Prevalence, trend, and inequality of prolonged exclusive breastfeeding among children aged 6-23 months old in India from 1992-2021: A cross-sectional study of nationally representative, individual-level data.

Background: Prolonged exclusive breastfeeding (PEB) for children older than six months old is a threat to appropriate complementary feeding practices. This study aims to examine the trend of PEB among children aged 6-23 months in India. Methods: We adopted five waves of National Family Health Survey (NFHS) data between 1992-93 and 2019-21. PEB was defined as children aged six months and above currently consuming breastmilk as the only source of energy, protein and micronutrients. We generated descriptive statistics and a series of multivariable logistic regressions to estimate the prevalence and trend in the PEB rate. Moreover, we assessed how child age and socioeconomic factors (i.e. child gender and age, place of residence, household wealth, and maternal education) were related with PEB using mutually and single-adjusted model. Results: There were 184 891 Indian children aged 6-23 months old included in this study with 48.0% being female. We found that the proportion of PEB increased from 4.3% in 1992 to 7.7% in 2021, of which the rate for children aged six-eight months rose from 14.0 to 20.1%. Our results showed that children who were from poorer households or with lower-educated mothers were more likely to experience prolonged exclusive breastfed. Take the year of 2019-21 as an example, compared to the households of the richest quintile, children from households of the poorer quintile were significantly more likely to experience PEB, with odds ratio (OR) of 1.33 (95% confidence interval (CI) = 1.09-1.61). Moreover, children with illiterate mothers had 21% higher odds of having prolonged exclusively breastfeeding (OR = 1.21; 95% CI = 1.01-1.44) compared with children with mothers who have college and above education. Conclusions: PEB among children over six months old is prevalent in India, particularly among children from disadvantaged households. Poverty reduction and maternal education are of great potential importance for policymakers to promote appropriate complementary feeding practice.

Unveiling Gambogenic Acid as a Promising Antitumor Compound: A Review.

Gambogenic acid is a derivative of gambogic acid, a polyprenylated xanthone isolated from Garcinia hanburyi. Compared with the more widely studied gambogic acid, gambogenic acid has demonstrated advantages such as a more potent antitumor effect and less systemic toxicity than gambogic acid according to early investigations. Therefore, the present review summarizes the effectiveness and mechanisms of gambogenic acid in different cancers and highlights the mechanisms of action. In addition, drug delivery systems to improve the bioavailability of gambogenic acid and its pharmacokinetic profile are included. Gambogenic acid has been applied to treat a wide range of cancers, such as lung, liver, colorectal, breast, gastric, bladder, and prostate cancers. Gambogenic acid exerts its antitumor effects as a novel class of enhancer of zeste homolog 2 inhibitors. It prevents cancer cell proliferation by inducing apoptosis, ferroptosis, and necroptosis and controlling the cell cycle as well as autophagy. Gambogenic acid also hinders tumor cell invasion and metastasis by downregulating metastasis-related proteins. Moreover, gambogenic acid increases the sensitivity of cancer cells to chemotherapy and has shown effects on multidrug resistance in malignancy. This review adds insights for the prevention and treatment of cancers using gambogenic acid.

Early Warning Effect of CHR, NLR and U-HBP on SIRS in Patients with Upper Urinary Tract Calculus After Flexible Ureteroscopic Lithotripsy.

