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The anti‐cancer potential of Cyclopia species (honeybush) has been demonstrated in several models. The present study investigated the effects of aqueous and polyphenol‐enriched (PE) extracts of C. subternata and C. genistoides, as well as mangiferin and hesperidin, on different cell growth parameters in human liver (HepG2) and colon (HT‐29) cancer cells. Mangiferin and hesperidin were most abundant in C. genistoides and C. subternata, respectively. Cyclopia subternata extracts had the highest ferric‐reducing antioxidant capacity. Following exposure of the cells to the extracts and compounds, cell viability, proliferation, and death (apoptosis and autophagy) were determined. Cyclopia subternata extracts reduced cell viability and inhibited cell proliferation the most, associated with depletion of ATP. In HepG2 cells, the PE extracts were less effective than the aqueous extracts in reducing cell viability but more effective in inhibiting cell proliferation. Despite disrupting cell growth, none of the extracts induced apoptosis. The aqueous extracts affected autophagy in both cancer cells. Disruption of mitochondrial membrane integrity by the different extracts, presumably via polyphenol/iron interactions, is postulated to be involved; however, mangiferin and hesperidin had no effect, suggesting that other polyphenols and/or complex interactions between compounds are likely responsible for the differential cytotoxic and/or cytoprotective effects of the extracts. [ABSTRACT FROM AUTHOR]

The anti-allergic effects of extracts prepared from two species of honeybush, Cyclopia genistoides and Cyclopia subternata, were demonstrated in vivo in a murine allergy model for inhaled antigen induced with ovalbumin (OVA) inhalation to mimic pollen allergy. Intake of the extracts increased the production of OVA-specific immunoglobulin (Ig) E (IgE), IgG1, and IgG2a antibodies in serum and significantly suppressed anaphylactic reaction-induced body temperature decline. Moreover, the extracts significantly inhibited antigen-antibodyinduced degranulation in RBL-2H3 cells. They also inhibited body temperature decline when the allergic mice were given them after antigen sensitization, indicating that anti-degranulation activity is the major mechanism underlying the anti-allergic effect of Cyclopia extracts. Despite their qualitative and quantitative differences in phenolic composition, the two extracts exhibited similar effects, suggesting that several active compounds might be involved in the activity. Therefore, oral administration of either Cyclopia extract potentially exerts a systemic anti-allergic effect, supporting the increased consumption of honeybush tea for general wellness and improved quality of life. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case of alobar holoprosencephaly and cyclopia emphasizes the value of prenatal check‐ups, particularly in low‐income countries. Early ultrasound diagnosis leads to early gestational termination, preventing psychological trauma for the parents. Alobar holoprosencephaly is a rare‐occurrence malformation with a bad prognosis linked to cyclopia, the most severe cranial feature. Prenatal examinations are essential for identifying these deformities and preventing parental mental health damage. [ABSTRACT FROM AUTHOR]

Ultra-high temperature oxidation (UHTO) was explored as an alternative to the standard oxidation of honeybush tea, aiming to shorten the processing time and enhance the fruity and sweet-associated sensory characteristics. Different UHTO temperature × time regimes were applied to Cyclopia subternata, C. genistoides, C. intermedia and C. longifolia. Descriptive sensory analysis showed that UHTO treatment, regardless of species, increased the intensities of fruity and sweet-associated aromas while decreasing the intensities of floral aromas. The optimal UHTO regime for each species was subsequently applied to a larger number of plant material batches (n = 10 per species) to introduce a wider range of intra-species variation and confirm broad trends for the sensory profile, as well as for the colour and phenolic composition, of the infusions over species. The effect of treatment conditions on the retention of the phenolic compounds varied, depending on the compound and species. The substantial decrease in the mangiferin and isomangiferin concentrations of C. genistoides infusions, which was not observed for the other species, was notable. The study highlights the potential of UHTO to reduce oxidation time while enhancing the fruity and sweet-associated aroma attributes of honeybush tea, changes that may be beneficial in attracting new consumers and expanding the honeybush tea market.

Cyclopia, an exceedingly rare congenital anomaly, presents intricate deformities affecting the skull, orbits, brain, and nasal cavity, often featuring a singular or partially divided eye within a solitary orbit. Despite medical advancements, the precise etiology of cyclopia remains elusive, with emerging evidence suggesting a potential association with chromosomal aberrations. Timely detection of cyclopia is crucial for effective management and can be facilitated through ultrasonographic techniques. This case report provides a comprehensive exploration of cyclopia, elucidating both gross and radiographic features. Gross examination of the affected fetus unveiled a dysmorphic face characterized by a centrally located single eye, atresia of the nasal conchae, and micrognathia, collectively indicative of cyclopia. Radiographic analysis further revealed a small, severely deformed head, emphasizing malformations in the maxilla and the notable absence of frontal, nasal, and incisive bones. Synthesizing gross and radiographic observations, this report enhances the existing knowledge on this rare congenital anomaly, contributing to a deeper understanding of its complexities for veterinary healthcare professionals and researchers. Such insights are essential for advancing effective management strategies and fostering ongoing research in the realm of veterinary medicine.

Key Clinical Message This case of alobar holoprosencephaly and cyclopia emphasizes the value of prenatal check‐ups, particularly in low‐income countries. Early ultrasound diagnosis leads to early gestational termination, preventing psychological trauma for the parents. Abstract Alobar holoprosencephaly is a rare‐occurrence malformation with a bad prognosis linked to cyclopia, the most severe cranial feature. Prenatal examinations are essential for identifying these deformities and preventing parental mental health damage.

• Xylocopid bees were the only pollinators of four commercially important Cyclopia species (C. maculata, C. subternata, C. intermedia and C. genistoides). • Honey bees were ineffective pollinators of Cyclopia owing to their inability to trip Cyclopia flowers and gain access to the floral reproductive parts. • Nectar measurements revealed low volume of nectar production with varied sugar concentration across species of Cyclopia. • The value of native non- Apis insects for crop pollination in a changing world is highlighted in Cyclopia. Pollination is an important ecosystem service. Animal-mediated pollination (mostly insects) increases the production of 35% of global crops. Honey bees (Apis mellifera) are considered important crop pollinators globally, but are under pressure and therefore the value of wild pollinators for crop production is receiving more attention. The importance of pollinators (including non- Apis) has been extensively studied in the agricultural sector of South Africa, however little research is available on the pollination of indigenous crops. With the considerable value of the indigenous honeybush (Cyclopia Vent.) in the tea industry, it is important to determine the pollinators since Cyclopia is widespread across the fynbos biome and the pollinators are largely unknown. Here we ask whether carpenter bees (xylocopid bees) are the only pollinators of commercially important Cyclopia species, or if honey bees contribute to pollination. Floral observations and camera trapping confirmed that six species of xylocopid bees were the only pollinators of four commercially important Cyclopia species. Honey bees were observed to be ineffective pollinators of Cyclopia owing to their inability to trip Cyclopia flowers and gain access to the floral reproductive parts. Similarly, an additional seven species including Diptera, Apidae and Lema sp. were unable to gain access to Cyclopia flowers, although were observed visiting. Nectar measurements revealed the highest nectar volume in C. genistoides, while C. intermedia had the highest nectar sugar concentration (above 35% for all species). The value of native non- Apis insects for crop pollination in a changing world is highlighted in Cyclopia, an indigenous legume gaining traction in the global tea market and therefore in cultivation. [ABSTRACT FROM AUTHOR]

