Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory.

The traditional medicinal mushroom Hericium erinaceus is known for enhancing peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity. Here, we purified and identified biologically new active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom, together with its hydrophobic derivative hericene A, were highly potent in promoting extensive axon outgrowth and neurite branching in cultured hippocampal neurons even in the absence of serum, demonstrating potent neurotrophic activity. Pharmacological inhibition of tropomyosin receptor kinase B (TrkB) by ANA-12 only partly prevented the NDPIH-induced neurotrophic activity, suggesting a potential link with BDNF signaling. However, we found that NDPIH activated ERK1/2 signaling in the absence of TrkB in HEK-293T cells, an effect that was not sensitive to ANA-12 in the presence of TrkB. Our results demonstrate that NDPIH acts via a complementary neurotrophic pathway independent of TrkB with converging downstream ERK1/2 activation. Mice fed with H. erinaceus crude extract and hericene A also exhibited increased neurotrophin expression and downstream signaling, resulting in significantly enhanced hippocampal memory. Hericene A therefore acts through a novel pan-neurotrophic signaling pathway, leading to improved cognitive performance.

Targeted health and social care interventions for women and infants who are disproportionately impacted by health inequalities in high-income countries: a systematic review.

BACKGROUND: Disadvantaged populations (such as women from minority ethnic groups and those with social complexity) are at an increased risk of poor outcomes and experiences. Inequalities in health outcomes include preterm birth, maternal and perinatal morbidity and mortality, and poor-quality care. The impact of interventions is unclear for this population, in high-income countries (HIC). The review aimed to identify and evaluate the current evidence related to targeted health and social care service interventions in HICs which can improve health inequalities experienced by childbearing women and infants at disproportionate risk of poor outcomes and experiences. METHODS: Twelve databases searched for studies across all HICs, from any methodological design. The search concluded on 8/11/22. The inclusion criteria included interventions that targeted disadvantaged populations which provided a component of clinical care that differed from standard maternity care. RESULTS: Forty six index studies were included. Countries included Australia, Canada, Chile, Hong Kong, UK and USA. A narrative synthesis was undertaken, and results showed three intervention types: midwifery models of care, interdisciplinary care, and community-centred services. These intervention types have been delivered singularly but also in combination of each other demonstrating overlapping features. Overall, results show interventions had positive associations with primary (maternal, perinatal, and infant mortality) and secondary outcomes (experiences and satisfaction, antenatal care coverage, access to care, quality of care, mode of delivery, analgesia use in labour, preterm birth, low birth weight, breastfeeding, family planning, immunisations) however significance and impact vary. Midwifery models of care took an interpersonal and holistic approach as they focused on continuity of carer, home visiting, culturally and linguistically appropriate care and accessibility. Interdisciplinary care took a structural approach, to coordinate care for women requiring multi-agency health and social services. Community-centred services took a place-based approach with interventions that suited the need of its community and their norms. CONCLUSION: Targeted interventions exist in HICs, but these vary according to the context and infrastructure of standard maternity care. Multi-interventional approaches could enhance a targeted approach for at risk populations, in particular combining midwifery models of care with community-centred approaches, to enhance accessibility, earlier engagement, and increased attendance. TRIAL REGISTRATION: PROSPERO Registration number: CRD42020218357.

Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control.

Due to their beneficial effects in an array of diseases, Mesenchymal Stromal Cells (MSCs) have been the focus of intense preclinical research and clinical implementation for decades. MSCs have multilineage differentiation capacity, support hematopoiesis, secrete pro-regenerative factors and exert immunoregulatory functions promoting homeostasis and the resolution of injury/inflammation. The main effects of MSCs include modulation of immune cells (macrophages, neutrophils, and lymphocytes), secretion of antimicrobial peptides, and transfer of mitochondria (Mt) to injured cells. These actions can be enhanced by priming (i.e., licensing) MSCs prior to exposure to deleterious microenvironments. Preclinical evidence suggests that MSCs can exert therapeutic effects in a variety of pathological states, including cardiac, respiratory, hepatic, renal, and neurological diseases. One of the key emerging beneficial actions of MSCs is the improvement of mitochondrial functions in the injured tissues by enhancing mitochondrial quality control (MQC). Recent advances in the understanding of cellular MQC, including mitochondrial biogenesis, mitophagy, fission, and fusion, helped uncover how MSCs enhance these processes. Specifically, MSCs have been suggested to regulate peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α)-dependent biogenesis, Parkin-dependent mitophagy, and Mitofusins (Mfn1/2) or Dynamin Related Protein-1 (Drp1)-mediated fission/fusion. In addition, previous studies also verified mitochondrial transfer from MSCs through tunneling nanotubes and via microvesicular transport. Combined, these effects improve mitochondrial functions, thereby contributing to the resolution of injury and inflammation. Thus, uncovering how MSCs affect MQC opens new therapeutic avenues for organ injury, and the transplantation of MSC-derived mitochondria to injured tissues might represent an attractive new therapeutic approach.

Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites.

Plants accumulate a vast array of secondary metabolites, which constitute a natural resource for pharmaceuticals. Oldenlandia corymbosa belongs to the Rubiaceae family, and has been used in traditional medicine to treat different diseases, including cancer. However, the active metabolites of the plant, their biosynthetic pathway and mode of action in cancer are unknown. To fill these gaps, we exposed this plant to eight different stress conditions and combined different omics data capturing gene expression, metabolic profiles, and anti-cancer activity. Our results show that O. corymbosa extracts are active against breast cancer cell lines and that ursolic acid is responsible for this activity. Moreover, we assembled a high-quality genome and uncovered two genes involved in the biosynthesis of ursolic acid. Finally, we also revealed that ursolic acid causes mitotic catastrophe in cancer cells and identified three high-confidence protein binding targets by Cellular Thermal Shift Assay (CETSA) and reverse docking. Altogether, these results constitute a valuable resource to further characterize the biosynthesis of active metabolites in the Oldenlandia group, while the mode of action of ursolic acid will allow us to further develop this valuable compound.

Transient Hypocalcemia After Total Thyroidectomy: The Obesity Paradox at Work?

INTRODUCTION: With increasing rates of obesity worldwide, a correlation between high body mass index (BMI) and postoperative morbidity after thyroid surgery remains unclear. Postoperative transient hypocalcemia is common after total thyroidectomy due to interruption of parathyroid function. This study examines the relationship between BMI and hypocalcemia after total thyroidectomy. MATERIALS AND METHODS: A retrospective review of prospectively collected data for 1135 patients who underwent total thyroidectomy for cancer, multinodular goiter (MNG), or Graves' disease between June 2009 and November 2020 at a single institution was performed. BMI groups followed the World Health Organization classification. Hypocalcemia was defined as serum calcium ≤8 mg/dL. Calcium levels measured on postoperative day 0 and the following morning were compared between the BMI groups. RESULTS: Of 1135 total thyroidectomy patients, 85% were women. The mean age and standard deviation of patients was 49 (± 13) y, with most of Hispanic origin (64%). Overall, 41.5% of patients had cancer, 45% nontoxic MNG, 5.8% toxic MNG, and 12% Graves' disease. Stratified by BMI, 27% of patients were normal, 34% overweight, and 39% obese. Overall, overweight and obese patients experienced less transient hypocalcemia at both time points compared to normal patients postoperatively (P = 0.01 and P = 0.009). Furthermore, overweight and obese patients with Graves' disease experienced less transient hypocalcemia at both time points (P = 0.04 and P = 0.05). There was no statistical difference in other groups. CONCLUSIONS: A protective role of higher BMI or "obesity paradox" for postoperative hypocalcemia may exist in those obese patients after total thyroidectomy.

DA-9801, a standardized Dioscorea extract, improves memory function via the activation of nerve growth factor-mediated signaling.

OBJECTIVES: Nerve growth factor (NGF) is a neurotrophin that plays a critical role in mammalian learning and memory functions. NGF also regulates neuronal cell differentiation and neurite outgrowth by activating ERK/CREB signaling. This present study examined the effects of a standardized Dioscorea extract (DA-9801), which is composed of Dioscorea japonica Thunb and Dioscorea nipponica Makino on memory function via its NGF-potentiating activities using an in vitro and in vivo paradigm. METHODS: Cells were incubated with or without different concentrations of DA-9801 (10, 25, and 50 µg/ml) extract for 24 h. The cultured conditioned medium from C6 glioma cells was used for NGF production assay, and neurite length in N2a cells was measured after every 2 h. Mice were orally treated with DA-9801 (10 and 100 mg/kg/day) once daily for 7 days. They were subjected to passive avoidance test to evaluate memory functions. The question of whether DA-9801 induced NGF synthesis was assessed by measuring the levels of NGF in the mouse cortical and hippocampal tissues. Hippocampal cell differentiation and NGF-mediated ERK/CREB signaling were evaluated by performing immunohistochemical analysis using BrdU, ki67, DCX, phosphorylated ERK and CREB in the mouse hippocampus. RESULTS: DA-9801 treatment increased the NGF contents and neurite length, respectively. Mice with DA-9801 administration showed memory enhancement in the passive avoidance test. DA-9801 also increased newborn cell differentiation, neurite length, NGF secretion, and ERK/CREB phosphorylation in the mouse hippocampus. DISCUSSION: These results suggest that DA-9801 treatment could improve memory function by inducing hippocampal NGF synthesis and ERK/CREB signaling.