Objective: Rising upper urinary tract calculus (UUTC) cases demand effective treatment. FUL, while efficient, poses infection risks and SIRS. This study explores CHR, NLR, and U-HBP as potential SIRS predictors post-FUL in UUTC patients, aiming to improve early detection and enhance SIRS management. Methods: A retrospective analysis was conducted on data from 216 UUTC patients who underwent FUL between April 2020 and April 2023. Occurrence of SIRS post-FUL was studied. Patients were categorized into SIRS and non-SIRS groups. CHR, NLR, and U-HBP levels were compared. Predictive value of CHR, NLR, and U-HBP for SIRS was assessed. Univariate and multivariate logistic regression analyses identified SIRS influencing factors. Results: In a study involving 216 patients undergoing Flexible Ureteroscopic Holmium Laser Lithotripsy (FUL), Systemic Inflammatory Response Syndrome (SIRS) occurred in 20.83% of cases. Patients with SIRS exhibited significantly elevated levels of C-reactive protein to High-density lipoprotein cholesterol ratio (CHR) (9.26 ± 2.17 vs. 3.89 ± 0.92), Neutrophil to Lymphocyte Ratio (NLR) (5.21 ± 0.98 vs. 2.62 ± 0.49), and Urinary Heparin Binding Protein (U-HBP) (3.01 ± 0.51 ng/L vs. 1.22 ± 0.19 ng/L) compared to the non-SIRS group. Multivariate analysis identified factors such as infected stones (OR = 3.294), stone size ≥ 30 mm (OR = 2.034), CHR ≥ 8.76 (OR = 4.554), NLR ≥ 3.74 (OR = 3.951), and U-HBP ≥ 1.55 ng/L (OR = 4.884) as significant predictors for SIRS. These findings emphasize the pivotal role of these biomarkers and stone characteristics in predicting inflammatory responses post-FUL surgery. Conclusion: This study establishes the predictive power of elevated C-reactive protein to High-density lipoprotein cholesterol ratio (CHR), Neutrophil to Lymphocyte Ratio (NLR), and Urinary Heparin Binding Protein (U-HBP) levels for Systemic Inflammatory Response Syndrome (SIRS) post Flexible Ureteroscopic Holmium Laser Lithotripsy (FUL) in upper urinary tract calculi patients. Stone characteristics, including infected stones and stone size ≥ 30 mm, are also key indicators of SIRS. These findings offer crucial insights for effective post-operative management, enhancing outcomes in urinary calculi treatment.

Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms.

Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA's significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, including potential toxicity and poor oral bioavailability, which need to be addressed when considering it as an anti-tumor candidate agent. Nevertheless, I given its promising anti-tumor attributes, WA remains an encouraging candidate for future drug development. Unveiling the exact target and comprehensive mechanism of WA's action represents a crucial research direction to pursue in the future.

Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

BACKGROUND: There is abundant evidence showing that iron deficiency is closely linked with delayed brain development, worse school performance, and behavioral abnormalities. However, evidence on the impact of iron supplementation among children and adolescents in low- and middle-income countries (LMICs) has been inconsistent. This study aims to examine the effect of oral iron supplementation on cognitive function among children and adolescents in LMICs. METHODS: A systematic review and meta-analysis was conducted to examine the impact of iron supplementation on cognitive function (including intelligence, attention, short-term memory, long-term memory, and school performance) among children and adolescents aged 5 to 19. We searched PubMed, Embase, Web of Science, CINAHL, and references of related articles published from the inception of the databases to 1 May 2022. Random-effects pooled standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated to estimate the effect of iron supplementation on cognitive function. We also investigated the heterogeneity of the effects using subgroup and meta-regression analyses. This review was registered with PROSPERO (CRD42020179064). RESULTS: Nine studies with 1196 individual participants from five countries were identified and included. Iron had a positive impact on intelligence test scores among children and adolescents (SMD = 0.47, 95% confidence interval [CI]: 0.10, 0.83). Meta-regression showed that the intelligence test scores improved with increasing the iron supplement dose (odds ratio [CI] = 1.02, 95% CI: 1.00, 1.04). There were no significant effects on attention, short-term memory, long-term memory, or school performance. CONCLUSIONS: Oral iron intake can improve the intelligence test scores of children and adolescents in LMICs and should be considered for future nutritional interventions.

Treatment of COVID-19 by monoclonal antibodies and the traditional Chinese medicine.

The mortality rate of the recent global pandemic corona virus disease 2019 (COVID-19) is currently as high as 7%. The SARS-CoV-2 virus is the culprit behind COVID-19. SARS-CoV-2 is an enveloped single-stranded RNA virus, the genome encodes four types of the structural proteins: S protein, E protein (envelope protein), M protein (matrix protein) and N protein (nucleocapsid protein). In COVID-19, monoclonal antibodies have played a significant role in diagnosis and treatment. This article briefly introduced the development of monoclonal antibodies targeting on S protein and N protein, which represents the main direction of monoclonal antibody drugs used in the diagnosis and treatment of COVID-19. Meanwhile, the traditional Chinese medicine also plays important role in the fight against COVID-19 by regulating human immunity. The article introduced the use of traditional Chinese medicine in fighting against COVID-19.

