Vitamin B12 supplementation during pregnancy for maternal and child health outcomes.

BACKGROUND: Vitamin B12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. OBJECTIVES: To evaluate the benefits and harms of oral vitamin B12 supplementation during pregnancy on maternal and child health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation during pregnancy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. MAIN RESULTS: The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B12 supplementation varied from 5 µg/day to 250 µg/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B12 supplementation during pregnancy on neural tube defects. Infant vitamin B12 status: children born to women who received vitamin B12 supplementation had higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). AUTHORS' CONCLUSIONS: Oral vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency and may improve maternal vitamin B12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain. The effects of vitamin B12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B12 supplementation during pregnancy may improve maternal and infant vitamin B12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

Purification and structural characterization of two polysaccharides with anti-inflammatory activities from Plumbago zeylanica L.

Plumbago zeylanica L., a traditional Chinese medicine, has anti-bacterial and anti-inflammatory effects, and it is critical important to explore the chemical compounds and evaluate their biological actions from the medicinal plant. However, the chemical structure and biological activities of polysaccharides from P. zeylanica. were still poorly understood. In this study, two water-soluble polysaccharides named WPZP-2-1 and WPZP-2-2 were purified from P. zeylanica L. Chemical and spectroscopic tests showed that the main chain of WPZP-2-1 was →4)-α-D-GalpA-(1 â†’ 2)-α-L-Rhap-(1→, and the branch chain was galactose or arabinose. The main chain of WPZP-2-2 was composed of →4)-α-D-GalpA-(1 â†’ 2)-α-L-Rhap-(1→, and the O-2 and O-3 of →4)-α-D-GalpA had a small amount of acetylation. In addition, in vitro test showed that WPZP-2-1 and WPZP-2-2 significantly improved the inflammatory damage of LPS + IFN-γ-induced THP-1 cells via reducing the protein levels of CD14, TLR4 and MyD88, thereby promoting IL-10 expression and inhibiting the mRNA levels of TNF-α and IL-1ß. Those findings indicated that WPZP-2-1 and WPZP-2-2 from the plant should be served as the potential anti-inflammatory agents.

[High-throughput screening of 54 alternative plasticizers in sesame oil using gas chromatography-quadrupole time-of-flight mass spectrometry].

Restrictions on the use of phthalates have led to the wide use of alternative plasticizers (APs) such as organophosphate, adipate, citrate, and sebacate. However, because plasticizers combine with polymers in plastic products via unstable noncovalent bonds, they can easily migrate out of these products, causing environmental pollution. In particular, their migration out of food packaging, containers, and other food-contact materials and into food has raised great concerns. Toxicological studies have shown that APs contain potentially toxic substances that can affect endocrine functions and cause neurotoxicity, genotoxicity, and other adverse effects. Thus, their potential risks to food should not be underestimated. Sesame oil is a necessity in daily cooking. The results of risk monitoring in recent years have indicated that sesame oil often contains phthalates in excess of the standard limits. However, the potential risks of APs in sesame oil have not yet been reported. Some common detection methods for APs include gas chromatography-mass spectrometry, gas chromatography-triple quadrupole mass spectrometry, and liquid chromatography-triple quadrupole mass spectrometry. Unfortunately, these methods use low-resolution mass spectrometry and are limited by the resolution, scan rate, and analysis mode. Gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF/MS) has the advantages of high resolution, sensitivity, and analysis speed. In full-scan mode, GC-Q-TOF/MS can accurately collect the full-spectrum mass number of target compounds with low content levels in complex substrates, thereby realizing efficient screening and quantitative analysis. It shows outstanding advantages in the trace analysis of pesticide residues and pollutants. Furthermore, it features strong qualitative and high screening abilities. Establishment of a personal compound database and library (PCDL) addresses limitations in the number of compounds that can be measured and enables the rapid identification of targets without the use of standard products. In addition, increasing the number of targets for synchronous screening enables the retrospective analysis of new targets. In this study, a method based on GC-Q-TOF/MS was developed for the determination of 54 APs in sesame oil. The samples were extracted with acetonitrile and purified using a PSA/silica solid-phase extraction column. The mass-spectral information of the samples was then collected by GC-Q-TOF/MS in full-scan mode, and the 54 APs were searched using an established high-resolution mass-spectrum database to simultaneously achieve the broad-spectrum screening, qualitative identification, and quantitative analysis of multiple targets. The effects of different extraction solvents and purification methods on sample extraction and purification were compared. The accuracy of the screening results was improved by optimizing the GC-separation conditions, quality-extraction window, retention-time deviation, and other screening parameters. The screening detection limits (SDLs) of the 54 APs ranged from 0.01 to 0.02 mg/kg; specifically, the SDL of 41 compounds was 0.01 mg/kg and that of 13 compounds were 0.02 mg/kg. The limits of quantification were in the range of 0.02-0.04 mg/kg. A total of 80 sesame-oil samples were rapidly screened using this method under optimal conditions. Five APs were identified from the 80 sesame-oil samples and quantitatively analyzed using the matrix-matched external-standard method. The results of this quantitative methodology showed that the five APs had good linear relationships in the range of 0.01-0.2 mg/L, with all correlation coefficients greater than 0.99. The accuracy and precision of the method were verified using a standard recovery test with blank sesame-oil samples. Under the three standard levels of 0.04, 0.08, and 0.2 mg/kg, the recoveries of the five APs ranged from 71.3% to 97.8%, and the relative standard deviations (RSDs) ranged from 0.4% to 6.1%(n=6). The developed method is fast, accurate, sensitive, and has high throughput. Thus, it can realize the efficient screening, qualitative identification, and quantitative analysis of the 54 APs in sesame oil and provides a potential solution for the monitoring of other contaminants in food.

