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The Journal of Pharmacology and... Jun 2024Estrogen receptor (ER)-negative breast cancers are known to be aggressive and unresponsive to anti-estrogen therapy, and triple negative breast cancers are associated...
Estrogen receptor (ER)-negative breast cancers are known to be aggressive and unresponsive to anti-estrogen therapy, and triple negative breast cancers are associated with poor prognosis and metastasis. Thus, new targeted therapies are needed. FOXM1 is abundantly expressed in human cancers and implicated in protecting tumor cells from oxidative stress by reducing the levels of intracellular reactive oxygen species (ROS). Aspirin, a prototypical anti-cancer agent with deleterious side effects, has been modified to release nitric oxide and hydrogen sulfide, called NOSH-aspirin (NOSH-ASA), generating a 'safer' class of new anti-inflammatory agents. We evaluated NOSH-ASA against (ER)-negative breast cancer using cell lines and a xenograft mouse model. NOSH-ASA strongly inhibited growth of MDA-MB-231 and SKBR3 breast cancer cells with low ICs of 90{plus minus}5 and 82{plus minus}5 nM, respectively, with marginal effects on a normal breast epithelial cell line. NOSH-ASA inhibited cell proliferation, caused G/G phase arrest, increased apoptosis, and was associated with increases in ROS. In MDA-MB-231 cell xenografts, NOSH-ASA reduced tumor size markedly, which was associated with reduced proliferation (decreased PCNA expression), induction of apoptosis (increased TUNEL positive cells), and increased ROS, while NF-kB and FoxM1 that were high in untreated xenografts were significantly reduced. mRNA data for FoxM1, p21 and CyclinD1 corroborated with the respective protein expressions and arrest of cells. Taken together, these molecular events contribute to NOSH-ASA mediated growth inhibition and apoptotic death of (ER)-negative breast cells in vitro and in vivo. Additionally, as a ROS-inducer and FOXM1-inhibitor, NOSH-ASA has potential as a targeted therapy. In this investigation, we examined the cellular effects and xenograft tumor inhibitory potential of NOSH-aspirin, an NO and HS-donating hybrid, against ER-negative breast cancer, which currently lacks effective therapeutic options. The induction of reactive oxygen species and subsequent downregulation of FOXM1 represents a plausible mechanism contributing to the observed decrease in cell proliferation and concurrent increase in apoptosis. NOSH-ASA demonstrated a remarkable reduction in tumor size by 90% without inducing any observable gross toxicity, underscoring its promising translational potential.
PubMed: 38936976
DOI: 10.1124/jpet.124.002240 -
Frontiers in Global Women's Health 2024Epilepsy, is a serious neurological condition, characterized by recurring, unprovoked seizures and affects over 50 million people worldwide. Epilepsy has an equal... (Review)
Review
Epilepsy, is a serious neurological condition, characterized by recurring, unprovoked seizures and affects over 50 million people worldwide. Epilepsy has an equal prevalence in males and females, and occurs throughout the life span. Women with epilepsy (WWE) present with unique challenges due to the cyclical fluctuation of sex steroid hormone concentrations during their life course. These shifts in sex steroid hormones and their metabolites are intricately intertwined with seizure susceptibility and affect epilepsy during the life course of women in a complex manner. Here we present a review encompassing neurosteroids-steroids that act on the brain regardless of their site of synthesis in the body; the role of neurosteroids in women with epilepsy through their life-course; exogenous neurosteroid trials; and future research directions. The focus of this review is on progesterone and its derived neurosteroids, given the extensive basic research that supports their role in modulating neuronal excitability.
PubMed: 38933454
DOI: 10.3389/fgwh.2024.1363470 -
Nutrients Jun 2024Irritable bowel syndrome (IBS) and vitamin D deficiency are common among children in Latin America. Previous studies show that improves IBS symptoms in adults. This...
Irritable bowel syndrome (IBS) and vitamin D deficiency are common among children in Latin America. Previous studies show that improves IBS symptoms in adults. This real-world, single-arm, open-label study conducted in Chile investigated the effects of 35624 (1 × 10 colony-forming units, 12 weeks) on gastrointestinal symptoms (adapted IBS severity scoring system [IBS-SSS]; adapted Questionnaire on Pediatric Gastrointestinal Symptoms [QPGS], and Bristol Stool Form Scale) in 64 children and adolescents (8-18 years) and explored the relationship with baseline vitamin D status. Improvements in all IBS-SSS domains and composite score were observed at week 6 and 12 ( < 0.0007 versus baseline), with 98.3% of participants experiencing numerical improvements in ≥3 domains. Clinically meaningful improvement was seen in 96.6% of participants. The distribution of IBS-SSS severity categories shifted from moderate/severe at baseline to mild/remission ( < 0.0001). Improvements were not maintained during the two-week washout. Low baseline serum vitamin D levels did not correlate to IBS severity or probiotic response. QPGS significantly decreased from baseline to week 6 ( = 0.0005) and 12 ( = 0.02). 35624 may improve IBS symptoms in children and adolescents, even those with vitamin D deficiency. A confirmatory randomized controlled trial and further exploration of probiotic response and vitamin D status are needed.