Impact of Helicobacter pylori Infection and Outcome of Anti-Helicobacter pylori Therapy in Patients with Reflux Laryngopharyngitis.

Objectives: This study was designed to explore the relationship between Helicobacter pylori (Hp) infection and reflux laryngopharyngitis (RLP) and to evaluate the outcome of anti-Hp therapy in improving RLP symptoms. Methods: A total of 410 patients with RLP were enrolled and tested for Hp infection. The association of Hp infection with reflux symptom index (RSI) and reflux finding score (RFS) was determined. Hp-positive patients received either a proton pump inhibitor (PPI) omeprazole alone (control group) or a combination regimen (experimental group) consisting of omeprazole, mosapride citrate, amoxicillin, and clarithromycin. Therapeutic outcomes were compared 4 weeks later. Results: Of the 410 participants, 290 were Hp-positive and 120 Hp-negative. Both RSI and RFS were significantly higher in Hp-positive patients than in Hp-negative patients. Hp infection status was positively correlated with RSI (P < 0.05) and RFS (P < 0.05). The overall response rate was higher in the experimental group than in the control group. Both the groups had a significant reduction in RSI and RFS after therapy, with a greater improvement in the experimental group (P < 0.05). Conclusion: Our findings establish a link between Hp infection and RLP. Anti-Hp therapy improves RSI and RFS in RLP patients. Therefore, Hp eradication drugs may be added to the PPI-based regimen in the treatment of RLP.

Effects of Long-Term and Multigeneration Exposure of Caenorhabditis elegans to 9.4 GHz Microwaves.

A large number of studies on the biological effects of microwaves are carried out using rodents and cells, but the conditions are difficult to control, and the irradiation period is short; the results obtained have always been controversial and difficult to reproduce. In this study, we expose nematodes to an electromagnetic environment for a long-term and multigeneration period to explore the possible biological effects. Wild-type N2 strains of Caenorhabditis elegans are exposed to 9.4 GHz microwaves at a specific adsorption rate of 4 W/kg for 10 h per day from L1 larvae to adults. Then, adult worms are washed off, and the laid eggs are kept to hatch L1 larvae, which are continuously exposed to microwaves until passing through 20 generations. The worms of the 10th, 15th, and 20th generations are collected for index detection. Interestingly, we found that the fecundity of C. elegans decreased significantly in the exposed group from the 15th generation. At the same time, we found that the growth of C. elegans decreased, motility decreased, and oxidative stress occurred in the exposed group from the 10th generation, which may play roles in the decreased spawning in worms. We preliminarily believe that the microwave energy received by worms leads to oxidative stress, which causes a decrease in the spawning rate, and the underlying mechanism needs to be further studied. © 2022 Bioelectromagnetics Society.

Genome-Wide Characterization and Expression Analysis of HD-ZIP Gene Family in Dendrobium officinale.

The homeodomain-leucine zipper (HD-ZIP) gene family, as one of the plant-specific transcription factor families, plays an important role in regulating plant growth and development as well as in response to diverse stresses. Although it has been extensively characterized in many plants, the HD-ZIP family is not well-studied in Dendrobium officinale, a valuable ornamental and traditional Chinese medicinal herb. In this study, 37 HD-ZIP genes were identified in Dendrobium officinale (Dohdzs) through the in silico genome search method, and they were classified into four subfamilies based on phylogenetic analysis. Exon-intron structure and conserved protein domain analyses further supported the prediction with the same group sharing similar gene and protein structures. Furthermore, their expression patterns were investigated in nine various tissues and under cold stress based on RNA-seq datasets to obtain the tissue-specific and cold-responsive candidates. Finally, Dohdz5, Dohdz9, and Dohdz12 were selected to validate their expression through qRT-PCR analysis, and they displayed significantly differential expression under sudden chilling stress, suggesting they might be the key candidates underlying cold stress response. These findings will contribute to better understanding of the regulatory roles of the HD-ZIP family playing in cold stress and also will provide the vital targets for further functional studies of HD-ZIP genes in D. officinale.

High-dose vitamin D metabolite delivery inhibits breast cancer metastasis.