Cyclopia is the most extreme form of holoprosencephaly. It is characterized by the failure of the embryonic prosencephalon to properly divide the orbits of the eye into two cavities which results in babies with a single or partially divided eye in a single orbit. We report a case of a 28 years old primigravida who came for medical termination at 25 weeks of gestation and delivered a 600 grams dead female fetus with cyclopia, fetal proboscis, and neurocutaneous marker. Its incompatibility with life makes early diagnosis using ultrasonography and fetal magnetic resonance imaging essential in early management and essential counseling to parents.

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Copyright of Bozok Veterinary Sciences is the property of Bozok Veterinary Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Breast cancer is the most diagnosed type of cancer amongst women in economically developing countries and globally. Most breast cancers express estrogen receptor alpha (ERα) and are categorized as positive (ER+ ) breast cancer. Endocrine therapies such as, selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and selective estrogen receptor downregulators (SERDs) are used to treat ER+ breast cancer. However, despite their effectiveness, severe side-effects and resistance are associated with these endocrine therapies. Thus, it would be highly beneficial to develop breast cancer drugs that are as effective as current therapies, but less toxic with fewer side effects, and less likely to induce resistance. Extracts of Cyclopia species, an indigenous South African fynbos plant, have been shown to possess phenolic compounds that exhibit phytoestrogenic and chemopreventive activities against breast cancer development and progression. In the current study, three well characterized Cyclopia extracts, SM6Met, cup of tea (CoT) and P104, were examined for their abilities to modulate the levels of the estrogen receptor subtypes, estrogen receptor alpha and estrogen receptor beta (ERβ), which have been recognized as crucial to breast cancer prognosis and treatment. We showed that the Cyclopia subternata Vogel (C. subternata Vogel) extracts, SM6Met and cup of tea, but not the C. genistoides extract, P104, reduced estrogen receptor alpha protein levels while elevating estrogen receptor beta protein levels, thereby reducing the ERα:ERβ ratio in a similar manner as standard of care breast cancer endocrine therapies such as fulvestrant (selective estrogen receptor downregulator) and 4-hydroxytamoxifen (elective estrogen receptor modulator). Estrogen receptor alpha expression enhances the proliferation of breast cancer cells while estrogen receptor beta inhibits the proliferative activities of estrogen receptor alpha. We also showed that in terms of the molecular mechanisms involved all the Cyclopia extracts regulated estrogen receptor alpha and estrogen receptor beta protein levels through both transcriptional and translational, and proteasomal degradation mechanisms. Therefore, from our findings, we proffer that the C. subternata Vogel extracts, SM6Met and cup of tea, but not the C. genistoides extract, P104, selectively modulate estrogen receptor subtypes levels in a manner that generally supportsinhibition of breast cancer proliferation, thereby demonstrating attributes that could be explored as potential therapeutic agents for breast cancer. [ABSTRACT FROM AUTHOR]

Abnormal embryonic development may result from mutations caused by genetics, environmental conditions or viruses. This study reports cases of cyclopia and a mouth malformation in two embryonic blue shark Prionace glauca collected off southern Brazil (South-western Atlantic). Such malformations are likely to reduce the chances of survival of embryos and neonates. [ABSTRACT FROM AUTHOR]

Breast cancer is the most diagnosed type of cancer amongst women in economically developing countries and globally. Most breast cancers express estrogen receptor alpha (ERα) and are categorized as positive (ER+) breast cancer. Endocrine therapies such as, selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and selective estrogen receptor downregulators (SERDs) are used to treat ER+ breast cancer. However, despite their effectiveness, severe side-effects and resistance are associated with these endocrine therapies. Thus, it would be highly beneficial to develop breast cancer drugs that are as effective as current therapies, but less toxic with fewer side effects, and less likely to induce resistance. Extracts of Cyclopia species, an indigenous South African fynbos plant, have been shown to possess phenolic compounds that exhibit phytoestrogenic and chemopreventive activities against breast cancer development and progression. In the current study, three well characterized Cyclopia extracts, SM6Met, cup of tea (CoT) and P104, were examined for their abilities to modulate the levels of the estrogen receptor subtypes, estrogen receptor alpha and estrogen receptor beta (ERβ), which have been recognized as crucial to breast cancer prognosis and treatment. We showed that the Cyclopia subternata Vogel (C. subternata Vogel) extracts, SM6Met and cup of tea, but not the C. genistoides extract, P104, reduced estrogen receptor alpha protein levels while elevating estrogen receptor beta protein levels, thereby reducing the ERα:ERβ ratio in a similar manner as standard of care breast cancer endocrine therapies such as fulvestrant (selective estrogen receptor downregulator) and 4-hydroxytamoxifen (elective estrogen receptor modulator). Estrogen receptor alpha expression enhances the proliferation of breast cancer cells while estrogen receptor beta inhibits the proliferative activities of estrogen receptor alpha. We also showed that in terms of the molecular mechanisms involved all the Cyclopia extracts regulated estrogen receptor alpha and estrogen receptor beta protein levels through both transcriptional and translational, and proteasomal degradation mechanisms. Therefore, from our findings, we proffer that the C. subternata Vogel extracts, SM6Met and cup of tea, but not the C. genistoides extract, P104, selectively modulate estrogen receptor subtypes levels in a manner that generally supports inhibition of breast cancer proliferation, thereby demonstrating attributes that could be explored as potential therapeutic agents for breast cancer.

