Effect of Vitamin D Supplementation on Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Dysmenorrhea causes pain and inconvenience during menstruation. In addition to medication, natural compounds are widely used to relieve various types of pain. In this study, we aimed to assess the effects of vitamin D (vit. D) supplementation in relieving the symptoms of primary dysmenorrhea. A comprehensive systematic database search of randomized controlled trials (RCTs) was performed. Oral forms of vit. D supplementation were included and compared with a placebo or standard care. The degree of dysmenorrhea pain was measured with a visual analogue scale or numerical rating scale. Outcomes were compared using the standardized mean difference (SMD) and 95% confidence intervals (CIs) in a meta-analysis. RCTs were assessed using the Cochrane risk-of-bias v2 (RoB 2) tool. The meta-analysis included 8 randomized controlled trials involving 695 participants. The results of the quantitative analysis showed a significantly lower degree of pain in the vit. D versus placebo in those with dysmenorrhea (SMD: -1.404, 95% CI: -2.078 to -0.731). The results of subgroup analysis revealed that pain lessened when the average weekly dose of vit. D was over 50,000 IU, in which dysmenorrhea was relieved regardless of whether vit. D was administered for more or less than 70 days and in any dose interval. The results revealed that vit. D treatment substantially reduced the pain level in the primary dysmenorrhea population. We concluded that vit. D supplementation is an alternative treatment for relieving the pain symptoms of dysmenorrhea.

Consumption of Artificial Sweetener Acesulfame Potassium Increases Preterm Risk and Uterine Contraction with Calcium Influx Increased via Myosin Light Chain Kinase-Myosin Light Chain 20 Related Signaling Pathway.

SCOPE: The consumption of artificial sweeteners has been rapidly increasing, with potentially hazardous effects on human reproduction. This study aims to explore the effect of Acesulfame Potassium (Ace K) and its potential mechanism to induce uterine contraction through in vitro, ex vivo, in vivo, and clinical observation studies. METHODS AND RESULTS: Used ex vivo and in vitro studies to analyze its effect on uterine contraction and involved signaling pathway. Used the long-term, high-dose exposure to examine Ace K's affection for contractive-related protein expression. By involving a cohort of 613 participants, to assess the dose-responsiveness of Ace K consumption and calculate the odd ratio of Ace K consumption and the relationship with preterm risk. Animal studies show increasing uterine contraction, cytokine secretion, and altered contraction-related protein expression. Human data show that higher consumption of Ace K may be related to early delivery. CONCLUSION: Long-term high-dose exposure to Ace K can induce uterine hypercontraction, increase cytokine secretion, and alters contraction-related protein expression. These findings suggest that women who suffer from uterine hypercontraction causes painfulness should pay more attention to the zero- or low-calorie soft drinks or food products containing Ace K.

Adlay Seed (Coix lacryma-jobi L. var. Ma-yuen Stapf.) Ethanolic Extract Fractions and Subfractions Induce Cell Cycle Arrest and Apoptosis in Human Breast and Cervical Cancer Cell Lines.

The antitumor effects of Coix lacryma-jobi L. var. ma-yuen Stapf. (adlay seed) ethanolic extract have been increasingly shown. This study aimed to investigate the beneficial effects of both the fractions and subfractions of adlay seed ethanolic extract on the human breast (MCF-7) and cervical (HeLa) cancer cell lines, as well as exploring their possible mechanisms of action. The ethanolic extracts were obtained from different parts of adlay seed, including AHE (adlay hull extract), ATE (adlay testa extract), ABE (adlay bran extract) and PAE (polished adlay extract). The results of a 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl- tetrazolium bromide (MTT) assay showed that AHE-Ea and ATE-Ea showed significant growth inhibitory effects in a dose-dependent manner. The results also showed that the AHE-Ea-K, AHE-Ea-L, ATE-Ea-E and ATE-Ea-F subfractions inhibited cell proliferation, induced cell cycle arrest in the G0/G1 phase and decreased CDK4/Cyclin D1 protein expression. Finally, the extract activated caspase-3 activity and PARP protein expression, which induced MCF-7 and HeLa cell apoptosis. We then used liquid chromatography-mass spectrometry (LC/MS) to identify the potential active components., Quercetin showed an anticancer capacity. In conclusion, the AHE-Ea-K, AHE-Ea-L, ATE-Ea-E and ATE-Ea-F subfractions showed antitumor effects through the inhibition of MCF-7 and HeLa cell line viability, as well as inducing apoptosis and cell cycle arrest.