Besides its well-known benefits on human health, calcitriol, the hormonally active form of vitamin D3, has been being evaluated in clinical trials as an anticancer agent. However, currently available results are contradictory and not fundamentally deciphered. To the best of our knowledge, hypercalcemia caused by high-dose calcitriol administration and its low bioavailability limit its anticancer investigations and translations. Here, we show that the one-step self-assembly of calcitriol and amphiphilic cholesterol-based conjugates leads to the formation of a stable minimalist micellar nanosystem. When administered to mice, this nanosystem demonstrates high calcitriol doses in breast tumor cells, significant tumor growth inhibition and antimetastasis capability, as well as good biocompatibility. We further reveal that the underlying molecular antimetastatic mechanisms involve downregulation of proteins facilitating metastasis and upregulation of paxillin, the key protein of focal adhesion, in primary tumors.

Ophiopogonin B alleviates cisplatin resistance of lung cancer cells by inducing Caspase-1/GSDMD dependent pyroptosis.

Drug resistance has become the main reason for the failure of tumor chemotherapy. Radix Ophiopogon Japonicus has long been used as traditional Chinese medicine to treat pulmonary disease, and Ophiopogonin B (OP-B) as a bioactive component of it has also been verified to inhibit cell proliferation of various non-small cell lung cancer (NSCLC) cells in vivo and in vitro. Therefore, we wonder whether OP-B is also effective to drug resistant lung cancer cells. Firstly, Cell Counting Kit-8 (CCK8) assay was used to compare the sensitivity of OP-B on NCI-H460, A549, cisplatin resistant A549 (A549/DDP) and paclitaxel resistant A549 (A549/PTX) cells, and A549/DDP cells were shown to be more sensitive to OP-B than other three cell lines, the results were further verified in orthotopic tumor nude mice model and zebrafish tumor model. Moreover, observation of cell morphological feature, mitochondrial membrane potential, LDH release rate, and production of IL-1ß all suggested that OP-B induced pyroptosis in A549/DDP cells more significantly than that in A549 cells. Meanwhile, transcriptomic sequencing results between OP-B treated and the Mock A549/DDP group also suggested that OP-B induced more significant Caspase-1/GSDMD dependent pyroptosis in A549/DDP group, which was further verified by VX-765, the inhibitor of Caspase-1. Together, the experimental results suggested that OP-B alleviated DDP resistance of A549 cells through inducing more significant Caspase-1/GSDMD-dependent pyroptosis.

Pulsed High-Peak Power Microwaves at 9.4 GHz Do Not Affect Basic Endpoints in Caenorhabditis elegans.

Because of the extensive application of electromagnetic technology, its health impact on humans has attracted widespread attention. Due to the lack of a model organism with a stable response to electromagnetic waves, the research conclusions on the biological effects of electromagnetic waves have been vague. Therefore, the aim of this study was to investigate the effects of irradiation by pulsed 9.4 GHz high-power microwaves with a peak power density of 2126 W/cm2 using Caenorhabditis elegans. The development, movement, egg production, ROS, and lifespan of C. elegans were detected at different times after irradiation with different repetitive frequencies of 10, 20, and 50 Hz for 30 min. The results indicated that no obvious changes in basic life indices were induced compared with the sham radiation group, but the survival rate of positive control was significantly decreased compared with other groups, which is of interest for microwave protection research based on C. elegans and provides data for updating safety standards with respect to pulsed high-peak power microwave. © 2021 Bioelectromagnetics Society.

Outcome of parathyroid function after total thyroidectomy when calcium supplementation is administered routinely versus exclusively to symptomatic patients: A prospective randomized clinical trial.