During the conventional production of traditional honeybush tea, the lengthy high-temperature oxidation process creates a bottleneck due to constrained equipment capacity, resulting in a backlog in production during peak harvesting. A delay in processing could cause deterioration of the fresh plant material, and ultimately a poor-quality finished product. Cyclopia subternata, C. genistoides and C. intermedia were used to evaluate the viability of preserving the freshly harvested plant material by pre-oxidation drying until equipment capacity becomes available. The quality of their herbal teas, manufactured by using fresh and dried plant material as raw materials, was assessed in terms of sensory characteristics, colour, turbidity and phenolic composition of the infusions. Pre-oxidation drying did not affect the intensities of the aroma attributes, nor were sweetness and astringency affected (p ≥ 0.05). However, the bitter intensity of C. genistoides infusions was slightly increased (p < 0.05). Pre-oxidation drying also resulted in infusions that were slightly lighter, less red and less yellow. The change in individual and overall phenolic content of the infusions was not consistent between species. The overall phenolic content of the infusions increased for C. genistoides, but decreased for C. subternata and C. intermedia. With sensory properties being key to the quality of honeybush tea, pre-oxidation drying of the plant material may be an effective solution to alleviate the manufacturing bottleneck. Not only could it extend the operating period of factories beyond the harvest season, but processing demands could be levelled out.

Synergistic drug combinations are not only popular in antibiotic, anti-microbial, immune disease (i.e., AIDS) and viral infection studies, but has also gained traction in the field of cancer research as a multi-targeted approach. It has the potential to lower the doses needed of standard of care (SOC) therapeutic agents, whilst maintaining an effective therapeutic level. Lower dosages could ameliorate the fundamental problems such as drug resistance and metastasis associated with current SOC therapies. In the current study, we show that the combination of SM6Met with (2)-4-hydroxytamoxifen (4-OH-Tam, the active metabolite of tamoxifen) produces a strong synergistic effect in terms of inhibiting MCF7 ER-positive (ER+) breast cancer cell proliferation and that a 20 times lower dose of 4-OH-Tam in combination with SM6Met is required to produce the same inhibitory effect on cell proliferation as 4-OH-Tam on its own. Cell cycle analyses of the best combination ratios of SM6Met and 4-OHTam also suggests that the combination results in increased accumulation of cells in the S-phase and in the apoptotic phase. Moreover, the best combination ratio (20:1) of SM6Met with 4-OH-Tam displayed greater anti-metastatic potential in terms of inhibiting ER+ breast cancer cell migration, invasion, and colony formation than the SOC therapy alone, suggesting that SM6Met together with 4-OH-Tam could be a viable drug combination for not only delaying resistance and ameliorating the negative side-effects associated with current SOC therapies, like tamoxifen, but could also provide a novel, more affordable therapeutic alternative for treating or preventing ER+ breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Synergistic drug combinations are not only popular in antibiotic, anti-microbial, immune disease (i.e., AIDS) and viral infection studies, but has also gained traction in the field of cancer research as a multi-targeted approach. It has the potential to lower the doses needed of standard of care (SOC) therapeutic agents, whilst maintaining an effective therapeutic level. Lower dosages could ameliorate the fundamental problems such as drug resistance and metastasis associated with current SOC therapies. In the current study, we show that the combination of SM6Met with (2)-4-hydroxytamoxifen (4-OH-Tam, the active metabolite of tamoxifen) produces a strong synergistic effect in terms of inhibiting MCF7 ER-positive (ER+) breast cancer cell proliferation and that a 20 times lower dose of 4-OH-Tam in combination with SM6Met is required to produce the same inhibitory effect on cell proliferation as 4-OH-Tam on its own. Cell cycle analyses of the best combination ratios of SM6Met and 4-OH-Tam also suggests that the combination results in increased accumulation of cells in the S-phase and in the apoptotic phase. Moreover, the best combination ratio (20:1) of SM6Met with 4-OH-Tam displayed greater anti-metastatic potential in terms of inhibiting ER+ breast cancer cell migration, invasion, and colony formation than the SOC therapy alone, suggesting that SM6Met together with 4-OH-Tam could be a viable drug combination for not only delaying resistance and ameliorating the negative side-effects associated with current SOC therapies, like tamoxifen, but could also provide a novel, more affordable therapeutic alternative for treating or preventing ER+ breast cancer metastasis.

Serotonin (5-HT) is known as a substance with a wide range of physiological effects. At the same time, its presence in the cells of the developing embryo is already shown from the earliest stages of development. However, the effect of increasing the level of intracellular serotonin on the processes of cleavage in representatives of Spiralia has not been studied in detail. For the first time, we investigated changes in the pattern of spiral cleavage in the freshwater mollusk Lymnaea stagnalis after incubation of eggs (during 24 h, from the stage of zygote/2 blastomeres) in a solution with serotonin—5-HTP precursor. During cleavage, the mutual arrangement of blastomeres was disrupted in all experimental embryos, starting from the apical rosette stage until the early gastrula. The delay in cytotomy of the blastomeres of the A and C quadrants led to the displacement of blastomeres in all quadrants, including B and D, as a result of which the blastomeres acquired contacts that are unusual for them normally. Subsequently, 80% of the embryos of the experimental group had irreversible impairment of gastrulation and the formation of exogastrula. In embryos that successfully passed gastrulation, malformations of the eyes and shell were observed in 10–15% of cases. Our results show that an increase in the level of intracellular serotonin leads to a disturbance of the mutual arrangement of blastomeres in a representative of Spiralia and may also lead to disorders of further development. [ABSTRACT FROM AUTHOR]

Background: Recent case reports described three cases of holoprosencephaly (HPE) in the area with high mining‐related pollution of the southern region of the Democratic Republic of the Congo (DRC). We reported two male neonates with clinically diagnosed HPE in the localities of Fizi and Kitutu, two mineral areas in the Eastern region of the same country (DRC), where artisanal surface mining is predominant with high exposure to radiation and heavy metals from mining. Cases' presentations: Two newborns from adult and multigravida mothers without pregnancy complication. The birth weights were 3,200 g and 2,500 g, respectively, and the malformations noticed were essentially the single median eye, the absent nose, polydactyly for one case, and proboscis for the other case. They both died a few minutes later after birth. Conclusion: The etiologic factors of HPE remain unknown but seem to be multifactorial from both genetic and environmental factors. We hypothesize under reserve for these two cases that mining and radiation expositions were likely potential environmental associated factors to the occurrence of these malformations. [ABSTRACT FROM AUTHOR]

The formal honeybush tea industry in South Africa is relatively new, and has tremendous growth potential. However, as with other cultivated crops, production and yield can be adversely affected by fungal diseases. A number of Diaporthe species are recognised as causal agents of plant disease symptoms such as dieback, twig blight and branch cankers. For the past few years, such symptoms have been observed on Cyclopia (honeybush) species in cultivated fields located in two districts in the Western Cape province of South Africa. In this study, Diaporthe species associated with honeybush dieback symptoms were identified. One hundred and fifteen isolates recovered from C. genistoides, C. longifolia and C. subternata exhibited cultural characteristics typical of Diaporthe. Representative isolates of the morphological groups were identified to species level, based on the sequence analysis of the rDNA internal transcribed spacer (ITS) region, β-tubulin (tub2), histone 3 (his3) and the translation elongation factor 1-alpha (tef1-α) genes. Seven Diaporthe species were found to be associated with honeybush, namely, D. aspalathi, D. cynaroidis, D. foeniculina, D. heterophyllae, D. inconspicua, D. nebulae and D. sojae. The isolates of each species used in the pathogenicity tests were all pathogenic on C. subternata. Diaporthe heterophyllae was the most virulent species, causing the longest internal lesions as well as typical dieback symptoms. Diaporthe nebulae was moderately virulent in comparison to D. heterophyllae, while the other species were significantly less virulent. [ABSTRACT FROM AUTHOR]

Abstract Cyclopia with a proboscis, a rare congenital anomaly, and a severe form of holoprosencephaly occur as a result of incomplete separation of prosencephalon into two halves of hemispheres during organogenesis. A prenatal anomaly scan can help in the early detection of the condition and timely termination of the pregnancy.

