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.

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.

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.

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.

Lactobacillus Casei-fermented Amomum Xanthioides Mitigates non-alcoholic fatty liver disease in a high-fat diet mice model.

Non-alcoholic fatty liver disease (NAFLD) is a substantial global health issue owing to its high prevalence and the lack of effective therapies. Fermentation of medicinal herbs has always been considered a feasible strategy for enhancing efficacy in treating various ailments. This study aimed to investigate the potential benefits of the Lactobacillus casei-fermented Amomum xanthioides (LAX) on NAFLD in a high-fat diet model. HFD-fed C57BL6/j mice were administered with 200 mg/kg of LAX or unfermented Amomum xanthioides (AX) or 100 mg/kg of metformin for 6 weeks from the 4th week. The 10-week HFD-induced alterations of hepatic lipid accumulation and hepatic inflammation were significantly attenuated by LAX dominantly (more than AX or metformin), which evidenced by pathohistological findings, lipid contents, inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 6 and IL-1ß, oxidative parameters such as reactive oxygen species (ROS) and malondialdehyde (MDA), and molecular changes reversely between lipogenic proteins such as glycerol-3-phosphate acyltransferase (GPAM) and sterol regulatory element-binding protein (SREBP)- 1, and lipolytic proteins including peroxisome proliferator-activated receptor (PPAR-α) and AMP-activated kinase (AMPK)-α in the liver tissues. In addition, the abnormal serum lipid parameters (triglyceride, total cholesterol and LDL-cholesterol) notably ameliorated by LAX. In conclusion, these findings support the potential of LAX as a promising plant-derived remedy for NAFLD.

Clinical and Laboratory Characteristics of Fatigue-dominant Long-COVID subjects: A Cross-Sectional Study.

BACKGROUND: Long-COVID is defined by persistent symptoms following COVID-19 infection. Approximately 71% of individuals with long-COVID experience ongoing fatigue, post-exertional malaise, and cognitive impairments, which share pathological similarities with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This similarity has prompted studies to explore the characteristics of long-COVID to gain a better understanding of ME/CFS. To gain insights, we investigated the clinical and laboratory characteristics of individuals with fatigue-dominant long-COVID. METHODS: We enrolled 100 subjects (36 males, 64 females) with long-COVID who had a higher score than 60 in modified Korean version of the Chalder Fatigue Scale (mKCFQ11) and higher than 5 in fatigue-focused Visual Analogue Scale (VAS). To investigate fatigue symptoms, the mKCFQ11, the Multidimensional Fatigue Inventory (MFI-20), and VAS for fatigue and brain-fog, along with the Short Form Survey (SF-12) were employed. We also measured three cytokines and cortisol levels for immunological and endocrinological indicators. As a cross-sectional observational study, the data were collected at a single point in time. RESULTS: The mean scores on the measurements showed severe fatigue, and these scores were significantly correlated, with no differences based on sex, the post-COVID period, or age. Among the laboratory tests, plasma cortisol levels had a significant negative correlation with fatigue scores and a positive correlation with living quality. The negative correlation between cortisol levels and mKCFQ11 scores appeared to be more specific to mental fatigue than physical, which conflicted with other measurements. CONCLUSION: Our findings provide the first insights into the characteristics of fatigue in individuals with long-COVID, particularly in terms of fatigue severity and cortisol levels. These results serve as valuable reference data for clinicians dealing with fatigue symptoms in long-COVID patients and for researchers exploring post-viral fatigue symptoms, including ME/CFS, in the future.

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.

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.

Central 5-HTergic hyperactivity induces myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like pathophysiology.

OBJECTIVES: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a significant medical challenge, with no indisputable pathophysiological mechanism identified to date. METHODS: Based on clinical clues, we hypothesized that 5-hydroxytryptamine (5-HT) hyperactivation is implicated in the pathogenic causes of ME/CFS and the associated symptoms. We experimentally evaluated this hypothesis in a series of mouse models. RESULTS: High-dose selective serotonin reuptake inhibitor (SSRI) treatment induced intra- and extracellular serotonin spillover in the dorsal raphe nuclei of mice. This condition resulted in severe fatigue (rota-rod, fatigue rotating wheel and home-cage activity tests) and ME/CFS-associated symptoms (nest building, plantar and open field test), along with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis response to exercise challenge. These ME/CFS-like features induced by excess serotonin were additionally verified using both a 5-HT synthesis inhibitor and viral vector for Htr1a (5-HT1A receptor) gene knockdown. CONCLUSIONS: Our findings support the involvement of 5-HTergic hyperactivity in the pathophysiology of ME/CFS. This ME/CFS-mimicking animal model would be useful for understanding ME/CFS biology and its therapeutic approaches.