Magnetic amino-rich hyper-crosslinked polymers for fat-rich foodstuffs pretreatment in nontargeted analysis of chemical hazards.

Nontargeted analysis for chemical hazards is highly desirable in controlling food safety to ensure human health. As the dominating interference in fat-rich foodstuffs, lipids removal is a great challenge in sample pretreatment. Herein, diverse lipids from both animal and vegetable oils are effectively removed and 565 chemical hazards with various physicochemical properties are used for method validation. These benefits are from the designed magnetic amino-rich hyper-crosslinked core-shell polymeric composites (Fe3O4@poly(MAAM-co-EGDMA)) and the application of an auto extraction system. Among them, the amino groups are the key factors for lipid removal. Theoretical calculations, isothermal titration calorimetry (ITC), and functional monomer replacement demonstrated that the mechanisms to universally capture free fatty acids (FFAs) and triglycerides (TGs) are electrostatic interaction and supplemented by hydrogen bonding. Overall, this work highlights the great application potentials of polymeric adsorbents as sample pretreatment materials for nontargeted analysis in food safety.

Characteristics of corticomuscular coupling during wheelchair Tai Chi in patients with spinal cord injury.

BACKGROUND: Wheelchair Tai Chi (WCTC) has been proved to have benefits for the brain and motor system of spinal cord injury (SCI) patients. However, the characteristics of corticomuscular coupling during WCTC are scarcely known. We aimed to investigate changes following SCI on corticomuscular coupling, and further compare the coupling characteristics of WCTC with aerobic exercise in SCI patients. METHODS: A total of 15 SCI patients and 25 healthy controls were recruited. The patients had to perform aerobic exercise and WCTC, while healthy controls needed to complete a set of WCTC. The participants accomplished the test following the tutorial video in a sitting position. The upper limb muscle activation was measured from upper trapezius, medial deltoid, biceps brachii and triceps brachii with surface electromyography. Cortical activity in the prefrontal cortex, premotor cortex, supplementary motor area and primary motor cortex was simultaneously collected by functional near-infrared spectroscopy. The functional connectivity, phase synchronization index and coherence values were then calculated and statistically analyzed. RESULTS: Compared to healthy controls, changes in functional connectivity and higher muscle activation were observed in the SCI group. There was no significant difference in phase synchronization between groups. Among patients, significantly higher coherence values between the left biceps brachii as well as the right triceps brachii and contralateral regions of interest were found during WCTC than during aerobic exercise. CONCLUSION: The patients may compensate for the lack of corticomuscular coupling by enhancing muscle activation. This study demonstrated the potential and advantages of WCTC in eliciting corticomuscular coupling, which may optimize rehabilitation following SCI.

