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Fulltext Low miR-19b-1-5p Expression Is Related to Aspirin Resistance and Major Adverse Cardio- Cerebrovascular Events in Patients With Acute Coronary Syndrome

Singh S, de Ronde MWJ, Creemers EE, Van der Made I, Meijering R, Chan MY, et al.

J Am Heart Assoc, 2021 01 19;10(2):e017120.
PMID: 33441016 DOI: 10.1161/JAHA.120.017120

Background Because of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR-19b-1-5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio-cerebrovascular (MACCE) events in patients with ACS. Methods and Results In this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR-19b-1-5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow-up time of 1.01±0.43 years. Low miR-19b-1-5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (-Log-miR-19b-1-5p, [unstandardized beta, 44.50; 95% CI, 2.20-86.80; P<0.05]), even after adjusting for age, sex, ethnicity, and prior history of stroke. Lower miR-19b-1-5p expression was independently associated with a higher risk of MACCE (-Log-miR-19b-1-5p, [hazard ratio, 1.85; 95% CI, 1.23-2.80; P<0.05]). Furthermore, a significant interaction was noted between the inverse miR-19b-1-5p expression and family history of premature coronary artery disease (P=0.01) on the risk of MACCE. Conclusions Lower miR-19b-1-5p expression was found to be associated with sustained platelet aggregation on aspirin, and a higher risk of MACCE in patients with ACS. Therefore, miR-19b-1-5p could be a suitable marker for aspirin resistance and might predict recurrence of MACCE in patients with ACS.

Matched MeSH terms: Platelet Aggregation Inhibitors/administration & dosage
Fulltext A Phase IIb Randomized Controlled Trial Investigating the Effects of Tocotrienol-Rich Vitamin E on Diabetic Kidney Disease

Koay YY, Tan GCJ, Phang SCW, Ho JI, Chuar PF, Ho LS, et al.

Nutrients, 2021 Jan 18;13(1).
PMID: 33477404 DOI: 10.3390/nu13010258

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20-200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: -4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. -3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. -1.45 ± 9.18), p = 0.022 and serum creatinine (MD: -7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.

Matched MeSH terms: Tocotrienols/administration & dosage*
Nose-to-brain delivery of teriflunomide-loaded lipid-based carbopol-gellan gum nanogel for glioma: Pharmacological and in vitro cytotoxicity studies

Gadhave D, Rasal N, Sonawane R, Sekar M, Kokare C

Int J Biol Macromol, 2021 Jan 15;167:906-920.
PMID: 33186648 DOI: 10.1016/j.ijbiomac.2020.11.047

The research work was intended to formulate teriflunomide (TFM) loaded nano lipid-based (TNLC) carbopol-gellan gum in situ gel (TNLCGHG) and to investigate its therapeutic efficacy against glioma, a brain and spine tumor. Nanoformulation was developed using gellan gum and carbopol 974P as gelling and mucoadhesive agents, respectively, Glyceryl di-behenate and Glyceryl mono-linoleate blend as lipids, and Gelucire 44/14: water blend as surfactant system. Globule size, PDI, zeta potential, encapsulation efficiency, mucoadhesive strength, and nasal permeation were found to be 117.80 nm, 0.56, -21.86 mV, 81.16%, 4.80 g, and 904 μg/cm2, respectively. Anticancer efficacy of TFM-loaded nano lipid-based carbopol-gellan gum in situ gel (TNLCGHG) was determined in human U-87MG glioma cell line. IC50 was found 7.0 μg/mL for TNLCGHG, 4.8 μg/mL for pure TFM, and 78.5 μg/mL for TNLC, which approve the superiority of surfactant along with gellan gum as permeation enhancer. Brain Cmax for technetium (99mTC) labeled intranasal (i.n.) 99mTC-TNLCGHG was found 2-folds higher than 99mTC-TNLC (i.n.) and 99mTC-TNLC intravenous (i.v.) because the TNLCGHG formulation contains surfactant with natural gelling polymers, which promisingly improved drug permeability. Finally, this research revealed encouraging outcomes and successfully developed intranasal TNLCGHG nanoformulation as a novel tool for safe delivery of TFM in glioma patients.