Background: Gene-environment interactions are likely to underlie most human birth defects. The most common known environmental contributor to birth defects is prenatal alcohol exposure. Fetal alcohol spectrum disorders (FASD) describe the full range of defects that result from prenatal alcohol exposure. Gene-ethanol interactions underlie susceptibility to FASD, but we lack a mechanistic understanding of these interactions. Here, we leverage the genetic tractability of zebrafish to address this problem. Results: We first show that vangl2, a member of the Wnt/planar cell polarity (Wnt/PCP) pathway that mediates convergent extension movements, strongly interacts with ethanol during late blastula and early gastrula stages. Embryos mutant or heterozygous for vangl2 are sensitized to ethanol-induced midfacial hypoplasia. We performed single-embryo RNA-seq during early embryonic stages to assess individual variation in the transcriptional response to ethanol and determine the mechanism of the vangl2-ethanol interaction. To identify the pathway(s) that are disrupted by ethanol, we used these global changes in gene expression to identify small molecules that mimic the effects of ethanol via the Library of Integrated Network-based Cellular Signatures (LINCS L1000) dataset. Surprisingly, this dataset predicted that the Sonic Hedgehog (Shh) pathway inhibitor, cyclopamine, would mimic the effects of ethanol, despite ethanol not altering the expression levels of direct targets of Shh signaling. Indeed, we found that ethanol and cyclopamine strongly, but indirectly, interact to disrupt midfacial development. Ethanol also interacts with another Wnt/PCP pathway member, gpc4, and a chemical inhibitor of the Wnt/PCP pathway, blebbistatin, phenocopies the effect of ethanol. By characterizing membrane protrusions, we demonstrate that ethanol synergistically interacts with the loss of vangl2 to disrupt cell polarity required for convergent extension movements. Conclusions: Our results show that the midfacial defects in ethanol-exposed vangl2 mutants are likely due to an indirect interaction between ethanol and the Shh pathway. Vangl2 functions as part of a signaling pathway that regulates coordinated cell movements during midfacial development. Ethanol exposure alters the position of a critical source of Shh signaling that separates the developing eye field into bilateral eyes, allowing the expansion of the midface. Collectively, our results shed light on the mechanism by which the most common teratogen can disrupt development. [ABSTRACT FROM AUTHOR]

Cyclopia is a severe form of holoprosencephaly which results in children being born with just one eye, absence of nose and presence of a proboscis above the median eye. Incidence of cyclopia is around 1.05 in 1, 00,000 births, including stillbirths. The association of anencephaly with spinal rachichisis varies from 17-50%. However, the existence of cyclopia with anencephaly and spinal rachischisis has been reported only in 9 cases till date. We report one more case of cyclopia with anencephaly and spinal rachischisis. Awareness of this spectrum of association with cyclopia, albeit rare, will help in early antenatal diagnosis by fetal ultrasonography. Public education and strict adherence to folic acid supplementation can prevent this unfortunate anomaly.

Holoprosencephaly (HPE) is a congenital malformation of the central nervous system (CNS) that is produced by the lack of segmentation of the prosencephalon in the two cerebral hemispheres. This defect occurs between the days 18th and 28th of gestation and affects both the telencephalon and the structures of the face. In 1964, De Myer classified holoprosencephaly according to the degree of severity into lobar, semilobar, allobar and mid-hemispheric. The etiology of HPE is heterogeneous. Chromosomal abnormalities are found in up to 60% of those affected, mainly trisomy of chromosome 13. The prognosis is bad, in most cases. Prenatal diagnosis of HPE is feasible during the three trimesters of pregnancy. In the first trimester it is performed through the finding of the fusion of the frontal horns of the lateral ventricles and the absence of the sign of the butterfly in a transthalamic axial section of the fetal head. From the second trimester, the findings show a single ventricle, absence of midbrain line and thalamus fused to the midbrain. In addition, other facial defects in the midline can be recognized. The aim of this work is to present a case of allobar HPE and to describe its main clinical features. Likewise, it is intended to show the relevance of recognizing the normal fetal anatomy by ultrasonography in order to detect early developmental alterations. This is a case of a 16 year-old, primigest patient, with a 27.1 week gestation, who consulted for polyhydramnios and fetal alterations evident in the last obstetric ultrasound. A new ultrasound scan is carried out which reports a single fetus with the following alterations: holoprosencephaly, cyclopia, proboscis, arrinia and absence of gastric chamber, findings compatible with trisomy 13. Finally, the pregnancy is terminated by cesarean section, obtaining a deceased newborn. Prenatal and early diagnosis, based on the recognition of normal and abnormal anatomical structures in an ultrasonographic study, allow progress to be made in the diagnostic algorithm and often leads to confirmatory tests (of trisomy, for example) through a prenatal genetic study such as the karyotype. This also makes it possible to carry out individualized attention in a Perinatal Health, High Obstetric Risk or Fetal Medicine unit and eventually make appropriate decisions, according to the legal framework, together with the family. [ABSTRACT FROM AUTHOR]

Cyclopia spp., commonly referred to as honeybush due to the honey scented flowers, are indigenous legumes mainly growing in the Cape Floristic Region of the Western Cape, South Africa. Dozens of species, including Cyclopia intermedia, C. subternata, C. plicata, C. genistoides are used to make the well-known, popular and widely enjoyed beverage called ‘honeybush tea’. In the past, most rhizosphere microbial studies associated with Cyclopia spp. focused mainly on the taxonomy and diversity of the root nodule associated symbiotic nitrogen fixing rhizobia. The work presented here is the first report on the microbial and functional diversity of rhizosphere microbiome associated with Cyclopia intermedia. Metagenomic shotgun sequencing was performed on the rhizosphere soil sample collected from this Cyclopia sp. using illumina Hiseq 2500 platform which resulted in an α- diversity of 312 species. Analysis of the metagenome sequence using the Metagenomic analysis server (MG-RAST) indicated that bacteria constitute the dominant domain followed by Eukaryota, Archaea and other sequences derived from fungi and viruses. Functional diversity of the metagenome based on analysis using the Cluster Orthologous Group (COG) method showed metabolism as the most important function in the community. The raw sequence data is uploaded in FASTQ format on MG-RAST server with ID mgm4855911.3 which can be accessed at http://www.mg-rast.org/linkin.cgi?project=mgp90368. The data on the microbial and functional diversity of the rhizosphere community of Cyclopia intermedia generates a baseline information about the microbial ecology of this indigenous legume. The microbial profile data can also be used as indicators of soil health characteristic of the rhizosphere of this important legume.

