Comparative study for fatigue prevalence in subjects with diseases: a systematic review and meta-analysis.

Fatigue is one of the common symptoms in individuals with diseases or disorders, significantly affecting quality of life (QoL) and the prognosis of diseases. This study aimed to comprehensively compare the features of fatigue across a wide range of diseases. We systematically searched the PubMed and Cochrane Library databases from inception to March 31st, 2021, and conducted a meta-analysis to generate precise estimates. The analyses were stratified by classification of diseases, gender, and severity of fatigue (moderate and severe), and study quality was assessed using the Newcastle-Ottawa Scale (NOS). In total, 214 articles (233 prevalence data) met our eligibility criteria, covering 102,024 participants (mean 438 ± 1,421) across 88 diseases. Among these, seventy-eight data sets (52,082 participants) and thirty-nine data sets (10,389 participants) reported gender- and severity-related fatigue prevalence. The overall prevalence among subjects with 88 diseases was 49.4% [95% CI 46.9-52.1]. According to the International Classification of Diseases-10 (ICD-10) classification, the highest prevalence of fatigue (65.9% [95% CI 54.9-79.6]) was observed in patients with mental/behavioral diseases, whereas the lowest prevalence (34.7% [95% CI 24.5-49.2]) was found among those with circulatory system diseases. A slight female dominance (43.5% vs. 49.8%) was observed in the total data, with the most notable female predominance (1.8-fold) seen in patients with low back pain. The top disease groups with a moderate to severe level of fatigue included gastroparesis (92.3%), pulmonary hypertension (90.0%), chronic obstructive pulmonary disease (COPD, 83.2%), and multiple sclerosis (80.0%). These results are the first to comprehensively show the comparative features of fatigue prevalence among subjects across 88 diseases. Our findings provide valuable reference data for future research on fatigue and for the management of patients with fatigue.Prospero registration number: CRD42021270494.

Additional effects of herbal medicine combined with bisphosphonates for primary osteoporosis: a systematic review and meta-analysis.

Background: Osteoporosis (OP) is a significant medical issue associated with population aging. Recent research on herbal medicines (HMs) for OP has been increasing, with these therapies sometimes used in conjunction with bisphosphonates (BPs), the standard treatment for OP. We conducted a systematic review and meta-analysis to evaluate the effects of combining HMs with BPs on improving bone mineral density (BMD) in patients with primary OP. Methods: We searched nine databases-PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Wanfang, KISS, Kmbase, Science On, and Oasis-up to 31 August 2023. We selected randomized controlled trials (RCTs) comparing BMD between HMs plus BPs and BPs alone in primary OP. A meta-analysis with BMD as the primary outcome was performed using RevMan version 5.4. Study quality and evidence certainty were assessed through Cochrane's risk of bias2 and GRADE. Results: Out of 43 RCTs involving 4,470 participants (mean age 65.8 ± 6.6 years), 35 RCTs with 3,693 participants were included in the meta-analysis. The combination of HMs and BPs was found to be more effective in improving BMD compared to BPs alone, with improvements of 0.10 g/cm2 at the lumbar spine (33 RCTs, 95% CI: 0.07-0.12, p < 0.001, I2 = 93%) and 0.08 g/cm2 at the femoral neck (20 RCTs, 95% CI: 0.05-0.12, p < 0.001, I2 = 94%), though this result was associated with high heterogeneity, high risk of bias, and very low certainty of evidence. Conclusion: Our data suggest the possibility that combining HMs with BPs may improve BMD in primary OP more effectively than using BPs alone. However, the results should be interpreted with caution due to the high heterogeneity and low quality of the studies included in the review. Therefore, further well-designed RCTs are needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023392139.

An evolutionary perspective for integrating mechanisms of acupuncture therapy.