A General and Efficient Strategy for Gene Delivery Based on Tea Polyphenols Intercalation and Self-Polymerization.

Gene therapy that employs therapeutic nucleic acids to modulate gene expression has shown great promise for diseases therapy, and its clinical application relies on the development of effective gene vector. Herein a novel gene delivery strategy by just using natural polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) as raw material is reported. EGCG first intercalates into nucleic acids to yield a complex, which then oxidizes and self-polymerizes to form tea polyphenols nanoparticles (TPNs) for effective nucleic acids encapsulation. This is a general method to load any types of nucleic acids with single or double strands and short or long sequences. Such TPNs-based vector achieves comparable gene loading capacity to commonly used cationic materials, but showing lower cytotoxicity. TPNs can effectively penetrate inside cells, escape from endo/lysosomes, and release nucleic acids in response to intracellular glutathione to exert biological functions. To demonstrate the in vivo application, an anti-caspase-3 small interfering ribonucleic acid is loaded into TPNs to treat concanavalin A-induced acute hepatitis, and excellent therapeutic efficacy is obtained in combination with the intrinsic activities of TPNs vector. This work provides a simple, versatile, and cost-effective gene delivery strategy. Given the biocompatibility and intrinsic biofunctions, this TPNs-based gene vector holds great potential to treat various diseases.

Folate and vitamin B12 usual intake and biomarker status by intake source in United States adults aged ≥19 y: NHANES 2007-2018.

BACKGROUND: Folate and vitamin B12 are important biomarkers of nutritional status of populations. OBJECTIVES: This study aims to estimate folate and vitamin B12 usual intakes among United States adults and examine folate and vitamin B12 biomarker status by intake source. METHODS: We analyzed data for United States adults aged ≥19 y from National Health and Nutrition Examination Survey 2007-2018 (n = 31,128), during which time voluntary corn masa flour (CMF) fortification was started. Usual intake was estimated using the National Cancer Institute method. Folate intake included folate from natural foods and folic acid from 4 sources: enriched cereal grain products (ECGPs), CMF, ready-to-eat cereals (RTEs), and folic acid-containing supplements (SUP). Vitamin B12 intake was mainly from food and supplements. RESULTS: The median natural food folate intake (222 µg dietary folate equivalents (DFE)/d) was below the estimated average requirement (EAR) of 320 µg DFE/d. The proportions of those who consumed folic acid from ECGP/CMF only, ECGP/CMF + RTE, ECGP/CMF + SUP, and ECGP/CMF + RTE + SUP were 50%, 18%, 22%, and 10%, respectively. Median usual folic acid intakes (µg/d) were 236 (IQR: 152, 439) overall and 134, 313, 496, and 695 in the ECGP/CMF only, ECGP/CMF + RTE, ECGP/CMF + SUP, and ECGP/CMF + RTE + SUP folic acid consumption groups, respectively. Overall, 2.0% (95% CI: 1.7%, 2.3%) of adults, all of whom used folic acid supplements, consumed greater than the tolerable upper intake level (UL) of 1000 µg/d folic acid. The median usual vitamin B12 intake (µg/d) was 5.2 for vitamin B12 supplement nonusers and 21.8 for users. Consumption of RTE and/or supplements with folic acid was associated with higher serum and red blood cell folate concentrations. Vitamin B12 supplement users had significantly higher serum vitamin B12 concentrations. CONCLUSIONS: Folic acid fortification plays a critical role in helping United States adults meet the folate EAR. At current fortification levels, United States adults who do not consume supplements do not have the usual folic acid intake exceeding the UL.

Liver lipidomics analysis reveals the anti-obesity and lipid-lowering effects of gypnosides from heat-processed Gynostemma pentaphyllum in high-fat diet fed mice.