Aim This study has three broad aims: to (a) develop genus-specific primers for High Resolution Melt analysis (HRM) of members of Cyclopia Vent., (b) test the haplotype discrimination of HRM compared to Sanger sequencing, and (c) provide an example of using HRM to detect novel haplotype variation in wild C. subternata Vogel. populations. Location The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods Polymorphic loci were detected through a screening process of sequencing 12 non-coding chloroplast DNA segments across 14 Cyclopia species. Twelve genus-specific primer combinations were designed around variable cpDNA loci, four of which failed to amplify under PCR; the eight remaining were applied to test the specificity, sensitivity and accuracy of HRM. The three top performing HRM Primer combinations were then applied to detect novel haplotypes in wild C. subternata populations, and phylogeographic patterns of C. subternata were explored. Results We present a framework for applying HRM to non-model systems. HRM accuracy varied across the PCR products screened using the genus-specific primers developed, ranging between 56 and 100%. The nucleotide variation failing to produce distinct melt curves is discussed. The top three performing regions, having 100% specificity (i.e. different haplotypes were never grouped into the same cluster, no false negatives), were able to detect novel haplotypes in wild C. subternata populations with high accuracy (96%). Sensitivity below 100% (i.e. a single haplotype being clustered into multiple unique groups during HRM curve analysis, false positives) was resolved through sequence confirmation of each cluster resulting in a final accuracy of 100%. Phylogeographic analyses revealed that wild C. subternata populations tend to exhibit phylogeographic structuring across mountain ranges (accounting for 73.8% of genetic variation base on an AMOVA), and genetic differentiation between populations increases with distance (p

Cyclopia is a rare and lethal congenital anomaly of the forebrain system, resulting from incomplete cleavage of prosencephalon into right and left hemispheres occurring between the 18th and the 28th day of gestation. Approximately 1.05 in 100,000 births are identified as infants with cyclopia, including stillbirths. Many teratogenic factors are identified as the causative factors for this anomaly which include irregular cholesterol biosynthesis, radiation exposure, viruses, alcohol intake and maternal diabetes. Many authors also suggest genetic etiology of this illness. We report a case of 35 year old lady G7P6L5 with previous history of normal vaginal delivery who presented to us in second stage of labor. She delivered a male baby with a large head, a median single eye and absent nose with intact mouth. The baby died soon after the birth. This case is presented because of its rarity. Early ultrasound diagnostics and proper management of this anomaly must be emphasized most strongly to prevent complication associated with this condition.

A rare form of cyclopia and arhinia was described in a kid born to a one and half year old primiparous Malabari eutocic doe. The most significant craniofacial malformation was the presence of a single median orbit that contained a single, large exophthalmic eyeball lacking vision. The congenital changes were confined to the head of the kid. The kid showed multiple birth defects like eyelid agenesis, arhinia and prognathism. The possible cause of this congenital defect could not be ascertained. [ABSTRACT FROM AUTHOR]

Aim. This study has three broad aims: to (a) develop genus-specific primers for High Resolution Melt analysis (HRM) of members of Cyclopia Vent., (b) test the haplotype discrimination of HRM compared to Sanger sequencing, and (c) provide an example of usingHRMto detect novel haplotype variation in wild C. subternata Vogel. populations. Location. The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods. Polymorphic loci were detected through a screening process of sequencing 12 non-coding chloroplast DNA segments across 14 Cyclopia species. Twelve genus-specific primer combinations were designed around variable cpDNA loci, four of which failed to amplify under PCR; the eight remaining were applied to test the specificity, sensitivity and accuracy of HRM. The three top performing HRM Primer combinations were then applied to detect novel haplotypes in wild C. subternata populations, and phylogeographic patterns of C. subternata were explored. Results. We present a framework for applying HRM to non-model systems. HRM accuracy varied across the PCR products screened using the genus-specific primers developed, ranging between 56 and 100%. The nucleotide variation failing to produce distinct melt curves is discussed. The top three performing regions, having 100% specificity (i.e. different haplotypes were never grouped into the same cluster, no false negatives), were able to detect novel haplotypes in wild C. subternata populations with high accuracy (96%). Sensitivity below 100% (i.e. a single haplotype being clustered into multiple unique groups during HRM curve analysis, false positives) was resolved through sequence confirmation of each cluster resulting in a final accuracy of 100%. Phylogeographic analyses revealed that wild C. subternata populations tend to exhibit phylogeographic structuring across mountain ranges (accounting for 73.8% of genetic variation base on an AMOVA), and genetic differentiation between populations increases with distance (p<0:05 for IBD analyses). Conclusions. After screening for regions with high HRM clustering specificity akin to the screening process associated with most PCR based markers the technology was found to be a high throughput tool for detecting genetic variation in non-model plants. [ABSTRACT FROM AUTHOR]

Although most of the medical terminology used in pathology derives from the regular forms for the formation of words, there are many terms coined from a proper name called eponyms, where mythonyms (medical terms related to Greek, Roman mythology among others) have a special chapter. Although some terms are derived from mythological figures, others are Greek words related to those figures and therefore have a common origin. Although their number is small, the knowledge of these words enriches our teaching of the pathology and the ability to understand how those who initially described a disease interpreted it. This review will cover the terms achantosis, arachnoiditis, cyclopia, eosin, hermaphrodite, Janus kinase, Klotho protein, lymphoma, caput medusae, chimera, sirenomelia, syringoma and triton tumor, terminology widely used today in our daily work as pathologists. [ABSTRACT FROM AUTHOR]

Cyclopia with a proboscis, a rare congenital anomaly, and a severe form of holoprosencephaly occur as a result of incomplete separation of prosencephalon into two halves of hemispheres during organogenesis. A prenatal anomaly scan can help in the early detection of the condition and timely termination of the pregnancy. [ABSTRACT FROM AUTHOR]

