Simultaneous estimation of paclitaxel and bortezomib via LC-MS/MS: pharmaceutical and pharmacokinetic applications.

This study evaluates the potential of combining paclitaxel (PTX) and bortezomib (BTZ) for breast cancer therapy. The nanoformulation was optimized via Box-Behnken Design (BBD), with method validation adhering to US-FDA guidelines. Multiple reaction monitoring transitions for PTX, BTZ and internal standard were m/z 855.

Oxidative DNA damage promotes vascular aging associated with changes in extracellular matrix-regulating proteins.

Aims: Vascular aging is characterized by vessel stiffening, with increased deposition of extracellular matrix (ECM) proteins including collagens. Oxidative DNA damage occurs in vascular aging, but how it regulates ECM proteins and vascular stiffening is unknown. We sought to determine the relationship between oxidative DNA damage and ECM regulatory proteins in vascular aging.

Development and approval of novel injectables: enhancing therapeutic innovations.

Introduction: Novel injectables possess applications in both local and systemic therapeutics delivery. The advancement in utilized materials for the construction of complex injectables has tremendously upgraded their safety and efficacy.

Areas Covered: This review focuses on various strategies to produce novel injectables, including oily dispersions, in situ forming implants, injectable suspensions, microspheres, liposomes, and antibody-drug conjugates.

Image quality in whole-body MRI using the MY-RADS protocol in a prospective multi-centre multiple myeloma study.

Background: The Myeloma Response Assessment and Diagnosis System (MY-RADS) guidelines establish a standardised acquisition and analysis pipeline for whole-body MRI (WB-MRI) in patients with myeloma. This is the first study to assess image quality in a multi-centre prospective trial using MY-RADS.

Methods: The cohort consisted of 121 examinations acquired across ten sites with a range of prior WB-MRI experience, three scanner manufacturers and two field strengths.

Cytokine-Mediated Degradation of the Transcription Factor ERG Impacts the Pulmonary Vascular Response to Systemic Inflammatory Challenge.

Background: During infectious diseases, proinflammatory cytokines transiently destabilize interactions between adjacent vascular endothelial cells (ECs) to facilitate the passage of immune molecules and cells into tissues. However, in the lung, the resulting vascular hyperpermeability can lead to organ dysfunction. Previous work identified the transcription factor ERG (erythroblast transformation-specific-related gene) as a master regulator of endothelial homeostasis.

Cytokine-Mediated Degradation of the Transcription Factor ERG Impacts the Pulmonary Vascular Response to Systemic Inflammatory Challenge.

Background: During infectious diseases, pro-inflammatory cytokines transiently destabilize interactions between adjacent vascular endothelial cells (ECs) to facilitate the passage of immune molecules and cells into tissues. However, in the lung the resulting vascular hyperpermeability can lead to organ dysfunction. Previous work identified the transcription factor ERG as a master regulator of endothelial homeostasis.

Prospective Assessment of Tumour Burden and Bone Disease in Plasma Cell Dyscrasias Using DW-MRI and Exploratory Bone Biomarkers.

Novel biomarkers for tumour burden and bone disease are required to guide clinical management of plasma cell dyscrasias. Recently, bone turnover markers (BTMs) and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) have been explored, although their role in the prospective assessment of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) is unclear. Here, we conducted a pilot observational cohort feasibility study combining serum BTMs and DW-MRI in addition to standard clinical assessment.

Implementation of Whole-Body MRI (MY-RADS) within the OPTIMUM/MUKnine multi-centre clinical trial for patients with myeloma.

Background: Whole-body (WB) MRI, which includes diffusion-weighted imaging (DWI) and T-w Dixon, permits sensitive detection of marrow disease in addition to qualitative and quantitative measurements of disease and response to treatment of bone marrow. We report on the first study to embed standardised WB-MRI within a prospective, multi-centre myeloma clinical trial (IMAGIMM trial, sub-study of OPTIMUM/MUKnine) to explore the use of WB-MRI to detect minimal residual disease after treatment.