Topics: Humans; Irritable Bowel Syndrome; Adolescent; Child; Probiotics; Male; Female; Bifidobacterium longum; Chile; Treatment Outcome; Severity of Illness Index; Vitamin D; Vitamin D Deficiency
PubMed: 38931319
DOI: 10.3390/nu16121967 -
Nutrients Jun 2024Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there...
Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters.
Topics: Humans; Carpal Tunnel Syndrome; Vitamin D; Female; Vitamin D Deficiency; Male; Middle Aged; Electromyography; Adult; Treatment Outcome; Dietary Supplements; Adrenal Cortex Hormones; Median Nerve; Aged
PubMed: 38931299
DOI: 10.3390/nu16121947 -
Nutrients Jun 2024This study investigated the association of preoperative 25-hydroxy (25 (OH)) vitamin D levels with postoperative complications in osteoporotic hip fracture patients... (Observational Study)
Observational Study
This study investigated the association of preoperative 25-hydroxy (25 (OH)) vitamin D levels with postoperative complications in osteoporotic hip fracture patients following surgery. We hypothesized that patients with low concentrations of 25 (OH) vitamin D might have an increased risk of developing adverse outcomes. Between January 2019 and December 2020, a retrospective observational study was conducted, including low-energy fragility fractures at the proximal femur. Regarding preoperative 25 (OH) vitamin D levels, patients were divided into two groups (<30 ng/mL and ≥30 ng/mL). Early and late postoperative complications were assessed and graded according to the Clavien-Dindo classification system. Logistic regression analysis was performed to demonstrate the association between preoperative 25 (OH) vitamin D levels (<30 ng/mL, ≥30 ng/mL) and postoperative complications after adjusting for age and sex. Of 314 patients, 222 patients (70.7%) had a 25 (OH) vitamin D level of <30 ng/mL. The mean serum 25 (OH) vitamin D level was 22.6 ng/mL (SD 13.2). In 116 patients (36.9%), postoperative complications were observed, with the most occurring in the short term (95 patients, 30.2%). Late postoperative complications were present in 21 patients (6.7%), most graded as Clavien I (57.1%). Logistic regression analysis identified a low vitamin D level (<30 ng/mL) as an independent risk factor for early postoperative complications (OR 2.06, 95% CI 1.14-3.73, = 0.016), while no significant correlation was found in late complications (OR 1.08, 95% CI 0.40-2.95, = 0.879). In conclusion, preoperative 25 (OH) vitamin D serum level might be an independent predictor for early postoperative complications. However, future studies are warranted to determine risk factors for long-term complications and establish appropriate intervention strategies.
Topics: Humans; Female; Male; Postoperative Complications; Vitamin D; Aged; Retrospective Studies; Hip Fractures; Osteoporotic Fractures; Aged, 80 and over; Vitamin D Deficiency; Risk Factors; Middle Aged
PubMed: 38931272
DOI: 10.3390/nu16121917 -
Nutrients Jun 2024Depression is a major global health concern expected to worsen by 2030. In 2019, 28 million individuals were affected by depressive disorders. Dietary and supplemental... (Review)
Review
Depression is a major global health concern expected to worsen by 2030. In 2019, 28 million individuals were affected by depressive disorders. Dietary and supplemental vitamins show overall favorable preventative and therapeutic effects on depression. B vitamins are crucial for neurological function and mood regulation. Deficiencies in these vitamins are linked to depression. Studies on individual B vitamins show promise in improving depressive symptoms, particularly thiamin, riboflavin, niacin, and folate. Vitamin C deficiency may heighten depressive symptoms, but its exact role is not fully understood. Seasonal Affective Disorder (SAD) is associated with insufficient sunlight exposure and vitamin D deficiency. Vitamin D supplementation for SAD shows inconsistent results due to methodological variations. Further investigation is needed to understand the mechanisms of vitamins in depression treatment. Moreover, more research on SAD and light therapy's efficacy and underlying mechanisms involving photoreceptors, enzymes, and immune markers is needed. Although dietary and supplemental vitamins show overall favorable preventative and therapeutic effects on depression, dietitians treating psychiatric disorders face challenges due to diverse study designs, making direct comparisons difficult. Therefore, this article reviews the current literature to assess the role of dietary and supplemental vitamins in the prevention and treatment of depression. This review found that, although evidence supports the role of B vitamins and vitamins C and D in preventing and treating depression, further research is needed to clarify their mechanisms of action and determine the most effective intervention strategies.
