Association between dietary calcium and depression among American adults: National health and nutrition examination survey.

Background: There is only limited evidence for an association between calcium (Ca) and depression, and the relationship was inconsistent. Therefore, the aim of this study was to assess the relationship between dietary Ca and the risk of depressive symptoms in individuals over the age of 18 in the US. Methods: We extracted 14,971 participants from the US National Health and Nutrition Examination Survey (NHANES) 2007-2016 to probe their associations. Dietary Ca intake was measured through 24 h dietary recall method. Patients with the Patient Health Questionnaire-9 (PHQ-9) ≥ 10 scores were believed to have depressive symptoms. The association between dietary Ca and depressive symptoms was investigated using multivariate logistic regression, sensitivity analysis, and restricted cubic spline regression. Results: In this study, 7.6% (1,144/14,971) of them had depressive symptoms. After adjusting for sex, age, race, poverty to income ratio (PIR), marital status, education, body mass index (BMI), caffeine intake, carbohydrates intake, total energy intake, smoking status, alcohol consumption, physical activity, diabetes, hypertension, severe cardiovascular disease (CVD), cancer, serum vitamin D, serum Ca, and Ca supplement, the adjusted ORs value [95% confidence interval (CI)] of depression for the lowest category (Q1 ≤ 534 mg/day) vs. Q2-Q4 of Ca intake were 0.83 (0.69-0.99), 0.97 (0.65-0.95), and 0.80 (0.63-0.98) with the p for trend (p = 0.014). The relationship between dietary Ca intake and depressive symptoms was linear (non-linear p = 0.148). None of the interactions were significant except among races (p for interaction = 0.001). Conclusion: Association between dietary Ca and the prevalence of depressive symptoms in US adults. And Ca intake was negatively associated with the risk of depressive symptoms. As Ca intake increased, the prevalence of depressive symptoms decreased.

Integrative analysis of multiomics data identifies selenium-related gene ALAD associating with keshan disease.

Keshan disease is an endemic fatal dilated cardiomyopathy that can cause heart enlargement, heart failure, and cardiogenic death. Selenium deficiency is considered to be the main cause of Keshan disease. However, the molecular mechanism underlying Keshan disease remains unclear. Our whole-exome sequencing from 68 patients with Keshan disease and 100 controls found 199 candidate genes by gene-level burden tests. Interestingly, using multiomics data, the selenium-related gene ALAD (δ-aminolevulinic acid dehydratase) was the only candidate causative gene identified by three different analysis approaches. Based on single-cell transcriptome data, ALAD was highly expressed in cardiomyocytes and double mutations of human ALAD dramatically reduced its enzyme activity in vitro compared to negative control. Functional analysis of ALAD inhibition in mice resulted in a Keshan phenotype with left ventricular enlargement and cardiac dysfunction, whereas administration of sodium selenite markedly reversed the changes caused by ALAD inhibition. In addition, sodium selenite reversed Keshan phenotypes by affecting energy metabolism and mitochondrial function in mice as shown by the transcriptomic and proteomic data and the ultrastructure of cardiac myocytes. Our findings are the first to demonstrate that the selenium-related gene ALAD is essential for cardiac function by maintaining normal mitochondrial activity, providing strong molecular evidence supporting the hypothesis of selenium deficiency in Keshan disease. These results identified ALAD as a novel target for therapeutic intervention in Keshan disease and Keshan disease-related dilated cardiomyopathy.

A Therapeutic Play Program for Children Undergoing Kidney Biopsy With Local Anesthesia: Construction and Feasibility Evaluation.