This study applies an evolutionary medicine perspective to comprehend the therapeutic effects of acupuncture. It draws upon modern evolutionary theory to integrate the currently fragmented theories regarding the efficacy of acupuncture in alleviating pain and promoting healing. We explore the interaction between the nervous and immune systems in the context of survival and homeostasis, and elucidate both the local and systemic effects of acupuncture therapy on pain relief and tissue healing. The mechanisms involved are categorized into two main types: local effects, which include immune cell migration, local vasodilation, and the release of adenosine; and distal systemic effects, which involve the regulation of the descending pain control system and the autonomic nervous system, with a particular focus on the parasympathetic nervous system. In conclusion, this integrated perspective not only deepens our understanding of acupuncture within a scientific narrative but also underscores the need for further research to validate and expand our knowledge, thereby enhancing its scientific credibility and clinical applicability.

Effectiveness of meditation for fatigue management: Insight from a comprehensive systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis revealed the effectiveness of meditation in addressing fatigue, given its widespread use as a remedy for sleep disturbances and fatigue. METHOD: We analyzed 29 randomized controlled trials from MEDLINE and the Cochrane Library, spanning from December 31, 2022. We conducted two metaanalyses using mean difference (MD) with normalized data and standardized mean difference (SMD) with original data. RESULTS: These trials included various populations, with baseline fatigue severity observed at 52.2 ± 16.0 points among 4104 participants. After an average meditation duration of 9.6 ± 4.7 weeks, fatigue scores decreased significantly by 6.4 points of MD [95% CI, 4.3-8.5] compared to controls. The most significant reduction occurred in the sub-healthy group (MD 8.2 [95% CI, 2.7 to 13.8]), followed by the general group (MD 6.9 [95% CI, 0.4 to 13.4]), and the disease group (MD 5.7 [95% CI, 3.4 to 8.0]). Notably, meditation-based anti-fatigue effects were particularly pronounced for mental fatigue (MD 10.0 [95% CI, 4.3 to 15.6]), especially with expert guidance and supplementary homework. CONCLUSION: These findings align with meta-analysis results using standardized mean difference (SMD), providing evidence for meditation as an effective nonpharmacological intervention for fatigue management, while also informing effective meditation approaches. REGISTRATION NUMBER: CRD42023395551 in PROSPERO.

A standardized herbal combination of Astragalus membranaceus and Paeonia japonica promotes skeletal muscle hypertrophy in a treadmill exercise mouse model.

Background: Maintaining a normal range of muscle mass and function is crucial not only for sustaining a healthy life but also for preventing various disorders. Numerous nutritional or natural resources are being explored for their potential muscle hypertrophic properties. Aim: We aimed to evaluate the muscle hypertrophic effects of APX, a 1:1 mixture of Astragalus membranaceus and Paeonia japonica. In addition to the myotube differentiation cell assay, we utilized a weighted exercise-based animal model and evaluated changes in muscle hypertrophy using dual-energy X-ray absorptiometry (DXA) and histological analysis. Results: The 8-week treadmill exercise led to notable decreases in body weight and fat mass but an increase in muscle mass compared to the control group. Administration of APX significantly accelerated muscle mass gain (p < 0.05) without altering body weight or fat mass compared to the exercise-only group. This muscle hypertrophic effect of APX was consistent with the histologic size of muscle fibers in the gastrocnemius (p > 0.05) and rectus femoris (p < 0.05), as well as the regulation of myogenic transcription factors (MyoD and myogenin), respectively. Furthermore, APX demonstrated a similar action to insulin-like growth factor 1, influencing the proliferation of C2C12 myoblast cells (p < 0.01) and their differentiation into myotubes (p < 0.05) compared to the control group. Conclusion: The present study provides experimental evidence that APX has muscle hypertrophic effects, and its underlying mechanisms would involve the modulation of MyoD and myogenin.

Evaluating myelophil, a 30% ethanol extract of Astragalus membranaceus and Salvia miltiorrhiza, for alleviating fatigue in long COVID: a real-world observational study.