Giving birth in a pandemic: women's birth experiences in England during COVID-19.

BACKGROUND: Expectant parents worldwide have experienced changes in the way they give birth as a result of COVID-19, including restrictions relating to access to birthing units and the presence of birthing partners during the birth, and changes to birth plans. This paper reports the experiences of women in England. METHODS: Data were obtained from both closed- and open-ended responses collected as part of the national COVID in Context of Pregnancy, Infancy and Parenting (CoCoPIP) Study online survey (n = 477 families) between 15th July 2020 - 29th March 2021. Frequency data are presented alongside the results of a sentiment analysis; the open-ended data was analysed thematically. RESULTS: Two-thirds of expectant women reported giving birth via spontaneous vaginal delivery (SVD) (66.1%) and a third via caesarean section (CS) (32.6%) or 'other' (1.3%). Just under half (49.7%) of the CS were reported to have been elective/planned, with 47.7% being emergencies. A third (37.4%) of participants reported having no changes to their birth (as set out in their birthing plan), with a further 25% reporting COVID-related changes, and 37.4% reporting non-COVID related changes (e.g., changes as a result of birthing complications). One quarter of the sample reported COVID-related changes to their birth plan, including limited birthing options and reduced feelings of control; difficulties accessing pain-relief and assistance, and feelings of distress and anxiety. Under half of the respondents reported not knowing whether there could be someone present at the birth (44.8%), with 2.3% of respondents reporting no birthing partner being present due to COVID-related restrictions. Parental experiences of communication and advice provided by the hospital prior to delivery were mixed, with significant stress and anxiety being reported in relation to both the fluctuating guidance and lack of certainty regarding the presence of birthing partners at the birth. The sentiment analysis revealed that participant experiences of giving birth during the pandemic were predominately negative (46.9%) particularly in relation to the first national lockdown, with a smaller proportion of positive (33.2%) and neutral responses (19.9%). CONCLUSION: The proportion of parents reporting birthing interventions (i.e., emergency CS) was higher than previously reported, as were uncertainties related to the birth, and poor communication, leading to increased feelings of anxiety and high levels of negative emotions. The implications of these findings are discussed.

Terpenoids from Glechoma hederacea var. longituba and their biological activities.

Glechoma hederacea var. longituba (common name: ground ivy) has been used for the treatment of asthma, bronchitis, cholelithiasis, colds, and inflammation. In the present study, three new sesquiterpene glycosides (1-3), two new diterpene glycosides (4 and 5), and four known compounds (6-9) were isolated from its MeOH extract. A structure elucidation was performed for the five new compounds (1-5) using 1D and 2D NMR, HRESIMS, DP4+ and ECD calculations, and chemical methods. All the isolates (1-9) were assessed for their antineuroinflammatory activities on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, nerve growth factor (NGF) secretion stimulation activities in C6 glioma cells, and cytotoxic activities against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15). Compounds 2 and 5-7 exhibited inhibitory effects on the NO production with IC50 values of 52.21, 47.90, 61.61, and 25.35 µM, respectively. Compound 5 also exhibited a significant stimulating effect on NGF secretion (122.77 ± 8.10%). Compound 9 showed potent cytotoxic activity against SK-OV-3 (IC50 = 3.76 µM) and SK-MEL-2 (IC50 = 1.48 µM) cell lines, while 7 displayed a strong cytotoxic activity against the SK-MEL-2 (IC50 = 9.81 µM) cell line.