BACKGROUND: In traditional Chinese medicine, Gynostemma pentaphyllum (G. pentaphyllum) is widely used to treat conditions associated with hyperlipidemia, and its therapeutic potential has been demonstrated in numerous studies. However, the mechanism of lipid metabolism in hyperlipidemic by G. pentaphyllum, especially heat-processed G. pentaphyllum is not yet clear. PURPOSE: The aim of this study was to investigate the therapeutic mechanism of gypenosides from heat-processed G. pentaphyllum (HGyp) in hyperlipidemic mice by means of a lipidomics. METHODS: The content of the major components of HGyp was determined by ultra-performance liquid chromatography-electrospray ionization ion trap mass spectrometry (UPLC-ESI-MS). An animal model of hyperlipidaemia was constructed using C57BL/6J mice fed with high-fat diet. HGyp was also administered at doses of 50, 100 and 200 mg/kg, all for 12 weeks. Serum parameters were measured, histological sections were prepared and liver lipidome analysis using UPLC-MS coupled with multivariate statistical analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyze the genes and proteins associated with lipid lowering in HGyp. RESULTS: HGyp reduced body weight, serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) and hepatic lipid accumulation in hyperlipidemic obese mice. To explore specific changes in lipid metabolism in relation to HGyp administration, lipid analysis of the liver was performed. Orthogonal partial least squares discriminant analysis (OPLS-DA) score plots showed that HGyp altered lipid metabolism in HFD mice. In particular, fatty acids (FA), triglycerides (DG), TG and ceramides (CER) were significantly altered. Eleven lipids were identified as potential lipid biomarkers, namely TG (18:2/20:5/18:2), TG (18:2/18:3/20:4), DG (18:3/20:0/0:0), Cer (d18:1/19:0), Cer (d16:1/23:0), Ceramide (d18:1/9Z-18:1), PS (19:0/18:3), PS (20:2/0:0), LysoPC (22:5), LysoPE (0:0/18:0), PE (24:0/16:1). Western blot and qRT-PCR analysis showed that these metabolic improvements played a role by down-regulating genes and proteins related to fat production (SREBP1, ACC1, SCD1), up-regulating genes and proteins related to lipid oxidation (CPTA1, PPARα) and lipid transport decomposition in the bile acid pathway (LXRα, PPARγ, FXR, BSEP). CONCLUSION: The lipid-lowering effect of gypenosides from heat-processed G. pentaphyllum is regulate lipid homeostasis and metabolism.

Novel methylated flavoalkaloids from Echa 1 green tea inhibit fat accumulation and enhance stress resistance in Caenorhabditis elegans.

Methylation is a common structural modification of catechins in tea, which can improve the bioavailability of catechins. Flavoalkaloids are catechin derivatives with a nitrogen containing five-membered ring at the C-6 or C-8 position. Here we isolated three new methylated flavoalkaloids from Echa 1 green tea (Camellia sinensis cv. Echa 1) and synthesized another four new methylated flavoalkaloids. The structures of the new ester-type methylated catechins (etmc)-pyrrolidinone A-G (1-7) were elucidated by various spectroscopic techniques, including nuclear magnetic resonance (NMR), optical rotation, infrared, UV-vis, experimental and calculated circular dichroism (CD) spectra, and high-resolution mass. Among them, 6 and 7 showed the strongest α-glucosidase inhibitory activity and significantly lowered lipid content of Caenorhabditis elegans with 73.50 and 67.39% inhibition rate, respectively. Meanwhile, 6 and 7 also exhibited strong antioxidant activity in vitro and stress resistance to heat, oxidative stress, and UV irradiation in nematodes.

Improving flavor of summer Keemun black tea by solid-state fermentation using Cordyceps militaris revealed by LC/MS-based metabolomics and GC/MS analysis.

Cordyceps militaris (C. militaris) has been approved and widely used in healthy food. The present study aimed to improve the flavor of summer Keemun black tea (KBT) using C. militaris solid-state fermentation. Combined with sensory evaluation, the volatile and non-volatile components of solid-state fermentation of KBT (SSF-KBT) and KBT were analyzed. The results showed that after the solid-state fermentation, the contents of total polyphenol, total flavonoid, and total free amino acids were significantly reduced. Further non-targeted metabolomics analysis revealed that the contents of non-galloylated catechins and d-mannitol increased, while the galloylated catechins and flavonoid glycosides decreased as did the bitterness and astringency of KBT. Dihydro-ß-ionone and ß-ionone (OAV = 59321.97 and 8154.17) were the aroma-active compounds imparting woody and floral odors in SSF-KBT, respectively. Current study provides a new avenue to develop summer-autumn KBT.