Background: Persistent post-infectious symptoms, predominantly fatigue, characterize Long COVID. This study investigated the efficacy of Myelophil (MYP), which contains metabolites extracted from Astragalus membranaceus and Salvia miltiorrhiza using 30% ethanol, in alleviating fatigue among subjects with Long COVID. Methods: In this prospective observational study, we enrolled subjects with significant fatigue related to Long COVID, using criteria of scores of 60 or higher on the modified Korean Chalder Fatigue scale (mKCFQ11), or five or higher on the Visual Analog Scale (VAS) for brain fog. Utilizing a single-arm design, participants were orally administered MYP (2,000 mg daily) for 4 weeks. Changes in fatigue severity were assessed using mKCFQ11, Multidimensional Fatigue Inventory (MFI-20), and VAS for fatigue and brain fog. In addition, changes in quality of life using the short form 12 (SF-12) were also assessed along with plasma cortisol levels. Results: A total of 50 participants (18 males, 32 females) were enrolled; 49 were included in the intention-to-treat analysis with scores of 66.9 ± 11.7 on mKCFQ11 and 6.3 ± 1.5 on the brain fog VAS. After 4 weeks of MYP administration, there were statistically significant improvements in fatigue levels: mKCFQ11 was measured at 34.8 ± 17.1 and brain fog VAS at 3.0 ± 1.9. Additionally, MFI-20 decreased from 64.8 ± 9.8 to 49.3 ± 10.8, fatigue VAS dropped from 7.4 ± 1.0 to 3.4 ± 1.7, SF-12 scores rose from 53.3 ± 14.9 to 78.6 ± 14.3, and plasma cortisol levels also elevated from 138.8 ± 50.1 to 176.9 ± 62.0 /mL. No safety concerns emerged during the trial. Conclusion: Current findings underline MYP's potential in managing Long COVID-induced fatigue. However, comprehensive studies remain imperative. Clinical Trial Registration: https://cris.nih.go.kr, identifier KCT0008948.

Sleep deprivation in adolescent mice impairs long-term memory till early adulthood via suppression of hippocampal astrocytes.

Sleep deficiency is a rampant issue in modern society, serving as a pathogenic element contributing to learning and memory impairment, with heightened sensitivity observed in children. Clinical observations suggest that learning disabilities associated with insufficient sleep during adolescence can persist through adulthood, but experimental evidence for this is lacking. In this study, we examined the impact of early-life sleep deprivation (SD) on both short-term and long-term memory, tracking the effects sequentially into adulthood. We employed a modified multiple-platform method mouse model to investigate these outcomes. SD induced over a 14-day period, beginning on postnatal day 28 (PND28) in mice, led to significant impairment in long-term memory (while short-term memory remained unaffected) at PND42. Notably, this dysfunction persisted into adulthood at PND85. The specific impairment observed in long-term memory was elucidated through histopathological alterations in hippocampal neurogenesis, as evidenced by bromodeoxyuridine (BrdU) signals, observed both at PND42 and PND85. Furthermore, the hippocampal region exhibited significantly diminished protein expressions of astrocytes, characterized by lowered levels of aquaporin 4 (AQP4), a representative molecule involved in brain clearance processes, and reduced protein expressions of brain-derived neurotrophic factors. In conclusion, we have presented experimental evidence indicating that sleep deficiency-related impairment of long-term memory in adolescence can endure into adulthood. The corresponding mechanisms may indicate that the modification of astrocyte-related molecules has led to changes in hippocampal neurogenesis.

