune cells.

The experience of surgical cancer patients during the COVID-19 pandemic at a large cancer centre in London.

Background: The COVID-19 pandemic has had an enormous impact on the experiences of patients across all health disciplines, especially those of cancer patients. The study aimed to understand the experiences of cancer patients who underwent surgery during the first two waves of the pandemic at Guy's Cancer Centre, which is a large tertiary cancer centre in London.

Methods: A mixed-methods approach was adopted for this study.

Advanced waveform analysis of the photoplethysmogram signal using complementary signal processing techniques for the extraction of biomarkers of cardiovascular function.

Introduction: Photoplethysmogram signals from wearable devices typically measure heart rate and blood oxygen saturation, but contain a wealth of additional information about the cardiovascular system. In this study, we compared two signal-processing techniques: fiducial point analysis and Symmetric Projection Attractor Reconstruction, on their ability to extract new cardiovascular information from a photoplethysmogram signal. The aim was to identify fiducial point analysis and Symmetric Projection Attractor Reconstruction indices that could classify photoplethysmogram signals, according to age, sex and physical activity.

Antiviral peptides inhibiting the main protease of SARS-CoV-2 investigated by computational screening and in vitro protease assay.

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in viral replication and transcription and received great attention as a vital target for drug/peptide development. Therapeutic agents such as small-molecule drugs or peptides that interact with the Cys-His present in the catalytic site of Mpro are an efficient way to inhibit the protease. Although several emergency-approved vaccines showed good efficacy and drastically dropped the infection rate, evolving variants are still infecting and killing millions of people globally.

Investigating the biochemical association of gestational diabetes mellitus with dyslipidemia and hemoglobin.

Aims: To investigate the biochemical correlation of hemoglobin (Hb), dyslipidemia, and HbA1c with gestational diabetes mellitus (GDM).

Background: GDM is a condition that develops during pregnancy and is characterized by high blood sugar levels. Biochemical parameters such as hemoglobin (Hb), dyslipidemia, and HbA1c have been implicated in the development of GDM.

Probing milk extracellular vesicles for intestinal delivery of RNA therapies.

Background: Oral delivery remains unattainable for nucleic acid therapies. Many nanoparticle-based drug delivery systems have been investigated for this, but most suffer from poor gut stability, poor mucus diffusion and/or inefficient epithelial uptake. Extracellular vesicles from bovine milk (mEVs) possess desirable characteristics for oral delivery of nucleic acid therapies since they both survive digestion and traverse the intestinal mucosa.

Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study.

Objective: To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer.

Design: Multinational, pooled cohort study.

Setting: Four large international cohorts.

Noninvasive hemodynamic indices of vascular aging: an in silico assessment.

Vascular aging (VA) involves structural and functional changes in blood vessels that contribute to cardiovascular disease. Several noninvasive pulse wave (PW) indices have been proposed to assess the arterial stiffness component of VA in the clinic and daily life. This study investigated 19 of these indices, identified in recent review articles on VA, by using a database comprising 3,837 virtual healthy subjects aged 25-75 yr, each with unique PW signals simulated under various levels of artificial noise to mimic real measurement errors.

FLT3-directed UniCAR T-cell therapy of acute myeloid leukaemia.

Adaptor chimeric antigen receptor (CAR) T-cell therapy offers solutions for improved safety and antigen escape, which represent main obstacles for the clinical translation of CAR T-cell therapy in myeloid malignancies. The adaptor CAR T-cell platform 'UniCAR' is currently under early clinical investigation. Recently, the first proof of concept of a well-tolerated, rapidly switchable, CD123-directed UniCAR T-cell product treating patients with acute myeloid leukaemia (AML) was reported.

Distinct Clinical and Prognostic Features of Myelodysplastic Syndrome in Patients from the Middle East, North Africa, and Beyond: A Systemic Review.

Myelodysplastic syndrome (MDS) describes a group of bone marrow malignancies with variable morphologies and heterogeneous clinical features. The aim of this study was to systematically appraise the published clinical, laboratory, and pathologic characteristics and identify distinct clinical features of MDS in the Middle East and North Africa (MENA) region. We conducted a comprehensive search of the PubMed, Web of Science, EMBASE, and Cochrane Library databases from 2000 to 2021 to identify population-based studies of MDS epidemiology in MENA countries.

Isolation and Characterization of One New Natural Compound with Other Potential Bioactive Secondary Metabolites from (Blume) Spreng. (Family: Rutaceae).

(Blume) Spreng is a plant in the Rutaceae family and a species in the Glycosmis genus that has received little attention. Therefore, this research aimed to report the chemical and biological analysis of (Blume) Spreng. The chemical analysis involved the isolation and characterization of secondary metabolites through an extensive chromatographic study, and the structures of these metabolites were elucidated on the basis of a detailed analysis of NMR and HRESIMS spectroscopic data and by comparison with those of related compounds reported in the literature.

Evaluation of changes to work patterns in multidisciplinary cancer team meetings due to the COVID-19 pandemic: A national mixed-method survey study.

Background: It is not well understood the overall changes that multidisciplinary teams (MDTs) have had to make in response to the COVID-19 pandemic, nor the impact that such changes, in addition to the other challenges faced by MDTs, have had on decision-making, communication, or participation in the context of MDT meetings specifically.

Methods: This was a mixed method, prospective cross-sectional survey study taking place in the United Kingdom between September 2020 and August 2021.

Results: The participants were 423 MDT members.

Isolation and In Silico Prediction of Potential Drug-like Compounds with a New Dimeric Prenylated Quinolone Alkaloid from (Roxb.) Root Extracts Targeted against SARS-CoV-2 (Mpro).

A new dimeric prenylated quinolone alkaloid, named 2,11-didemethoxy-vepridimerine A, was isolated from the root bark of , together with twelve known compounds. The structure of the new compound was elucidated on the basis of spectroscopic investigations (NMR and Mass). The interaction of the isolated compounds with the main protease of SARS-CoV-2 (Mpro) was evaluated using molecular docking followed by MD simulations.

A critical review on the availability of substandard and falsified medicines online: Incidence, challenges and perspectives.

Simultaneous expansion of the Internet and increased globalisation of the pharmaceutical industry have meant medication can be accessed transnationally from both legal and illicit sources. This has coincided with the rise of substandard and falsified medicines (SFMs) online. These products fail to meet regulatory or quality standards and/or are constituted with substandard ingredients, causing undesired pharmacological effects, including possible injury and death.

Cardiovascular waveforms - can we extract more from routine signals?

Cardiovascular waveforms such as blood pressure, ECG and photoplethysmography (PPG), are routinely acquired by specialised monitoring devices. Such devices include bedside monitors, wearables and radiotelemetry which sample at very high fidelity, yet most of this numerical data is disregarded and focus tends to reside on single point averages such as the maxima, minima, amplitude, rate and intervals. Whilst, these measures are undoubtedly of value, we may be missing important information by simplifying the complex waveform signal in this way.

Neutrophils Dominate the Cervical Immune Cell Population in Pregnancy and Their Transcriptome Correlates With the Microbial Vaginal Environment.

The cervicovaginal environment in pregnancy is proposed to influence risk of spontaneous preterm birth. The environment is shaped both by the resident microbiota and local inflammation driven by the host response (epithelia, immune cells and mucous). The contributions of the microbiota, metabolome and host defence peptides have been investigated, but less is known about the immune cell populations and how they may respond to the vaginal environment.