Structure-based virtual screening of plant-derived natural compounds as potential PPARα agonists for the treatment of dyslipidemia

Original Research

Abstract

Background: Nowadays, metabolic disorders such as dyslipidemia have become serious health problems in the modern world. PPARs are regulators of numberous metabolic pathways, hence there has been a huge increase in the development and use of the PPARs agonists, especially PPARα agonists as main therapeutic of dyslipidemia.

Objectives: The study aimed to explore potential plant-derived natural compounds as PPARα agonist agent for drug discovery of dyslipidemia. Methods: Structure-based virtual screening through molecular docking was conducted for 142 bioactive compounds from 29 medicinal plants on the main binding site of PPARα (PDB ID: 5HYK). Binding affinities and binding interactions between the ligands and PPARα were investigated.

Results: Screening results showed that 34 compounds had strong binding affinities into the PPARα (binding affinities of less than -8.0 kcal.mol-1), including 20 flavonoid, 4 terpenoid and 10 alkaloid compounds. Flavonoid was found as the best group which fitted well in the binding site of the PPARα. Top compounds were identified, including formononetin from Thermopsis alterniflora (-10.2 kcal.mol-1), diosmetin from Musa spp. (-10.1 kcal.mol-1), luteolin from Elsholtzia ciliate (-9.9 kcal.mol-1); steviol from Stevia rebaudiana (-9.4 kcal.mol-1); and tuberocrooline from Stemona tuberosa (-10.5 kcal.mol-1), respectively. These compounds showed the potential agonistic activities due to forming the hydrogen bonds as well as hydrophobic interactions with four key residues of the receptor such as Ser280, Tyr314, His440 and Tyr464.

Conclusions: These potential natural compounds may provide useful information in the drug design and discovery for anti-dyslipidemia agents.

Graphical abstract

Effectiveness of hydrocolloid nasal dressing pads in preventing nasal ulceration in preterm infants using non-invasive ventilation

Original Research

Abstract

Background: The use of non-invasive ventilation (NIV) in preterm infants is becoming increasingly common. The use of cannula in NIV can cause ulceration of the nasal bridge with the current practices using the thin foam patches. This study aims to evaluate the effectiveness of hydrocolloid nasal dressing pads in preventing nasal ulceration comparing to that of the thin foam patches.

Methods: A prospective cohort study using hydrocolloid dressing pads (1 November to 30 April 2020) was compared to that of a historical control group using thin foam dressing (1 April to 15 October 2019) to evaluate the effectiveness of hydrocolloid dressing pads. All participants were preterm infants (less than 37 weeks of gestational age) and used nasal cannula NIV at the Department of Neonatal Intensive Care (NICU), Children's Hospital 1.

Results: 71 infants used hydrocolloid dressing pads, and 42 used ordinary thin foam nasal dressings. In the hydrocolloid dressings group, two infants (2.8%) had nasal ulcers; among them, one was mild, and the other was moderate. In comparison, ten infants (23.8%) using thin foam dressings developed ulcers, of which seven were mild, two were moderate, and one was severe. Using hydrocolloid nasal dressings significantly reduced nasal ulceration compared to thin foam dressings (OR = 0.09, 95%CI = 0.02 – 0.45).

Conclusion: Using hydrocolloid nasal dressings for preterm infants on nasal cannula NIV significantly reduced nasal ulceration compared to ordinary thin foam dressings.

Graphical abstract

Knowledge, attitude and practice towards Covid-19 pandemic of pharmacy students in University of Medicine and Pharmacy at Ho Chi Minh city, Vietnam

Original Research

Abstract

Introduction: The rapid increase of infected cases and fatalities during the COVID-19 pandemic has created a huge health crisis to the world and Vietnam in particular. Health professionals were put under massive pressure in preventing pandemic. This study was conducted to assess the knowledge, attitude and practice (KAP) during the COVID-19 disease through an online survey as well as related infection control practices among pharmacy students in the University of Medicine and Pharmacy at Ho Chi Minh City (UMP).

Methods: The cross-sectional study was conducted based on the data obtained from an online questionnaire. Correlation analysis was performed using statistical tests and linear regression model for practice. The total study sample, chosen based on the inclusion and exclusion criteria was taken from pharmacy students in UMP during the study period.

Results: A scale of KAP towards COVID-19 was developed with 43 questions and received 1,089 responses. We acknowledged that the awareness and practice of these students were at a good level (with a mean score of 8.37±0.77 and 8.46±1.33, respectively) and the attitude was optimistic with a mean score of 6.22±0.68. Related factors to practice included gender (p=0.005), year of study (p=0.013); to knowledge included the time spent in university (p=0.040); to attitude included social distancing (p=0.024). Multivariable regression analysis showed that practice is related with male gender (β=-0.254; p=0.001), the first 3 school years (β = 0.173; p=0.020), knowledge score (β =0.154; p=0.003).