Recent Advances in Glycyrrhiza glabra (Licorice)-Containing Herbs Alleviating Radiotherapy- and Chemotherapy-Induced Adverse Reactions in Cancer Treatment.

Cancers represent a significant cause of morbidity and mortality worldwide. They also impose a large economic burden on patients, their families, and health insurance systems. Notably, cancers and the adverse reactions to their therapeutic options, chemotherapy and radiotherapy, dramatically affect the quality of life of afflicted patients. Therefore, developing approaches to manage chemotherapy- and radiotherapy-induced adverse reactions gained greater attention in recent years. Glycyrrhiza glabra (licorice), a perennial plant that is one of the most frequently used herbs in traditional Chinese medicine, has been heavily investigated in relation to cancer therapy. Licorice/licorice-related regimes, used in combination with chemotherapy, may improve the adverse effects of chemotherapy. However, there is little awareness of licorice-containing herbs alleviating reactions to radiotherapy and chemotherapy, or to other induced adverse reactions in cancer treatment. We aimed to provide a descriptive review, and to emphasize the possibility that licorice-related medicines could be used as an adjuvant regimen with chemotherapy to improve quality of life (QoL) and to reduce side effects, thus, improving compliance with chemotherapy. The experimental method involved searching different databases, including PubMed, the Cochrane Library, and Wang Fang database, as of May 2022, to identify any relevant studies. Despite a lack of high-quality and large-scale randomized controlled trials, we still discovered the potential benefits of licorice-containing herbs from published clinical studies. These studies find that licorice-containing herbs, and their active ingredients, reduce the adverse reactions caused by chemotherapy and radiotherapy, and improve the QoL of patients. This comprehensive review will serve as a cornerstone to encourage more scientists to evaluate and develop effective Traditional Chinese medicine prescriptions to improve the side effects of chemotherapy and radiation therapy.

Ethanolic Extracts of Adlay Testa and Hull and Their Active Biomolecules Exert Relaxing Effect on Uterine Muscle Contraction through Blocking Extracellular Calcium Influx in Ex Vivo and In Vivo Studies.

Dysmenorrhea is one of the most prevalent disorders in gynecology. Historically, adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been explored for its anti-tumor, pain relief, anti-inflammatory, and analgesic effects. The aim of this study was to evaluate the effects of adlay seeds on the inhibition of uterine contraction and thus dysmenorrhea relief, in vitro and in vivo. HPLC-MS and GC were used to elucidate the ethyl acetate fraction of adlay testa ethanolic extract (ATE-EA) and ethyl acetate fraction of adlay hull ethanolic extract (AHE-EA). Elucidation yielded flavonoids, phytosterols, and fatty acids. Uterine leiomyomas and normal adjacent myometrial tissue were evaluated by oxytocin- and PG-induced uterine contractility. ATE-EA and AHE-EA suppressed uterine contraction induced by prostaglandin F2 alpha (PGF2α), oxytocin, carbachol, and high-KCl solution ex vivo. In addition, the external calcium (Ca2+) influx induced contraction, and increased Ca2+ concentration was inhibited by ATE-EA and AHE-EA on the uterine smooth muscle of rats. Furthermore, ATE-EA and AHE-EA effectively attenuated the contraction of normal human myometrium tissues more than adjacent uterine leiomyoma in response to PGF2α. 3,5,6,7,8,3',4'-Heptamethoxyflavone and chrysoeriol produced a remarkable inhibition with values of IC50 = 24.91 and 25.59 µM, respectively. The experimental results showed that treatment with ATE-EA at 30 mg/day effectively decreased the writhing frequency both on the oxytocin-induced writhing test and acetic acid writhing test of the ICR mouse.

Antioxidative Activity of Soy, Wheat and Pea Protein Isolates Characterized by Multi-Enzyme Hydrolysis.

Hydrolysis of protein by proteases produces small molecular weights (MWs) peptides as nanomaterials that are easily absorbed. This study investigated the physicochemical properties and antioxidant activity of three plant protein isolates (PIs) including soy, wheat and pea after multi-enzyme hydrolysis. The MWs, particle size and microstructure of PI hydrolysate (PIH) were determined by SDS-PAGE and MALDI-TOF-MS mass spectrometry, dynamic light scattering and transmission electron microscopy, respectively. Cell viability was determined in vitro using a mouse skeletal muscle cell line (C2C12) and crystal violet staining. The MWs and particle sizes of the three plant PIs were reduced after hydrolysis by three proteases (bromelain, Neutrase and Flavourzyme). The MWs of soy, wheat and pea PIH were 103.5-383.0 Da, 103.5-1146.5 Da and 103.1-1937.7 Da, respectively, and particle size distributions of 1.9-2.0 nm, 3.2-5.6 nm and 1.3-3.2 nm, respectively. All three plant PIHs appeared as aggregated nanoparticles. Soy PIH (100 µg/mL) provided better protection against H2O2-induced oxidative damage to C2C12 than wheat or pea PIH. In summary, soy PIH had the best antioxidant activity, and particle size than wheat PIH and pea PIH. Therefore, soy PIH might be a dietary supplement for healthy diet and medical applications.

