Rice bran arabinoxylan compound as a natural product for cancer treatment - an evidence-based assessment of the effects and mechanisms.

CONTEXT: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties. OBJECTIVE: This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment. METHODS: This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis. RESULTS: The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year. CONCLUSION: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.

Rice Bran Arabinoxylan Compound and Quality of Life (RBAC-QoL) of Cancer Patients: An Interim Analysis of the RBAC-QoL Study.

Background The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design The RBAC-QoL study, a double-blind, randomised, controlled pilot feasibility study, aimed to determine RBAC's effects on QoL and the associated action mechanisms. Primary outcomes were the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods Participants were adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions were RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data was collected from five study visits six weeks apart. The trial remained ongoing as of December 2023. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance was observed and adjusted with covariates. Results Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F1,8 = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at Week 6 (p = 0.032, Cohen's d = 1.454) and marginally at Week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (Week 18) and total protein (Weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson's r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups.  Conclusions RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway - these findings, though preliminary, are valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

Modified Rice Bran Arabinoxylan by Lentinus edodes Mycelial Enzyme as an Immunoceutical for Health and Aging-A Comprehensive Literature Review.

Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran enzymatically treated with Lentinus edodes mycelium. This review explores biologically active compounds and mechanisms of action that support RBAC as an immunomodulating nutraceutical in generally healthy and/or aging individuals. Thirty-seven (n = 37) primary research articles fulfilled the selection criteria for review. Most research is based on Biobran MGN-3, which consists of complex heteropolysaccharides with arabinoxylan as its primary structure while also containing galactan and glucan. RBAC was found to invoke immunological activities through direct absorption via the digestive tract and interaction with immune cells at the Peyer's patches. RBAC was shown to promote innate defence by upregulating macrophage phagocytosis and enhancing natural killer cell activity while lowering oxidative stress. Through induction of dendritic cell maturation, RBAC also augments adaptive immunity by promoting T and B lymphocyte proliferation. RBAC acts as an immunomodulator by inhibiting mast cell degranulation during allergic reactions, attenuating inflammation, and downregulating angiogenesis by modulating cytokines and growth factors. RBAC has been shown to be a safe and effective nutraceutical for improving immune health, notably in aging individuals with reduced immune function. Human clinical trials with geriatric participants have demonstrated RBAC to have prophylactic benefits against viral infection and may improve their quality of life. Further research should explore RBAC's bioavailability, pharmacodynamics, and pharmacokinetics of the complex heteropolysaccharides within. Translational research to assess RBAC as a nutraceutical for the aging population is still required, particularly in human studies with larger sample sizes and cohort studies with long follow-up periods.

Modified rice bran arabinoxylan as a nutraceutical in health and disease-A scoping review with bibliometric analysis.

Rice bran arabinoxylan compound (RBAC) is a polysaccharide modified by Lentinus edodes mycelial enzyme widely used as a nutraceutical. To explore translational research on RBAC, a scoping review was conducted to synthesise research evidence from English (MEDLINE, ProQuest, CENTRAL, Emcare, CINAHL+, Web of Science), Japanese (CiNii, J-Stage), Korean (KCI, RISS, ScienceON), and Chinese (CNKI, Wanfang) sources while combining bibliometrics and network analyses for data visualisation. Searches were conducted between September and October 2022. Ninety-eight articles on RBAC and the biological activities related to human health or disease were included. Research progressed with linear growth (median = 3/year) from 1998 to 2022, predominantly on Biobran MGN-3 (86.73%) and contributed by 289 authors from 100 institutions across 18 countries. Clinical studies constitute 61.1% of recent articles (2018 to 2022). Over 50% of the research was from the USA (29/98, 29.59%) and Japan (22/98, 22.45%). A shifting focus from immuno-cellular activities to human translations over the years was shown via keyword visualisation. Beneficial effects of RBAC include immunomodulation, synergistic anticancer properties, hepatoprotection, antiinflammation, and antioxidation. As an oral supplement taken as an adjuvant during chemoradiotherapy, cancer patients reported reduced side effects and improved quality of life in human studies, indicating RBAC's impact on the psycho-neuro-immune axis. RBAC has been studied in 17 conditions, including cancer, liver diseases, HIV, allergy, chronic fatigue, gastroenteritis, cold/flu, diabetes, and in healthy participants. Further translational research on the impact on patient and community health is required for the evidence-informed use of RBAC in health and disease.

