The effects of prenatal and postnatal high-dose vitamin B-12 supplementation on human milk vitamin B-12: a randomized, double-blind, placebo-controlled trial in Tanzania.

BACKGROUND: Vitamin B-12 status in human milk (HM) has critical implications for infant growth and development. Few studies have separately evaluated the effects of prenatal and postnatal maternal high-dose vitamin B-12 supplementation on HM vitamin B-12 concentration. OBJECTIVES: This randomized controlled trial aimed to assess the effects of prenatal and postnatal vitamin B-12 supplementation on HM vitamin B-12 at 6 wk and 7 mo postpartum. METHODS: Pregnant women were enrolled in Dar es Salaam, Tanzania, between 2001 and 2004. From recruitment (12-27 weeks of gestation) through 6 wk postpartum, participants were randomly assigned to daily oral multiple micronutrient supplementation or placebo. From 6 wk to 18 mo postpartum, a subset of participants was randomly assigned to a postnatal supplement or placebo. The supplement included 50 µg/d of vitamin B-12 and various other vitamins. HM vitamin B-12 concentrations were analyzed at 6 wk and 7 mo postpartum for 412 participants. RESULTS: The prevalence of HM vitamin B-12 of <310 pmol/L was 73.3% and 68.4% at 6 wk and 7 mo postpartum, respectively. Prenatal supplementation increased HM vitamin B-12 concentration (percent difference: 34.4; 95% CI: 17.0, 54.5; P < 0.001) at 6 wk; this effect was not present at 7 mo. Postnatal supplementation increased HM vitamin B-12 concentration (percent difference: 15.9; 95% CI: 1.91, 31.9; P = 0.025) at 7 mo. Effect modification between prenatal and postnatal supplementation on HM vitamin B-12 status at 7 mo was found, with the effects of prenatal and postnatal supplements more pronounced among those receiving control during the other period; the prenatal supplement had a greater effect with postnatal control, and the postnatal supplement had a greater effect with prenatal control. CONCLUSIONS: Prenatal maternal vitamin B-12 supplementation has benefits on short-term HM status, and postnatal maternal vitamin B-12 supplementation has benefits on long-term HM status. This trial was registered at clinicaltrials.gov as NCT00197548. https://clinicaltrials.gov/ct2/show/NCT00197548.

Clinical Application of Tonsillectomy with Preservation of Capsule and Support Tissue.

Objective: The clinical effect of tonsillectomy with the preservation of tonsillar capsule and stent tissue and punctuated suture of tonsillar capsule and stent tissue was analyzed retrospectively. Methods: From January 2013 to January 2022, a total of 960 patients underwent tonsillectomy, consisting of 530 males and 430 females with ages ranging from 4 to 60 years (median age: 11 years). The capsule and scaffold tissues were preserved in all patients during the operation, and the surrounding mucosa, capsule, and scaffold tissues were sutured without tension. Indexes such as operation time, intraoperative blood loss, tonsillar white membrane, incidence of postoperative bleeding, postoperative pain score, and incidence of tonsillar remnant were recorded, and the school attendance of children (≤12 years old) was recorded. Results: The mucosal covering of tonsillar fossa healed well in all patients, and the sutures were completely removed at 4 weeks after reexamination. All patients were followed up for 1-8 years, and there was no residual hyperplasia or residual inflammation. Children under 12 years old could return to school 4 days after surgery without any postoperative complications. Conclusion: Tonsillectomy, preserving the tonsillar capsule and scaffold tissue followed by punctate suturing, offered several advantages: it resulted in less intraoperative blood loss and postoperative pain. Patients could resume a normal diet 6 hours after the surgery without an increased risk of complications. Moreover, it significantly reduced the risk of postoperative bleeding.

Acteoside ameliorates learning and memory impairment in APP/PS1 transgenic mice by increasing Aß degradation and inhibiting tau hyperphosphorylation.