Effect of Bushen Chushi() decoction combined with platelet-rich plasma on regulating TGF-β1 and Smad-1 expression in serum of knee osteoarthritis patient / 中国骨伤

OBJECTIVE@#To investigate the effect of Bushen Chushi decoction combined with platelet-rich plasma(PRP) to treat knee osteoarthritis(KOA) in early and middle stage and its regulation on TGF-β1 and Smad-1 expression in serum.@*METHODS@#Total of 45 patients with KOA in early and middle stage from May 2020 to April 2022 were treated and divided into control group and observation group. In control group, there were 30 patients including 12 males and 18 females, aged from 43 to 69 years old with an average of(57.3±6.5) years old and disease duration ranged from 1.5 to 5.0 years with an average of(3.8±1.7) years, and there were 8 cases in gradeⅠ, 13 cases in gradeⅡ, and 9 cases in grade Ⅲ according to Kellgren-Lawrence Grade, PRP 5 ml was injected into knee joint on the first day of No1, 3 week together for 2 times. In the observation group, there were 15 cases including 7 males and 8 females, aged from 45 to 70 years old with an average of (56.7±6.2) years old and disease duration ranged from 1.8 to 5.7 years with an average of (4.0±1.8) years, there were 4 cases in gradeⅠ, 9 cases in gradeⅡand 4 cases in grade Ⅲ according to the Kellgren-Lawrence Grade, PRP 5 ml were injected into knee joints that the time and frequency were the same as those in the control group, and at the same time Bushen Chushi decoction orally were taken 1 dose per day with a total of 28 doses. All patients were treated for four weeks. Visual analogue scale(VAS) and Lequesne MG score before and after treatment were used to evaluate improvement of knee pain and joint function. The TGF-β1 and Smad-1 levels in serum were measured before and after treatment in two groups. The incidence of complications in two groups was observed.@*RESULTS@#All patients were followed up for 26 to 30 days with an average of (28.0±0.6) days. There was no significant difference in VAS and knee Lequesne MG scores between two groups before treatment(P>0.05). The scores of VAS and knee Lequesne MG on the first day after treatment in both groups were lower than those before treatment(P<0.05). The VAS and knee Lequesne MG scores in observation group were lower than those in control group(P<0.05) on the first day after treatment. The TGF-β1 level in serum after treatment were higher significantly than that before treatment in two groups(P<0.05). After treatment, TGF-β1 level in serum in observation group were lower than those in control group with statistically significant differences(P<0.05). The Smad-1 levels in serum after treatment in observation group were higher significantly than that in control group(P<0.05). The levels of Smad-1 were not statistically significant between before and after treatment(P>0.05). There was no significant difference in postopertaive complications between two groups (P>0.05).@*CONCLUSION@#The efficacy of Bushen Chushi decoction combined with PRP in treatment of early and middle KOA is better than that of PRP injection alone. The combined treatment could reduce TGF-β1 level and increase Smad-1 level in serum, which may be a mechanism to inhibit inflammation and alleviate cartilage degeneration to some extent.

Exploring new catechin derivatives as SARS-CoV-2 Mpro inhibitors from tea by molecular networking, surface plasma resonance, enzyme inhibition, induced fit docking, and metadynamics simulations.