PURPOSE: To construct a therapeutic play program for children undergoing preparation for kidney biopsy under local anesthesia and explore the feasibility of the program from stakeholders' perspectives. DESIGN: The program was constructed by a multidisciplinary team and the feasibility and acceptability of the program were explored by a descriptive qualitative study. METHODS: Based on Lazarus & Folkman's stress-coping model and Piaget's theory of play, and using on-site participatory field observation, a multidisciplinary team constructed a therapeutic play program for children undergoing kidney biopsy under local anesthesia. The feasibility and acceptability of the program were evaluated by interviewing children, their caregivers, and physicians. FINDINGS: The main tools constructed for the intervention were a 15-page picture book titled Kidney Biopsy Treasure Hunt and a homemade kidney biopsy play package. The therapeutic play intervention for kidney biopsy under local anesthesia was led by nurses and followed the steps of kidney biopsy, using the picture book, and group play simulation. Through informed in-depth interviews with 10 children and their caregivers, we showed that the therapeutic play program materials were accessible, clinically feasible, and necessary for kidney biopsy under local anesthesia in children. The children and their caregivers had high acceptance of the content of the picture book, the format of the play, and high satisfaction with the overall program. CONCLUSIONS: The therapeutic play program we constructed for children undergoing kidney biopsy with local anesthesia was simple, feasible, and well accepted in the clinical setting.

Huangqi-Honghua Combination Prevents Cerebral Infarction with Qi Deficiency and Blood Stasis Syndrome in Rats by the Autophagy Pathway.

BACKGROUND: Cerebral ischemia/reperfusion injury (CI/RI) contributes to the process of autophagy. Huangqi-Honghua combination (HQ-HH) is a traditional Chinese medicine (TCM) combination that has been widely used in the treatment of cerebrovascular diseases in China. The role of autophagy in HQ-HH-mediated treatment of CI/RI is unclear. METHODS: Sprague-Dawley (SD) rats were used to establish the middle cerebral artery occlusion (MCAO) with QDBS syndrome model and evaluate the function of HQ-HH in protecting against CI/RI. RESULTS: HQ-HH significantly improved the neuronal pathology and reduced infarct volume, neurological deficits, and whole blood viscosity in rats with CI/RI. Western blot results showed that the expression of autophagy marker proteins LC3II/LC3I and Beclin1 in the HQ-HH group was significantly lower than that in the model group, while the expression of p62 was significantly higher in the HQ-HH group as compared with the model group. There were no significant differences in PI3K, Akt, and mTOR levels between the HQ-HH group and the model group; however, p-PI3K, p-Akt, and p-mTOR were significantly upregulated. In addition, HQ-HH also changed the composition and function of intestinal flora in MCAO + QDBS model rats. CONCLUSION: HQ-HH protects from CI/RI, and its underlying mechanism may involve the activation of the PI3K-Akt-mTOR signaling pathway, relating to the changes in the composition of intestinal flora.

Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Coronavirus Infection.

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.

Exploration of the Two-Way Adjustment Mechanism of Rhei Radix et Rhizoma for Cardiovascular Diseases.

AIM AND OBJECTIVE: Myocardial infarction, cerebral infarction, and other diseases caused by vascular obstruction have always jeopardized human life and health. Several reports indicate that Rhei Radix et Rhizoma has a good clinical effect in the prevention and treatment of cardiovascular diseases. Owing to the complexity of herbal medicine, the pharmacodynamic mechanism of Rhei Radix et Rhizoma is still unclear. The objectives of this study were to explore the two-way adjustment mechanism of Rhei Radix et Rhizoma and provide a new solution for the prevention and treatment of cardiovascular disease. MATERIALS AND METHODS: This study used data mining, reverse pharmacophore matching, network construction, GO and KEGG Analysis, and molecular docking to investigate the two-way adjustment mechanism of Rhei Radix et Rhizoma. The methods used were based on systems pharmacology and big data analysis technology. RESULTS: The results suggest that Rhei Radix et Rhizoma uses a two-way adjustment of activating blood circulation, as well as blood coagulation in the prevention and treatment of cardiovascular diseases. The components involved in activating blood circulation are mainly anthraquinone components. The corresponding targets are NOS2, NOS3, CALM1, and the corresponding pathways are calcium signaling pathway, VEGF signaling pathway, platelet activation, and the PI3K-Akt signaling pathway. For blood coagulation, the components are mainly tannin components; the corresponding targets are F2, F10, ELANE, and the corresponding pathways are the neuroactive ligand-receptor interaction, complement and coagulation cascades. CONCLUSION: This study indicated that Rhei Radix et Rhizoma exerts the two-way adjustment of activating blood circulation and blood coagulation in the prevention and treatment of cardiovascular diseases. It can make up for the side effects of the existing blood circulation drugs for cardiovascular disease, only activating blood circulation, and the uncontrollable large-area bleeding due to the long-term use of the drugs. This study provides a material basis for the development of new blood-activating drugs based on natural medicine.