Alzheimer's disease (AD) is a neurodegenerative disease. Senile plaques and intracellular neurofibrillary tangles are pathological hallmarks of AD. Recent studies have described the improved cognitive and neuroprotective functions of acteoside (AS). This study aimed to investigate whether the improved cognition of AS was mediated by Aß degradation and tau phosphorylation in APP/PS1 mice. The open field, Y maze, and novel object recognition tests were used to assess cognitive behavioral changes. We evaluated the levels of Aß40 and Aß42 in serum, cortex, and hippocampus, and Aß-related scavenging enzymes, phosphorylated GSK3ß and hyperphosphorylated tau in the cortex and hippocampus of APP/PS1 mice by western blotting. Our results revealed that AS treatment ameliorated anxious behaviors, spatial learning, and memory impairment in APP/PS1 mice and significantly reduced Aß deposition in their serum, cortex, and hippocampus. AS significantly increased Aß degradation, inhibited the hyperphosphorylation of tau, and significantly decreased the activity of GSK3ß, which is involved in tau phosphorylation. Altogether, these findings indicated that the beneficial effects of AS on AD-associated anxious behaviors and cognitive impairments could be attributed to promoting Aß degradation and inhibiting tau hyperphosphorylation, which might be partly mediated by GSK3ß.

Boosting chemotherapy of bladder cancer cells by ferroptosis using intelligent magnetic targeting nanoparticles.

A versatile nano-delivery platform was reported to enhance the tumor suppression effect of chemotherapy by augmenting tumor cells' ferroptosis. The platform consists of pomegranate-like magnetic nanoparticles (rPAE@SPIONs) fabricated by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) within a reduced poly(ß-amino ester)s-PEG amphiphilic copolymer (rPAE). The resulting platform exhibits several functionalities. Firstly, it promotes the doxorubicin (DOX) release by leveraging the mild hyperthermia generated by NIR irradiation. Secondly, it triggers ferroptosis in tumor cells, inducing their demise. Thirdly, it induces polarization of macrophages towards an anti-tumor M1 phenotype, contributing to ferroptosis of tumor cells and enhanced tumor cell suppression. This study effectively capitalizes on the versatility of SPIONs and offers a simple yet powerful strategy for developing a new nanosized ferroptosis-inducing agent, ultimately improving the inhibition of bladder cancer cells.

School-based supplementation with iron-folic acid or multiple micronutrient tablets to address anemia among adolescents in Burkina Faso: a cluster-randomized trial.

BACKGROUND: Iron-deficiency anemia is a leading cause of morbidity among adolescents (aged 10-19 y), especially in low- and middle-income settings. Few policies and programs have targeted adolescent health. OBJECTIVES: This study aimed to evaluate the effectiveness of school-based supplementation with iron-folic acid (IFA) or multiple micronutrient supplements (MMSs) in addressing anemia among adolescents in Burkina Faso. METHODS: In this cluster-randomized trial, 3123 secondary school students aged 10 to 18 y in Burkina Faso were either supplemented with weekly IFA, daily MMSs, or received standard nutrition education as controls. Supplementation occurred between April 2021 and April 2022 over 2 supplementation periods (10 wk, then 16 wk) separated by a gap of 20 wk without supplementation. Hemoglobin was evaluated 4 times: at baseline prior to each supplementation period and at the end of each period. Anemia was categorized by the World Health Organization hemoglobin level cutoffs as none, mild, moderate, or severe. Associations between treatment arm and anemia or continuous hemoglobin (g/dL) were assessed using multilevel mixed effects generalized linear models with schools as a random effect, controlling for baseline hemoglobin or anemia status. RESULTS: Baseline anemia prevalence was similar across study arms, with 32.7% in IFA, 31.2% in MMS, and 29.5% in the control arm. Over the full study period, adolescents provided IFA had hemoglobin levels higher than those in the control arm (adjusted ß: 0.32; 95% CI: 0.02, 0.62). No significant associations were observed for MMS or for anemia outcomes; however, the direction and magnitude of nonsignificant associations indicate potential protective effects of IFA and MMSs on anemia. CONCLUSIONS: The results do not provide strong evidence that weekly IFA or daily MMS alone is effective, but supplementation may play a role in addressing adolescent anemia if combined with cointerventions. Additional research is required to determine the best strategy to address anemia. This trial was registered at clinicaltrials.gov as NCT04657640.

