Autophagy is an important degradation pathway, which is induced after starvation, where it buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. While the classical pathway mediating this response is via mTOR inhibition, there are likely to be additional pathways that support the process. Here, we identify Annexin A2 as an autophagy modulator that regulates autophagosome formation by enabling appropriate ATG9A trafficking from endosomes to autophagosomes via actin. This process is dependent on the Annexin A2 effectors ARP2 and Spire1. Annexin A2 expression increases after starvation in cells in an mTOR-independent fashion. This is mediated via Jun N-terminal kinase activation of c-Jun, which, in turn, enhances the trans-activation of the Annexin A2 promoter. Annexin A2 knockdown abrogates starvation-induced autophagy, while its overexpression induces autophagy. Hence, c-Jun-mediated transcriptional responses support starvation-induced autophagy by regulating Annexin A2 expression levels.

There is accumulating evidence that aggregating, misfolded proteins may have an impact on autophagic function, suggesting that this could be a secondary pathological mechanism in many diseases. In this review, we focus on the role of autophagy in four major neurodegenerative diseases: Alzheimer disease (AD), Huntington's disease (HD), Parkinson's disease (PD) and amyotropic lateral sclerosis.

The mistletoes, stem hemiparasites of Asia and Europe, have been used as medicinal herbs for many years and possess sophisticated systems to obtain nutrients from their host plants. Although knowledge about ethnomedicinal uses of mistletoes is prevalent in Asia, systematic scientific study of these plants is still lacking, unlike its European counterparts. This review aims to evaluate the literature on Scurrula and Viscum mistletoes. Both mistletoes were found to have anticancer, antimicrobial, antioxidant and antihypertensive properties. Plants from the genus Scurrula were found to inhibit cancer growth due to presence of phytoconstituents such as quercetin and fatty acid chains. Similar to plants from the genus Viscum, Scurrula also possesses TNFα activity to strengthen the immune system to combat cancer. In line with its anticancer activity, both mistletoes are rich in antioxidants that confer protection against cancer as well as neurodegeneration. Extracts from plants of both genera showed evidence of vasodilation and thus, antihypertensive effects. Other therapeutic effects such as weight loss, postpartum and gastrointestinal healing from different plants of the genus Scurrula are documented. As the therapeutic effects of plants from Scurrula are still in exploration stage, there is currently no known clinical trial on these plants. However, there are few on-going clinical trials for Viscum album that demonstrate the functionalities of these mistletoes. Future work required for exploring the benefits of these plants and ways to develop both parasitic plants as a source of pharmacological drug are explained in this article.

Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by abnormal polyglutamine expansion in the huntingtin protein (Exp-Htt). Currently, there are no effective treatments for HD. We used bidirectional lentiviral transfer vectors to generate in vitro and in vivo models of HD and to test the therapeutic potential of vascular endothelial growth factor 165 (VEGF₁₆₅). Lentiviral-mediated expression of Exp-Htt caused cell death and aggregate formation in human neuroblastoma SH-SY5Y and rat primary striatal cultures. Lentiviral-mediated VEGF₁₆₅ expression was found to be neuroprotective in both of these models. Unilateral stereotaxic vector delivery of Exp-Htt vector in adult rat striatum led to progressive inclusion formation and striatal neuron loss at 10 weeks post-transduction. Coinjection of a lower dose VEGF₁₆₅ significantly attenuated DARPP-32⁺ neuronal loss, enhanced NeuN staining and reduced Exp-Htt aggregation. A tenfold higher dose VEGF₁₆₅ led to overt neuronal toxicity marked by tissue damage, neovascularization, extensive astrogliosis, vascular leakage, chronic inflammation and distal neuronal loss. No overt behavioral phenotype was observed in these animals. Expression of VEGF₁₆₅ at this higher dose in the brain of wild-type rats led to early mortality with global neuronal loss. This report raises important safety concerns about unregulated VEGF₁₆₅ CNS applications.

