SIRT1 and antioxidants in infertile females: Exploration of the role of vitamin D.

BACKGROUND: Deficiency of silent information regulator 1 (SIRT1) can trigger inflammation, mitochondrial malfunctioning, and apoptosis through the hypothalamic-pituitary-ovarian axis, producing poor quality oocytes, leading to infertility. Normal vitamin D (VD) levels promote SIRT1 activity required for optimal fertility, and low levels of either may result in fertility problems owing to cell-membrane de-stabilization, increased autophagy, DNA damage leading to increased reactive oxygen species and mitochondrial dysfunction. Therefore, in this study, we want to estimate the levels of VD, SIRT1 and antioxidants (MnSOD; manganese superoxide dismutase, GR; glutathione reductase, visfatin) and oxidants (adrenaline & cortisol) in individuals living with infertility and explore the association of VD with SIRT1 expression (levels), antioxidants, and oxidants contributing to infertility in women. The significance of this study is that it highlights the importance of maintaining optimal levels of VD for reproductive health in females. METHODS: This cross-sectional study included 342 (135 infertile and 207 fertile) female subjects. Serum levels of MnSOD, SIRT1, visfatin, GR, VD, adrenaline, and cortisol were analyzed by ELISA and were compared in fertile and infertile samples using the Mann Whitney U test. RESULTS: There were significantly high levels of VD, SIRT1, GR, MnSOD and visfatin in fertile female participants. However, mean adrenaline and cortisol levels were higher in infertile samples with a significant negative correlation with VD. A significant negative correlation of VD with MnSOD, SIRT1, visfatin and GR was observed (p <0.01). In VD subset groups, MnSOD levels were significantly high in VD sufficient groups however, adrenaline and cortisol levels were significantly high in groups suffering from VD deficiency. CONCLUSIONS: Deficiency of VD is associated with a decrease in SIRT1 and other antioxidants, which may deter natural reproductive functions leading to infertility. Further studies are required to determine the cause-effect relationship of VD deficiency on conception and interpretation of the involved mechanism.

Applications of next generation sequencing in the screening and diagnosis of thalassemia: A mini-review.

Thalassemias are a group of inherited blood disorders that affects 5-7% of the world population. Comprehensive screening strategies are essential for the management and prevention of this disorder. Today, many clinical and research laboratories have widely utilized next-generation sequencing (NGS) technologies to identify diseases, from germline and somatic disorders to infectious diseases. Yet, NGS application in thalassemia is limited and has just recently surfaced due to current demands in seeking alternative DNA screening tools that are more efficient, versatile, and cost-effective. This review aims to understand the several aspects of NGS technology, including its most current and expanding uses, advantages, and limitations, along with the issues and solutions related to its integration into routine screening and diagnosis of thalassemias. Hitherto, NGS has been a groundbreaking technology that offers tremendous improvements as a diagnostic tool for thalassemia in terms of its higher throughput, accuracy, and adaptability. The superiority of NGS in detecting rare variants, solving complex hematological problems, and providing non-invasive alternatives to neonatal diagnosis cannot be overlooked. However, several pitfalls still preclude its use as a stand-alone technique over conventional methods.

Anthelmintic Effect of Leucaena leucocephala Extract and Its Active Compound, Mimosine, on Vital Behavioral Activities in Caenorhabditis elegans.

Helminth infections continue to be a neglected global threat in tropical regions, and there have been growing cases of anthelmintic resistance reported towards the existing anthelmintic drugs. Thus, the search for a novel anthelmintic agent has been increasing, especially those derived from plants. Leucaena leucocephala (LL) is a leguminous plant that is known to have several pharmacological activities, including anthelmintic activity. It is widely known to contain a toxic compound called mimosine, which we believed could be a potential lead candidate that could exert a potent anthelmintic effect. Hence, this study aimed to validate the presence of mimosine in LL extract and to investigate the anthelmintic effect of LL extract and mimosine on head thrashing, egg-laying, and pharyngeal pumping activities using the animal model Caenorhabditis elegans (C. elegans). Mimosine content in LL extract was confirmed through an HPLC analysis of spiking LL extract with different mimosine concentrations, whereby an increasing trend in peak heights was observed at a retention time of 0.9 min. LL extract and mimosine caused a significant dose-dependent increase in the percentage of worm mortality, which produced LC50s of 73 mg/mL and 6.39 mg/mL, respectively. Exposure of C. elegans to different concentrations of LL extract and mimosine significantly decreased the head thrashing, egg-laying, and mean pump amplitude of pharyngeal pumping activity. We speculated that these behavioral changes are due to the inhibitory effect of LL extract and mimosine on an L-type calcium channel called EGL-19. Our findings provide evidential support for the potential of LL extract and its active compound, mimosine, as novel anthelmintic candidates. However, the underlying mechanism of the anthelmintic action has yet to be elucidated.