Physicochemical and Antioxidative Characteristics of Potato Protein Isolate Hydrolysate.

This study investigated the physicochemical characteristics of potato protein isolate hydrolysate (PPIH) and its antioxidant activity. Potato protein isolate (PPI) was hydrolyzed into PPIH by the proteases bromelain, Neutrase, and Flavourzyme. Compared with PPI, the resulting PPIH had a lower molecular weight (MW, from 103.5 to 422.7 Da) and smaller particle size (<50 nm), as well as a higher solubility rate (>70%) under acidic conditions (pH 3-6). PPIH presented good solubility (73%) across the tested pH range of 3-6. As the pH was increased, the zeta potential of PPIH decreased from -7.4 to -21.6. Using the 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical-scavenging assay, we determined that the half-maximal effective concentration (EC50) values of ascorbic acid, PPIH, and PPI were 0.01, 0.89, and >2.33 mg/mL, respectively. Furthermore, PPIH (50 µg/mL) protected C2C12 cells from H2O2 oxidation significantly better than PPI (10.5% higher viability rate; p < 0.01). These findings demonstrated the possible use of PPIH as an antioxidant in medical applications.

Protective Effects of Epigallocatechin Gallate (EGCG) on Endometrial, Breast, and Ovarian Cancers.

Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly antiproliferation, antimetastasis, and apoptosis induction. Many studies have widely investigated the anticancer and synergistic effects of EGCG due to the side effects of conventional cytotoxic agents. This review summarizes recent knowledge of underlying mechanisms of EGCG on protective roles for endometrial, breast, and ovarian cancers based on both in vitro and in vivo animal studies. EGCG has the ability to regulate many pathways, including the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), inhibition of nuclear factor-κB (NF-κB), and protection against epithelial-mesenchymal transition (EMT). EGCG has also been found to interact with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which affect epigenetic modifications. Finally, the action of EGCG may exert a suppressive effect on gynecological cancers and have beneficial effects on auxiliary therapies for known drugs. Thus, future clinical intervention studies with EGCG will be necessary to more and clear evidence for the benefit to these cancers.

The effects of isoliquiritigenin on endometriosis in vivo and in vitro study.

BACKGROUND: Endometriosis is a common gynaecological disease characterized by growth of uterine endometrial tissue, outside the uterine cavity, on the ovaries, oviduct and pelvic peritoneum. Isoliquiritigenin (ISL) is a natural flavonoid isolated from the root of licorice (Glycyrrhiza uralensis) and shallot (Allium cepa). ISL has previously shown antioxidant, anti-inflammatory, anti-proliferation and anti-tumor activities. PURPOSE: This study aimed to investigate the effects of ISL on endometriosis in vivo and in vitro. METHODS: End1/E6E7 endometriosis cells were treated with ISL and ß-estradiol. The MTT assay was used to detect cell viability. Cell migration was evaluated by the wound-healing assay. The expression of epithelial-to-mesenchymal transition (EMT)-related proteins were detected by western blot. Female Balb/c mice, surgically induced to have endometriosis by transplanting uterine tissue into the abdominal cavity, were treated with ISL or vehicle for 4 weeks. Lesion growth was subsequently analyzed by high-resolution ultrasound imaging. Serum and lesion inflammatory cytokines were measured by ELISA. EMT-related proteins and apoptosis-related proteins of endometriotic lesions were detected by western blot. RESULTS: It was observed that ISL treatment inhibited the viability and migration of End1/E6E7. ISL treatment increased the expression of E-cadherin, and decreased the expression of N-cadherin, Slug and Snail. In the animal model, ISL treatment reduced the volume and weight of endometriotic lesions, decreased serum and lesion inflammatory cytokines, inhibited EMT, and induced apoptosis of the lesions. CONCLUSION: ISL inhibited the viability, migration and EMT-related proteins of End1/E6E7 cells, reduced the volume and weight of endometriotic lesions, inhibited inflammatory cytokines and EMT, and induced apoptosis of the lesions to improve endometriosis.