Systematic review of fatigue severity in ME/CFS patients: insights from randomized controlled trials.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness medically unexplained, affecting approximately 1% of the global population. Due to the subjective complaint, assessing the exact severity of fatigue is a clinical challenge, thus, this study aimed to produce comprehensive features of fatigue severity in ME/CFS patients. METHODS: We systematically extracted the data for fatigue levels of participants in randomized controlled trials (RCTs) targeting ME/CFS from PubMed, Cochrane Library, Web of Science, and CINAHL throughout January 31, 2024. We normalized each different measurement to a maximum 100-point scale and performed a meta-analysis to assess fatigue severity by subgroups of age, fatigue domain, intervention, case definition, and assessment tool, respectively. RESULTS: Among the total of 497 relevant studies, 60 RCTs finally met our eligibility criteria, which included a total of 7088 ME/CFS patients (males 1815, females 4532, and no information 741). The fatigue severity of the whole 7,088 patients was 77.9 (95% CI 74.7-81.0), showing 77.7 (95% CI 74.3-81.0) from 54 RCTs in 6,706 adults and 79.6 (95% CI 69.8-89.3) from 6 RCTs in 382 adolescents. Regarding the domain of fatigue, 'cognitive' (74.2, 95% CI 65.4-83.0) and 'physical' fatigue (74.3, 95% CI 68.3-80.3) were a little higher than 'mental' fatigue (70.1, 95% CI 64.4-75.8). The ME/CFS participants for non-pharmacological intervention (79.1, 95% CI 75.2-83.0) showed a higher fatigue level than those for pharmacological intervention (75.5, 95% CI 70.0-81.0). The fatigue levels of ME/CFS patients varied according to diagnostic criteria and assessment tools adapted in RCTs, likely from 54.2 by ICC (International Consensus Criteria) to 83.6 by Canadian criteria and 54.2 by MFS (Mental Fatigue Scale) to 88.6 by CIS (Checklist Individual Strength), respectively. CONCLUSIONS: This systematic review firstly produced comprehensive features of fatigue severity in patients with ME/CFS. Our data will provide insights for clinicians in diagnosis, therapeutic assessment, and patient management, as well as for researchers in fatigue-related investigations.

Evaluating the Safety of Herbal Medicine on Renal Function: A Comprehensive Analysis from Six Randomized Controlled Trials Conducted with Four Formulations from Traditional Korean Medicine.

The growing popularity of herbal medicine raises concerns about potential nephrotoxicity risks, while limited evidence hinders a comprehensive impact assessment. This study aims to investigate the overall risk features of herbal medicine on kidney injury. We conducted a retrospective analysis on renal function changes, including blood urea nitrogen (BUN), serum creatinine, and estimated glomerular filtration rate (eGFR), through data from six randomized controlled trials (RCTs) in South Korea. A total of 407 participants (142 males, 265 females) received either one of four different herbal medicines (240 participants) or a placebo (167 participants). When comparing changes in eGFR regarding the mean, 90th-percentile value, and 20% reduction after treatment, there was no significant difference between the herbal-treated and placebo groups. This study provided a helpful reference for examining the safety issues of herbal remedies, especially regarding kidney function.

Lactobacillus casei-fermented Amomum xanthioides ameliorates metabolic dysfunction in high-fat diet-induced obese mice.

Amomum xanthioides (AX) has been used as an edible herbal medicine to treat digestive system disorders in Asia. Additionally, Lactobacillus casei is a well-known probiotic commonly used in fermentation processes as a starter. The current study aimed to investigate the potential of Lactobacillus casei-fermented Amomum xanthioides (LAX) in alleviating metabolic disorders induced by high-fat diet (HFD) in a mouse model. LAX significantly reduced the body and fat weight, outperforming AX, yet without suppressing appetite. LAX also markedly ameliorated excessive lipid accumulation and reduced inflammatory cytokine (IL-6) levels in serum superior to AX in association with UCP1 activation and adiponectin elevation. Furthermore, LAX noticeably improved the levels of fasting blood glucose, serum insulin, and HOMA-IR through positive regulation of glucose transporters (GLUT2, GLUT4), and insulin receptor gene expression. In conclusion, the fermentation of AX demonstrates a pronounced mitigation of overnutrition-induced metabolic dysfunction, including hyperlipidemia, hyperglycemia, hyperinsulinemia, and obesity, compared to non-fermented AX. Consequently, we proposed that the fermentation of AX holds promise as a potential candidate for effectively ameliorating metabolic disorders.

Anatomical Exploration of the KI1 Acupoint: Implications for Medial and Lateral Plantar Nerve Stimulation.