Associations of Diet Quality, Socioeconomic Factors, and Nutritional Status with Gestational Weight Gain among Pregnant Women in Dar es Salaam, Tanzania.

Background: Gestational weight gain (GWG) is a modifiable factor associated with maternal and child health outcomes, but the relationship between diet quality and GWG has not been evaluated using metrics validated for low-income and middle-income countries (LMICs). Objective: This study aimed to investigate relationships between diet quality, socioeconomic characteristics, and GWG adequacy using the novel Global Diet Quality Score (GDQS), the first diet quality indicator validated for use across LMIC. Methods: Weights of pregnant women enrolled between 12 and 27 wk of gestation (N = 7577) were recorded in Dar es Salaam, Tanzania, from 2001 to 2005 during a prenatal micronutrient supplementation trial. GWG adequacy was the ratio of measured GWG to Institute of Medicine-recommended GWG, categorized into severely inadequate (<70%), inadequate (70 to <90%), adequate (90 to <125%), or excessive (≥125%). Dietary data were collected using 24-h recalls. Multinomial logit models were used to estimate relationships between GDQS tercile, macronutrient intake, nutritional status, and socioeconomic characteristics and GWG. Results: GDQS scores in the second [relative risk (RR): 0.82; 95% confidence interval (CI): 0.70, 0.97] tercile were associated with lower risk of inadequate weight gain than those in the first tercile. Increased protein intake was associated with higher risk of severely inadequate GWG (RR: 1.06; 95% CI: 1.02, 1.09). Nutritional status and socioeconomic factors were associated with GWG: underweight prepregnancy BMI (in kg/m2) with a higher risk of severely inadequate GWG (RR: 1.49; 95% CI: 1.12, 1.99), overweight or obese BMI with a higher risk of excessive GWG (RR: 6.80; 95% CI: 5.34, 8.66), and a higher education (RR: 0.61; 95% CI: 0.42, 0.89), wealth (RR: 0.68; 95% CI: 0.48, 0.80), and height (RR: 0.96; 95% CI: 0.95, 0.98) with a lower risk of severely inadequate GWG. Conclusions: Dietary indicators showed few associations with GWG. However, stronger relationships were revealed between GWG, nutritional status, and several socioeconomic factors.This trial was registered at clinicaltrials.gov as NCT00197548.

Scaling-up high-impact micronutrient supplementation interventions to improve adolescents' nutrition and health in Burkina Faso and Tanzania: protocol for a cluster-randomised controlled trial.

INTRODUCTION: Adolescence is a critical time for growth and development, but this age group is often neglected in research and development of nutrition interventions. Despite recommendations from the WHO to provide nutrient supplements to adolescents, evidence remains scarce on the most effective supplementation strategy. This study aims to compare weekly iron and folic acid (IFA) supplementation with daily multiple micronutrient supplements (MMSs) in prevention of anaemia and improvement of school outcomes among adolescents in Burkina Faso and Tanzania. METHODS AND ANALYSIS: A three-arm cluster-randomised, school-based supplementation trial will be conducted among 84 schools (42 schools per site) and roughly 4500 students aged 10-17. Schools will be matched on three characteristics: number of students, school ranking profile, distance to main road (Tanzania) or distance to city council (Burkina Faso). Each school will be randomised to receive either weekly IFA, daily MMSs or serve as a control. Supplements will be delivered to students by teachers, who will provide monitoring data to the study team. Baseline and endline surveys will be conducted prior to and after each supplementation cycle (12 weeks in Burkina Faso; 1 year in Tanzania) to assess haemoglobin, anthropometry and sociodemographic variables. The primary outcome of haemoglobin will be analysed continuously using linear regression, and anaemia status will be analysed using logistic or multinomial regression, depending on categorisation level of the outcome. Secondary analyses of school performance indicators will also be conducted with either logistic or linear regression. ETHICS AND DISSEMINATION: This protocol has been approved by the Institutional Review Board of the Harvard TH Chan School of Public Health (IRB20-1108) and the Research Ethics Committees for the Ministries of Health in Tanzania (Zanzibar) and Burkina Faso. Results will be disseminated during meetings with the Ministries of Health and the participating communities as well as through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04657640; NCT05104554.