Changes in the Human Gut Microbiome during Dietary Supplementation with Modified Rice Bran Arabinoxylan Compound.

This study investigated the effects of a modified rice bran arabinoxylan compound (RBAC) as a dietary supplement on the gut microbiota of healthy adults. Ten volunteers supplemented their diet with 1 g of RBAC for six weeks and 3 g of RBAC for another six weeks, with a three-week washout period. Faecal samples were collected every 3 weeks over 21 weeks. Microbiota from faecal samples were profiled using 16S rRNA sequencing. Assessment of alpha and beta microbiota diversity was performed using the QIIME2 platform. The results revealed that alpha and beta diversity were not associated with the experimental phase, interventional period, RBAC dosage, or time. However, the statistical significance of the participant was detected in alpha (p < 0.002) and beta (weighted unifrac, p = 0.001) diversity. Explanatory factors, including diet and lifestyle, were significantly associated with alpha (p < 0.05) and beta (p < 0.01) diversity. The individual beta diversity of six participants significantly changed (p < 0.05) during the interventional period. Seven participants showed statistically significant taxonomic changes (ANCOM W ≥ 5). These results classified four participants as responders to RBAC supplementation, with a further two participants as likely responders. In conclusion, the gut microbiome is highly individualised and modulated by RBAC as a dietary supplement, dependent on lifestyle and dietary intake.

Editorial: A Feasible Approach for Natural Products to Treatment of Diseases.

The potential of natural products from both plant and animal sources to treat diseases remains enormous, as our understating forms just the tip of the iceberg [...].

Analgesic effects and metabolome analyses of laser- and electro-acupuncture combined therapies in paclitaxel-induced neuropathic pain model.

Introduction: Allodynia, which can be induced by paclitaxel administration, is the presence of pain as a result of a stimulus that does not usually provoke pain. Many studies have investigated the analgesic efficacy of acupuncture, including laser acupuncture (LA) and electroacupuncture (EA). Although pain-related diseases are relatively common, few studies have analyzed the analgesic effects and mechanisms of LA combined with EA. The purpose of this study was to investigate the therapeutic effect and mechanism of manual acupuncture (MA), EA, LA, and combined therapy (LA + EA) in a paclitaxel-induced allodynia rat model. Methods: A total of 56 rats were classified into eight groups: a normal (Nor, n = 7), a control (Con, n = 7), an MA (n = 7), an EA (n = 7), a 650-nm LA (650LA, n = 7), an 830-nm LA (830LA, n = 7), a 650-nm LA combined with EA (650LA + EA, n = 7), and an 830-nm LA combined with EA group (830LA + EA, n = 7). Allodynia was induced by intraperitoneal injection of 2 mg/kg of paclitaxel every other day for a total of four times except the Nor group. Acupuncture treatments were conducted at the points of Jungwan (CV12) and Joksamni (ST36) once every other day for 6 min, for a total of nine times. Withdrawal response reaction times and force intensity of the foot were measured before the start of the experiment, after the 4th paclitaxel administration (day 8), and after the 9th and last treatment (day 15). On the 16th day, mRNA and protein expression in the spinal nerves was assessed, and a metabolome analysis of the animals' feces was performed. Results and discussion: Our analyses show that 650LA + EA treatment resulted in an upregulation of protein expression related to pain relief and nerve regeneration, whereas 830LA + EA treatment led to significant changes in metabolomes. This study demonstrates that a combination treatment of EA and LA can suppress allodynia and promote upregulation of protein expression related to nerve regeneration and is effective in changing the intestinal microbiome. Further large-scale research is required to assess the exact mechanism underlying the therapeutic effect of this combination treatment in pain-related diseases.