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. It is the second leading cause of cancer death in men and women in Brunei Darussalam in 2017, posing a major burden on society. This retrospective cohort study (n = 1035 patients diagnosed with CRC in Brunei Darussalam from 1st January 2002 until 31st December 2017) aims to compare the overall survival rates of CRC patients (2002–2017), to compare survival rates between two study periods (2002–2009 and 2010–2017) and to identify prognostic factors of CRC. Kaplan-Meier estimator and log-rank tests were performed to analyse the overall survival rates of CRC patients. Multiple Cox regression was performed to determine the prognostic factors of CRC with adjusted hazard ratios (Adj. HRs) reported. The 1-, 3- and 5-year survival rates of CRC patients are 78.6, 62.5, and 56.0% respectively from 2002 to 2017. The 1-, 3-, and 5-year survival rates of CRC patients for 2002–2009 are 82.2, 69.6, and 64.7%; 77.0, 59.1, and 51.3% for 2010–2017 respectively. A significant difference in CRC patients’ survival rate was observed between the two study periods, age groups, ethnic groups, cancer stages, and sites of cancer (p < 0.05). The Adjusted Hazard Ratios (Adj. HRs) were significantly higher in the 2010–17 period (Adj. HR = 1.78, p < 0.001), older age group ( ≥ 60 years) (Adj. HR = 1.93, p = 0.005), distant cancer (Adj. HR = 4.69, p < 0.010), tumor at transverse colon and splenic flexure of colon (Adj. HR = 2.44, p = 0.009), and lower in the Chinese(Adj. HR = 0.63, p = 0.003). This study highlights the lower survival rates of CRC patients in 2010–2017, Malays, older patients, distant cancer, and tumors located at the latter half of the proximal colon (transverse colon), and predominantly LCRC (splenic flexure, descending colon, sigmoid colon, overlapping lesion colon and colon (NOS), as well as the rectosigmoid junction and rectum (NOS)). Age, ethnicity, cancer stage, and tumor location are significant prognostic factors for CRC. These findings underscore the importance of public health policies and programmes to enhance awareness on CRC from screening to developing strategies for early detection and management, to reduce CRC-associated mortality.

Background: Despite the global increase in the prevalence of autism spectrum disorders (ASD), relevant research studies are lacking in Brunei Darussalam. Various studies have shown a significant association between a lowered 2D:4D ratio (ratio of second digit/index finger to the fourth digit/ring finger) and ASD, making it one of the potential phenotypic biomarkers for early detection of autism, which is important for early intervention and management. Objective: The objective of this study is to explore the association between 2D:4D ratio and ASD in Brunei Darussalam, as a potential tool to complement early ASD diagnosis. Methods: We conducted a case–control study comprising 28 ASD and 62 typically developing (TD) children in the case and control group, respectively (age range: 3–11 years old; median age: 6 years old). Median 2D:4D ratios were measured, compared and analysed between the two groups. Logistic regression models were used to explore potential associations between the median 2D:4D ratio and ASD in respective gender, for both left and right hands, independently. Results: Our study shows that the median 2D:4D ratio of left hand in ASD males is significantly lower than those in TD males, after adjusting for ethnicity and age [Odds Ratio (OR) = 0.57 (95% Confidence Interval (CI): 0.31–0.96); p = 0.044]. For females, there is no association of ASD with the median left hand 2D:4D ratio [OR = 3.09 (95% CI: 0.98–19.86); p = 0.144] or the median right hand 2D:4D ratio [OR = 1.23 (95% CI: 0.42–3.88); p = 0.702]. Our study also shows a significant positive correlation and/or a reduced asymmetry between the average 2D:4D ratio of left hands and right hands in ASD males (Pearson’s correlation (r) = 0.48; 95% CI: 0.076–0.75, p = 0.023). Conclusions: There is significant association between a lowered median 2D:4D ratio of the left hand (in males only) and ASD diagnosis. Once validated in a larger sample size, a lowered median 2D:4D ratio on the left hand may be a potential tool to complement ASD diagnosis for males in our study population. There is no association between the median 2D:4D ratio (left or right hands) and ASD in females, which could be due to the small female sample size and/or the possibility of different aetiology for ASD in females. Reduced asymmetry between the average 2D:4D ratio of left and right hands observed in ASD males only (not in ASD females) also suggests the importance of considering gender-specific biomarkers for ASD diagnosis.