The anti-allergic effects of extracts prepared from two species of honeybush, Cyclopia genistoides and Cyclopia subternata , were demonstrated in vivo in a murine allergy model for inhaled antigen induced with ovalbumin (OVA) inhalation to mimic pollen allergy. Intake of the extracts increased the production of OVA-specific immunoglobulin (Ig) E (IgE), IgG1, and IgG2a antibodies in serum and significantly suppressed anaphylactic reaction-induced body temperature decline. Moreover, the extracts significantly inhibited antigen-antibody-induced degranulation in RBL-2H3 cells. They also inhibited body temperature decline when the allergic mice were given them after antigen sensitization, indicating that anti-degranulation activity is the major mechanism underlying the anti-allergic effect of Cyclopia extracts. Despite their qualitative and quantitative differences in phenolic composition, the two extracts exhibited similar effects, suggesting that several active compounds might be involved in the activity. Therefore, oral administration of either Cyclopia extract potentially exerts a systemic anti-allergic effect, supporting the increased consumption of honeybush tea for general wellness and improved quality of life., Competing Interests: The authors have no conflicts of interest to declare., (©2024 BMFH Press.)

The formal honeybush tea industry has reached a 20-year milestone on 24 February 2019, giving an opportunity to reflect on the research targeting phenolic composition, quality and bioactivity, since a previous review published in 2008. This research underpins ongoing endeavours to unlock the potential of this indigenous agricultural commodity. The current review illustrates that the bulk of the research followed a clear 'vision' to enhance consumer confidence in the product and by exploring value-adding opportunities. Gaps in knowledge were highlighted that could drive future research directions. • Phenolic composition underpinned honeybush product research. • Optimisation of plant material 'fermentation' was driven by sensory quality. • Quality parameters should be tailored to each Cyclopia species. • Clinical evaluation is needed to confirm in vitro/in vivo bioactivities. • Bioactivity research outcomes need translation into nutraceutical products. [ABSTRACT FROM AUTHOR]

Purpose: Imaging modalities such as micro-CT scanning and three-dimensional reconstruction are providing a mechanism for detailed analysis of skeletal components not only of normal specimens but also through revisitation of the abnormal. The aim of this study was to analyse the craniofacial skeleton of five human fetuses with cyclopia by means of micro-CT scanning and three-dimensional reconstruction. Materials and methods: The study consisted of five cyclopean individuals from the paediatric collection of the School of Anatomical Sciences, University of the Witwatersrand. The specimens ranged in age from 22 to 42 weeks of gestation. The osteological features of each bone of the skull were analysed with the aid of micro-CT scanning and analysis using VG studiomax software. Results: A detailed analysis of all the bones of the skull revealed that the upper two-thirds of the viscerocranium and the anterior region of the basicranium were the most affected regions of the cyclopean fetuses. The ethmoid, nasal, inferior concha and the lacrimal bones were absent in all the cases of cyclopia. Major abnormalities were found in the premaxillary region which affected the development of the anterior dentition. Conclusion: This study supports the suggestion that the malformations of the visceral bones are secondary to defective development of the presphenoid and mesethmoid cartilages. The ethmoidal bones are important midline struts during normal development and their absence in cyclopia leads to non-laterality of facial features. [ABSTRACT FROM AUTHOR]

Cyclopia is a congenital anomaly characterized by the presence of a single or partially divided eye in a single orbit at the body midline. This condition is usually associated with other severe facial malformations, such as the absence of the nose and, on rare occasions, the presence of a proboscis located above the ocular structures. The developmental origin of cyclopia in vertebrates is the failure of the embryonic prosencephalon to divide properly during the formation of the two bilateral eyes. Although the developmental origin of the cyclopia‐associated proboscis is not clear, it has been suggested that this unique structure results from the disrupted morphogenesis of the olfactory placodes, the main organizers of the developing nose. In this study, we report a spontaneous congenital case of cyclopia with a proboscis‐like appendage in a chick embryo. By means of both conventional histology and immunohistochemical methods, we have analyzed this anomaly in detail to suggest an alternative identity for the anatomical embryonic features of cyclopic vertebrate embryos displaying a proboscis. Our findings are discussed in the context of previously reported cases of cyclopia, and provide additional insight into this complex congenital malformation. Research Highlights: We have analyzed a chick embryo cyclops with a proboscis and suggested an alternative identity for the anatomical features of anomaly.Our findings provide a new interpretation of this complex congenital malformation. [ABSTRACT FROM AUTHOR]

Cycloferin is an extract of the chemicals from the Cyclopia species, which grows only in small areas in the southwest and southeast of South Africa and has been consumed traditionally as a nourishing tea to treat numerous health issues and illnesses. Previous studies report that some of the active compounds in Cycloferin, such as pinitol (a modified sugar) and mangiferin (a glucoside), may reduce blood sugar levels and therefore may be used as a treatment for diabetes. Mangiferin, in particular, has been shown to stimulate carbohydrate oxidation and alleviate some effects of insulin resistance and hyperglycemia. Other active components of Cycloferin include flavones, isoflavones, coumestans, luteolin, 4-hydroxycinnamic acid, polyphenols, and xanthones. These active compounds are antioxidants, which can enhance glucose breakdown, lower blood lipids, and reduce the number of highly reactive compounds known as free radicals, which can alter cellular structure and function when present in large amounts. In this study, we explored the ameliorative effects of Cycloferin by treating streptozotocin- (STZ) injected rats with Cycloferin and evaluating its long-term and short-term effect on blood glucose levels and kidney and liver conditions of the diabetic-rendered rats. Our results demonstrated the ability of Cycloferin to both lower the blood glucose levels and reduce evidence of damage in kidney and liver in diabetic rats with and without exogenous insulin treatment for partial control of diabetic state. [ABSTRACT FROM AUTHOR]