Matched MeSH terms: Crotonates/administration & dosage*; Toluidines/administration & dosage*
Simple and fast LC-MS/MS method for quantification of terazosin in human plasma and application to bioequivalence study

Loh GOK, Wong EYL, Tan YTF, Ong LM, Ng RS, Wee HC, et al.

J Chromatogr B Analyt Technol Biomed Life Sci, 2021 Jan 15;1163:122517.
PMID: 33429127 DOI: 10.1016/j.jchromb.2020.122517

A simple, fast and sensitive LC-MS/MS method was developed to quantify terazosin in human plasma. The mobile phase consisted of acetonitrile-0.1% (v/v) formic acid (70:30, v/v). Prazosin was used as internal standard (IS). As deproteinization agent, acetonitrile produced a clean sample. A higher response intensity with more symmetrical peak was obtained using Agilent Poroshell 120 EC-C18 - Fast LC column (100 × 2.1mmID, 2.7 μm) compared with Kinetex XB-C18 (100 × 2.1 mm, 2.6 µm) column. The response of terazosin and IS were approximately two times in citrate phosphate dextrose (CPD) plasma compared with dipotassium ethylenediaminetetraacetic acid (K2EDTA) plasma. Plasma calibration curve was linear from 1.0 to 100.0 ng/mL, with coefficient of determination r2 ≥ 0.99. The within-run and between-run precision values (CV, %) were <5.2% and <7.8%, while accuracy values were 102.8-112.7% and 103.4-112.2%. The extended run accuracy was 98.6-102.8% and precision (CV, %) 4.3-10.4%. The recovery of analyte was >98% and IS >94%. Terazosin in plasma kept at benchtop was stable for 24 h, in autosampler tray for 48 h, in instrumentation room for 48 h, for 7 freeze-thaw cycles and in freezer for 140 days. Terazosin and IS stock standard solutions were stable for 140 days at room temperature and in the chiller. The high throughput method was successfully utilized to measure 935 samples in a bioequivalence study of terazosin.

Matched MeSH terms: Prazosin/administration & dosage
Treatment of benzodiazepine withdrawal syndrome in a severe traumatic brain injury patient

Teah MK, Chan GK, Wong MTF, Yeap TB

BMJ Case Rep, 2021 Jan 08;14(1).
PMID: 33419751 DOI: 10.1136/bcr-2020-238318

Prolonged exposure to benzodiazepines (BDZ) may contribute towards physical dependence, which is manifested by iatrogenic Benzodiazepine Withdrawal Syndrome (BWS), a condition often underdiagnosed. Current evidence recommends precluding BDZ infusion as sedation in the intensive care unit to avoid possible withdrawal and delirium issues. Administration of dexmedetomidine should be considered to facilitate weaning in patients with BWS.

Matched MeSH terms: Hypnotics and Sedatives/administration & dosage; Midazolam/administration & dosage
Three-Year Follow-up of 2-Dose Versus 3-Dose HPV Vaccine

Bornstein J, Roux S, Kjeld Petersen L, Huang LM, Dobson SR, Pitisuttithum P, et al.

Pediatrics, 2021 01;147(1).
PMID: 33386332 DOI: 10.1542/peds.2019-4035

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) antibody responses to the 9-valent human papillomavirus (9vHPV) vaccine among girls and boys (aged 9-14 years) receiving 2-dose regimens (months 0, 6 or 0, 12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16-26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36.
METHODS: Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0, 12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36.
RESULTS: Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%-100%; IgG-LIA: 91%-100%) and young women who received 3 doses (cLIA: 78%-98%; IgG-LIA: 91%-100%) remained seropositive 2 to 2.5 years after the last regimen dose.
CONCLUSIONS: Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.