SARS-CoV-2 Mpro (Mpro) is the critical cysteine protease in coronavirus viral replication. Tea polyphenols are effective Mpro inhibitors. Therefore, we aim to isolate and synthesize more novel tea polyphenols from Zhenghedabai (ZHDB) white tea methanol-water (MW) extracts that might inhibit COVID-19. Through molecular networking, 33 compounds were identified and divided into 5 clusters. Further, natural products molecular network (MN) analysis showed that MN1 has new phenylpropanoid-substituted ester-catechin (PSEC), and MN5 has the important basic compound type hydroxycinnamoylcatechins (HCCs). Thus, a new PSEC (1, PSEC636) was isolated, which can be further detected in 14 green tea samples. A series of HCCs were synthesized (2-6), including three new acetylated HCCs (3-5). Then we used surface plasmon resonance (SPR) to analyze the equilibrium dissociation constants (KD) for the interaction of 12 catechins and Mpro. The KD values of PSEC636 (1), EGC-C (2), and EC-CDA (3) were 2.25, 2.81, and 2.44 µM, respectively. Moreover, compounds 1, 2, and 3 showed the potential Mpro inhibition with IC50 5.95 ± 0.17, 9.09 ± 0.22, and 23.10 ± 0.69 µM, respectively. Further, we used induced fit docking (IFD), binding pose metadynamics (BPMD), and molecular dynamics (MD) to explore the stable binding pose of Mpro-1, showing that 1 could tightly bond with the amino acid residues THR26, HIS41, CYS44, TYR54, GLU166, and ASP187. The computer modeling studies reveal that the ester, acetyl, and pyrogallol groups could improve inhibitory activity. Our research suggests that these catechins are effective Mpro inhibitors, and might be developed as therapeutics against COVID-19.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

BACKGROUND: Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria sTo examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (inclu

Thermosensitive Biomimetic Hybrid Membrane Camouflaged Hollow Gold Nanoparticles for NIR-Responsive Mild-Hyperthermia Chemo-/Photothermal Combined Tumor Therapy.

As an appealing biomimetic strategy for various medical applications, cell membrane coating lacks sensitive on-demand breaking capability. Herein, we incorporated thermosensitive lipid (TSL) membrane into red blood cell (RBC) and MCF-7 cancer cell (MC) hybrid membrane ([RBC-MC]M) vesicles. The [RBC-MC-TSL]M was coated onto doxorubicin (Dox)-loaded hollow gold nanoparticles to enhance chemo-/photothermal combined tumor therapy at a mild hyperthermia temperature (≤49 °C). Double-layer coating with TSL and [RBC-MC-TSL]M as the inner and outer layer, respectively, presented better antileakage and higher NIR-responsivity than single-layer coating. The Dox release ratio upon NIR laser irradiation (≤49 °C) was 74.6%, much higher than that (33.5%) without NIR laser. The nanodrug can be efficiently and specifically taken up by MCF-7 cells. In addition, the nanodrug exhibited excellent tumor-targeting property, with 4.08- and 1.12-times Dox accumulation in MCF-7 tumors compared to free Dox and [RBC-MC]M-coated counterpart, respectively. Most importantly, TSL incorporation significantly enhanced NIR-responsive antitumor efficiency, with tumor growth inhibition ratio increased from 35.1% to 48.6% after a single dose administration. Besides, the nanodrug exhibited very good biocompatibility. Camouflaging nanoparticles with the thermosensitive biomimetic hybrid membrane provides a painless and promisingly clinical-applicable approach for effective chemo-/photothermal combined mild-hyperthermia tumor therapy.

Quantification of Chemical Groups and Quantitative HPLC Fingerprint of Poria cocos (Schw.) Wolf.