PURPOSE: Current guidelines for calcium supplementation for parathyroid function recovery after thyroidectomy are based on low-quality evidence. The present trial compared the effects of oral calcium and vitamin D supplementation on the recovery of parathyroid function when administered routinely or exclusively to symptomatic patients. METHODS: This prospective, randomized, open-label clinical trial analyzed 203 patients who underwent total thyroidectomy and developed hypoparathyroidism on postoperative day 1 (POD1) with median age of 41 years and proportion of women of 77.8%. Participants were randomized to group A (calcium and vitamin D supplementation administered only to symptomatic patients) and group B (routine supplementation). The primary outcome was the incidence of protracted hypoparathyroidism in the two groups. Secondary outcomes included risk factors for postoperative protracted hypoparathyroidism and the incidence of symptomatic hypocalcemia. RESULTS: The incidence of protracted hypoparathyroidism was not significantly different between group A and group B (11 of 99 vs. 17 of 104, P = 0.280). Parathyroid hormone (PTH) in group B exhibited a better recovery tendency. The incidence of postoperative symptomatic hypocalcemia in group B was significantly lower than group A (26.92% vs. 42.42%, P = 0.020). Independent factors predicting protracted hypoparathyroidism included sex, preoperative serum calcium, and POD1 PTH. CONCLUSION: Calcium and vitamin D supplementation administered exclusively to symptomatic patients achieved the same effect on protracted hypoparathyroidism as routine supplementation. However, routine supplementation significantly reduced postoperative hypocalcemia. Extra attention is necessary in female patients with high preoperative serum calcium and patients with low POD1 PTH. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR1900022194. Registered March 30, 2019.

Network Pharmacology for Analyzing the Key Targets and Potential Mechanism of Wogonin in Gliomas.

Objective: To analyze the key targets and potential mechanisms underlying the volatile components of Scutellaria baicalensis Georgi acting on gliomas through network pharmacology combined with biological experiments. Methods: We have extracted the volatile components of Scutellaria baicalensis by gas chromatography-mass spectrometry (GC-MS) and determined the active components related to the onset and development of gliomas by combining the results with the data from the Traditional Chinese Medicine Systems Pharmacology database. We screened the same targets for the extracted active components and gliomas through network pharmacology and then constructed a protein-protein interaction network. Using a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we analyzed the protein effects and regulatory pathways of the common targets. Lastly, we employed ELISA and Western blot in verifying the key targets in the regulatory pathway. Results: We ultimately determined that the active component in S. baicalensis Georgi related to the onset and development of gliomas was Wogonin. The results of the network pharmacology revealed 85 targets for glioma and Wogonin. We used gene ontology to analyze these target genes and found that they involved 30 functions, such as phosphatidylinositol phosphokinase activation, while the KEGG analysis showed that there were 10 regulatory pathways involved. Through the following analysis, we found that most of the key target genes are distributed in the PI3K-Akt and interleukin 17 signaling pathways. We then cultured U251 glioma cells for the experiments. Compared with the control group, no significant change was noted in the caspase-3 expression; however, cleaved caspase-3 expression increased significantly and was dose-dependent on Wogonin. The expression of Bad and Bcl-2 with 25 µM of Wogonin has remained unchanged, but when the Wogonin dose was increased to 100 µM, the expression of Bad and Bcl-2 was noted to change significantly (Bad was significantly upregulated, while Bcl-2 was significantly downregulated) and was dose-dependent on Wogonin. The ELISA results showed that, compared with the control group, the secretion of tumor necrosis factor alpha, IL-1ß, and IL-6 decreased as the Wogonin concentration increased. Tumor necrosis factor alpha downregulation had no significant dose-dependent effect on Wogonin, the inhibitory effect of 25 µM of Wogonin on IL-6 was not significant, and IL-1ß downregulation had a significant dose-dependent effect on Wogonin. Conclusion: Wogonin might promote the apoptosis of glioma cells by upregulating proapoptotic factors, downregulating antiapoptotic factors, and inhibiting the inflammatory response, thereby inhibiting glioma progression.

Molecular Targets and Associated Signaling Pathways of Jingshu Granules in Ovarian Cysts Based on Systemic Pharmacological Analysis.