Matched MeSH terms: Papillomavirus Vaccines/administration & dosage*
Fulltext Nocardia kroppenstedtii: a rare pathogen isolated from the spinal vertebral abscess of a patient on long-term immunosuppressive therapy

Tay ST, Wong PL, Chiu CK, Tang SN, Lee JL, Hamdan NW, et al.

Eur Rev Med Pharmacol Sci, 2021 01;25(2):605-608.
PMID: 33577013 DOI: 10.26355/eurrev_202101_24618

OBJECTIVE: Nocardia kroppenstedtii was isolated from the spinal vertebral abscess of a 78-year-old patient presenting with mid-thoracic pain and bilateral lower limb weakness and numbness. The patient was on long-term immunosuppressive therapy with steroids for underlying autoimmune hemolytic anemia. Investigations showed a T5 pathological fracture and vertebra plana with the erosion of the superior and inferior endplates. There was evidence of paraspinal collection from the T4-T6 vertebrae with an extension into the spinal canal. Analysis of Nocardia 16S rRNA (99.9%, 1395/1396 nt) and secA1 gene (99.5%, 429/431 nt) fragments showed the highest sequence similarity with Nocardia kroppenstedtii type strain (DQ157924), and next with Nocardia farcinica (Z36936). The patient was treated with intravenous carbapenem and oral trimethoprim-sulfamethoxazole for four weeks, followed by another six months of oral trimethoprim-sulfamethoxazole. Despite the improvement of neurological deficits, the patient required assistive devices to ambulate at discharge. This study reports the first isolation of N. kroppenstedtii from the spinal vertebral abscess of a patient from Asia. Infections caused by N. kroppenstedtii may be underdiagnosed as the bacterium can be misidentified as N. farcinica in the absence of molecular tests in the clinical laboratory.

Matched MeSH terms: Anti-Bacterial Agents/administration & dosage; Sulfamethoxazole/administration & dosage; Trimethoprim/administration & dosage
Therapeutic applications of transdermal microneedles

Kumar Singla S, Muthuraman A, Sahai D, Mangal N, Dhamodharan J

Front Biosci (Elite Ed), 2021 01 01;13:158-184.
PMID: 33048780

Transdermal drug-delivery systems (TDDS) offer an attractive alternative to the oral route for delivery of biotherapeutics. Technological advancements in the past few decades have revolutionized the fabrication of micro-structured devices including creation of microneedles (MC). These devices are used for delivering peptides, macromolecules such as proteins and DNA, and other therapeutics through the skin. Here, we review the current use of MCs as a cost effective method for the self-administration of therapeutics. We will then review the current and common use of MCs as an effective treatment strategy for a broad range of diseases and their utility in the generation of effective vaccination delivery platforms. Finally, we will summarize the currently FDA approved MCs and their applications, along with the ongoing clinical trials that use such devices.

Matched MeSH terms: DNA/administration & dosage; Proteins/administration & dosage
Improved DNA Delivery Efficiency of Bacterial Vectors by Co-Delivery with Exogenous Lipid and Antimicrobial Reagents

Osahor AN, Narayanan K

Methods Mol Biol, 2021;2211:15-27.
PMID: 33336267 DOI: 10.1007/978-1-0716-0943-9_2

Gene delivery using invasive bacteria as vectors is a robust method that is feasible for plasmid and artificial chromosome DNA construct delivery to human cells presenting β1 integrin receptors. This technique is relatively underutilized owing to the inefficiency of gene transfer to targeted cell populations. Bacterial vectors must successfully adhere to the cell membrane, internalize into the cytoplasm, undergo lysis, and deliver DNA to the nucleus. There are limited studies on the use of exogenous reagents to improve the efficiency of bacteria-mediated gene delivery to mammalian cells. In this chapter, we describe how cationic lipids, conventionally used for DNA and protein transfection, as well as antimicrobial compounds, can be used to synergistically enhance the adherence of invasive bacterial vectors to the cell membrane and improve their predisposition to internalize into the cytoplasm to deliver DNA. Using simple combinatorial methods, functional DNA transfer can be improved by up to four-fold of invaded cell populations. These methods are easy to perform and are likely to be applicable for other bacterial vectors including Listeria and Salmonella.