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.

Effects of prenatal nutritional supplements on gestational weight gain in low- and middle-income countries: a meta-analysis of individual participant data.

BACKGROUND: Gestational weight gain (GWG) below or above the Institute of Medicine (IOM) recommendations has been associated with adverse perinatal outcomes. Few studies have examined the effect of prenatal nutrient supplementations on GWG in low- and middle-income countries (LMICs). OBJECTIVES: We aimed to investigate the effects of multiple micronutrient supplements (MMSs) and small-quantity lipid-based nutrient supplements (LNSs) on GWG in LMICs. METHODS: A 2-stage meta-analysis of individual participant data was conducted to examine the effects of MMSs (45,507 women from 14 trials) and small-quantity LNSs (6237 women from 4 trials) on GWG compared with iron and folic acid supplements only. Percentage adequacy of GWG and total weight gain at delivery were calculated according to the IOM 2009 guidelines. Binary outcomes included severely inadequate (percentage adequacy <70%), inadequate (<90%), and excessive (>125%) GWG. Results from individual trials were pooled using fixed-effects inverse-variance models. Heterogeneity was examined using I2, stratified analysis, and meta-regression. RESULTS: MMSs resulted in a greater percentage adequacy of GWG [weighted mean difference (WMD): 0.86%; 95% CI: 0.28%, 1.44%; P < 0.01] and higher GWG at delivery (WMD: 209 g; 95% CI: 139, 280 g; P < 0.01) than among those in the control arm. Women who received MMSs had a 2.9% reduced risk of severely inadequate GWG (RR: 0.971; 95% CI: 0.956, 0.987; P < 0.01). No association was found between small-quantity LNSs and GWG percentage adequacy (WMD: 1.51%; 95% CI: -0.38%, 3.40%; P = 0.21). Neither MMSs nor small-quantity LNSs were associated with excessive GWG. CONCLUSIONS: Maternal MMSs were associated with greater GWG percentage adequacy and total GWG at delivery than was iron and folic acid only. This finding is consistent with previous results on birth outcomes and will inform policy development and local recommendations of switching routine prenatal iron and folic acid supplements to MMSs.

Micronutrient Supplementation for Pregnant and Lactating Women to Improve Maternal and Infant Nutritional Status in Low- and Middle-Income Countries: Protocol for a Systematic Review and Meta-analysis.