Conclusions: Based on a constructive scale, the study noted students' knowledge-attitude-practice towards COVID-19 at a good level. School year and knowledge scores positively affected practice scores, while male students had a negative effect.

Graphical abstract

Relationship between Protein kinase C isoforms, Telomerase and Alpha- fetoprotein through PI3K/AKT/mTOR pathway in Hepatocellular carcinoma

Original Research

Abstract

Protein kinase C (PKC) family has been an alluring objective for new cancer drug discovery. It has been reported to regulate telomerase in several cancer types. Our team had previously used telomerase to elucidate alpha-fetoprotein (AFP) modulation in hepatocellular carcinoma (HCC). The aim of this study was to investigate the interrelationships among PKC isoforms, telomerase and AFP in HCC. PKCα and PKCδ were the most expressed isoforms in HepG2/C3A, PLC/PRF/5, SNU-387 and SKOV-3 cells. Following the upregulation of AFP using pCMV3-AFP and the human telomerase reverse transcriptase (hTERT) using a construct expressing a wild-type hTERT, and after their inhibition with all-trans retinoic acid and hTERT siRNA each respectively, we found that the expression of PKCα, PKCβI, PKCβII and PKCδ was affected by the variation of AFP and hTERT mRNA levels. An increase in AFP expression and secretion was observed after gene silencing of PKCα, PKCβ, PKCδ, and PKCε in HepG2/C3A. A similar pattern was observed in transfected PLC/PRF/5 cells, however PKCδ isoform silencing decreased AFP expression. Furthermore, telomerase activity was quantified using quantitative telomeric repeat amplification protocol. The variations in hTERT expression and telomerase activity were similar to those of AFP. Further investigation showed that PKC isoforms regulate AFP and hTERT expression levels through PI3K/AKT/mTOR pathway in HepG2/C3A and PLC/PRF/5 cells. Thus, these results show for the first time a possible interrelationship that links PKC isoforms to both AFP and hTERT via PI3K/AKT/mTOR pathway in HCC.

Graphical abstract

Short-term results of sutureless closure for primary total anomalous pulmonary venous connection: seventeen cases

Original Research

Abstract

Introduction: Total anomalous pulmonary venous connection (TAPVC) is a rare condition. Mortality of TAPVC has improved dramatically in the present. Sutureless closure had initially used for congenital pulmonary venous stenosis (PVS) or post-repair PVS. Recently, it had been adopted for primary TAPVC to prevent postoperative pulmonary venous obstruction, a leading cause of death. This technique had gradually applied at our institute for primary TAPVC since 2018.

Methods: Prospective case series was conducted from mid-2019. Including criteria consists of patients with primary TAPVC. These are all supracardiac, infracardiac, mixed type and intracardiac TAPVC with pulmonary venous stenosis. Excluding measures are TAPVC with single ventricle, isomerism or heterotaxy. End-point outcomes were mortality and short-term PVS.

Results: Seventeen TAPVC cases were enrolled in this study from 06/2019-12/2020 at Children's Hospital 1. Male/female ratio was 12/5. Median age at admission was 44 (3-1010) days old. The median operative weight was 3.9 kg (2.4-11). Of those, fourteen (82.4%) cases were supracardiac TAPVC and 3 (17.6%) cases were infracardiac TAPVC. Nine (52.9%) cases were emergency operations. Median aortic clamp time was 66 (32-138) mins. Median bypass time was 112 (86-212) mins. There were 9 (52.9%) cases with arrhythmias, 2 (11.8%) cases with chylothorax. Mean ventilation time was 3.6±0.5 days; mean CICU time was 6.5 (1-20), median LOS was 14.5 (8-39). In-hospital mortality was 5.9% (1). Mean follow-up time was 12.3±6.4 months (range 4-24), there was no PVS with median pulmonary venous score of 0 (range 0-1).

Conclusions: Sutureless technique could be a safe option for primary TAPVC repair.

Graphical abstract

Challenging intraorbital foreign body: a case report

Case Study

Abstract

Purpose: To report a case of large intraorbital foreign body after a trauma.

Case report: A 38-year-old male patient admitted to hospital because of blurry vision and pain in left eye after being hit by a windscreen wiper on left eye (OS). Lid laceration was treated in a tertiary center before the patient was admitted to Ho Chi Minh City Eye Hospital with diagnosis orbital cellulitis and intraorbital foreign body of OS. High dose of antibiotics had been indicated before he underwent surgery to remove the foreign body. The foreign body was made of plastic, 7×10×35mm in size with many edges and adjacent to the orbital apex.

Conclusion: Taking history and trauma mechanism carefully may aid to early diagnosis and appropriate treatment to a patient with intraorbital foreign body. CT-scan images of the orbit, the globe, the sinuses and the cranial bones not only help locate the foreign body, but also aid to find out injuries of adjacent structures.

Graphical abstract

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