Systematic Review of Medicinal Plants Used for Treatment of Diabetes in Human Clinical Trials: An ASEAN Perspective.

Traditionally, there are some medicinal plants believed to treat diabetes, as they have been proven in research studies to possess antidiabetic properties, such as improved insulin sensitivity and hypoglycemic activities, due to their high level of phenolic compounds, flavonoids, terpenoids, alkaloids, and glycosides. We conducted a systematic review to identify potential medicinal plants used during human clinical trials in the Association of Southeast Asian Nation (ASEAN) countries on prediabetic or type 2 diabetic individuals and to potentially identify any bioactive compounds involved in effectively treating symptoms of diabetes such as lowering of blood glucose. A total of 1209 reference titles were retrieved from four selected databases (Science Direct, Scopus, Springer Link, and PubMed) and only three met the inclusion criteria. Upon evaluation of the selected articles, four medicinal plants were identified: turmeric (Curcuma longa), garlic (Allium sativum L.), bitter melon (Momordica charantia), and Rosella flower (Hibiscus sabdariffa L.). Of these, only the bitter melon study did not show any significant change in the blood glucose of participants after intervention. This review demonstrates the limitations in published articles of human clinical trials for medicinal plants' intervention for diabetes. Upon further investigations on the four identified medicinal plants included in the animal studies, the findings showed positive effects in the management of diabetes, such as hyperglycemia. Hence, further testing and standardization of the methods in the studies can be suggested for human clinical trials for reliable data collections such as methods of extract preparation, duration of intervention, and conditions set for the study design.

Academic experiences, physical and mental health impact of COVID-19 pandemic on students and lecturers in health care education.

BACKGROUND: In keeping with nation-wide efforts to contain the spread of COVID-19, Universiti Brunei Darussalam (UBD) transformed fully its pedagogical delivery to online mode, where we investigated teaching and learning experiences, physical and mental health of undergraduate students and lecturers during the COVID-19 pandemic. METHODS: We conducted a cross-sectional study on undergraduate students and lecturers in a health science faculty using a self-developed pretested questionnaire through anonymous online data collection method. RESULTS: Fifty-six lecturers (100% response rate) and 279 students (93.3% response rate) participated. The positive experiences reported by students include becoming independent (72.8%) and adapting to online learning (67.4%), while lecturers learned new teaching techniques (50.0%) and became more innovative (50.0%) by learning new tools (48.2%). However, studying at home caused students to feel more distracted (72.0%) with a feeling of uncertainty towards examinations (66.7%), while lecturers felt that students' laboratory skills were compromised (44.6%). Even though online delivery of assessments enabled lecturers to explore all options (50.0%), they found it difficult to maintain appropriate questions (41.1%) and fair assessments (37.5%). Majority of students missed eating out (68.8%) and felt a lack of participation in extracurricular activities (64.9%), while lecturers reported more time for exercise (51.8%), despite having more screen time (50.0%) and computer-related physical stress (44.6%). In terms of mental health, increased stress in students was reported (64.9%), though they had more time for self-reflection (54.8%). Although lecturers reported a closer relationship with family (44.6%), they also felt more stressed due to deadlines, unexpected disruptions and higher workloads (44.6%) as well as concerns related to work, family and self (39.3%). CONCLUSION: In this abrupt shift to online teaching, students and lecturers in our study identified both positive and negative experiences including the impact on their physical and mental health. Our findings are important to provide the evidence for online pedagogical benefits and can serve to promote the enhancement and adaptation of digital technology in education. Our findings also aim to promote the importance of addressing physical and mental health issues of the university community's well-being through provision of emotional and mental health support and appropriate programs.