Effectiveness and Safety of Pattern Identification-Based Herbal Medicine for Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Objective: Alzheimer's disease (AD), the most common cause of dementia, has only symptomatic treatments in conventional Western medicine (WM). Disease-modifying drugs are still under development. This study evaluated the efficacy and safety of herbal medicine (HM) based on pattern identification (PI) as a whole system practice for treating AD. Methods: Thirteen databases were searched from inception to August 31, 2021. Twenty-seven randomized controlled trials (RCTs) with 2069 patients were included in the evidence synthesis. Results: The meta-analysis showed that, compared with WM, HM prescription based on PI, either alone or in combination with WM, could significantly improve the cognitive functions of AD patients (Mini-Mental State Examination [MMSE]-HM vs. WM: mean difference [MD] = 1.96, 95% confidence intervals [CIs]: 0.28-3.64, N = 981, I2 = 96%; HM+WM vs. WM: MD = 1.33, 95% CI: 0.57-2.09, N = 695, I2 = 68%) and their ability to perform activities of daily living (ADL-HM vs. WM: standardized mean difference [SMD] = 0.71, 95% CI: 0.04-1.38, N = 639, I2 = 94%; HM+WM vs. WM: SMD = 0.60, 95% CI: 0.27-0.93, N = 669, I2 = 76%). Duration-wise, 12 weeks of HM+WM were superior to 12 weeks of WM and 24 weeks of HM were superior to 24 weeks of WM. None of the included studies found any severe safety concerns. The odds of mild-to-moderate adverse events were marginally lower in HM than in WM (odds ratio = 0.34, 95% CI: 0.11-1.02, N = 689, I2 = 55%). Conclusion: Hence, prescribing PI-based HM is a safe and effective therapeutic option for AD, either as first-line therapy or adjuvant treatment. However, most of the included studies have a high or uncertain risk of bias. Thus, well-designed RCTs with proper blinding and placebo controls are needed.

Polyphenol-Rich Ginger (Zingiber officinale) for Iron Deficiency Anaemia and Other Clinical Entities Associated with Altered Iron Metabolism.

Ginger (Zingiber officinale) is rich in natural polyphenols and may potentially complement oral iron therapy in treating and preventing iron deficiency anaemia (IDA). This narrative review explores the benefits of ginger for IDA and other clinical entities associated with altered iron metabolism. Through in vivo, in vitro, and limited human studies, ginger supplementation was shown to enhance iron absorption and thus increase oral iron therapy's efficacy. It also reduces oxidative stress and inflammation and thus protects against excess free iron. Ginger's bioactive polyphenols are prebiotics to the gut microbiota, promoting gut health and reducing the unwanted side effects of iron tablets. Moreover, ginger polyphenols can enhance the effectiveness of erythropoiesis. In the case of iron overload due to comorbidities from chronic inflammatory disorders, ginger can potentially reverse the adverse impacts and restore iron balance. Ginger can also be used to synthesise nanoparticles sustainably to develop newer and more effective oral iron products and functional ingredients for IDA treatment and prevention. Further research is still needed to explore the applications of ginger polyphenols in iron balance and anaemic conditions. Specifically, long-term, well-designed, controlled trials are required to validate the effectiveness of ginger as an adjuvant treatment for IDA.

Serum Magnesium Levels in Patients with Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis.

Aims: Obstructive sleep apnoea (OSA) affects patients' quality of life and health. Magnesium (Mg) is an essential mineral and a potent antioxidant. Mg deficiency can worsen oxidative stress caused by sleep deprivation or disorders. The impact of OSA on serum Mg levels and its health consequences remain unclear. Data Synthesis: This study systematically reviewed clinical studies investigating the serum Mg levels of OSA patients and the potential relationships with other biomarkers. Six articles were included for qualitative synthesis and quantitative analysis. Two out of four studies that compared OSA patients to healthy controls found them to have significantly lower serum Mg levels. Our meta-analysis with three studies shows that patients with OSA had significantly lower serum Mg with an effect size of -1.22 (95% CI: -2.24, -0.21). However, the mean serum Mg level of OSA patients (n = 251) pooled from five studies (1.90 mg/dL, 95% CI: 1.77, 2.04) does not differ significantly from the normal range between 1.82 to 2.30 mg/dL. OSA severity appears to affect serum Mg negatively. Serum Mg levels generally improve after treatment, coinciding with the improvement of OSA severity. Low serum Mg levels correlate with the worsening of cardiovascular risk biomarkers of C-reactive protein, ischaemia-modified albumin, and carotid intima-media thickness. The serum Mg levels also potentially correlate with biomarkers for lipid profile, glucose metabolism, calcium, and heavy metals. Conclusions: Sleep deprivation appears to deplete Mg levels of OSA patients, making them at risk of Mg deficiency, which potentially increases systemic inflammation and the risk of cardiovascular and metabolic diseases.

Health-Promoting Properties of Medicinal Mushrooms and Their Bioactive Compounds for the COVID-19 Era-An Appraisal: Do the Pro-Health Claims Measure Up?