Comparative characteristics of fatigue in irritable bowel syndrome and inflammatory bowel disease: A systematic review and meta-analysis.

OBJECTIVE: Fatigue is a common symptom in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to distinguish fatigue characteristics in IBS and IBD, two functional and organic disorders. METHODS: We systematically searched the PubMed and Cochrane Library databases from inception to June 30, 2023, and conducted a meta-analysis to generate precise estimates and 95% confidence intervals. The analyses were stratified by fatigue type, severity, sex, disease phase, and comorbidities, and study quality was assessed using Newcastle-Ottawa Scale (NOS). RESULTS: Our analysis included 74 data (13 IBS, 31 CD, 30 UC) encompassing 16,689 participants (6484 males, 7402 females, and 2803 unknown). Overall, fatigue prevalence trended higher in IBS (54.5% [95%CI, 44.5-64.6]), followed by CD (49.8% [95%CI, 44.0-55.5]) and UC (43.6% [95%CI, 38.5-48.7]). This pattern persisted across sub-analyses, including general fatigue (63.4% vs. 51.3% vs. 45.3%) and moderate to severe fatigue (73.8% vs. 59.5% vs. 52.7%) for IBS, CD, and UC, respectively. Female predominance was observed in all three diseases (odds ratio: 1.5 in IBS and CD, 1.8 in UC). Fatigue prevalence significantly varied between disease phases (active vs. remission) in CD (61.3% vs. 36.3%) and UC (53.8% vs. 32.6%). Anemia, anxiety/depression, and/or IBS-like symptoms also contributed to fatigue in CD and UC. CONCLUSIONS: This study is the first extensive comparison of fatigue prevalence and features in IBS, CD, and UC. The findings offer valuable insights for treatment and management, aiding our understanding of functional and organic diseases.

The Clinical Diagnosis-Based Nationwide Epidemiology of Metabolic Dysfunction-Associated Liver Disease in Korea.

BACKGROUND: Although most epidemiological studies have been conducted using a relatively small population or subjects who had medical screenings, the present study aimed to investigate the incidence and prevalence of MASLD (formerly NAFLD) in Korea using nationwide registry data provided by the Health Insurance Review and Assessment Service (HIRA). METHODS: Using nationwide medical records provided by HIRA, we analyzed the entire dataset of patients with MASL (KCD10-K76.0) and MASH (KCD10-K75.8) from 2010 to 2021 and calculated the incidence and prevalence by year, age, and gender. The prevalence and incidence rates were calculated by analyzing the HIRA data covering almost the entire population of Korea for 12 years, from 2010 to 2021, with an average population of 50,856,244 during this period. Statistical analyses included calculating confidence intervals using Ulm's formula and conducting sex- and age-specific analyses with a Cochran-Armitage test for trends. RESULTS: The annual incidence of MASL/MASH increased significantly from 9.71/0.37 in 2010 to 13.95/5.52 per 1000 persons in 2021 (p < 0.01). The annual prevalence of MASL increased from 15.69 in 2010 to 34.23 per 1000 persons in 2021, while the annual prevalence of MASH increased from 0.49 to 9.79 per 1000 persons between 2010 and 2021 (p < 0.01). Regarding the sex-dimorphic feature of MASLD, there was a male predominance in those < 50 years old but a female predominance in those ≥ 50 years old for the incidence and prevalence of MASL and the incidence of MASH. CONCLUSION: The incidence of MASL increased by 3% to 4% every year, while the incidence of MASH increased 14.91-fold from 2010 to 2021. The increasing trend is noteworthy compared with previous reports.

