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The vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) axis is indispensable in the process of angiogenesis and has been implicated as a key driver of tumor vascularization. Consequently, several strategies that target VEGF and its cognate receptors, VEGFR-1 and VEGFR-2, have been designed to treat cancer. While therapies targeting full-length VEGF have resulted in an improvement in both overall survival and progression-free survival in various cancers, these benefits have been modest. In addition, the inhibition of VEGFRs is associated with undesirable off-target effects. Moreover, VEGF splice variants that modulate sprouting and non-sprouting angiogenesis have been identified in recent years. Cues within the tumor microenvironment determine the expression patterns of these variants. Noteworthy is that the mechanisms of action of these variants challenge the established norm of VEGF signaling. Furthermore, the aberrant expression of some of these variants has been observed in several cancers. Herein, developments in the understanding of the VEGF/VEGFR axis and the splice products of these molecules, as well as the environmental cues that regulate these variants are reviewed. Furthermore, strategies that incorporate the targeting of VEGF variants to enhance the effectiveness of antiangiogenic therapies in the clinical setting are discussed.

Resveratrol (RES) has a low bioavailability. This limitation was addressed in an earlier review and several recommendations were offered. A literature search was conducted in order to determine the extent of the research that was conducted in line with these recommendations, along with new developments in this field. Most of the identified studies were pre-clinical and confirmed the heightened activity of RES analogues compared to their parent compound. Although this has provided additional scientific kudos for these compounds and has strengthened their potential to be developed into phytopharmaceutical products, clinical trials designed to confirm this increased activity remain lacking and are warranted.

Objective Retinoic acid (RA) is known to transition proliferating SH-SY5Y neuroblastoma cells towards functional neurons. However, the activity of RA is restricted due to its photolability where any findings from prolonged time course observations using microscopy may alter outcomes. The aim of the study was to establish a real-time, long-term (9-day) protocol for the screening of differentiation events using Electrical cell-substrate impedance sensing (ECIS). Results and discussion A differentiation baseline for SH-SY5Y cells was established. Cells were seeded and exposed to repeated spikes of RA using the xCELLigence real-time cell analyser single plate (RTCA-SP) for real-time monitoring and identification of differentiation activity over a 9 day period in order to be more representative of differentiation over a prolonged timeline. Specific features associated with differentiation (growth inhibition, neurite outgrowths) were confirmed by end-point analysis. RA-induced growth inhibition and assumed phenotypic changes (i.e. neurite outgrowth) were identified by the xCELLigence analysis and further confirmed by end-point metabolic and phenotypic assays. Change in cellular morphology and neurite outgrowth length was identified by end-point fluorescence detection followed by computational analysis. Based on this it was possible to identify SH-SY5Y phenotypic differentiation with distinct phases observed over 9 days using Electric cell-substrate impedance sensing (ECIS) cell index traces providing a path to application in larger scale neurotrophic factor screening using this scalable technology.

Background Fetal calf serum (FCS) is a key supplement in cell culture, providing nutrients, and growth factors that support cancer cell proliferation. Studies suggest that compound cytotoxicity profiles in vitro vary depending on FCS concentration in culture medium. The study aimed to examine how extracellular conditions influence the in vitro response of cancer cells to phytocannabinoids, with particular emphasis on serum supplementation. Methods and Results Cells were exposed to CBD and THC in media containing 0.5% or 10% FCS for 24–72 h. Cell viability was assessed using the sulforhodamine B assay and live‐cell imaging. Significantly enhanced cytotoxic effects of CBD and THC were noted under low‐serum conditions (0.5% FCS) compared to standard conditions (10% FCS), particularly after 72 h incubation. THC demonstrated greater cytotoxicity than CBD in SiHa cells, while both compounds showed similar effects in HeLa cells. Conclusion The study demonstrates that serum concentration critically modulates the cytotoxic potency of cannabinoids. Reduced FCS enhances cannabinoid efficacy by limiting protein binding, emphasizing the need to optimize serum conditions for accurate in vitro cytotoxicity assessments.