BACKGROUND: Steam treatment of shredded, fresh C. maculata (honeybush) plant material improves the aroma of this green herbal tea with a slight impact on color and phenolic content, but the effect on storage stability is not known. RESULTS: Steam‐treated (60 s before drying) and untreated (control) dried plant material was stored under normal storage conditions in semi‐permeable sachets at 25 °C and 60% relative humidity. Reference samples of treated (steamed) and untreated (control) material were stored at 0 °C in impermeable pouches for maximum retention of quality. The stability of the herbal tea was assessed in terms of sensory profile, phenolic composition and color over a storage period of 6 months. Normal storage conditions resulted in a significant (P < 0.05) decrease in green color, especially in steamed samples. Intensities of fruity and sweet‐associated aroma attributes increased progressively during storage, while the opposite was observed for vegetal and cereal‐like attributes. These changes in the aroma profile were more pronounced in untreated (control) samples. Individual phenolic content remained stable during storage. CONCLUSIONS: Storage of 3 to 6 months may result in a more appealing aroma profile and enhanced product quality, despite loss of green color. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The most common defect of the forebrain is holoprosencephaly (HPE), characterized by absence in the forebrain division. Holoprosencephaly has a prevalence of 1 / 10,000 in newborns; the cyclopia of 1 / 100,000 births and the agnathia, in a series of cases of holoprosencephaly ranges from 0.8 to 10 %. The objective was the description of the morphological and histopathological characteristics of fetus with holoprosencephaly and its associated malformations. A male fetus was studied. Microdissection was performed under the stereomicroscope, taking microphotographs with AxioCam camera and AxioVision 4.8 software, and histopathological study. The estimated gestational age was 12.4-13.2 weeks, the findings were semilobar HPE, associated with cyclopia, hypoplastic oral outline without buccal opening, covered by a membrane and lips absence. The histopathological study reported: eye with lens, retina and cornea only; in the face, proboscis with tubular cartilage in formation associated with mesenchyme and musculoskeletal sheath, and small oral cavity, delimited by hypoplastic mandible conformed by cartilage. The literature is reviewed and reaffirmed the need for multidisciplinary studies of this disease to improve their understanding. [ABSTRACT FROM AUTHOR]

Holoprosencephaly is a complex developmental abnormality of the brain arising from the failure of cleavage of the prosencephalon. The condition termed “holoprosencephaly” includes cyclopia, cebocephaly, ethmocephaly, and median cleft. We present two cases of antenatally diagnosed alobar holoprosencephaly with multiple associations, which were confirmed after termination of pregnancy. One of them had a proboscis and a single midline eye. The other had multiple facial abnormalities such as hypotelorism, median cleft lip and palate, and preauricular skin tag.

Breast cancer (BC) is the leading cause of cancer-related deaths in women. Chemoprevention of BC by using plant extracts is gaining attention. SM6Met, a well-characterized extract of Cyclopia subternata with reported selective estrogen receptor subtype activity, has shown tumor suppressive effects in a chemically induced BC model in rats, which is known to be estrogen responsive. However, there is no information on the estrogen sensitivity of the relatively new orthotopic model of LA7 cell-induced mammary tumors. In the present study, the potential chemopreventative and side-effect profile of SM6Met on LA7 cell-induced tumor growth was evaluated, as was the effects of 17β-estradiol and standard-of-care (SOC) endocrine therapies, such as tamoxifen (TAM), letrozole (LET), and fulvestrant (FUL). Tumor growth was observed in the tumor-vehicle control group until day 10 post tumor induction, which declined afterward on days 12–14. SM6Met suppressed tumor growth to the same extent as TAM, while LET, but not FUL, also showed substantial anti-tumor effects. Short-term 17β-estradiol treatment reduced tumor volume on days prior to day 10, whereas tumor promoting effects were observed during long-term treatment, which was especially evident at later time points. Marked elevation in serum markers of liver injury, which was further supported by histological evaluation, was observed in the vehicle-treated tumor control, TAM, LET, and long-term 17β-estradiol treatment groups. Alterations in the lipid profiles were also observed in the 17β-estradiol treatment groups. In contrast, SM6Met did not augment the increase in serum levels of liver injury biomarkers caused by tumor induction and no effect was observed on lipid profiles. In summary, the results from the current study demonstrate the chemopreventative effect of SM6Met on mammary tumor growth, which was comparable to that of TAM, without eliciting the negative side-effects observed with this SOC endocrine therapy. Furthermore, the results of this study also showed some responsiveness of LA7-induced tumors to estrogen and SOC endocrine therapies. Thus, this model may be useful in evaluating potential endocrine therapies for hormone responsive BC.

As the embryonic ectoderm is induced to form the neural plate, cells inside this epithelium acquire restricted identities that will dictate their behavior and progressive differentiation. The first behavior adopted by most neural plate cells is called neurulation, a morphogenetic movement shaping the neuroepithelium into a tube. One cell population is not adopting this movement: the eye field. Giving eye identity to a defined population inside the neural plate is therefore a key neural fate decision. While all other neural population undergo neurulation similarly, converging toward the midline, the eye field moves outwards, away from the rest of the forming neural tube, to form vesicles. Thus, while delay in acquisition of most other fates would not have significant morphogenetic consequences, defect in the establishment of the eye field would dramatically impact the formation of the eye. Yet, very little is understood of the molecular and cellular mechanisms driving them. Here, we summarize what is known across vertebrate species and propose a model highlighting what is required to form the essential vesicles that initiate the vertebrate eyes.

Objective: To present perinatal detection of distal 3p duplication and terminal 7q deletion associated with nuchal edema and cyclopia in a fetus, and to review the literature. Materials and methods: A 32-year-old, G9P0, woman who had experienced eight spontaneous abortions was found to have fetal nuchal edema, alobar holoprosencephaly, and cyclopia by prenatal ultrasound at 15 weeks of gestation. The pregnancy was subsequently terminated, and a malformed fetus was delivered with cyclopia. Molecular and conventional cytogenetic analyses were made to determine the genetic pathogenesis of fetal abnormalities. Results: The father had a karyotype of 46,XY,t(3;7)(p22.1;q36.1). The mother had a karyotype of 46,XX. The fetus had a karyotype of 46,XY,der(7)t(3;7)(p22.1;q36.1)pat. The analysis of array comparative genomic hybridization analysis revealed a 43.68-Mb duplication of 3p26.3-3p22.1 encompassing CHL1 and CNTN4, and an 8.66-Mb deletion of 7q36.1-7q36.3 encompassing SHH in the fetus. Conclusion: Simultaneous occurrence of 7q deletion and 3p duplication can be associated with alobar holoprosencephaly. For the couple with a parental translocation involving 7q and 3p, prenatal ultrasound should include a detailed investigation of central nervous system anomalies.