Brain-regional characteristics and neuroinflammation in ME/CFS patients from neuroimaging: A systematic review and meta-analysis.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by an elusive etiology and pathophysiology. This study aims to evaluate the pathological role of neuroinflammation in ME/CFS by conducting an exhaustive analysis of 65 observational studies. Four neuroimaging techniques, including magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), and positron emission tomography (PET), were employed to comparatively assess brain regional structure, metabolite profiles, electrical activity, and glial activity in 1529 ME/CFS patients (277 males, 1252 females) and 1715 controls (469 males, 1246 females). Clinical characteristics, including sex, age, and fatigue severity, were consistent with established epidemiological patterns. Regional alterations were most frequently identified in the cerebral cortex, with a notable focus on the frontal cortex. However, our meta-analysis data revealed a significant hypoactivity in the insular and thalamic regions, contrary to observed frequencies. These abnormalities, occurring in pivotal network hubs bridging reason and emotion, disrupt connections with the limbic system, contributing to the hallmark symptoms of ME/CFS. Furthermore, we discuss the regions where neuroinflammatory features are frequently observed and address critical neuroimaging limitations, including issues related to inter-rater reliability. This systematic review serves as a valuable guide for defining regions of interest (ROI) in future neuroimaging investigations of ME/CFS.

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis.

BACKGROUND: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients. METHODS: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections' contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased). RESULTS: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a "moderate association" by Cohen's d test) compared to both healthy and diseased controls. CONCLUSION: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

Feasibility of combination of Gun-Chil-Jung and cytokine-induced killer cells-based immunotherapy for terminal hepatocellular carcinoma patient: a case report.

Introduction: Terminal-stage hepatocellular carcinoma (HCC) is inoperable and currently has no form of adjuvant therapy. This study examined the anticancer herbal extract Gun-Chil-Jung (GCJ) combined with cytokine-induced killer (CIK)-cell-based immunotherapy as a palliative therapy for terminal HCC. We report the case of an HCC patient with extended overall survival and improved symptoms and tumor marker levels following combination therapy with GCJ and CIK cell-based immunotherapy. Baseline Characteristics: From March to July 2020, a 57-year-old man who had been diagnosed with HCC underwent combination treatment with GCJ and CIK cell-based immunotherapy. By August 2021, he was prescribed GCJ. After treatment, the patient's condition was evaluated with respect to overall survival, tumor markers, symptoms, abdominal computed tomography findings, chest x-ray results, and Eastern Cooperative Oncology Group (ECOG) grade. Results: The patient's overall survival, tumor marker levels, ECOG grade, and symptoms, including ascites, lower limb edema, jaundice, pleural effusion, and fatigue, were largely alleviated. Conclusion: We expect that this combination therapy may be an option for palliative therapy of terminal HCC.

The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis.

Background: Fatigue is one of the most common subjective symptoms that impairs daily life and predict health-related events. This study aimed to estimate the prevalence of fatigue in the global population. Methods: PubMed and the Cochrane Library were used to search for relevant articles from inception to December 31, 2021. Studies with prevalence data of fatigue in the general population were selected and reviewed by three authors independently and cross-checked. Regarding subgroups, adults (≥18 years), minors (<18 years), and specific occupation population (participants in each study being limited to a specific occupational group), and fatigue types and severity, meta-analysis was conducted to produce point estimates and 95% confidence intervals (95% CI). Results: From the initial 3,432 studies, 91 studies accounting for 115 prevalence data points (623,624 participants) were finally selected. The prevalence of general fatigue (fatigue lasting < 6 months, or fatigue of unspecified duration) was 20.4% (95% CI, 16.7-25.0) in adults, 11.7% (95% CI, 5.2-26.6) in minors, and 42.3% (95% CI, 33.0-54.2) in specific occupations. Chronic fatigue (fatigue lasting more than 6 months) affected 10.1% (95% CI, 8.2-12.5) of adults, 1.5% (95% CI, 0.5-4.7) of minors, and 5.5% (95% CI, 1.4-21.6) of subjects in specific occupations. There was an overall female-predominant prevalence for all subgroup analyses, with a total odds ratio of 1.4 (95% CI, 1.3-1.6). Regarding the severity and presence of medical causes, the total prevalence of moderate fatigue [14.6% (95% CI, 9.8-21.8)] was 2.4-fold that of severe fatigue [6.1% (95% CI, 3.4-11.0)], while unexplained fatigue (fatigue experienced by individuals without any underlying medical condition that can explain the fatigue) was ~2.7-fold that of explained fatigue (fatigue experienced by individuals with a medical condition that can explain the fatigue); as proportion of 40.0% of physical, 8.6% of mental, and 28.4% of mixed cause. Conclusions: This study has produced the first comprehensive picture of global fatigue prevalence in the general population, which will provide vital reference data contributing to fatigue-related research, including the prevention of diseases. Systematic review registration: Identifier: CRD42021270498.