Background and Objectives: This study aims to identify the precise anatomical location and therapeutic mechanisms of the KI1 acupoint (Yongquan) in relation to foot muscles and nerves, known for treating neurological disorders and pain. Materials and Methods: Dissection of six cadavers at Chungnam National University College of Medicine examined KI1's relation to the foot's four-layer structure. Results: The KI1 acupoint was located in the superficial and deep layers of the plantar foot, adjacent to significant nerves like the medial and lateral plantar nerves. Differences in the acupoint's exact location between genders were noted, reflecting variances in foot morphology. KI1 acupuncture was found to stimulate the muscle spindles and nerve fibers essential for balance and bipedal locomotion. This stimulation may enhance sensory feedback, potentially improving cognitive functions and balance control. Conclusions: This anatomical insight into KI1 acupuncture underpins its potential in neurological therapies and pain management.

The additive effect of herbal medicines on lifestyle modification in the treatment of non-alcoholic fatty liver disease: a systematic review and meta-analysis.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is difficult to manage because of its complex pathophysiological mechanism. There is still no effective treatment other than lifestyle modification (LM) such as dietary modifications, regular physical activity, and gradual weight loss. Herbal medicines from traditional Chinese Medicine and Korean Medicine have been shown to be effective in the treatment of NAFLD based on many randomized controlled trials. This systematic review and meta-analysis aims to evaluate the additive effects of herbal medicines on LM in the treatment of NAFLD. Methods: Two databases (PubMed and Cochrane library) were searched using keywords related to NAFLD and herbal medicines. Then the randomized controlled trials (RCTs) evaluating the therapeutic effects of herbal medicines combined with LM were selected. The pooled results were analyzed as mean difference (MD) with 95% confidence interval (CI) for continuous data, and risk ratio (RR) with 95% CI for dichotomous data. Results and Discussion: Eight RCTs with a total of 603 participants were included for this review study. Participants were administered with multi-herbal formulas (Yiqi Sanju Formula, Tiaogan Lipi Recipe, and Lingguizhugan Decoction) or single-herbal extracts (Glycyrrhiza glabra L., Magnoliae offcinalis, Trigonella Foenum-graecum L. semen, Portulaca oleracea L., and Rhus Coriaria L. fructus) along with LM for 12 weeks. The meta-analysis showed a significant improvement in ultrasoundbased liver steatosis measured by odds ratio (OR) in the herbal medicine group than those with LM alone (OR = 7.9, 95% CI 0.7 to 95.2, p < 0.1). In addition, herbal medicines decreased the levels of aspartate transferase (MD -7.5, 95% CI -13.4 to -1.7, p = 0.01) and total cholesterol (MD -16.0, 95% CI -32.7 to 0.7, p = 0.06) more than LM alone. The meta-analysis partially showed clinical evidence supporting the additive benefits of herbal medicines for NAFLD in combination with LM. Whereas, it is necessary to provide a solid basis through higher-quality studies using a specific herbal medicine.

Clinical evidence of the link between gut microbiome and myalgic encephalomyelitis/chronic fatigue syndrome: a retrospective review.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous disorder with elusive causes, but most likely because of clinical and other biological factors. As a vital environmental factor, the gut microbiome is increasingly emphasized in various refractory diseases including ME/CFS. The present study is aimed to enhance our understanding of the relationship between the gut microbiome and ME/CFS through data analysis of various clinical studies. We conducted a literature search in four databases (PubMed, Cochrane Library, Web of Science, and Google Scholar) until May 31, 2023. Our analysis encompassed 11 clinical studies with 553 ME/CFS patients and 480 healthy controls. A comparative analysis of meta data revealed a significant decrease in α-diversity and a noticeable change in ß-diversity in the gut microbiome of ME/CFS patients compared to healthy controls. The notable ratio of Firmicutes and Bacteroides was 2.3 times decreased, and also, there was a significant reduction in the production of microbial metabolites such as acetate, butyrate, isobutyrate, and some amino acids (alanine, serine, and hypoxanthine) observed in ME/CFS patients. The lack of comparison under similar conditions with various standardized analytical methods has impeded the optimal calculation of results in ME/CFS patients and healthy controls. This review provides a comprehensive overview of the recent advancements in understanding the role of the gut microbiome in ME/CFS patients. Additionally, we have also discussed the potentials of using microbiome-related interventions and associated challenges to alleviate ME/CFS.