BACKGROUND: Two billion people in low- and middle-income countries (LMICs) are deficient in key nutrients. Nutritional deficiencies worsen during pregnancy, causing adverse outcomes for the mother and the fetus, with consequences after pregnancy. These effects may be mitigated by providing micronutrient supplementation to women during pregnancy and lactation. However, the effects of micronutrient supplementation on the nutritional status of pregnant and lactating women and that of their infants remain largely unclear in LMICs. OBJECTIVE: The purpose of this systematic review and meta-analysis is to determine the effects of single, double, or multiple micronutrient supplements during pregnancy or lactation on maternal and infant nutritional status in LMICs. METHODS: Randomized controlled trials of single, double, or combinations of micronutrients assessing effects on the maternal (serum, plasma, and breastmilk) and infant (serum and plasma) nutritional status will be included. MEDLINE (through PubMed), EMBASE, CENTRAL (through Cochrane Library), and the World Health Organization (WHO) library database will be used to identify relevant published studies, starting from the inception of each database until February 28, 2022. The Cochrane Risk of Bias Tool will be used to assess the risk of bias in the included studies. The selection of studies, data extraction, and risk of bias assessment will be carried out independently by 2 reviewers. A narrative summary will be provided of all the included studies. Meta-analyses will be performed whenever possible, and the heterogeneity of effects will be evaluated using I2, subgroup analyses, and metaregression. The certainty of the evidence for each outcome will be assessed using the GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach. RESULTS: We will conduct meta-analyses using Stata software (version 16, StataCorp) and present both a narrative and systematic summary of all studies included in this review in text and table form. For continuous outcomes, effect estimates will be expressed as mean differences and standardized mean differences, while for binary outcomes, they will be expressed as risk ratios, rate ratios, hazards ratios, or odds ratios, all with 95% CIs and comparing the intervention group with the control group. When studies for an outcome are adequately consistent with respect to intervention, comparator, and definition of the outcome, a random-effects, inverse variance-weighted meta-analysis will be conducted. We will provide a narrative synthesis for outcomes with insufficient data or extreme heterogeneity. CONCLUSIONS: This review will provide evidence upon which to base policy and programming for women in LMICs to supplement micronutrients in pregnancy and lactation. Detailed results disaggregated by variables such as maternal age, sex of infant, duration, and dose of intervention may also help policy makers, researchers, practitioners, and government agencies to adopt more effective maternal and child health policies and programs in LMICs. The review will also identify any gaps in the existing evidence. TRIAL REGISTRATION: PROSPERO CRD42022308715; https://tinyurl.com/y33cxekr. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/40134.

Associations between Gestational Weight Gain Adequacy and Neonatal Outcomes in Tanzania.

INTRODUCTION: Gestational weight gain (GWG) is associated with fetal and newborn health; however, data from sub-Saharan Africa are limited. METHODS: We used data from a prenatal micronutrient supplementation trial among a cohort of human immunodeficiency virus-negative pregnant women in Dar es Salaam, Tanzania to estimate the relationships between GWG and neonatal outcomes. GWG adequacy was defined as the ratio of the total observed weight gain over the recommended weight gain based on the Institute of Medicine body mass index-specific guidelines. Neonatal outcomes assessed were stillbirth, perinatal death, preterm birth, low birthweight, macrosomia, small-for-gestational age (SGA), large-for-gestational age (LGA), stunting at birth, and microcephaly. Modified Poisson regressions with robust standard error were used to estimate the relative risk of newborn outcomes as a function of GWG adequacy. RESULTS: Of 7,561 women included in this study, 51% had severely inadequate (<70%) or inadequate GWG (70 to <90%), 31% had adequate GWG (90 to <125%), and 18% had excessive GWG (≥125%). Compared to adequate GWG, severely inadequate GWG was associated with a higher risk of low birthweight, SGA, stunting at birth, and microcephaly, whereas excessive GWG was associated with a higher risk of LGA and macrosomia. CONCLUSION: Interventions to support optimal GWG are needed and may contribute to preventing adverse neonatal outcomes.

Effects of prenatal and postnatal maternal multiple micronutrient supplementation on child growth and morbidity in Tanzania: a double-blind, randomized-controlled trial.

BACKGROUND: Maternal micronutrient status is critical for child growth and nutrition. It is unclear whether maternal multiple micronutrient supplementation (MMS) during pregnancy and lactation improves child growth and prevents child morbidity. METHODS: This study aimed to determine the effects of prenatal and postnatal maternal MMS on child growth and morbidity. In this double-blind, randomized-controlled trial, 8428 HIV-negative pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. From pregnancy (12-27 weeks of gestation) through to 6 weeks postpartum, participants were randomized to receive daily oral MMS or placebo. All women received daily iron and folic acid during pregnancy. From 6 weeks postpartum through to 18 months postpartum, 3100 women were re-randomized to MMS or placebo. Child-growth measures, haemoglobin concentrations and infectious morbidities were assessed longitudinally from birth to ≤18 months. RESULTS: Prenatal MMS led to modest increases in weight-for-age z-scores (mean difference: 0.050; 95% confidence interval: 0.002, 0.099; p = 0.04) and length-for-age z-score (mean difference: 0.062; 95% confidence interval: 0.013, 0.111; p = 0.01) during the first 6 months of life but not thereafter. Prenatal or postnatal MMS did not have benefits for other child outcomes. CONCLUSIONS: Whereas maternal MMS is a proven strategy to prevent adverse birth outcomes, other approaches may also need to be considered to curb the high burdens of child morbidity and growth faltering.