Methods: The standardised MY-RADS WB-MRI protocol was set up on a local 1.

In-silico and in-vivo evaluation of sesamol and its derivatives for benign prostatic hypertrophy.

Unlabelled: Pharmacological treatment for BPH includes 5- reductase inhibitors as Finasteride and Dutasteride as a monotherapy or in combination with antimuscarinic drugs, alpha-blockers, 5-phosphodiesterase inhibitor drugs. Androgen receptor inhibitors revealed several adverse events as decreased libido, erectile dysfunction, ejaculatory dysfunction, and gynecomastia. Hence, the emergence of complementary and alternative medications having safety profile-preferably, edible natural products-would be highly desirable.

Clinical effects and safety of ferric carboxymaltose in pregnancy: An Indian real-life experience.

Background: There is limited clinical evidence of ferric carboxymaltose injection (FCM) usage in Indian pregnant women. We assessed the efficacy and safety of FCM in Indian pregnant women with moderate-to-severe anemia.

Methods: Single-center, retrospective, observational data collection was conducted at a tertiary care research institute.

Cyclodextrin based bone regenerative inclusion complex for resveratrol in postmenopausal osteoporosis.

Recent preclinical studies have shown that resveratrol (RSV), is a promising remedy for osteoporosis owing to its estrogenic, anti-inflammatory, and antioxidant properties. However, RSV has met limited success due to its poor oral bioavailability and inefficient systemic delivery. In this study, we prepared the inclusion complex of RSV with sulfo-butyl ether β-cyclodextrin (SBE-β-CD) to enhance the aqueous solubility of RSV.

Efficacy and limitations of senolysis in atherosclerosis.

Aims: Traditional markers of cell senescence including p16, Lamin B1, and senescence-associated beta galactosidase (SAβG) suggest very high frequencies of senescent cells in atherosclerosis, while their removal via 'senolysis' has been reported to reduce atherogenesis. However, selective killing of a variety of different cell types can exacerbate atherosclerosis. We therefore examined the specificity of senescence markers in vascular smooth muscle cells (VSMCs) and the effects of genetic or pharmacological senolysis in atherosclerosis.

Histone Deacetylase Inhibitors Prevented the Development of Morphine Tolerance by Decreasing IL6 Production and Upregulating μ-Opioid Receptors.

Background: Morphine tolerance on long-term usage leads to chronic pain conditions. Preclinical studies demonstrated that the upregulation of HDACs is associated with a decrease in the sensitivity of μ-opioid receptors, which results in morphine tolerance.

Objective: The present study was designed to assess the influence of the selected known HDAC inhibitors (NMJ2 and NMJ3) on the pain tolerance induced by chronic administration of morphine in Balb/c mice.

Vascularity of Intra-testicular Lesions: Inter-observer Variation in the Assessment of Non-neoplastic Versus Neoplastic Abnormalities After Vascular Enhancement With Contrast-Enhanced Ultrasound.

The aim of this study is to assess the additional benefit of contrast-enhanced ultrasound (CEUS) over conventional ultrasonography (US) in identifying intra-testicular abnormalities among observers of different experiences. In this study, 91 focal testicular lesions (46 neoplastic, 45 non-neoplastic) imaged with gray-scale US/Doppler US and CEUS were classified using a 5-point scale. Three experienced and four inexperienced observers rated each lesion using gray-scale/color Doppler US alone and then with the addition of CEUS.

Ultrasound-Guided High Intensity Focused Ultrasound Ablation for Symptomatic Uterine Fibroids: Preliminary Clinical Experience.

Objective:  To evaluate the middle-term efficacy and complications of ultrasound-guided high intensity focused ultrasound (USgHIFU) for the treatment of symptomatic uterine fibroids in an NHS population.

Methods:  A prospective observational single-center study at a single university hospital in Oxford, UK. Patients with symptomatic uterine fibroids who declined standard surgical/radiological intervention and were referred to the HIFU unit were considered for USgHIFU treatment.