BACKGROUND: More than a third of women could develop ovarian cysts during their lifetime. Jingshu granules are used for the treatment of gynecological disease of primary dysmenorrhea. However, the molecular mechanisms of Jingshu granules in ovarian cysts are still unreported. We aimed to find the active ingredients, molecular targets, and potential signaling pathways of Jingshu granules in ovarian cysts by using the systemic pharmacological analysis. METHODS: Firstly, the effect of Jingshu granules on female hormones and reproductive organs of young female rats was evaluated. Secondly, candidate pharmaceutical ingredients of Jingshu granules were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform. Potential protein targets for the active ingredients in Jingshu granules were then identified according to the oral bioavailability and drug-likeness indices. Thirdly, ovarian cyst-related gene targets were screened based on different databases. Finally, enrichment analysis was used to analyze the potential biological function of intersection targets between Jingshu granules and ovarian cysts. RESULTS: In young female rats, Jingshu granules reduced the secretion of estradiol, progesterone, and prolactin and could affect the development of the uterus. This suggested that Jingshu granules played roles in hormone secretion and reproduction. From the TCMSP, a total of 1021 pharmaceutical ingredients of Jingshu granules were retrieved. After further screening, a total of 166 active ingredients and 159 protein targets of Jingshu granules were identified. In addition, 4488 gene targets of ovarian cysts were screened out. After taking the intersection, a total of 110 intersection targets were identified between potential protein targets of Jingshu granules and gene targets of ovarian cysts. In the functional analysis of 110 intersection targets, 8 signaling pathways including progesterone-mediated oocyte maturation (MAPK8 and CDK1 involved), GnRH signaling pathway (JUN involved), T cell receptor signaling pathway and Toll-like receptor signaling pathway (MAPK1 involved), NOD-like receptor signaling pathway (TNF, IL6, and IL1B involved), p53 signaling pathway (CDK2 and CDK4 involved), VEGF signaling pathway (MAPK14 involved), and PPAR signaling pathway (PPARG involved) were obtained. CONCLUSION: Our study revealed that Jingshu granules could function in patients with ovarian cysts through a number of molecular targets and signaling pathways. Our study may provide a new field into the mechanisms of Jingshu granules in ovarian cysts, from the molecular to the signaling pathway level.

Inhibitory effects of Coptidis Rhizoma on the intestinal absorption and metabolism of Scutellariae Radix.

ETHNOPHARMACOLOGICAL RELEVANCE: The Scutellariae Radix (SR) and Coptidis Rhizoma (CR) herb couple is widely used in traditional Chinese medicine prescriptions for the treatment of diabetes mellitus due to its interaction and synergistic effect compared to either herb alone, but the underlying mechanism of interaction between these herbs is unclear. This study aimed to investigate the effects of CR on the metabolism and absorption of SR. MATERIALS AND METHODS: After rats were treated with normal saline (NS group) or the CR extract (CR-treated group) for seven consecutive days, the intestinal flora was extracted from rat faeces for a co-incubation with the SR extract to investigate the metabolism of SR flavonoids, and a non-everted gut sac was prepared in vitro to evaluate the intestinal absorption of the SR extract. The components of the SR extract, the metabolites of the SR extract that was co-incubated with intestinal flora, and the dialysate acquired from non-everted gut sacs were identified and determined by an HPLC-MS/MS method. The absorption rate constant (Ka) and the apparent permeability (Papp) of each compound were calculated, and the effects of CR on the metabolism and absorption of flavonoids in SR were evaluated, by comparison the Ka and Papp between two groups using Student's t-test. RESULTS: Twenty-nine flavonoids were detected and identified in the SR extract, including 16 glycosides and 13 aglycones. In the co-incubation with the intestinal flora, differences in metabolite classes were not observed between the NS group and CR-treated group; however, the metabolic rates of 17 flavonoids in the CR-treated group were significantly higher than the NS group. The Papp of 11 compounds (4 glycosides and 7 aglycones) across the gut sac were greater than 2 × 10-5 cm/s in both groups, while the Papp values of 7 compounds including wogonoside (WG) and other aglycones were significantly decreased in the CR-treated group. CONCLUSION: Based on these results, CR decreased the metabolism and absorption of SR flavonoids, and exerted much greater inhibitory effects on aglycones than glycosides, which may be one of the potential mechanisms underlying the therapeutic effects of the combination of SR and CR on diabetes mellitus.

Jiaotai Pill () Alleviates Insomnia through Regulating Monoamine and Organic Cation Transporters in Rats.