Matched MeSH terms: Anti-Infective Agents/administration & dosage*; DNA/administration & dosage*; Genetic Vectors/administration & dosage
Rationalization of Mushroom-Based Preventive and Therapeutic Approaches to COVID-19: Review

Rahman MA, Rahman MS, Bashir NMB, Mia R, Hossain A, Saha SK, et al.

Int J Med Mushrooms, 2021;23(5):1-11.
PMID: 34347990 DOI: 10.1615/IntJMedMushrooms.2021038285

Since December 2019, a de novo pattern of pneumonia, later named coronavirus disease 2019 (COVID-19), has caused grave upset throughout the global population. COVID-19 is associated with several comorbidities; thus, preventive and therapeutic strategies targeting those comorbidities along with the causative agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seem imperative. In this state-of-the-art review, edible and medicinal mushrooms are featured in the treatment of SARS-CoV-2, COVID-19 pathomanifestations, and comorbid issues. Because this is not an original research article, we admit our shortcomings in inferences. Yet we are hopeful that mushroom-based therapeutic approaches can be used to achieve a COVID-free world. Among various mushroom species, reishi or lingzhi (Ganoderma lucidum) seem most suitable as anti-COVID agents for the global population.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/administration & dosage; Antiviral Agents/administration & dosage; Biological Products/administration & dosage; Immunologic Factors/administration & dosage
Fulltext Strategies and Future Opportunities for the Prevention, Diagnosis, and Management of Cow Milk Allergy

Zepeda-Ortega B, Goh A, Xepapadaki P, Sprikkelman A, Nicolaou N, Hernandez REH, et al.

Front Immunol, 2021;12:608372.
PMID: 34177882 DOI: 10.3389/fimmu.2021.608372

The prevalence of food allergy has increased over the last 20-30 years, including cow milk allergy (CMA) which is one of the most common causes of infant food allergy. International allergy experts met in 2019 to discuss broad topics in allergy prevention and management of CMA including current challenges and future opportunities. The highlights of the meeting combined with recently published developments are presented here. Primary prevention of CMA should start from pre-pregnancy with a focus on a healthy lifestyle and food diversity to ensure adequate transfer of inhibitory IgG- allergen immune complexes across the placenta especially in mothers with a history of allergic diseases and planned c-section delivery. For non-breastfed infants, there is controversy about the preventive role of partially hydrolyzed formulae (pHF) despite some evidence of health economic benefits among those with a family history of allergy. Clinical management of CMA consists of secondary prevention with a focus on the development of early oral tolerance. The use of extensive Hydrolysate Formulae (eHF) is the nutrition of choice for the majority of non-breastfed infants with CMA; potentially with pre-, probiotics and LCPUFA to support early oral tolerance induction. Future opportunities are, among others, pre- and probiotics supplementation for mothers and high-risk infants for the primary prevention of CMA. A controlled prospective study implementing a step-down milk formulae ladder with various degrees of hydrolysate is proposed for food challenges and early development of oral tolerance. This provides a more precise gradation of milk protein exposure than those currently recommended.

Matched MeSH terms: Protein Hydrolysates/administration & dosage; Prebiotics/administration & dosage
Fulltext Effects of tocotrienols supplementation on markers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials

Khor BH, Tiong HC, Tan SC, Wong SK, Chin KY, Karupaiah T, et al.