Multivitamin Supplementation Is Associated with Greater Adequacy of Gestational Weight Gain among Pregnant Women in Tanzania.

BACKGROUND: Gestational weight gain (GWG) is a modifiable risk factor associated with adverse birth outcomes. Studies have shown that the provision of multiple micronutrient supplements to pregnant women reduces the risk of low birth weight. However, the effect of multiple micronutrient supplements on GWG has been understudied. OBJECTIVES: We examined the effect of daily supplementation of pregnant women with multivitamins on GWG in relation to the GWG recommendation by the Institute of Medicine (IOM). METHODS: Pregnant women with gestational age between 12 and 27 wk were randomly assigned to receive daily multivitamins or placebo until delivery. Weight was measured at enrollment and every follow-up visit. Percentage adequacy of GWG was calculated as actual GWG divided by the recommended GWG according to the IOM recommendation. Binary outcomes included severely inadequate (<70%), inadequate (<90%), and excessive GWG (≥125%). The analysis included 7573 women with singleton pregnancies. Multiple linear regression models were used to examine the association between multivitamin supplementation and percentage adequacy of GWG, and log-binomial models were used for binary outcomes. RESULTS: The mean percentage adequacy of GWG was 96.7% in the multivitamin arm and 94.4% in the placebo arm, with a mean difference of 2.3% (95% CI: 0.3%, 4.2%; P = 0.022). Compared with women in the placebo arm, those who received multivitamins had a lower risk of severely inadequate GWG (RR: 0.90; 95% CI: 0.83, 0.97; P = 0.008) and inadequate GWG (RR: 0.95; 95% CI: 0.91, 0.99; P = 0.018). No significant difference was found in excessive GWG. CONCLUSIONS: Multivitamin supplementation increased GWG and reduced the risk of severely inadequate and inadequate GWG among pregnant women in Tanzania. Together with previously reported beneficial effects of the supplements on birth outcomes in low- and middle-income countries, our findings support scaling up the use of prenatal supplements that include multivitamins in addition to iron and folic acid.This trial was registered at clinicaltrials.gov as NCT00197548.

Application of Implantable Polylactic-Co-Glycolic Acid Microcapsule in Repairing Alveolar Bone Defects.

Alveolar bone defects (ABDs) were a perennial problem, especially in the aged. Bisphosphonates, especially etidronate sodium (ET), were frequently used in clinical treatment of ABD. However, the oral administration of ET had poor absorption (<1%). Therefore, optimization of a suitable dosage form substituted with ET to locally repair the ABD was a straightforward approach. Polylactide-co-glycolide (PLGA) is a biodegradable material and had been used in locally implanted medical devices. Therefore, an ET-PLGA microcapsule may help local delivery and prolong the activity of healing ABD. In this paper, a preparation method of ET-PLGA microcapsule was optimized by the single-factor investigation and response surface method. Subsequently, the rat ABD model was used to evaluate the enhancement effect of these microcapsules. Finally, the optimum parameters were determined as follows: 40% dichloromethane, 160 mg/mL PLGA, 10% internal aqua/oil phase, 4% PVA, and emulsifying for 10 min. These microcapsules were spherical in shape and fairly monodisperse in a particle size of 27,51 µm (PDI = 0.3), encapsulation rate 96.6%, and drug loading 4.58%. Compared with the ET groups, the total healing volume of ABD in ET-PLGA groups was significantly increased (P < 0.05). ET-PLGA microcapsules significantly enhanced the effect of ET on ABD. This study provided important technical support for the treatment of ABD with bisphosphonates by local administration. This paper has an exploratory significance for the development of water-soluble bioactive components with low bioavailability for ABD.