OBJECTIVE: To reveal the effect and mechanism of Jiaotai Pill (, JTP) on insomniac rats. METHODS: The insomniac model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). In behavioral experiments, rats were divided into control, insomniac model, JTP [3.3 g/(kg•d)], and diazepam [4 mg/(kg•d)] groups. The treatment effect of JTP was evaluated by weight measurement (increasement of body weight), open field test (number of crossings) and forced swimming test (immobility time). A high performance liquid chromatography-electrochemical detection (HPLC-ECD) method was built to determine the concentration of monoamine transmitters in hypothalamus and peripheral organs from normal, model, JTP, citalopram [30 mg/(kg•d)], maprotiline [40 mg/(kg•d)] and bupropion [40 mg/(kg•d)] groups. Expressions of serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) were analyzed by quantitative polymerase chain reaction (qPCR) and Western blot in normal, model and JTP groups. A high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) method was established to determine the pharmacokinetics, urine cumulative excretion of metformin in vivo, and tissue slice uptake in vitro, which were applied to assess the activity of organic cation transporters (OCTs) in hypothalamus and peripheral organs. RESULTS: Compared with the insomniac model group, the body weight and spontaneous locomotor were increased, and the immobility time was decreased after treatment with JTP (P<0.01). Both serotonin and dopamine contents in hypothalamus and peripheral organs were increased (P<0.01). The norepinephrine content was increased in peripheral organs and decreased in hypothalamus (P<0.05 or P<0.01). At the same time, SERT, DAT, OCT1, OCT2, and OCT3 were down-regulated in hypothalamus and peripheral organs (P<0.05). NET was down-regulated in peripheral organs and up-regulated in hypothalamus (P<0.05 or P<0.01). Moreover, the activity of OCTs in hypothalamus and peripheral organs was inhibited (P<0.05). CONCLUSION: JTP alleviates insomnia through regulation of monoaminergic system and OCTs in hypothalamus and peripheral organs.

Study on metastasis inhibition of Kejinyan decoction on lung cancer by affecting tumor microenvironment.

BACKGROUND: Kejinyan decoction, as an experienced formula of Zhou Zhongying (the Master of Traditional Chinese Medicine) has been widely used in clinic for lung cancer treatment in China, while the anti-lung cancer mechanism of it is still remained to be elucidated. Herein, our basic study found that the survival of lung cancer xenograft mice was significantly prolonged after intragastrically administered high dose of Kejinyan decoction (3.8 g per kg BW) for 15 days. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. Thus in this study, we aim to elucidate the anti-metastasis effects of Kejinyan decoction. METHODS: RNA-Seq was used to find out the gene regulation of Kejinyan decoction on the mice, flow cytometry assay was used to detect the immunocytes in the spleen, ELISA assay was used to detect the inflammatory factors in the serum and spleen, and immunofluorescence assay was used to detect the level of immune cells and the expression of glycol-metabolism related enzymes in situ. Also, we established a lung cancer orthotopic xenograft tumor model to assess the influence of Kejinyan decoction on the metastatic ability of lung cancer cells in vivo. RESULTS: GO analysis of gene sequencing of tumor tissue samples showed that Kejinyan decoction regulated immune response. Further flow cytometry analysis of splenic lymphocyte showed that Kejinyan decoction upregulated M1 macrophages and downregulated M2 macrophages, while the total level of macrophages changed little, which was verified by detection of CD68, F4/80, CD206, and CD86 in tumor tissue section. Moreover, detection of inflammatory cytokines showed that Kejinyan decoction downregulated TNF-α, IFN-γ, IL-6, as well as IL-4, IL-13 in tumor microenvironment. Further studies also showed that Kejinyan decoction had little effect on tumor hypoxia, but downregulated glycolysis in tumor tissues. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. CONCLUSION: Our findings conclude that Kejinyan decoction inhibited lung cancer cell metastasis through affecting macrophage polarization and energy reprogramming.

Activation of HIF-1 signaling ameliorates liver steatosis in zebrafish atp7b deficiency (Wilson's disease) models.

Wilson's disease is an autosomal recessive disease characterized by excess copper accumulated in the liver and brain. It is caused by mutations in the copper transporter gene ATP7B. However, based on the poor understanding of the transcriptional program involved in the pathogenesis of Wilson's disease and the lack of more safe and efficient therapies, the identification of novel pathways and the establishment of complementary model systems of Wilson's disease are urgently needed. Herein, we generated two zebrafish atp7b-mutant lines using the CRISPR/Cas9 editing system, and the mutants developed hepatic and behavioral deficits similar to those observed in humans with Wilson's disease. Interestingly, we found that atp7b-deficient zebrafish embryos developed liver steatosis under low-dose Cu exposure, and behavioral deficits appeared under high-dose Cu exposure. Analyses of publicly available transcriptomic data from ATP7B-knockout HepG2 cells demonstrated that the HIF-1 signaling pathway is downregulated in ATP7B-knockout HepG2 cells compared with wildtype cells following Cu exposure. The HIF-1 signaling pathway was also downregulated in our atp7b-deficient zebrafish mutants following Cu exposure. Furthermore, we demonstrate that activation of the HIF-1 signaling pathway with the chemical compound FG-4592 or DMOG ameliorates liver steatosis and reduces accumulated Cu levels in zebrafish atp7b deficiency models. These findings introduce a novel prospect that modulation of the HIF-1 signaling pathway should be explored as a novel strategy to reduce copper toxicity in Wilson's disease patients.