Many mushroom species are consumed as food, while significant numbers are also utilised medicinally. Mushrooms are rich in nutrients and bioactive compounds. A growing body of in vitro, in vivo, and human research has revealed their therapeutic potentials, which include such properties as anti-pathogenic, antioxidant, anti-inflammatory, immunomodulatory, gut microbiota enhancement, and angiotensin-converting enzyme 2 specificity. The uses of medicinal mushrooms (MMs) as extracts in nutraceuticals and other functional food and health products are burgeoning. COVID-19 presents an opportunity to consider how, and if, specific MM compounds might be utilised therapeutically to mitigate associated risk factors, reduce disease severity, and support recovery. As vaccines become a mainstay, MMs may have the potential as an adjunct therapy to enhance immunity. In the context of COVID-19, this review explores current research about MMs to identify the key properties claimed to confer health benefits. Considered also are barriers or limitations that may impact general recommendations on MMs as therapy. It is contended that the extraction method used to isolate bioactive compounds must be a primary consideration for efficacious targeting of physiological endpoints. Mushrooms commonly available for culinary use and obtainable as a dietary supplement for medicinal purposes are included in this review. Specific properties related to these mushrooms have been considered due to their potential protective and mediating effects on human exposure to the SARS CoV-2 virus and the ensuing COVID-19 disease processes.

Is 6-Shogaol an Effective Phytochemical for Patients With Lower-risk Myelodysplastic Syndrome? A Narrative Review.

Myelodysplastic syndrome (MDS) evolves due to genomic instability, dysregulated signaling pathways, and overproduction of inflammatory markers. Reactive oxygen species contribute to the inflammatory response, which causes gene damage, cellular remodeling, and fibrosis. MDS can be a debilitating condition, and management options in patients with MDS aim to improve cytopenias, delay disease progression, and enhance quality of life. High serum ferritin levels, a source of iron for reactive oxygen species production, correlate with a higher risk of progression to acute myeloid leukemia, and iron overload is compounded by blood transfusions given to improve anemia. 6-shogaol is a natural phenolic compound formed when ginger is exposed to heat and/or acidic conditions, and it has been shown to possess anti-tumor activity against leukemia cell lines and antioxidant effects. This narrative review assessed the potential benefits of this phytochemical in lower-risk MDS patients through examining the current evidence on the pharmacological and therapeutic properties of ginger and 6-shogaol.

Nutraceuticals in Immune Function.

Nutraceutical, a term derived from 'nutrition' and 'pharmaceutical', refers to any product isolated from herbs, nutrients, specific diets, processed foods, and beverages used not only for nutritional but also for medicinal purposes [...].

What Is the Mechanism Driving the Reduction of Cardiovascular Events from Glucagon-like Peptide-1 Receptor Agonists?-A Mini Review.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are considered the standard of care for type 2 diabetes in many countries worldwide. These molecules have profound anti-hyperglycaemic actions with a favourable safety profile. They are now being considered for their robust cardiovascular (CV) protective qualities in diabetic patients. Most recent CV outcome trials have reported that GLP-1 RAs reduce major adverse cardiovascular events (MACE). Furthermore, the GLP-1 RAs seem to target the atherosclerotic CV disease processes preferentially. GLP-1 RAs also improve a wide range of routinely measured surrogate markers associated with CV risk. However, mediation analysis suggests these modest improvements may contribute indirectly to the overall anti-atherogenic profile of the molecules but fall short in accounting for the significant reduction in MACE. This review explores the body of literature to understand the possible mechanisms that contribute to the CV protective profile of GLP-1 RAs.

Herbal Medicine and Acupuncture Combined Treatment Attenuates Colitis in Rats.

This study aimed to verify the efficacy of a combined treatment of Jakyakgamcho-tang (JGT) and acupuncture (CV12, ST25, CV4) on colitis induced by dextrane sulfate sodium (DSS). Changes in immuno-mediated factors and metabolites were investigated. Colitis symptoms such as body weight loss and elevated disease activity index were alleviated by the combined treatment. Moreover, treatment with JGT and acupuncture restored the disturbed architecture of colon by suppressing inflammatory cytokine levels of IFN-[Formula: see text] ([Formula: see text] < 0.05), IL-5 ([Formula: see text] < 0.05), and IL-13 ([Formula: see text] < 0.0001) compared with the DSS group. Analysis of metabolic profiles of serum revealed that treatment groups were clearly separated from the DSS group, suggesting that JGT and acupuncture treatment altered serum metabolites. Furthermore, treatments caused opposite metabolite patterns for dimethylbenzimidazole, 1,5-anhydro-D-glucitol, proline, phosphate, glycolic acid, aspartic acid, tryptophan, phthalic acid, ornithine, and glutamic acid compared with the DSS group. The combined treatment group induced more effective metabolite patterns than the JGT group, implying that acupuncture treatment can restore metabolic changes caused by DSS induction. These results indicate that the simultaneous treatment of JGT administration and acupuncture procedure provides better management of the immune function and inflammatory expression of colitis than a single treatment. It is assumed that intestinal microbial control can be achieved by acupuncture stimulation as well as by taking herbal medicine.