Starchy Vegetables and Metabolic Syndrome in Costa Rica.

Only a few studies primarily examined the associations between starchy vegetables (other than potatoes) and metabolic syndrome (MetS). We aimed to evaluate the association between starchy vegetables consumption and MetS in a population-based sample of Costa Rican adults. We hypothesized that a higher overall intake of starchy vegetables would not be associated with higher MetS prevalence. In this cross-sectional study, log-binomial regression models were used to estimate prevalence ratios (PRs) of MetS across quintiles of total, unhealthy, healthy starchy vegetables, and individual starchy vegetables (potatoes, purple sweet potatoes, etc.), among 1881 Costa Rican adults. Least square means and 95% confidence intervals (CIs) from linear regression models were estimated for each MetS component by categories of starchy vegetable variables. Higher intakes of starchy vegetables were associated with a higher prevalence of MetS in crude models, but no significant trends were observed after adjusting for confounders. A significant inverse association was observed between total starchy and healthy starchy vegetables consumption and fasting blood glucose. In this population, starchy vegetables might be part of a healthy dietary pattern.

Acteoside-improved streptozotocin-induced learning and memory impairment by upregulating hippocampal insulin, glucose transport, and energy metabolism.

Alzheimer's disease (AD), a neurodegenerative disease, has been, by and large, correlated to insulin pathway, glucose level, and energy metabolism in the brain. Intracerebroventricular administration of streptozotocin (ICV-STZ) leads to glucose and energy metabolism dysfunction, cognitive impairment, and increased oxidative stress in the brain. Acteoside has a myriad of pharmacological effects on the brain, namely, neuroprotection and recuperation of cognitive functions. The primary focus of the current study was to examine the effect of acteoside on insulin, glucose transport, and energy metabolism in the hippocampal area of the brain. The behavioral experiments such as spatial memory, active learning, and passive memory suggested that acetoside ameliorated the ICV-STZ-induced learning and cognitive impairment. The acteoside induced increase in the protein expression of glucose transporters (Glu T1, Glu T3, and Glu T4), glucose, and insulin levels in the hippocampus for maintaining normal learning and memory function were demonstrated by Western blot. In addition, acteoside's long-term oral administration increased the the ratio of ATP content divided by ADP content (ATP/ADP) ratio, which, in turn, reduced the reactiveoxygen species (ROS) level and improved the cellular oxidative stress response. Compared with the model group, the above results show significant differences in different degrees (p < .05 or p < .01). This study suggests that acteoside can ameliorate the ICV-STZ-induced learning and memory impairment caused due to insulin receptor, insulin receptor substrate 1, Glu T1, Glu T3, and Glu T4 pathways by triggering intracerebral metabolism.

In vitro antimicrobial effect of curcumin-based photodynamic therapy on Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans.