Virtual Screening of the Multi-pathway and Multi-gene Regulatory Molecular Mechanism of Dachengqi Decoction in the Treatment of Stroke Based on Network Pharmacology.

BACKGROUND: Stroke is ranked second among diseases that cause mortality worldwide. Owing to its complicated pathogenesis, no satisfactory treatment strategies for stroke are available. Dachengqi decoction (DCQD), a traditional Chinese herbal medicine, has been widely used in China for a long time, as it has a good effect on stroke. However, the molecular mechanism underlying this effect of DCQD is unclear. OBJECTIVE: In the present study, we aimed to reveal and explore the multi-pathway and multi-gene regulatory molecular mechanism of Dachengqi decoction in the treatment of stroke. METHODS: In this study, a network pharmacology method, in combination with oral bioavailability prediction and drug-likeness evaluation, was employed to predict the active ingredients of DCQD. The target genes of the active components and the traced pathways related to these target genes were predicted. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using clusterProfiler software package on the R platform and ClueGo+CluePedia plug-ins. Finally, the key DCQD targets were verified using the Gene Expression Omnibus (GEO) dataset. RESULTS AND DISCUSSION: According to the ADME model, 52 active components were screened from 296 active components of DCQD. After prediction and screening, 215 stroke-related targets were obtained and analyzed via GO and KEGG analyses. GO analysis showed that DCQD targets were mainly involved in the regulation of oxidative stress, lipid metabolism, inflammation, and other biological processes. KEGG pathway analysis further revealed pathways involved in stroke, such as arachidonic acid metabolic, HIF-1 signaling pathway, estrogen signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, platelet activation pathway, VEGF signaling pathway, and cAMP signaling pathway. Network analysis revealed that DCQD might be involved in the regulation of lipid metabolism, blood pressure, inflammation, angiogenesis, neuroprotection, platelet aggregation, apoptosis, and oxidation in stroke treatment. GEO dataset analysis showed that DCQD's therapeutic effects might be exerted via the bidirectional regulation principle. CONCLUSION: Based on the methods of network pharmacology and GEO analysis, it was found that, during stroke treatment, DCQD regulates and controls multiple genes and multiple pathways in a synergistic manner, providing a new strategy for stroke treatment.

Identification and characterization of a polysaccharide from the roots of Morinda officinalis, as an inducer of bone formation by up-regulation of target gene expression.

Morinda officinalis is an important traditional tonic herbal medicine. In the present study, we found that crude polysaccharides extracted from M. officinalis, named MO90, could significantly increase the bone mineral density (BMD) of the whole femur, distal femur, and proximal femur in ovariectomized (OVX) rats. In addition, MO90 decreased the level of bone turnover markers and prevented the deterioration of trabecular microarchitecture. To investigate the fractions responsible for anti-osteoporosis activity, one novel inulin-type fructan, MOW90-1, was isolated from MOP90. Structural analysis indicated that MOW90-1 consists of a backbone of (2→1)-linked-ß-D-Fruf, and is terminated with (1→)-linked-α-D-Glcp and (2→)-linked-ß-D-Fruf. Furthermore, an in vitro anti-osteoporosis assay indicated that MOW90-1 promoted proliferation, differentiation, and mineralization of MC3T3-E1 cells by up-regulating the expression of runt-related transcription factor 2, osterix, osteopontin, and osteocalcin. In conclusion, our studies provide supporting evidence for future use of this novel M. officinalis fructan as a key nutrient of health products.