The Health-Promoting Properties and Clinical Applications of Rice Bran Arabinoxylan Modified with Shiitake Mushroom Enzyme-A Narrative Review.

Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran hydrolyzed with Lentinus edodes mycelial enzyme. It has been marketed as a functional food and a nutraceutical with health-promoting properties. Some research has demonstrated this rice bran derivative to be a potent immunomodulator, which also possesses anti-inflammatory, antioxidant, and anti-angiogenic properties. To date, research on RBAC has predominantly focused on its immunomodulatory action and application as a complementary therapy for cancer. Nonetheless, the clinical applications of RBAC can extend beyond cancer therapy. This article is a narrative review of the research on the potential benefits of RBAC for cancer and other health conditions based on the available literature. RBAC research has shown it to be useful as a complementary treatment for cancer and human immunodeficiency virus infection. It can positively modulate serum glucose, lipid and protein metabolism in diabetic patients. Additionally, RBAC has been shown to ameliorate irritable bowel syndrome and protect against liver injury caused by hepatitis or nonalcoholic fatty liver disease. It can potentially ease symptoms in chronic fatigue syndrome and prevent the common cold. RBAC is safe to consume and has no known side effects at the typical dosage of 2-3 g/day. Nevertheless, further research in both basic studies and human clinical trials are required to investigate the clinical applications, mechanisms, and effects of RBAC.

Administration of Kyung-Ok-Ko reduces stress-induced depressive behaviors in mice through inhibition of inflammation pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Kyung-Ok-Ko (KOK), a traditional medicinal formula composed of Rehmannia glutinosa (Gaertn.) DC, Poria cocos (Schw.) Wolf, Korean Red Panax ginseng C.A.Mey, and honey, has been used to treat amnesia and dementia. KOK has also been shown to ameliorate transient cerebral global ischemia-induced brain damage, but the antidepressant-like effect of KOK has not been examined. AIM OF THE STUDY: This study examined the antidepressant-like effect of KOK in an immobilization-induced stress mouse and its mechanisms of action. MATERIALS AND METHODS: The animals in the stress group were immobilized for two hours a day for two weeks. KOK at a dose of 1 g/kg/day was administered orally to the stressed mice for two weeks in advance of their immobilization. A forced swimming test was performed to analyze their depressive behaviors. To examine the anti-inflammatory or antioxidative effects of KOK, the murine macrophage cell line, RAW 264.7 cells and human neuroblastoma cell, SH-SY5Y cells, were treated with lipopolysaccharide (LPS) and hydrogen peroxide, respectively. RESULT: The KOK extract showed no significant toxicity when the cells were treated with a KOK extract at 5, 10, 25, 50, and 100 µg/mL. The KOK ethanol extract reduced LPS-induced TNF-α production, inducible nitric oxide (iNOS) mRNA level, and the levels of MAPK and p38 phosphorylation in RAW 264.7 cells. KOK also suppressed H2O2-induced cell death and the production of reactive oxygen species (ROS) in SH-SY5Y cells. In the forced swimming test, KOK induced a decrease in immobility and an increase in climbing activity. Finally, the administration of KOK reversed the up-regulation of IkB-α phosphorylation in the stressed mouse cortex. CONCLUSION: KOK might be useful for the treatment of depression caused by environmental and lifestyle-related stress.

Rice bran arabinoxylan compound and quality of life of cancer patients (RBAC-QoL): Study protocol for a randomized pilot feasibility trial.