Introduction: Obesity is increasing worldwide. Due to the unavailability of affordable obesity drugs in most parts of Nigeria, many overweight and obese people rely on medicinal plants to manage obesity. Thus, the aim of this study is to document medicinal plants traditionally used in the treatment and management of obesity in the North Central Zone of Nigeria, determine the plants to which pharmacological assessment of their use in obesity management has not been reported, and assess their toxicity based on the literature. Methods: Semistructured questionnaires and interviews were used to assess sociodemographic information of the 700 herb sellers/practitioners (100 for each state) who consented to participate in the study. Information gathered on plants that are traditionally used in the management of obesity included administration/dosage, method of preparation, plant part used, method of growth, and plant type. The field study was conducted over a one‐year period, from March 2018 to March 2019. Reports of pharmacological activity pertaining to obesity as well as toxicity of the plants were obtained from the literature via scientific databases (Scopus, Web of Science, PubMed, Google Scholar, SciFinder, AJOL, PubChem, and other web sources) after the field survey. Results: A total of 39 families and 70 plant species were used to treat or manage obesity. The majority of plant species used resulted in the family Leguminosae. The relative frequency of citation (RFC) and percentage values for the five most frequently used plants were as follows: Citrus aurantifolia (0.0500; 3.56%), Citrus limon (0.0457; 3.26%), Garcinia kola (0.0429; 3.05%), Zingiber officinale (0.0429; 3.05%), and Allium sativum (0.0414; 2.95%). The majority of the medications were prepared as decoctions (50.5%), and cultivated plants (62.86%) were in the majority of plants used. Results showed that 23 plants have no pharmacological report for antiobesity activities while among the five frequently used plants, only Garcinia kola was reported toxic in preclinical models. Conclusions: This paper provides a valuable compilation of the plants used in obesity treatment in the study area by indigenous healers, highlights plants with no reported pharmacological activity pertaining to obesity, and indicates the toxicity profile of used plants. However, further studies on the mechanism of action are warranted, especially where no reports were obtained.

Three-dimensional cell culture models are increasingly adopted as preferred pre-clinical drug testing platforms, as they circumvent limitations associated with traditional monolayer cell cultures. However, many of these models are not fully characterized. This study aimed to characterize a BT-20 triple-negative breast carcinoma spheroid model and assess its susceptibility to doxorubicin in comparison to a monolayer model. Spheroids were developed using the liquid overlay method. Phenotypic attributes were analyzed by characterizing changes in size, gross morphology, protein content, metabolic activity, hypoxic status, and cell–cell junctions. The cytotoxic range of doxorubicin in monolayers was determined using the sulforhodamine B assay, and the comparative effect of toxic and sub-toxic concentrations was assessed in both spheroids and monolayers. Similar to the in vivo microenvironment, spheroids had a heterogeneous spatial cytoarchitecture, inherent hypoxia and strong adherens junctions. Doxorubicin induced dose-dependent cytotoxicity in monolayers (IC25: 130 nM, IC50: 320 nM and IC75: 1580 nM); however, these concentrations did not alter the spheroid size or acid phosphatase activity. Only concentrations ≥6 µM had any effect on spheroid integrity. In comparison to monolayers, the BT-20 spheroid model has decreased sensitivity to doxorubicin and could serve as a better model for susceptibility testing in triple-negative breast cancer.

The use of the word cosmetics comes from kosmétikos, an Ancient Greek term. This word can be translated as “skilled in adornment,” with the variant kosmein meaning “arrange” or “adorn” and kosmos meaning “order”: Further interpretations include “to make for beauty,” especially of the complexion, or beautifying and “done or made for the sake of appearance,” or “correcting defects especially of the face,” primarily it is “decorative” or “ornamental” (Oumeish, 2001). The concept of beauty is one of the aspects of the Greek word komes, which means harmony, and was used to attain perfection. Gradually its meaning has changed until it became connected with the idea that was more closely related to the masking, concealing and camouflaging, as true beauty originates from the inner being and could not be created externally. Since primeval time, numerous civilisations have been subjected to the use of herbs as cosmetic applications. Even today, the demand and the utilization of phytocosmetics have increased in the personal care system (Mahomoodally and Ramjuttun, 2016). Research into the value and use of plant and mineral resources in cosmetics continued over the centuries evolving into what we consider to be cosmeceuticals. Interestingly, there is a great tendency of consumers to return to the use of herbs/herbal products for various applications to implement a more natural mode of life (Mahomoodally and Ramjuttun, 2016).

Background: Guiera senegalensis (Ghibaish) is a medicinal plant extensively used in central and west Africa for the management of various diseases.Aim: This study aimed to determine the antioxidant activity of the ethanol leaf extract of the plant.Method: The ethanol leaf extract was sequentially sub-fractionated using liquid–liquid extraction, vacuum-liquid chromatography and preparative thin layer chromatography. Ultra-performance liquid chromatography with accurate mass spectrometry and nuclear magnetic resonance were employed to isolate and confirm the identity of the most abundant compound. The antioxidant activity of the fractions and isolated compound was assessed by bioautography analysis and the 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) radical scavenging assay.Results: The dichloromethane subfraction contained the most promising antioxidant activity (IC50 = 3.18 µg/mL). Purification of this subfraction led to the isolation of a brown crystalline compound, which was identified as 5-methyldihydroflavasperone (IC50 4000 µg/mL).Conclusion: This is the first report of the isolation of 5-methyldihydroflavasperone from the ethanol leaf extracts of G. senegalensis. This compound was not found to be responsible for the antioxidant activity observed. Further research is warranted to identify the compound responsible for the antioxidant activity.