Molecular Testing Has Limited Utility in the Surgical Evaluation of Bethesda III Thyroid Nodules.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology has 6 diagnostic categories, each with an implied cancer risk of malignancy (ROM). Bethesda III, defined as atypia or follicular lesions of undetermined significance (AUS/FLUS) on fine needle aspiration (FNA), has an indeterminate ROM. This study investigates the utility of Afirma Gene Expression Classifier (GEC) and Thyroid Sequencing (ThyroSeq) molecular testing to predict malignancy in AUS/FLUS thyroid nodules. METHODS: A retrospective review of prospectively collected data of 1457 patients with index thyroid nodules who underwent FNA and thyroidectomy at a single academic institution was performed. Use of GEC or ThyroSeq for AUS/FLUS thyroid nodules was examined. GEC testing was reported benign or suspicious for malignancy whereas ThyroSeq testing was reported on a spectrum of low, intermediate or high ROM. Descriptive statistics were utilized to compare the ROM among AUS/FLUS thyroid nodules. RESULTS: Of 1457 patients with FNA thyroid cytology, 359 (25%) corresponded to AUS/FLUS results. There were 132 (37%) patients with GEC testing and 88 (24%) had ThyroSeq testing. ROM without GEC or ThyroSeq testing was 49%, whereas ROM with suspicious GEC was 55%. ROM with positive ThyroSeq was 73%. Among ThyroSeq patients, 43 had intermediate-risk mutations with 60% malignancy, and 23 had high-risk mutations with 96% malignancy (P < 0.01). CONCLUSION: Surgical patients with AUS/FLUS thyroid nodules have a high ROM. High-risk ThyroSeq testing may have some utility in predicting malignancy, but GEC and intermediate-risk TGC results have limited value. Surgeons should carefully consider the utility of molecular tests to determine surgical resection.

Neurotrophic isoindolinones from the fruiting bodies of Hericium erinaceus.

Four compounds, hericerin (1), isohericerinol A (2), N-de-phenylethyl isohericerin (3) and corallocin A (4) were isolated from the fruiting bodies of Hericium erinaceus, a lion's mane mushroom (Hericiaceae). Among them, isohericerinol A (2) was newly reported in nature. Further investigation of the neurotrophic effect of isolated compounds demonstrated that isohericerinol A (2) strongly increased the nerve growth factor (NGF) production in C6 glioma cells followed by corallocin A (4) and hericerin (1). Increased NGF production by these compounds promoted the neurite outgrowth in N2a neuronal cells. Western blot analysis also showed the increased protein expression of NGF, brain-derived neurotrophic factor (BDNF) and synaptophysin (SYP) in C6-N2a cells. Taken together, our present study characterized the neurotrophic constituents of H. erinaceus, which may support the potential use of memory improvement.

Military metaphors and pandemic propaganda: unmasking the betrayal of 'Healthcare Heroes'.

Dr Caitríona L Cox's recent article expounds the far-reaching implications of the 'Healthcare Hero' metaphor. She presents a detailed overview of heroism in the context of clinical care, revealing that healthcare workers, when portrayed as heroes, face challenges in reconciling unreasonable expectations of personal sacrifice without reciprocity or ample structural support from institutions and the general public. We use narrative medicine, a field primarily concerned with honouring the intersubjective narratives shared between patients and providers, in our attempt to deepen the discussion about the ways Healthcare Heroes engenders military metaphor, antiscience discourse, and xenophobia in the USA. We argue that the militarised metaphor of Healthcare Heroes not only robs doctors and nurses of the ability to voice concerns for themselves and their patients, but effectively sacrifices them in a utilitarian bargain whereby human life is considered the expendable sacrifice necessary to 'open the U.S. economy'. Militaristic metaphors in medicine can be dangerous to both doctors and patients, thus, teaching and advocating for the critical skills to analyse and alter this language prevents undue harm to providers and patients, as well as our national and global communities.

Foliar exposure of zinc oxide nanoparticles improved the growth of wheat (Triticum aestivum L.) and decreased cadmium concentration in grains under simultaneous Cd and water deficient stress.