Abstract Normal development involves the interplay of genetic and epigenetic regulatory mechanisms. Pax6 is an eye-selector factor responsible for initiating the regulatory cascade for the development of the eyes. For the olive ridley sea turtle (Lepidochelys olivacea), a threatened species, eye malformations have been reported. In order to study the DNA methylation status of the putative promoter of the Pax6 gene in embryos with ocular malformations, an exploratory study was carried out in which DNA was isolated from embryos with anophthalmia, microphthalmia, and cyclopia, as well as from their normal counterparts. The 5′-flanking region from the Pax6 gene was isolated, showing two CpG islands (CGIs). The methylation status of CGIs in malformed embryos was compared with that of normal embryos by bisulfite sequencing. Putative transcription factor binding sites and regulatory features were identified. Methylation patterns were observed in both CpG and non-CpG contexts, and were unique for each malformed embryo; in the CpG context, an embryo with cyclopia showed a methylated cytosine upstream the CGI-1 not present in other embryos, an embryo with left anophthalmia presented two methylated cytosines in the CGI-1, whereas an embryo with left anophthalmia and right microphthalmia showed two methylated cytosines in the CGI-2. Normal embryos did not show methylated cytosines in the CGI-1, but one of them showed one methylcytosine in the CGI-2. Methylated transcription factor-binding sites may affect Pax6 expression associated to the cellular response to environmental compounds and hypoxia, signal transduction, cell cycle, lens physiology and development, as well as the transcription rate. Although preliminary, these results suggest that embryos with ocular malformations present unique DNA methylation patterns in the putative promoter of the Pax6 gene in L. olivacea , and probably those subtle, random changes in the methylation status can cause (at least in part) the aberrant phenotypes observed in these embryos. Graphical abstract Unlabelled Image Highlights • The olve ridley Pax6 putative promoter region was isolated and characterized. • The methylation status was analyzed in embryos with eye malformations. • Malformed embryos showed different methylcytosines in specific TFBS. • The methylation status was apparently random and individual. • Subtle changes in methylation may be associated to aberrant phenotypes. [ABSTRACT FROM AUTHOR]

Cyclopia (honeybush) species are widely-used in the production of a South African herbal tea and are endemic to the fynbos region of the Western and Eastern Cape Provinces. Honeybush is still one of the orphan agriculture crops and recent breeding efforts by researchers are hampered by the lack of basic genetic information e.g. basic chromosome numbers and ploidy levels. This study determined nuclear DNA content and ploidy level of various genotypes of three Cyclopia species using flow cytometry and cytological counting of chromosomes. Nuclei analysis of young leaves of C. genistoides, C. longifolia and C. subternata were done using a flow cytometer, while root tip squashes were carried out in order to correlate flow cytometry results. Flow cytometry analysis indicated differences in the nuclear DNA content among and within species whilst the DNA ploidy level only differed among species. Cyclopia genistoides had a higher DNA ploidy level (≥ 10C) and DNA content (10.63 pg) than C. longifolia (6.09 pg) and C. subternata (5.99 pg), with no differences observed between the ploidy level of the latter two species (6C). The inferred ploidy level from nuclear DNA content by flow cytometry was consistent in all 30 genotypes of C. longifolia, and 24 of the 25 C. subternata and in only four of the 15 C. genistoides studied genotypes. These findings are important in breeding new cultivars with desired horticultural traits, thus improving the commercial characteristics for the sustainable production of honeybush. [ABSTRACT FROM AUTHOR]

Agnathia is an extremely rare condition. Disorder has also been termed agnathia-holoprosencephaly spectrum, agnathiaotocephaly complex, agnathia-astomia-synotia, or cyclopia-otocephaly association. The spectrum of agnathia ranges from isolated agnathia or virtual absence of the mandible to otocephaly. Agnathia-otocephaly can occur alone or in association with other abnormalities, Holoprosencephaly being the most common. A severe form of holoprosencephaly resulting in children being born with Cyclopia. It results from failure of the cerebral hemisphere to separate during fetal development. It is incompatible with life. Majority result in miscarriages or stillbirths. In this report we present a male preterm baby with cyclopia, otocephaly, agnathia, astomia and synotia (Kanwar Syndrome). As it is a lethal syndrome, knowledge of every variant of this is important for prenatal diagnosis and prognostication. To the best of our knowledge, this unique combination is the first case reported by us in the world. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the leading cause of cancer-related deaths in women. Chemoprevention of BC by using plant extracts is gaining attention. SM6Met, a well-characterized extract of Cyclopia subternata with reported selective estrogen receptor subtype activity, has shown tumor suppressive effects in a chemically induced BC model in rats, which is known to be estrogen responsive. However, there is no information on the estrogen sensitivity of the relatively new orthotopic model of LA7 cell-induced mammary tumors. In the present study, the potential chemopreventative and side-effect profile of SM6Met on LA7 cell-induced tumor growth was evaluated, as was the effects of 17β-estradiol and standard-of-care (SOC) endocrine therapies, such as tamoxifen (TAM), letrozole (LET), and fulvestrant (FUL). Tumor growth was observed in the tumor-vehicle control group until day 10 post tumor induction, which declined afterward on days 12–14. SM6Met suppressed tumor growth to the same extent as TAM, while LET, but not FUL, also showed substantial anti-tumor effects. Short-term 17β-estradiol treatment reduced tumor volume on days prior to day 10, whereas tumor promoting effects were observed during long-term treatment, which was especially evident at later time points. Marked elevation in serum markers of liver injury, which was further supported by histological evaluation, was observed in the vehicle-treated tumor control, TAM, LET, and long-term 17β-estradiol treatment groups. Alterations in the lipid profiles were also observed in the 17β-estradiol treatment groups. In contrast, SM6Met did not augment the increase in serum levels of liver injury biomarkers caused by tumor induction and no effect was observed on lipid profiles. In summary, the results from the current study demonstrate the chemopreventative effect of SM6Met on mammary tumor growth, which was comparable to that of TAM, without eliciting the negative side-effects observed with this SOC endocrine therapy. Furthermore, the results of this study also showed some responsiveness of LA7-induced tumors to estrogen and SOC endocrine therapies. Thus, this model may be useful in evaluating potential endocrine therapies for hormone responsive BC. [ABSTRACT FROM AUTHOR]

ABSTRACT: BACKGROUND: The need for a convenience herbal iced tea product with reduced kilojoules merited investigation of the shelf‐life of powder mixtures containing a green Cyclopia subternata Vogel (honeybush) extract with proven blood glucose‐lowering activity and alternative sweetener mixture. RESULTS: Prior to long‐term storage testing, the wettability of powder mixtures containing food ingredients and the compatibility of their components were confirmed using the static sessile drop method and isothermal microcalorimetry, respectively. The powders packed in semi‐sealed containers remained stable during storage at 25 °C/60% relative humidity (RH) for 6 months, except for small losses of specific phenolic compounds, namely mangiferin, isomangiferin, 3‐β‐ d‐glucopyranosyliriflophenone, vicenin‐2 and 3′,5′‐di‐β‐ d‐glucopyranosylphloretin, especially when both citric acid and ascorbic acid were present. These acids drastically increased the degradation of phenolic compounds under accelerated storage conditions (40 °C/75% RH). Accelerated storage also caused changes in the appearance of powders and the colour of the reconstituted beverage solutions. Increased moisture content and aw of the powders, as well as moisture released due to dehydration of citric acid monohydrate, contributed to these changes. CONCLUSION: A low‐kilojoule honeybush iced tea powder mixture will retain its functional phenolic compounds and physicochemical properties during shelf‐life storage at 25 °C for 6 months. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]