Linking alterations in estrogen receptor expression to memory deficits and depressive behavior in an ovariectomy mouse model.

The high risk of neurological disorders in postmenopausal women is an emerging medical issue. Based on the hypothesis of altered estrogen receptors (ERα and ß) after the decline of estrogen production, we investigated the changes in ERs expressions across brain regions and depressive/amnesic behaviors. C57BL/6J female mice were ovariectomized (OVX) to establish a menopausal condition. Along with behavior tests (anxiety, depression, and memory), the expression of ERs, microglial activity, and neuronal activity was measured in six brain regions (hippocampus, prefrontal cortex, striatum, raphe nucleus, amygdala, and hypothalamus) from 4 to 12 weeks after OVX. Mice exhibited anxiety- and depressive-like behaviors, as well as memory impairment. These behavioral alterations have been linked to a suppression in the expression of ERß. The decreased ERß expression coincided with microglial-derived neuroinflammation, as indicated by notable activations of Ionized calcium-binding adapter molecule 1 and Interleukin-1beta. Additionally, the activity of brain-derived neurotrophic factor (BDNF), particularly in the hippocampus, decreased in a time-dependent manner from 4 to 12 weeks post-OVX. Our study provides evidence shedding light on the susceptibility to memory impairment and depression in women after menopause. This susceptibility is associated with the suppression of ERß and alteration of ERα in six brain regions.

Experimental evidence for anti-metastatic actions of apigenin: a mini review.

Cancer metastasis is responsible for the majority of cancer-related deaths. Accordingly, to reduce metastasis remains a vital challenge in clinical practice, and phytochemicals have taken an attention as anti-metastatic agents. Apigenin, a plant flavone, showed anti-cancer effects against in various animal models, moreover its potentials inhibiting tumor metastasis have been reported. Herein, we analyzed the overall features at what apigenin inhibited metastasis and its action modes. We searched for articles in MEDLINE (Pubmed), EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) through March 2023. Total 6 animal studies presented anti-metastatic effects of apigenin using 5 difference experimental models, while the mechanisms involved modulations of epithelial-mesenchymal transition (EMT), matrix metalloproteinases (MMPs), angiogenesis, and various metastasis-related signaling pathways. This review provides an overall potential of apigenin as a candidate reducing the risk of cancer metastasis.

Determination of the Combined Effects of Asian Herbal Medicine with Calcium and/or Vitamin D Supplements on Bone Mineral Density in Primary Osteoporosis: A Systematic Review and Meta-Analysis.

Our review of 52 RCTs from 5 databases suggests a tendency for notable improvement in BMD when combining herbal medicine with supplements (calcium and vitamin D variants) compared to supplement monotherapy in primary osteoporosis. However, caution is needed in interpreting results due to substantial heterogeneity among included studies. PURPOSE: To conduct a systematic review and meta-analysis to determine whether herbal medicine (HM) plus supplements such as calcium (Ca) or vitamin D (Vit.D) improves bone mineral density (BMD) compared to supplements alone in primary osteoporosis (OP) patients. METHODS: We searched 5 databases for randomized controlled trials (RCTs) using HMs with supplements (Ca or Vit.D variants) as interventions for primary OP patients published until August 31, 2022. Meta-analysis using BMD score as the primary outcome was performed using RevMan 5.4 version. Risk of bias in the included studies was assessed useing RoB 2.0 tool. RESULTS: In total, 52 RCTs involving 4,889 participants (1,408 men, 3,481 women) were included, with average BMD scores of 0.690 ± 0.095 g/cm2 (lumbar) and 0.625 ± 0.090 g/cm2 (femoral neck). As a result of performing meta-analysis using BMD scores for all 52 RCTs included in this review, combination of HMs with Ca and Vit.D variants improved the BMD score by 0.08 g/cm2 (lumbar, 38 RCTs, 95% CI: 0.06-0.10, p < 0.001, I2 = 97%) and 0.06 g/cm2 (femoral neck, 19 RCTs, 95% CI: 0.04-0.08, p < 0.001, I2 = 92%)compared to controls. However, statistical significance of the lumbar BMD improvement disappeared after adjusting for potential publication bias. CONCLUSION: Our data suggest that combining of HM and supplements tends to be more effective in improving BMD in primary OP than supplements alone. However, caution is needed in interpretation due to the reporting bias and high heterogeneity among studies, and well-designed RCTs are required in the future.