PLoS One, 2021;16(7):e0255205.
PMID: 34297765 DOI: 10.1371/journal.pone.0255205

Studies investigating the effects of tocotrienols on inflammation and oxidative stress have yielded inconsistent results. This systematic review and meta-analysis aimed to evaluate the effects of tocotrienols supplementation on inflammatory and oxidative stress biomarkers. We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception until 13 July 2020 to identify randomized controlled trials supplementing tocotrienols and reporting circulating inflammatory or oxidative stress outcomes. Weighted mean difference (WMD) and corresponding 95% confidence interval (CI) were determined by pooling eligible studies. Nineteen studies were included for qualitative analysis, and 13 studies were included for the meta-analyses. A significant reduction in C-reactive protein levels (WMD: -0.52 mg/L, 95% CI: -0.73, -0.32, p < 0.001) following tocotrienols supplementation was observed, but this finding was attributed to a single study using δ-tocotrienols, not mixed tocotrienols. There were no effects on interleukin-6 (WMD: 0.03 pg/mL, 95% CI: -1.51, 1.58, p = 0.966), tumor necrosis factor-alpha (WMD: -0.28 pg/mL, 95% CI: -1.24, 0.68, p = 0.571), and malondialdehyde (WMD: -0.42 μmol/L, 95% CI: -1.05, 0.21, p = 0.189). A subgroup analysis suggested that tocotrienols at 400 mg/day might reduce malondialdehyde levels (WMD: -0.90 μmol/L, 95% CI: -1.20, -0.59, p < 0.001). Future well-designed studies are warranted to confirm the effects of tocotrienols on inflammatory and oxidative stress biomarkers, particularly on different types and dosages of supplementation. PROSPERO registration number: CRD42020198241.

Matched MeSH terms: Anti-Inflammatory Agents/administration & dosage; Antioxidants/administration & dosage; Vitamins/administration & dosage; Tocotrienols/administration & dosage
Fulltext Combined application of zinc and silicon alleviates terminal drought stress in wheat by triggering morpho-physiological and antioxidants defense mechanisms

Sattar A, Wang X, Abbas T, Sher A, Ijaz M, Ul-Allah S, et al.

PLoS One, 2021;16(10):e0256984.
PMID: 34618822 DOI: 10.1371/journal.pone.0256984

Wheat is an important global staple food crop; however, its productivity is severely hampered by changing climate. Erratic rain patterns cause terminal drought stress, which affect reproductive development and crop yield. This study investigates the potential and zinc (Zn) and silicon (Si) to ameliorate terminal drought stress in wheat and associated mechanisms. Two different drought stress levels, i.e., control [80% water holding capacity (WHC) was maintained] and terminal drought stress (40% WHC maintained from BBCH growth stage 49 to 83) combined with five foliar-applied Zn-Si combinations (i.e., control, water spray, 4 mM Zn, 40 mM Si, 4 mM Zn + 40 mM Si applied 7 days after the initiation of drought stress). Results revealed that application of Zn and Si improved chlorophyll and relative water contents under well-watered conditions and terminal drought stress. Foliar application of Si and Zn had significant effect on antioxidant defense mechanism, proline and soluble protein, which showed that application of Si and Zn ameliorated the effects of terminal drought stress mainly by regulating antioxidant defense mechanism, and production of proline and soluble proteins. Combined application of Zn and Si resulted in the highest improvement in growth and antioxidant defense. The application of Zn and Si improved yield and related traits, both under well-watered conditions and terminal drought stress. The highest yield and related traits were recorded for combined application of Zn and Si. For grain and biological yield differences among sole and combined Zn-Si application were statistically non-significant (p>0.05). In conclusion, combined application of Zn-Si ameliorated the adverse effects of terminal drought stress by improving yield through regulating antioxidant mechanism and production of proline and soluble proteins. Results provide valuable insights for further cross talk between Zn-Si regulatory pathways to enhance grain biofortification.

Matched MeSH terms: Silicon/administration & dosage; Zinc/administration & dosage
Fulltext Recurrent haemorrhagic ovarian cyst and anticoagulant therapy: a case report with review of treatment modalities

Nagandla K, Jamli MFBM, Hanim F, Xu Mei JL, Din SFS

Pan Afr Med J, 2021;40:52.
PMID: 34795832 DOI: 10.11604/pamj.2021.40.52.30961

The common gynaecological causes of acute pelvic pain include ruptured ectopic pregnancy, haemorrhagic corpus luteal cyst or torsion of an ovarian cyst. Ovarian vascular accidents are reported in women on oral anticoagulation presenting as an acute pelvic pain. Although such vascular accidents with anticoagulation therapy are an unusual entity, a meticulous history, clinical examination, and laboratory workup to confirm the diagnosis and timely intervention is needed to reduce attending morbidity and mortality. However, a standard algorithm for management is not described in the literature. We hereby report successful management of recurrent hemorrhagic ovarian cyst due to coagulopathy in a woman with mechanical heart valves with timely surgical intervention. This case report discusses operative versus non operative management approach and may provide value addition to readers encountering such cases in their clinical practice.