Conducting multiple mini-interviews in the midst of COVID-19 pandemic.

Multiple mini-interview (MMI) is a 'multiple sample-based' approach comprising multiple focused encounters intended to access and assess a range of attributes in order to gain more objectively multiple impressions of an applicant's interpersonal skills, thoughtfulness and general demeanour. It is designed to focus on four domains that are not considered to be comprehensive, but are considered to be vital for a successful career in the health sciences: critical thinking, ethical decision making, communication and knowledge of the healthcare system. Traditionally, the MMI is conducted face-to-face, but with COVID-19 pandemic and the implementation of social distancing measures, no onsite or campus teaching, banning of mass gatherings and cancellation of face-to-face interviews, Pengiran Anak Puteri Rashidah Sa'adatul Bolkiah Institute of Health Sciences at Universiti Brunei Darussalam explored the feasibility of conducting MMI through virtual means. This report provides an account of our experience in conducting internet-MMI for the selection of new applicants into the August 2020 cohort of the Medicine programme. We also aimed to determine whether the scores derived from internet-MMI were reliable and equivalent to the scores derived from traditional MMI.

Curcumin Ameliorates the Impaired Insulin Signaling Involved in the Pathogenesis of Alzheimer's Disease in Rats.

To date, dysregulation of the insulin signaling pathway in the brain has not been demonstrated unequivocally in Alzheimer's disease (AD). The purpose of the study was to examine the possible dysregulation of insulin signaling pathway in an AD rat model. Furthermore, the present study investigated the effect of Donepezil and Curcumin on insulin signaling, insulin, and glucose levels in AD rat brain. The rats were induced to develop AD by intraperitoneal administration of Scopolamine. We found that glucose levels in plasma and brain were decreased in AD rats, whereas the insulin levels was increased in plasma but decreased in brain in AD rats. In addition, insulin signaling proteins IR-ß, IGF-1, IRS-1, IRS-2 p-Akt (Ser473), and Akt were markedly reduced in the AD rats. Furthermore, GLUT3 and GLUT4 levels in the brain were markedly reduced in AD rats. All these data were compared to Saline-treated control rats. Curcumin significantly increased glucose levels in plasma and in brain. However, insulin levels was decreased in plasma and was increased in AD rats' brain. Moreover, GLUT3 and GLUT4 levels were significantly increased in Curcumin-treated AD rats. All these data were compared to Scopolamine- induced AD rats. Thus amelioration of impaired insulin signaling and improved glucose regulation in AD rats by Curcumin may be beneficial in the management of AD.

Development and evaluation of exemestane-loaded lyotropic liquid crystalline gel formulations.

Introduction: The use of liquid crystalline (LC) gel formulations for drug delivery has considerably improved the current delivery methods in terms of bioavailability and efficacy. The purpose of this study was to develop and evaluate LC gel formulations to deliver the anti-cancer drug exemestane through transdermal route. Methods: Two LC gel formulations were prepared by phase separation coacervation method using glyceryl monooleate (GMO), Tween 80 and Pluronic® F127 (F127). The formulations were characterized with regard to encapsulation efficiency (EE), vesicle size, Fourier transform infrared (FTIR) spectroscopy, surface morphology (using light and fluorescence microscopy), in vitro release, ex vivo permeation, in vitro effectiveness test on MDA-MB231 cancer cell lines and histopathological analysis. Results: Results exhibited that the EE was 85%-92%, vesicle size was 119.9-466.2 nm while morphology showed spherical vesicles after hydration. An FTIR result also revealed that there was no significant shift in peaks corresponding to Exemestane and excipients. LC formulations release the drug from cellulose acetate and Strat-MTM membrane from 15%-88.95%, whereas ex vivo permeation ranges from 37.09-63%. The in vitro effectiveness study indicated that even at low exemestane concentrations (12.5 and 25 µg/mL) the formulations were able to induce cancer cell death, regardless of the surfactant used. Histopathological analysis thinning of the epidermis as the formulations penetrate into the intercellular regions of squamous cells. Conclusion: The results conjectured that exemestane could be incorporated into LC gels for the transdermal delivery system and further preclinical studies such as pharmacokinetic and pharmacodynamic studies will be carried out with suitable animal models.