BACKGROUND: Photodynamic therapy (PDT) is a bactericidal method, which has recently been introduced in the field of dental medicine and therapy. Curcumin, a compound isolated from Curcuma longa L., exerts potent phototoxic effects at micromolar concentrations. The aim of our study was to explore the in vitro antimicrobial effect of curcumin-based PDT on two major etiological agents of periodontitis, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. METHODS: P. gingivalis ATCC33277 and A. actinomycetemcomitans ATCC24523 suspension was irradiated with blue LED (BL) (450-470 nm, output power density 1.2 W/cm2) for 20-60 s (6-18 J/cm2), treated with curcumin (2 min), or subjected to a combination of curcumin treatment and BL irradiation (60 s, 18 J/cm2). A suspension of chlorhexidine gluconate (CHG) was used as the positive control. All bacterial suspensions used were serially diluted, plated, and incubated anaerobically or microaerobically. The numbers of colony-forming units (CFUs) were counted on day 7. One-way analysis of variance (ANOVA) and Tukey's HSD tests were used for statistical analysis. RESULTS: BL irradiation at 6, 12, and 18 J/cm2 alone reduced the number of CFUs of both P. gingivalis and A. actinomycetemcomitans, but the reduction was not statistically significant. Compared with BL irradiation alone, curcumin solution at 20 µmol/L used alone achieved a lower reduction in the number of CFUs. Combined use of BL at 18 J/cm2 20 µmol/L curcumin treatment yielded a log reduction of 0.43 and 1.51 for P. gingivalis and A. actinomycetemcomitans CFUs, respectively. Suspensions treated with 0.12 % CHG showed a log reduction of 0.29 and 0.28 for P. gingivalis and A. actinomycetemcomitans CFUs, respectively. CONCLUSIONS: Although the bactericidal and growth-inhibitory effects of BL alone on P. gingivalis and A. actinomycetemcomitans were not significant, A. actinomycetemcomitans was susceptible to photodynamic inactivation by the combination of BL and curcumin.

A surface convertible nanoplatform with enhanced mitochondrial targeting for tumor photothermal therapy.

Photothermal therapy emerges as a promising approach in antitumor treatment. A major challenge for conventional photothermal therapy is its unselective hyperthermia distribution within tumor tissues, which leads to detrimental effects on surrounding healthy tissues and compromised therapeutic effectiveness. In this study, a targeted photothermal delivery nanoplatform (P-D-CS-CNTs) was facilely fabricated by decoration of an acidity-labile polyethylene glycol (PEG) derivative onto chitosan nanoparticles encapsulating single-walled carbon nanotubes. P-D-CS-CNTs displayed a good stability in serum at normal physiological pH and convertibility of surface charges upon exposure to tumoral acidic pH, which was attributed to the acidity-triggered dePEGylation. The confocal laser scanning microscopic observations suggested that such surface-convertibility of nanoparticles facilitated tumor cell uptake, endo/lyososomal escape, and enhanced mitochondrial targeting. Furthermore, upon irradiation with an 808 nm laser, P-D-CS-CNTs could sabotage mitochondria with mild hyperthermia, which further induced the ROS burst from damaged mitochondria. The overdosed ROS ultimately resulted in mitochondrial damage and cell death. These findings indicate that the surface-convertible nanoplatform is promising for improved photothermal anticancer therapy.

Pifithrin-µ incorporated in gold nanoparticle amplifies pro-apoptotic unfolded protein response cascades to potentiate synergistic glioblastoma therapy.

Conventional radiotherapy has a pivotal role in the treatment of glioblastoma; nevertheless, its clinical utility has been limited by radiation resistance. There is emerging evidence that upregulated heat shock protein A5 (HSPA5) in cancer cells maintains or restores the homeostasis of a cellular microenvironment and results in cancer resistance in various treatments. Therefore, we describe a bioresponsive nanoplatform that can deliver a HSPA5 inhibitor (pifithrin-µ, PES) and radiosensitizer (gold nanosphere, AuNS), to expand the synergistic photothermal therapy and radiotherapy, as well as to monitor the progression of cancer therapy using computer tomography/magnetic resonance imaging. The nanoplatform (PES-Au@PDA, 63.3 ± 3.1 nm) comprises AuNS coated with the photothermal conversion agent polydopamine (PDA) for enhanced radiotherapy and photothermal therapy, as well as PES (loading efficiency of PES approximately 40%), a small molecular inhibitor against HSPA5 to amplify the pro-apoptotic unfolded protein response (UPR). The reported nanoplatform enables hyperthermia-responsive release of PES. Results from in vitro and in vivo studies demonstrate that PES-Au@PDA can specially activate pro-apoptotic UPR cascades, leading to remarkably improved radiotherapy and photothermal therapy efficiencies. Considered together, a versatile theranostic nanosystem is reported for promoting the synergistic radiophotothermal therapy by selectively activating pro-apoptotic UPR cascade pathways.