Matched MeSH terms: Anticoagulants/administration & dosage
Fulltext Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis

Cheah KL, Norhayati MN, Husniati Yaacob L, Abdul Rahman R

PLoS One, 2021;16(9):e0257843.
PMID: 34559859 DOI: 10.1371/journal.pone.0257843

OBJECTIVE: To determine the effect of Ashwagandha extract on sleep.
METHODS: A comprehensive search was conducted in CENTRAL, MEDLINE, SCOPUS, Google Scholars, World Health Organization Trials Portal, ClinicalTrials.gov, Clinical Trial Registry of India, and AYUSH Research Portal for all appropriate trials. Randomized controlled trials that examined the effect of Ashwagandha extract versus placebo on sleep in human participants 18 years old and above were considered. Two authors independently read all trials and independently extracted all relevant data. The primary outcomes were sleep quantity and sleep quality. The secondary outcomes were mental alertness on rising, anxiety level, and quality of life.
RESULTS: A total of five randomized controlled trials containing 400 participants were analyzed. Ashwagandha extract exhibited a small but significant effect on overall sleep (Standardized Mean Difference -0.59; 95% Confidence Interval -0.75 to -0.42; I2 = 62%). The effects on sleep were more prominent in the subgroup of adults diagnosed with insomnia, treatment dosage ≥600 mg/day, and treatment duration ≥8 weeks. Ashwagandha extract was also found to improve mental alertness on rising and anxiety level, but no significant effect on quality of life. No serious side effects were reported.
CONCLUSION: Ashwagandha extract appears to has a beneficial effect in improving sleep in adults. However, data on the serious adverse effects of Ashwagandha extract are limited, and more safety data would be needed to assess whether it would be safe for long-term use.

Matched MeSH terms: Plant Extracts/administration & dosage*
Fulltext Phytoantioxidant Functionalized Nanoparticles: A Green Approach to Combat Nanoparticle-Induced Oxidative Stress

Balkrishna A, Kumar A, Arya V, Rohela A, Verma R, Nepovimova E, et al.

Oxid Med Cell Longev, 2021;2021:3155962.
PMID: 34737844 DOI: 10.1155/2021/3155962

Nanotechnology is gaining significant attention, with numerous biomedical applications. Silver in wound dressings, copper oxide and silver in antibacterial preparations, and zinc oxide nanoparticles as a food and cosmetic ingredient are common examples. However, adverse effects of nanoparticles in humans and the environment from extended exposure at varied concentrations have yet to be established. One of the drawbacks of employing nanoparticles is their tendency to cause oxidative stress, a significant public health concern with life-threatening consequences. Cardiovascular, renal, and respiratory problems and diabetes are among the oxidative stress-related disorders. In this context, phytoantioxidant functionalized nanoparticles could be a novel and effective alternative. In addition to performing their intended function, they can protect against oxidative damage. This review was designed by searching through various websites, books, and articles found in PubMed, Science Direct, and Google Scholar. To begin with, oxidative stress, its related diseases, and the mechanistic basis of oxidative damage caused by nanoparticles are discussed. One of the main mechanisms of action of nanoparticles was unearthed to be oxidative stress, which limits their use in humans. Secondly, the role of phytoantioxidant functionalized nanoparticles in oxidative damage prevention is critically discussed. The parameters for the characterization of nanoparticles were also discussed. The majority of silver, gold, iron, zinc oxide, and copper nanoparticles produced utilizing various plant extracts were active free radical scavengers. This potential is linked to several surface fabricated phytoconstituents, such as flavonoids and phenols. These phytoantioxidant functionalized nanoparticles could be a better alternative to nanoparticles prepared by other existing approaches.