Long-term effects of exercise and physical therapy in people with Parkinson disease.

Parkinson disease (PD) is a progressive, neurodegenerative movement disorder with symptoms reflecting various impairments and functional limitations, such as postural instability, gait disturbance, immobility and falls. In addition to pharmacological and surgical management of PD, exercise and physical therapy interventions are also being actively researched. This Review provides an overview of the effects of PD on physical activity - including muscle weakness, reduced aerobic capacity, gait impairment, balance disorders and falls. Previously published reviews have discussed only the short-term benefits of exercises and physical therapy for people with PD. However, owing to the progressive nature of PD, the present Review focuses on the long-term effects of such interventions. We also discuss exercise-induced neuroplasticity, present data on the possible risks and adverse effects of exercise training, make recommendations for clinical practice, and describe new treatment approaches. Evidence suggests that a minimum of 4 weeks of gait training or 8 weeks of balance training can have positive effects that persist for 3-12 months after treatment completion. Sustained strength training, aerobic training, tai chi or dance therapy lasting at least 12 weeks can produce long-term beneficial effects. Further studies are needed to verify disease-modifying effects of these interventions.

Elucidation of the Anti-Inflammatory Mechanisms of Bupleuri and Scutellariae Radix Using System Pharmacological Analyses.

Objective. This study was aimed at elucidating the molecular mechanisms underlying the anti-inflammatory effect of the combined application of Bupleuri Radix and Scutellariae Radix and explored the potential therapeutic efficacy of these two drugs on inflammation-related diseases. Methods. After searching the databases, we collected the active ingredients of Bupleuri Radix and Scutellariae Radix and calculated their oral bioavailability (OB) and drug-likeness (DL) based on the absorption-distribution-metabolism-elimination (ADME) model. In addition, we predicted the drug targets of the selected active components based on weighted ensemble similarity (WES) and used them to construct a drug-target network. Gene ontology (GO) analysis and KEGG mapper tools were performed on these predicted target genes. Results. We obtained 30 compounds from Bupleuri Radix and Scutellariae Radix of good quality as indicated by ADME assays, which possess potential pharmacological activity. These 30 ingredients have a total of 121 potential target genes, which are involved in 24 biological processes related to inflammation. Conclusions. Combined application of Bupleuri Radix and Scutellariae Radix was found not only to directly inhibit the synthesis and release of inflammatory cytokines, but also to have potential therapeutic effects against inflammation-induced pain. In addition, a combination therapy of these two drugs exhibited systemic treatment efficacy and provided a theoretical basis for the development of drugs against inflammatory diseases.

Systems Pharmacology Based Study of the Molecular Mechanism of SiNiSan Formula for Application in Nervous and Mental Diseases.

Background. Mental disorder is a group of systemic diseases characterized by a variety of physical and mental discomfort, which has become the rising threat to human life. Herbal medicines were used to treat mental disorders for thousand years in China in which the molecular mechanism is not yet clear. Objective. To systematically explain the mechanisms of SiNiSan (SNS) formula on the treatment of mental disorders. Method. A systems pharmacology method, with ADME screening, targets prediction, and DAVID enrichment analysis, was employed as the principal approach in our study. Results. 60 active ingredients of SNS formula and 187 mental disorders related targets were discovered to have interactions with them. Furthermore, the enrichment analysis of drug-target network showed that SNS probably acts through "multi-ingredient, multitarget, and multisystems" holistic coordination in different organs pattern by indirectly regulating the nutritional and metabolic pathway even their serial complications. Conclusions. Our research provides a reference for the molecular mechanism of medicinal herbs in the treatment of mental disease on a systematic level. Hopefully, it will also provide a theoretical basis for the discovery of lead compounds of natural medicines for other diseases based on traditional medicine.