Efficacy of Moxibustion for Cancer-Related Fatigue in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Breast cancer is the most commonly diagnosed cancer worldwide, and most patients experience fatigue. However, there are no effective treatments for cancer-related fatigue (CRF). Several randomized controlled trials (RCTs) have suggested that moxibustion improves CRF. We conducted a systematic review and meta-analysis to compare the differences in fatigue scale scores, quality of life, and clinical efficacy in patients with breast cancer who developed CRF and did versus did not receive moxibustion. METHODS: RCTs were searched in 7 databases using a standardized search method from database inception to March 2023, and RCTs that met the inclusion criteria were selected. RESULTS: Among 1337 initially identified RCTs, 10 RCTs involving 744 participants were selected for this study. The meta-analysis involved assessment of the revised Piper Fatigue Scale scores, Cancer Fatigue Scale scores, Karnofsky Performance Scale scores, Athens Insomnia Scale scores, clinical efficacy, and Qi deficiency syndrome scale scores. Compared with the control, moxibustion was associated with significantly better Piper Fatigue Scale scores (P < 0.0001), quality of life [Karnofsky Performance Scale scores (P < 0.0001)], clinical efficacy (P = 0.0007), and Qi deficiency syndrome scale scores (P = 0.02). CONCLUSIONS: Moxibustion improves CRF in patients with breast cancer. The efficacy of moxibustion should be further examined by high-quality studies in various countries with patients subdivided by their breast cancer treatment status. REGISTRATION: PROSPERO ID: CRD42023451292.

A Capsicum annuum L. seed extract exerts anti-neuroexcitotoxicity in HT22 hippocampal neurons.

The hippocampal memory deficit stands out as a primary symptom in neurodegenerative diseases, including Alzheimer's disease. While numerous therapeutic candidates have been proposed, they primarily serve to delay disease progression. Given the irreversible brain atrophy or injury associated with these conditions, current research efforts are concentrated on preventive medicine strategies. Herein, we investigated whether the extracts of Capsicum annuum L. seeds (CSE) and Capsicum annuum L. pulp (CPE) have preventive properties against glutamate-induced neuroexcitotoxicity (one of the main causes of Alzheimer's disease) in HT22 hippocampal neuronal cells. Pretreatment with CSE demonstrated significant anti-neuroexcitotoxic activity, whereas CPE did not exhibit such effects. Specifically, CSE pretreatment dose-dependently inhibited the elevation of excitotoxic elements (intracellular calcium influx and reactive oxygen species; ROS) and apoptotic elements (p53 and cleaved caspase-3). In addition, the glutamate-induced alterations of neuronal activity indicators (brain-derived neurotrophic factor; BDNF and cAMP response element-binding protein phosphorylation; CREB) were significantly attenuated by CSE treatment. We also found that luteolin is the main bioactive compound corresponding to the anti-neuroexcitotoxic effects of CSE. Our results strongly suggest that Capsicum annuum L. seeds (but not its pulp) could be candidates for neuro-protective resources especially under conditions of neuroexcitotoxicity. Its underlying mechanisms may involve the amelioration of ROS-mediated cell death and BDNF-related neuronal inactivity and luteolin would be an active compound.