Matched MeSH terms: Metal Nanoparticles/administration & dosage*
Fulltext Wheat Germ Agglutinin-Conjugated Disulfide Cross-Linked Alginate Nanoparticles as a Docetaxel Carrier for Colon Cancer Therapy

Chiu HI, Lim V

Int J Nanomedicine, 2021;16:2995-3020.
PMID: 33911862 DOI: 10.2147/IJN.S302238

PURPOSE: In chemotherapy, oral administration of drug is limited due to lack of drug specificity for localized colon cancer cells. The inability of drugs to differentiate cancer cells from normal cells induces side effects. Colonic targeting with polymeric nanoparticulate drug delivery offers high potential strategies for delivering hydrophobic drugs and fewer side effects to the target site. Disulfide cross-linked polymers have recently acquired high significance due to their potential to degrade in reducing colon conditions while resisting the upper gastrointestinal tract's hostile environment. The goal of this project is, therefore, to develop pH-sensitive and redox-responsive fluorescein-labeled wheat germ agglutinin (fWGA)-mounted disulfide cross-linked alginate nanoparticles (fDTP2) directly targeting docetaxel (DTX) in colon cancer cells.
METHODS: fDTP2 was prepared by mounting fWGA on DTX-loaded nanoparticles (DTP2) using the two-step carbodiimide method. Morphology of fDTP2 was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Dynamic light scattering (DLS) study was carried out to determine the mean diameter, polydispersity index (PDI) and zeta potential of fDTP2. Cellular uptake efficiency was examined using fluorescence microplate reader. Biocompatibility and active internalization of fDTP2 were conducted on HT-29.
RESULTS: fDTP2 was found to exhibit a DTX loading efficiency of 19.3%. SEM and TEM tests revealed spherical nanoparticles. The in vitro DTX release test showed a cumulative release of 54.7%. From the DLS study, fDTP2 reported a 277.7 nm mean diameter with PDI below 0.35 and -1.0 mV zeta potential. HT-29 which was fDTP2-treated demonstrated lower viability than L929 with a half maximal inhibitory concentration (IC50) of 34.7 µg/mL. HT-29 (33.4%) internalized fDTP2 efficiently at 2 h incubation. The study on HT-29 active internalization of nanoparticles through fluorescence and confocal imaging indicated such.
CONCLUSION: In short, fDTP2 demonstrated promise as a colonic drug delivery DTX transporter.

Matched MeSH terms: Antineoplastic Agents/administration & dosage; Drug Carriers/administration & dosage; Nanoparticles/administration & dosage*
Fulltext The Photocatalytic Effects of Modified Hydrothermal Nanotitania Extraction on the Skin and Behavior of Sprague-Dawley Rats

Harun AM, Awang H, Noor NFM, Makhatar NM, Yusoff ME, Affandi NDN, et al.

Biomed Res Int, 2021;2021:6173143.
PMID: 34859102 DOI: 10.1155/2021/6173143

BACKGROUND: Potential antibacterial substances, such as titanium dioxide (TiO2), are being extensively studied throughout the research world. A modified hydrothermal nanotitania extraction was shown to inhibit Staphylococcus aureus growth in the laboratory. However, the toxicity effect of the extract on rats is unknown. In this study, we observed the effects of a modified hydrothermal nanotitania extraction on the skin and behavior of Sprague-Dawley rats.
METHODS: Sprague-Dawley (Rattus norvegicus) rats were used as the experimental animals. The skin around the dorsum of the tested animals was shaved and pasted with 0.1 mg and 0.5 mg of the nanotitania extraction. The color and condition of the pasted area and the behavior of the animals were observed.
RESULTS: 0.1 mg nanotitania extraction application on the dorsum of the rat produced no skin color changes at day 1, day 3, day 5, or day 7 postapplication. There were no changes in their behavior up to day 7 with no skin rashes or skin scratches seen or fur changes. However, 0.5 mg of nanotitania extraction resulted in redness and less fur regrowth at day 7.
CONCLUSIONS: A 0.1 mg modified nanotitania extraction was observed to have no effect on the skin of Sprague-Dawley rats.