(1)Objective: In this study, a quantitative analysis of chemical groups (the triterpenoids, water-soluble polysaccharides, and acidic polysaccharides) and quantitative high liquid performance chromatography (HPLC) fingerprint of Poria cocos (Schw.) Wolf (PC) for quality control was developed. (2) Methodology: First, three main chemical groups, including triterpenoids, water-soluble polysaccharides, and acidic polysaccharides, in 16 batches of PC were evaluated by ultraviolet spectrophotometry. Afterward, the quantitative fingerprint of PC was established, and the alcohol extract of PC was further evaluated. The method involves establishing 16 batches of PC fingerprints by HPLC, evaluating the similarity of different batches of PC, and identifying eight bioactive components, including poricoic acid B (PAB), dehydrotumulosic acid (DTA), poricoic acid A (PAA), polyporenic acid C (PAC), 3-epidehydrotumulosic acid (EA), dehydropachymic acid (DPA), dehydrotrametenolic acid (DTA-1), and dehydroeburicoic acid (DEA), in PC by comparison with the reference substance. Combined with the quantitative analysis of multi-components by a single marker (QAMS), six bioactive ingredients, including PAB, DTA, PAC, EA, DPA, and DEA, in PC from different places were established. In addition, the multivariate statistical analyses, such as principal component analysis and heatmap hierarchical clustering analysis are more intuitive, and the visual analysis strategy was used to evaluate the content of bioactive components in 16 batches of PC. Finally, the analysis strategy of three main chemical groups in PC was combined with the quantitative fingerprint strategy, which reduced the error caused by the single method. (3) Results: The establishment of a method for the quantification of chemical groups and quantitative HPLC fingerprint of PC was achieved as demonstrated through the quantification of six triterpenes in PC by a single marker. (4) Conclusions: Through qualitative and quantitative chemical characterization, a multi-directional, simple and efficient routine evaluation method of PC quality was established. The results reveal that this strategy can provide an analytical method for the quality evaluation of PC and other Chinese medicinal materials.

Folic Acid and the Prevention of Birth Defects: 30 Years of Opportunity and Controversies.

For three decades, the US Public Health Service has recommended that all persons capable of becoming pregnant consume 400 µg/day of folic acid (FA) to prevent neural tube defects (NTDs). The neural tube forms by 28 days after conception. Fortification can be an effective NTD prevention strategy in populations with limited access to folic acid foods and/or supplements. This review describes the status of mandatory FA fortification among countries that fortify (n = 71) and the research describing the impact of those programs on NTD rates (up to 78% reduction), blood folate concentrations [red blood cell folate concentrations increased ∼1.47-fold (95% CI, 1.27, 1.70) following fortification], and other health outcomes. Across settings, high-quality studies such as those with randomized exposures (e.g., randomized controlled trials, Mendelian randomization studies) are needed to elucidate interactions of FA with vitamin B12 as well as expanded biomarker testing.

The discovery of potentially active diterpenoids to inhibit the pyroptosis from Callicarpa arborea.

Pyroptosis is a programmed-inflammatory cell death, which leads to release of inflammatory cellular contents and formation of inflammation. Uncontrollable pyroptosis can result in serious immune diseases, such as cytokine release syndrome (CRS), sepsis, disseminated intravascular coagulation (DIC), and acute organ damage, including acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Members of the Callicarpa genus are significant raw materials for traditional Chinese medicine, widely used for analgesia, hemostasis, and anti-inflammation. Previously, we have reported some ent-clerodane diterpenoids from Callicarpa arborea, shown potent inhibitory effects against pyroptosis. In this study, we went on investigating this kind of diterpenoids, and yielded 66 ent-clerodane diterpenoids, including 52 new compounds, from Callicarpa arborea. Their structures featured with a 5/6- (1-25) or a 6/6- (26-66)-fused double-ring scaffolds, were elucidated using spectroscopic data, electrostatic circular dichroism (ECD) and X-ray diffraction analyses. Screening for the inhibitory activity against pyroptosis by detecting of IL-1ß secretion in J771A.1 cells, revealed 28 compounds with an IC50 below 10.5 µM. Compound 1 was the most potent with an IC50 of 0.68 µM and inhibited the J774A.1 macrophage pyroptosis by blocking the NLR pyrin domain containing 3 (NLRP3) inflammasome activation. An in vivo study further revealed that compound 1 decreased infiltration of CD11b + F4/80 + macrophages into lung and attenuated the lipopolysaccharide (LPS)-induced lung injury. Taken together, this study indicated the potential of compound 1 as a candidate for pyroptosis-related inflammation treatment, as well as provided the chemical and pharmacological basis for the further development of Callicarpa genus as a herbal medicine.

Bioactive Components and Potential Mechanism Prediction of Kui Jie Kang against Ulcerative Colitis via Systematic Pharmacology and UPLC-QE-MS Analysis.