Topics: Humans; Seasonal Affective Disorder; Vitamin D; Dietary Supplements; Vitamins; Depression; Adult; Ascorbic Acid; Vitamin B Complex; Vitamin D Deficiency; Female; Solubility
PubMed: 38931257
DOI: 10.3390/nu16121902 -
Nutrients Jun 2024Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life....
Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life. Typically, OA is treated using painkillers and non-steroidal anti-inflammatory drugs (NSAIDs). While current pharmacologic treatments are common, their potential side effects have prompted exploration into functional dietary supplements. Recently, eggshell membrane (ESM) has emerged as a potential functional ingredient for joint and connective tissue disorders due to its clinical efficacy in relieving joint pain and stiffness. Despite promising clinical evidence, the effects of ESM on OA progression and its mechanism of action remain poorly understood. This study evaluated the efficacy of Ovomet, a powdered natural ESM, against joint pain and disease progression in a monosodium iodoacetate (MIA)-induced rodent model of OA in mice and rats. The results demonstrate that ESM significantly alleviates joint pain and attenuates articular cartilage destruction in both mice and rats that received oral supplementation for 5 days prior to OA induction and for 28 days thereafter. Interestingly, ESM significantly inhibited mRNA expression levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as inflammatory mediators, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase in the knee joint cartilage at the early stage of OA, within 7 days after OA induction. However, this effect was not observed in the late stage at 28 days after OA induction. ESM further attenuates the induction of protein expression for cartilage-degrading enzymes like matrix metalloproteinase (MMPs) 3 and 13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in the late-stage. In addition, MIA-induced reduction of the protein expression levels of cartilage components, cartilage oligomeric matrix protein (COMP), aggrecan (ACAN) and collagen type II α-1 chain (COL2α1), and cartilage extracellular matrix (ECM) synthesis promoting transcriptional factor SRY-Box 9 (SOX-9) were increased via ESM treatment in the cartilage tissue. Our findings suggest that Ovomet, a natural ESM powder, is a promising dietary functional ingredient that can alleviate pain, inflammatory response, and cartilage degradation associated with the progression of OA.
Topics: Animals; Egg Shell; Cartilage, Articular; Osteoarthritis; Male; Mice; Nitric Oxide Synthase Type II; Rats; Inflammation; Dietary Supplements; Cytokines; Disease Models, Animal; Rats, Sprague-Dawley; Arthralgia; Time Factors; Iodoacetic Acid; Anti-Inflammatory Agents
PubMed: 38931240
DOI: 10.3390/nu16121885 -
Nutrients Jun 2024Atherosclerosis is one of the most important causes of cardiovascular diseases. A disintegrin and metalloprotease (ADAM)10 and ADAM17 have been identified as important...
Atherosclerosis is one of the most important causes of cardiovascular diseases. A disintegrin and metalloprotease (ADAM)10 and ADAM17 have been identified as important regulators of inflammation in recent years. Our study investigated the effect of inhibiting these enzymes with selective inhibitor and propolis on atherosclerosis. In our study, C57BL/6J mice ( = 16) were used in the control and sham groups. In contrast, ApoE mice ( = 48) were used in the case, water extract of propolis (WEP), ethanolic extract of propolis (EEP), GW280264X (GW-synthetic inhibitor), and solvent (DMSO and ethanol) groups. The control group was fed a control diet, and all other groups were fed a high-cholesterol diet for 16 weeks. WEP (400 mg/kg/day), EEP (200 mg/kg/day), and GW (100 µg/kg/day) were administered intraperitoneally for the last four weeks. Animals were sacrificed, and blood, liver, aortic arch, and aortic root tissues were collected. In serum, total cholesterol (TC), triglycerides (TGs), and glucose (Glu) were measured by enzymatic colorimetric method, while interleukin-1β (IL-1β), paraoxonase-1 (PON-1), and lipoprotein-associated phospholipase-A2 (Lp-PLA2) were measured by ELISA. Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-12 (IL-12) levels were measured in aortic arch by ELISA and ADAM10/17 activities were measured fluorometrically. In addition, aortic root and liver tissues were examined histopathologically and immunohistochemically (ADAM10 and sortilin primary antibody). In the WEP, EEP, and GW groups compared to the case group, TC, TG, TNF-α, IL-1β, IL-6, IL-12, PLA2, MPO, ADAM10/17 activities, plaque burden, lipid accumulation, ADAM10, and sortilin levels decreased, while IL-10 and PON-1 levels increased ( < 0.003). Our study results show that propolis can effectively reduce atherosclerosis-related inflammation and dyslipidemia through ADAM10/17 inhibition.