Matched MeSH terms: Metal Nanoparticles/administration & dosage
Fulltext Factors Associated with Low Bone Density in Opioid Substitution Therapy Patients: A Systematic Review

Ramli FF, Syed Hashim SA, Mohd Effendy N

Int J Med Sci, 2021;18(2):575-581.
PMID: 33390827 DOI: 10.7150/ijms.52201

Background: Long-term opioid therapy is a risk factor for low bone mineral density (BMD). However, other factors may also contribute to low BMD. Several studies have examined the variables that might contribute to low BMD in patients receiving opioid replacement therapy (OST). However, to our knowledge, there was no systemic review conducted to address this particular issue. Thus, we reviewed the articles on the factors associated with low BMD in the population of opioid use disorder receiving substitution therapy. Methods: The articles that examined correlates or risk factors of low BMD in OST population were retrieved from OVID, SCOPUS, and PUBMED from inception until July 2020 by two independent investigators. Results: A total of 429 articles from three databases were retrieved initially. After screening based on eligibility criteria, five articles were included in the final analysis. The risk factors or correlates found to be significantly associated with low BMD in the OST population include male gender, low body mass index, low testosterone level, methadone or heroin use, and longer duration of heavy alcohol use. The review limitations include small sample sizes and inconsistent definition of variables. Conclusion: OST patients should be screened for BMD and its associated factors. Guidelines and training of practitioners involving in the OST service should be provided to increase the detection of low BMD in the OST population.

Matched MeSH terms: Buprenorphine/administration & dosage; Methadone/administration & dosage; Narcotic Antagonists/administration & dosage
Comparison between Iberet Folic® and Zincofer® in treatment of iron deficiency anaemia in pregnancy

Abu MA, Borhan AS, Abdul Karim AK, Ahmad MF, Mahdy ZA

Horm Mol Biol Clin Investig, 2020 Dec 14;42(1):49-56.
PMID: 33781008 DOI: 10.1515/hmbci-2020-0034

OBJECTIVES: To compare the effect of Iberet Folic® and Zincofer® on haemoglobin (Hb) and serum ferritin level; and its adverse effect.
METHODS: This randomised controlled trial conducted from January 2018 until December 2018. Pregnant women below 34 weeks of gestation, with Hb concentration less than 11 g/dL and serum ferritin level less than 12 ug/L were randomised to receive either one tablet Zincofer® or one tablet Iberet Folate® daily for four weeks. Both groups were compared in terms of effect on Hb level, serum ferritin level, and other haematological indices adverse effect related to treatment, and treatment cost.
RESULTS: Hundred and thirty patients were recruited in this study with 68 patients in Iberet Folic group and 62 patients in Zincofer group. The change in the Hb and serum ferritin level from baseline to day 30 did not differ significantly between treatment groups. The mean (±SD) change from baseline to day 30 was 2.15 (±0.59) g/dL in the Iberet Folic group, and 1.98 (±0.49) in the Zincofer (p value = 0.08). Mean serum ferritin at day 30 was 17.2 (±3.68) ug/L and 16.7 (±4.28) ug/L with 8.44 (±3.41) and 8.55 (±3.50) difference, respectively (p = 0.86). Adverse events were comparable in between groups, with p value >0.05. GI intolerance and constipation were among the common side effects, occurred in 34.6 and 29.2% cases, respectively.
CONCLUSIONS: Zincofer® offers equivalent efficacy and side effect profile in comparison with Iberet Folic® for the treatment of iron deficiency anaemia (IDA) during pregnancy, but with lower cost.

Matched MeSH terms: Ferrous Compounds/administration & dosage

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