Factors Associated With Child Stunting, Wasting, and Underweight in 35 Low- and Middle-Income Countries.

Importance: Evidence on the relative importance of various factors associated with child anthropometric failures (ie, stunting, underweight, and wasting) and their heterogeneity across countries can inform global and national health agendas. Objective: To assess the relative significance of factors associated with child anthropometric failures in 35 low- and middle-income countries (LMICs). Design, Setting, and Participants: This cross-sectional study of 299 353 children who were born singleton and aged 12 to 59 months with nonpregnant mothers and valid anthropometric measures assessed the strengths of associations of 26 factors with child stunting, underweight, and wasting, using Demographic and Health Surveys (2007-2018) from 35 LMICs. Data analysis was conducted from July 2019 to February 2020. Exposures: A total of 9 direct factors (ie, dietary diversity score; breastfeeding initiation; vitamin A supplements; use of iodized salt; infectious disease in past 2 weeks; oral rehydration therapy for children with diarrhea; care seeking for suspected pneumonia; full vaccination; and indoor pollution) and 17 indirect factors (household wealth; maternal and paternal education; maternal and paternal height and body mass index; maternal autonomy for health care, movement, and money; water source; sanitation facility; stool disposal; antenatal care; skilled birth attendant at delivery; family planning needs; and maternal marriage age) were assessed. Main Outcomes and Measures: Three anthropometric failure outcomes were constructed based on the 2006 World Health Organization child growth standards: stunting (height-for-age z score less than -2 standard deviations [SDs]), underweight (weight-for-age z score less than -2 SDs), and wasting (weight-for-height z score less than -2 SDs). Results: Among the 299 353 children aged 12 to 59 months included in the analysis, 38.8% (95% CI, 38.6%-38.9%) had stunting, 27.5% (95% CI, 27.3%-27.6%) had underweight, and 12.9% (95% CI, 12.8%-13.0%) had wasting. In the pooled sample, short maternal height was the strongest factor associated with child stunting (odds ratio [OR], 4.7; 95% CI, 4.5-5.0; P < .001), followed by lack of maternal education (OR, 1.9; 95% CI, 1.8-2.0; P < .001), poorest household wealth (OR, 1.7; 95% CI,1.6-1.8; P < .001), and low maternal body mass index (OR, 1.6; 95% CI, 1.6-1.7; P < .001). Short paternal height was also significantly associated with higher odds of stunting (OR, 1.9; 95% CI, 1.7-2.2; P < .001). Consistent results were found for underweight (eg, short maternal height: OR, 3.5; 95% CI, 3.3-3.7; P < .001; lack of maternal education: OR, 1.8; 95% CI, 1.7-2.0; P < .001) and wasting (eg, low maternal body mass index: OR, 2.3; 95% CI, 2.1-2,4; P < .001; poorest household wealth: OR, 1.2; 95% CI, 1.1-1.3; P < .001). Parental nutritional status and household socioeconomic conditions ranked the strongest (1st to 4th) for most countries, with a few exceptions (eg, lack of maternal education ranked 18th-20th in 8 countries for child wasting). Other factors were not associated with anthropometric failures in pooled analysis and had large country-level heterogeneity; for example, unsafe water was not associated with child underweight in the pooled analysis (OR, 0.97; 95% CI, 0.95-1.00; P < .001), and it ranked from 4th to 20th across countries. Conclusions and Relevance: In this study, socioeconomic conditions and parental nutritional status were the strongest factors associated with child anthropometric failures. Poverty reduction, women's education, and nutrition programs for households could be important strategies for reducing child undernutrition; however, country-specific contexts should be considered in national policy discussions.