A pot study was conducted to explore the effectiveness of zinc oxide nanoparticles (ZnO NPs) foliar exposure on growth and development of wheat, zinc (Zn) and cadmium (Cd) uptake in Cd-contaminated soil under various moisture conditions. Four different levels (0, 25, 50, 100 mg/L) of these NPs were foliar-applied at different time periods during the growth of wheat. Two soil moisture regimes (70% and 35% of water holding capacity) were maintained from 6 weeks of germination till plant harvesting. The results revealed that the growth of wheat increased with ZnO NPs treatments. The best results were found in 100 mg/L ZnO NPs under normal moisture level. The lowest Cd and highest Zn concentrations were also examined when 100 mg/L NPs were applied without water deficit stress. In grain, Cd concentrations decreased by 26%, 81% and 87% in normal moisture while in water deficit conditions, the Cd concentrations decreased by 35%, 66% and 81% compared to control treatment when ZnO NPs were used at 25, 50 and 100 mg/L. The foliar exposure of ZnO NPs boosted up the leaf chlorophyll contents and also decreased the oxidative stress and enhanced the leaf superoxide dismutase and peroxidase activities than the control. It can be suggested that foliar use of ZnO NPs might be an efficient way for increasing wheat growth and yield with maximum Zn and minimum Cd contents under drought stress while decreasing the chances of NPs movement to other environmental compartment which may be possible in soil applied NPs.

Effect of Regiochemistry and Methylation on the Anticancer Activity of a Ferrocene-Containing Organometallic Nucleoside Analogue.

Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group and either a thyminyl or methylthyminyl group have been synthesised and characterised by a range of spectroscopic and analytical techniques. They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound, 1-(S,Rp ), a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside 1-(S,Rp ), which only differs from the lead compound in being substituted on two cyclopentadienyl rings rather than one, was over 20 times less cytotoxic. On the other hand, methylated derivatives of 1-(S,Rp ) showed comparable cytotoxicities to the lead compound. Overall these studies indicate that a mechanism of action for 1-(S,Rp ) cannot proceed through alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity.

Antineurodegenerative Labdane Diterpenoid Glycosides from the Twigs of Pinus koraiensis.

Eleven new labdane-type diterpenoid glycosides, koraiensides A-K (1-11), together with two known analogues were isolated from the twigs of Pinus koraiensis. Their structures were elucidated via NMR, HRMS, and ECD data, DP4+ statistical analysis, and hydrolysis. The metabolites were tested for induction of nerve growth factor in C6 glioma cells to evaluate their potential neuroprotective activity. The compounds were measured for production of nitric oxide levels in lipopolysaccharide (LPS)-activated murine microglia BV2 cells to assess their antineuroinflammatory activity. Compounds 10 and 13 showed NGF secretion inducing effects from C6 glioma cells (162.3 ± 13.9% and 162.7 ± 6.9%, respectively). Compound 6 showed an IC50 value of 24.1 µM, implying significant inhibition of NO production.

Chemical constituents of Chaenomeles sinensis twigs and their biological activity.

A new megastigmane-type norsesquiterpenoid glycoside, chaemeloside (1), was isolated from the twigs of Chaenomeles sinensis together with 11 known phytochemicals through chromatographic methods. The chemical structure of the new isolate 1 was determined by conventional 1D and 2D NMR data analysis, ECD experiment, hydrolysis followed by a modified Mosher's method, and LC-MS analysis. The characterized compounds' biological effects including cytotoxicity against cancer cell lines, antineuroinflammatory activity, and potential neurotrophic effect were evaluated.

Additional 20-Minute Intraoperative Parathormone Measurement Can Minimize Unnecessary Bilateral Neck Exploration.

BACKGROUND: Parathyroidectomy guided by intraoperative parathormone (ioPTH) monitoring for primary hyperparathyroidism (pHPT) confirms removal of all hyperfunctioning parathyroid glands. This study evaluates the utility of an additional 20-min ioPTH measurement in patients who fail to meet the >50% ioPTH drop criterion. METHODS: A retrospective review of prospectively collected data of 706 patients with pHPT who underwent parathyroidectomy guided by ioPTH monitoring was performed. When a >50% ioPTH decrease from the highest either preincision or preexcision level was achieved after 10 min, parathyroidectomy was completed. If this criterion was not met, further exploration was performed or an additional 20-min ioPTH measurement was obtained. RESULTS: Of 706 patients, 72 (10%) patients did not meet the >50% ioPTH drop criterion at 10 min. Of these patients, 67% (48/72) underwent immediate bilateral neck exploration (BNE). For the other 33% of patients (24/72), a 20-min parathormone (PTH) measurement was drawn. Of patients with an additional 20-min PTH measurement, 46% (11/24) had a >50% ioPTH decrease at 20 min where BNE was avoided and parathyroidectomy completed, whereas 54% (13/24) did not. Compared to patients with insufficient ioPTH drop at 10 min and subsequent BNE, there was a statistically significant 46% reduction of BNE in patients with a 20-min PTH level (P < 0.01). CONCLUSIONS: A 20-min ioPTH measurement is useful in preventing unnecessary BNE in some patients who undergo focused parathyroidectomy with a delayed >50% ioPTH drop.