INTRODUCTION: Rice bran arabinoxylan compound (RBAC) is a nutraceutical for enhancing a depleted immune system during and after cancer treatment. This pilot feasibility trial aims to evaluate the effects of RBAC on cancer patients' quality of life during active treatment, compared to placebo, using a validated questionnaire. Other outcome measures include changes in inflammatory and nutritional status, cytokine profile, and gut microbiota. METHODS/DESIGN: The study will recruit 50 participants from a regional cancer center in Australia. Patients aged 18-70, diagnosed with solid organ cancers stage II and above, and currently undergoing active systemic therapies, are eligible. Random allocation of participants into two groups is stratified based on metastatic status and treatment type. The dosage is either 3 g/day of RBAC or placebo in identical packaging. The participants, study coordinator, and treating oncologists are blinded to the interventions. Data collections are at baseline and at four follow-up sessions, which are six weeks apart (24 weeks). Statistical analysis will involve a protected p-value with multiple dependent values and analyzed by ANOVA with repeated measures on the occasion of testing and with both a full Bonferroni or Sidak corrections applied to protect against Type I errors. Any observed significance warrants further analysis with pairwise comparisons. Analysis of covariance will also be performed to assess any influence of the demographic data, cancer diagnosis, as well as changes in physical activity, dietary habits, and complementary medicine usage. Comparisons of gut microbiota will be based on the analysis of the fecal microbiome using 16S ribosomal ribonucleic acid amplicon sequencing. The proposed research timeline is from October 2018 to May 2022. TRIAL REGISTRATION: ANZCTR. Reg No: ACTRN12619000562178p.

Vitex Agnus-Castus for the Treatment of Cyclic Mastalgia: A Systematic Review and Meta-Analysis.

Background: Cyclic mastalgia (CM) is premenstrual bilateral and diffuse breast pain that presents cyclically and affects women in their reproductive years. It may associate with latent hyperprolactinemia due to the insufficient inhibitory effect of dopamine on the pituitary gland. Vitex agnus-castus (VAC) is known for its dopaminergic activity and its possible actions on CM and latent hyperprolactinemia. However, the treatment effect of VAC on CM remains unclear. Materials and Methods: To perform a systematic review and meta-analysis of clinical trials that report on the efficacy of VAC treatment in CM patients, literature search was performed in major research databases. Results: This review includes 25 studies (17 randomized control trials plus eight nonrandomized trials). VAC was effective in relieving breast pain intensity and lowering the increased serum prolactin level in reproductive age CM patients (18-45 years) with or without premenstrual syndromes. Typical dosage was 20-40 mg/day with a treatment duration of 3 months. A conservative meta-analysis included only six studies (n = 718, VAC = 356, placebo = 362) and revealed a moderate effect size (SMD: 0.67, 95% CI: 0.5-0.85) favoring VAC over a placebo. Seven trials demonstrated VAC to be a noninferior alternative to pharmaceutical therapies for CM, including dopamine agonists, nonsteroidal anti-inflammatory drugs, serotonin reuptake inhibitors, and hormonal contraceptives. VAC was safe and associated with only mild and reversible adverse events. However, the risk of bias in most studies was unclear due to insufficient information. Conclusions: VAC is a safe and effective treatment option for CM. More high-quality clinical trials are needed to strengthen the evidence base.

Nasal Cavity Administration of Melanin-Concentrating Hormone Improves Memory Impairment in Memory-Impaired and Alzheimer's Disease Mouse Models.

Melanin-concentrating hormone (MCH) is a highly conserved neuropeptide known to exhibit important functions in the brain. Some studies have reported that MCH improves memory by promoting memory retention. However, the precise molecular mechanisms by which MCH enhances memory impairment have yet to be fully elucidated. In this study, MCH was administered to the scopolamine-induced memory-impaired mice via the nasal cavity to examine the acute effects of MCH and Alzheimer's disease (AD) mouse models to evaluate the chronic effects of MCH. MCH improved memory impairment in both models and reduced soluble amyloid beta in the cerebral cortex of APP/PS1 transgenic mice. In vitro assays also showed that MCH inhibits amyloid beta-induced cytotoxicity. Furthermore, MCH increased long-term potentiation (LTP) in the hippocampus of wild-type and 5XFAD AD mouse model. To further elucidate the mechanisms of the chronic effect of MCH, the levels of phosphorylated CREB and GSK3ß, and the expression of BDNF, TrkB and PSD95 were examined in the cerebral cortex and hippocampus. Our findings indicate that MCH might have neuroprotective effects via downstream pathways associated with the enhancement of neuronal synapses and LTP. This suggests a therapeutic potential of MCH for the treatment of neurodegenerative diseases such as AD.