Non-Propellant Foams of Green Nano-Silver and Sulfadiazine: Development and In Vivo Evaluation for Burn Wounds.

Purpose: A non-propellant based foam (NPF) system was developed incorporating the antibiotics, pectin capped green nano-silver and sulfadiazine (SD) for the topical treatment of burn wounds as a convenient alternative to the existing therapies.

Methods: NPF were prepared using various surfactants and oils forming a nanoemulsion. Anti-microbial studies by resazurin microtitre assay, ex vivo diffusion, in vivo skin permeation and deposition studies, and acute irritation studies were carried out.

Reduction of Leukocyte Microvascular Adherence and Preservation of Blood-Brain Barrier Function by Superoxide-Lowering Therapies in a Piglet Model of Neonatal Asphyxia.

Asphyxia is the most common cause of brain damage in newborns. Substantial evidence indicates that leukocyte recruitment in the cerebral vasculature during asphyxia contributes to this damage. We tested the hypothesis that superoxide radical ( ) promotes an acute post-asphyxial inflammatory response and blood-brain barrier (BBB) breakdown.

The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program.

Rationale: The ETS (E-26 transformation-specific) transcription factor ERG (ETS-related gene) is essential for endothelial homeostasis, driving expression of lineage genes and repressing proinflammatory genes. Loss of ERG expression is associated with diseases including atherosclerosis. ERG's homeostatic function is lineage-specific, because aberrant ERG expression in cancer is oncogenic.

Defective Base Excision Repair of Oxidative DNA Damage in Vascular Smooth Muscle Cells Promotes Atherosclerosis.

Background: Atherosclerotic plaques demonstrate extensive accumulation of oxidative DNA damage, predominantly as 8-oxoguanine (8oxoG) lesions. 8oxoG is repaired by base excision repair enzymes; however, the mechanisms regulating 8oxoG accumulation in vascular smooth muscle cells (VSMCs) and its effects on their function and in atherosclerosis are unknown.

Methods: We studied levels of 8oxoG and its regulatory enzymes in human atherosclerosis, the mechanisms regulating 8oxoG repair and the base excision repair enzyme 8oxoG DNA glycosylase I (OGG1) in VSMCs in vitro, and the effects of reducing 8oxoG in VSMCs in atherosclerosis in ApoE mice.

A Comparative Study of Microneedling with Platelet-rich Plasma Plus Topical Minoxidil (5%) and Topical Minoxidil (5%) Alone in Androgenetic Alopecia.

Context: There are very few studies evaluating efficacy of platelet-rich plasma (PRP) in hair restoration and its combination with microneedling. As far as ascertained, there is no study to evaluate efficacy of microneedling with PRP plus topical minoxidil (5%) versus topical minoxidil (5%) alone in androgenetic alopecia (AGA).

Aims: This study aims (1) to compare the efficacy of (a) topical minoxidil (5%) alone and (b) topical minoxidil (5%) + microneedling with PRP in men between 18 and 50 years with AGA Grade III to V vertex (Norwood-Hamilton scale) and (2) to perform objective and subjective evaluation based on clinical improvement and photographic evidence.

Detection of Atherosclerotic Inflammation by Ga-DOTATATE PET Compared to [F]FDG PET Imaging.

Background: Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([F]FDG PET), [F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover.

Objectives: This study tested the efficacy of gallium-68-labeled DOTATATE (Ga-DOTATATE), a somatostatin receptor subtype-2 (SST)-binding PET tracer, for imaging atherosclerotic inflammation.

DNA damage-dependent mechanisms of ageing and disease in the macro- and microvasculature.

A decline in the function of the macro- and micro-vasculature occurs with ageing. DNA damage also accumulates with ageing, and thus DNA damage and repair have important roles in physiological ageing. Considerable evidence also supports a crucial role for DNA damage in the development and progression of macrovascular disease such as atherosclerosis.