Kui Jie Kang (KJK)-a traditional Chinese medicine-has demonstrated clinical therapeutic efficacy against ulcerative colitis (UC). However, the active compounds and their underlying mechanisms have not yet been fully characterized. Therefore, the current study sought to identify the volatile compounds in KJK responsible for eliciting the therapeutic effect against UC, while also analyzing key targets and potential mechanisms. To this end, systematic network pharmacology analysis was employed to obtain UC targets by using GeneCards, DisGeNET, OMIM, among others. A total of 145 candidate ingredients, 412 potential targets of KJK (12 herbs), and 1605 UC targets were identified. Of these KJK and UC targets, 205 intersected and further identified AKT1, JUN, MAPK, ESR, and TNF as the core targets and the PI3K/AKT signaling pathway as the top enriched pathway. Moreover, molecular docking and ultra-performance liquid chromatography Q Exactive-mass spectrometry analysis identified quercetin, kaempferol, luteolin, wogonin, and nobiletin as the core effective compounds of KJK. In vivo murine studies revealed that KJK exposure increases the body weight and colon length, while reducing colonic epithelial injury, and the expression of inflammatory factors in colitis tissues such as TNF-α, IL-6, and IL-1ß. Furthermore, KJK treatment downregulates the expression of pi3k and akt genes, as well as p-PI3K/PI3K and p-AKT/AKT proteins. Collectively, these findings describe the therapeutic effects and mechanisms of KJK in UC and highlight KJK as a potentially valuable therapeutic option for UC via modulation of the PI3K/AKT signaling pathway, thus providing a theoretical reference for the broader application of KJK in the clinical management of UC.

Dioscin alleviates myocardial infarction injury via regulating BMP4/NOX1-mediated oxidative stress and inflammation.

BACKGROUND: Dioscin, a steroidal saponin natural product, has various pharmacological activities, such as anti-inflammatory, antioxidant, lipid-lowering. However, little is known about its effects on myocardial infarction (MI) injury. Thus, the study aimed to investigate the protective effects and possible mechanisms of dioscin. METHODS: We evaluated protective effects of Dioscin on HL-1 cells after hypoxia based on MTT and ROS in vitro. In vivo, we ligated left anterior descending (LAD) of C57BL/6 mice to establish MI model and assess serum levels of LDH, CK-MB, cTnI, SOD, MDA and CAT treated by dioscin. In addition, myocardial damages were reflected by H&E, masson and ultrastructural examination and Electrocardiograph (ECG) was detected in MI mice. And the BMP4/NOX1 pathway was measured by western blotting, immunofluorescence assay and Real-time PCR. Furthermore, to investigate cardio-protective effects of dioscin via targeting BMP4, we transfected siBMP4 into HL-1 cells in vitro and injected BMP4 siRNA though tail veins in vivo. RESULTS: In vitro, dioscin significantly increased the viability of HL-1 cells and inhibited ROS level under hypoxia. In vivo, dioscin markedly reduced the elevation of ST segment and alleviated myocardial infarct area in mice. In terms of serology, dioscin evidently decreased LDH, CK-MB, cTnI, MDA levels, and increased SOD level. In addition, dioscin improved the pathological status of myocardial tissue and restrained the production of collagen fibers. Mechanism study proved that dioscin notablely regulated the levels of Nrf2, Keap1, HO-1, p-NF-κB, nNF-κB, TNF-α, IL-1ß and IL-6 by down-regulating the protein levels of BMP4 and NOX1 against oxidative stress and inflammation. Further investigation showed that siBMP4 transfection diminished hypoxia and MI-induced oxidative and inflammation injury. The transfection decreased LDH, CK-MB and cTnI levels, improved ischemia T-wave inversion and reduced striated muscle necrosis, nucleus dissolution, collagen fibrosis and mitochondrial swelling in mice. In addition, siBMP4 decreased ROS and MDA levels, increased SOD and CAT levels and down-regulated mRNA levels of TNF-α, IL-1ß and IL-6. Moreover, BMP4, NOX1 and nNF-κB protein levels were decreased and Nrf2 levels were increased by siBMP4. CONCLUSION: Our study confirmed that dioscin showed an outstanding anti-myocardial infarction effect via regulating BMP4/NOX1-mediated oxidative stress and inflammation, which has a promising application value and development prospect against MI injury in the future.