Prevalence of cancer-related fatigue based on severity: a systematic review and meta-analysis.

Cancer-related fatigue (CRF) affects therapeutic compliance and clinical outcomes including recurrence and mortality. This study aimed to comprehensively and comparatively assess the severity-based prevalence of CRF. From two public databases (PubMed and Cochrane Library), we extracted data containing information on both prevalence and severity of fatigue in cancer patients through December 2021. We conducted a meta-analysis to produce point estimates using random effects models. Subgroup analyses were used to assess the prevalence and severity by the organ/system tumor development, treatment phase, therapeutic type, sex and assessment method. A total of 151 data (57 studies, 34,310 participants, 11,805 males and 22,505 females) were selected, which indicated 43.0% (95% CI 39.2-47.2) of fatigue prevalence. The total CRF prevalence including 'mild' level of fatigue was 70.7% (95% CI 60.6-83.3 from 37 data). The prevalence of 'severe' fatigue significantly varied by organ/system types of cancer origin (highest in brain tumors 39.7% vs. lowest in gynecologic tumors 3.9%) and treatment phase likely 15.9% (95% CI 8.1-31.3) before treatment, 33.8% (95% CI 27.7-41.2) ongoing treatment, and 24.1% (95% CI 18.6-31.2) after treatment. Chemotherapy (33.1%) induced approximately 1.5-fold higher prevalence for 'severe' CRF than surgery (22.0%) and radiotherapy (24.2%). The self-reported data for 'severe' CRF was 20-fold higher than those assessed by physicians (23.6% vs. 1.6%). Female patients exhibited a 1.4-fold higher prevalence of 'severe' fatigue compared to males. The present data showed quantitative feature of the prevalence and severity of CRF based on the cancer- or treatment-related factors, sex, and perspective of patient versus physician. In the context of the medical impact of CRF, our results provide a comparative reference to oncologists or health care providers making patient-specific decision.

A Review of Herbal Resources Inducing Anti-Liver Metastasis Effects in Gastrointestinal Tumors via Modulation of Tumor Microenvironments in Animal Models.

Liver metastases remain a major obstacle for the management of all types of tumors arising from digestive organs, and the tumor microenvironment has been regarded as an important factor in metastasis. To discover herbal candidates inhibiting the liver metastasis of tumors originating from the digestive system via the modulation of the tumor microenvironment and liver environment, we searched three representative public databases and conducted a systematic review. A total of 21 studies that employed experimental models for pancreatic (9), colon (8), and stomach cancers (4) were selected. The herbal agents included single-herb extracts (5), single compounds (12), and multiherbal decoctions (4). Curcuma longa Linn was most frequently studied for its anti-colon-liver metastatic effects, and its possible mechanisms involved the modulation of tumor microenvironment components such as vascular endothelial cells and immunity in both tumor tissues and circulating cells. The list of herbal agents and their mechanisms produced in this study is helpful for the development of anti-liver metastasis drugs in the future.

Anti-Melanogenic Effects of Fractioned Cynanchum atratum by Regulation of cAMP/MITF Pathway in a UVB-Stimulated Mice Model.

Based on traditional pharmacological applications and partial in vitro data, Cynanchum atratum (CA) is proposed to act on skin whitening. However, its functional evaluation and underlying mechanisms have yet to be identified. This study aimed to examine the anti-melanogenesis activity of CA fraction B (CAFB) on UVB-induced skin hyperpigmentation. Forty C57BL/6j mice were exposed to UVB (100 mJ/cm2, five times/week) for eight weeks. After irradiation, CAFB was applied to the left ear once a day for 8 weeks (the right ear served as an internal control). The results showed that CAFB significantly reduced melanin production in the ear skin, as indicated by the gray value and Mexameter melanin index. In addition, CAFB treatment notably decreased melanin production in α-MSH-stimulated B16F10 melanocytes, along with a significant reduction in tyrosinase activity. Cellular cAMP (cyclic adenosine monophosphate), MITF (microphthalmia-associated transcription factor), and tyrosinase-related protein 1 (TRP1) were also noticeably downregulated by CAFB. In conclusion, CAFB is a promising ingredient for treating skin disorders caused by the overproduction of melanin and its underlying mechanisms involving the modulation of tyrosinase, mainly mediated by the regulation of the cAMP cascade and MITF pathway.