Thiohydantoin and Hydantoin Derivatives from the Roots of Armoracia rusticana and Their Neurotrophic and Anti-neuroinflammatory Activities.

Two new thiohydantoins (1 and 3) and three new hydantoins (2, 4, and 5) along with three known compounds (6-8) were isolated from roots of horseradish. Physical data analysis including NMR (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC), HRESIMS, and ECD were employed for structure elucidation of the new compounds 1-5. Potential neuroprotective effects of all compounds (1-8) on nerve growth factor (NGF) induction in C6 glioma were also evaluated. Among these compounds, 1b and 2a exhibited potent NGF secretion stimulation activities (NGF secretion levels: 153.59 ± 5.44% and 141.99 ± 5.21%, respectively). Their anti-neuroinflammatory activities were also assessed based on their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide-stimulated murine microglia. Compound 7 marginally inhibited NO production with an IC50 value of 32.6 µM.

Securinega Alkaloids from the Twigs of Securinega suffruticosa and Their Biological Activities.

Seven new Securinega alkaloids, securingines A-G (1-7), together with seven known analogues (8-14), were isolated from the twigs of Securinega suffruticosa. Their chemical structures were elucidated by a combined approach of spectroscopic analysis, chemical methods, ECD calculations, and DP4+ probability analysis. The full NMR assignments and the absolute configuration of compound 8 are also reported. In addition, all the isolated phytochemicals (1-14) were assessed for their cytotoxic, anti-inflammatory, and potential neuroprotective activities. Compound 4 showed cytotoxic activity (IC50 values of 1.5-6.8 µM) against four human cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15). Compounds 3, 10, 12, and 13 showed potent inhibitory effects on nitric oxide production (IC50 values of 12.6, 12.1, 1.1, and 7.7 µM, respectively) in lipopolysaccharide-stimulated murine microglia BV-2 cells. Compound 5 exhibited a nerve growth factor production effect (172.6 ± 1.2%) in C6 glioma cells at 20 µg/mL.

New bis-thioglycosyl-1,1'-disulfides from Nasturtium officinale R. Br. and their anti-neuroinflammatory effect.

As a part of our continuing search for bioactive constituents from Brassicaceae family, three new bis-thioglycosides (1-3) were isolated from the 80% MeOH extract of Nasturtium officinale, together with 13 known compounds (4-16). The chemical structures of three new bis-thioglycosides (1-3) were elucidated using NMR techniques (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC), HRESIMS, and a chemical method. All the compounds were evaluated for their inhibitory effects on nitric oxide (NO) levels in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cells. Among the isolates, compound 5 exhibited a strong inhibitory effect on NO production, and compounds 4 and 15 showed moderate inhibitory activities, suggesting the neuroprotective and anti-neuroinflammatory effects of bis-thioglycosides from N. officinale.

How do women with social risk factors experience United Kingdom maternity care? A realist synthesis.

BACKGROUND: Echoing international trends, the most recent United Kingdom reports of infant and maternal mortality found that pregnancies to women with social risk factors are over 50% more likely to end in stillbirth or neonatal death and carry an increased risk of premature birth and maternal death. The aim of this realist synthesis was to uncover the mechanisms that affect women's experiences of maternity care. METHODS: Using realist methodology, 22 papers exploring how women with a wide range of social risk factors experience maternity care in the United Kingdom were included. The data extraction process identified contexts (C), mechanisms (M), and outcomes (0). RESULTS: Three themes, Resources, Relationships, and Candidacy, overarched eight CMO configurations. Access to services, appropriate education, interpreters, practical support, and continuity of care were particularly relevant for women who are unfamiliar with the United Kingdom system and those living chaotic lives. For women with experience of trauma, or those who lack a sense of control, a trusting relationship with a health care professional was key to regaining trust. Many women who have social care involvement during their pregnancy perceive health care services as a system of surveillance rather than support, impacting on their engagement. This, as well as experiences of paternalistic care and discrimination, could be mitigated through the ability to develop trusting relationships. CONCLUSIONS: The findings provide underlying theory and practical guidance on how to develop safe services that aim to reduce inequalities in women's experiences and birth outcomes.