Topics: Animals; ADAM10 Protein; Mice, Inbred C57BL; Propolis; Inflammation; Dyslipidemias; Mice; Male; Amyloid Precursor Protein Secretases; Atherosclerosis; Cholesterol, Dietary; Diet, High-Fat; Membrane Proteins; Disease Models, Animal
PubMed: 38931216
DOI: 10.3390/nu16121861 -
Nutrients Jun 2024We analyzed the impact of social distancing (SD) on vitamin D status and associated morbidity in neonates during the coronavirus disease (COVID-19) pandemic.
BACKGROUND
We analyzed the impact of social distancing (SD) on vitamin D status and associated morbidity in neonates during the coronavirus disease (COVID-19) pandemic.
METHODS
Serum levels of 25-hydroxy vitamin D (25OHD) and clinical characteristics of newborn infants before (2019) and during SD (2021) were compared.
RESULTS
A total of 526 neonates (263 in 2019 and 263 in 2021) were included. The rate of vitamin D deficiency in neonates (47.1% vs. 35.4 %, = 0.008) decreased and the rate of maternal vitamin D intake increased (6.8% vs. 37.6%, < 0.001), respectively, during SD compared to those in 2019. The rates of hypocalcemia (12.5% vs. 3.8%, < 0.001) and respiratory illness (57.0% vs. 43.0%, = 0.002) decreased during SD. Neonatal vitamin D deficiency during SD was associated with maternal vitamin D supplementation (odds ratio [OR] = 0.463, = 0.003) but was not associated with SD (OR = 0.772, = 0.189). The mediation effect of SD on neonatal morbidity by neonatal vitamin D status was statistically insignificant.
CONCLUSIONS
SD might affect the increased maternal vitamin D intake and decreased neonatal vitamin D deficiency. However, neonatal morbidity was not affected by SD, even with neonatal vitamin D status changes.
Topics: Humans; COVID-19; Vitamin D; Vitamin D Deficiency; Infant, Newborn; Female; Male; Physical Distancing; SARS-CoV-2; Dietary Supplements; Pandemics; Nutritional Status; Hypocalcemia
PubMed: 38931213
DOI: 10.3390/nu16121858 -
Nutrients Jun 2024Contemporary evidence has been established demonstrating that stunted vitamin D levels are associated with depression, poor mood, and other mental disorders. Individuals... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Contemporary evidence has been established demonstrating that stunted vitamin D levels are associated with depression, poor mood, and other mental disorders. Individuals with normal vitamin D levels have a much lower probability of developing depression. Improving vitamin D levels by supplementation has shown betterment in depressive patients among different age groups. The objective of this study was to assess the effect of vitamin D supplementation on depression scores among rural adolescents.
MATERIAL AND METHODS
This study was a cluster randomized controlled trial carried out for a period of 3 years among adolescents from rural Kolar. The sample size was calculated based on previous research and was determined to be 150 for each group. The intervention arm received 2250 IU of vitamin D, and the control arm received a lower dose of 250 IU of vitamin D for 9 weeks. To assess sociodemographic status, a pretested, semi-structured questionnaire was used, and, to assess depression, the Beck Depression Inventory (BDI-II) was used. A baseline assessment was carried out for vitamin D status and depression status, followed by a post-intervention assessment. From the start of the trial, the participants were contacted every week by the pediatric team to investigate any side effects.
RESULTS
Out of 235 school students in the vitamin D supplementation arm, 129 (54.9%) belonged to the 15 years age group, 124 (52.8%) were boys, and 187 (79.6%) belonged to a nuclear family. Out of 216 school students in the calcium supplementation arm, 143 (66.2%) belonged to the 15 years age group, 116 (53.7%) were girls, and 136 (63%) belonged to a nuclear family. By comparing Beck depression scores before and after the intervention, it was found that the vitamin D intervention arm showed a statistically significant reduction in Beck depression scores.
CONCLUSIONS
The present study showed that vitamin D supplementation reduced depression scores, showing some evidence that nutritional interventions for mental health issues such as depression are an excellent option. Vitamin D supplementation in schools can have numerous beneficiary effects on health while mutually benefiting mental health.
Topics: Humans; Adolescent; Male; Female; Dietary Supplements; Depression; Cholecalciferol; Rural Population; Vitamin D Deficiency; Vitamin D; India
PubMed: 38931184
DOI: 10.3390/nu16121828