Gene expression profiling of host lipid metabolism in SARS-CoV-2 infected patients: a systematic review and integrated bioinformatics analysis.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic occurred due to the dispersion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe symptoms can be observed in COVID-19 patients with lipid-related comorbidities such as obesity and diabetes. Yet, the extensive molecular mechanisms of how SARS-CoV-2 causes dysregulation of lipid metabolism remain unknown. METHODS: Here, an advanced search of articles was conducted using PubMed, Scopus, EBSCOhost, and Web of Science databases using terms from Medical Subject Heading (MeSH) like SARS-CoV-2, lipid metabolism and transcriptomic as the keywords. From 428 retrieved studies, only clinical studies using next-generation sequencing as a gene expression method in COVID-19 patients were accepted. Study design, study population, sample type, the method for gene expression and differentially expressed genes (DEGs) were extracted from the five included studies. The DEGs obtained from the studies were pooled and analyzed using the bioinformatics software package, DAVID, to determine the enriched pathways. The DEGs involved in lipid metabolic pathways were selected and further analyzed using STRING and Cytoscape through visualization by protein-protein interaction (PPI) network complex. RESULTS: The analysis identified nine remarkable clusters from the PPI complex, where cluster 1 showed the highest molecular interaction score. Three potential candidate genes (PPARG, IFITM3 and APOBEC3G) were pointed out from the integrated bioinformatics analysis in this systematic review and were chosen due to their significant role in regulating lipid metabolism. These candidate genes were significantly involved in enriched lipid metabolic pathways, mainly in regulating lipid homeostasis affecting the pathogenicity of SARS-CoV-2, specifically in mechanisms of viral entry and viral replication in COVID-19 patients. CONCLUSIONS: Taken together, our findings in this systematic review highlight the affected lipid-metabolic pathways along with the affected genes upon SARS-CoV-2 invasion, which could be a potential target for new therapeutic strategies study in the future.

COVID-19 Pandemic Fatigue and Its Sociodemographic, Mental Health Status, and Perceived Causes: A Cross-Sectional Study Nearing the Transition to an Endemic Phase in Malaysia.

This study aimed to explore the socio-demographic characteristics, mental health status, and perceived causes of pandemic fatigue with COVID-19 pandemic fatigue among the general population of Malaysia. The data was collected online during the transition from the COVID-19 pandemic phase to the endemic phase in Malaysia from 1 to 30 April 2022. Sociodemographic data, Depression Anxiety Stress Scale-21 (DASS-21), perceived causes of pandemic fatigue, and the Fatigue Assessment Scale (FAS) were included in the survey. The chi-square test and a simple logistic regression analysis were used to identify predictors of pandemic fatigue. The completed survey (N = 775) included individuals aged 18 years or above [mean 31.98 (SD = 12.16)] from all states in Malaysia. Pandemic fatigue prevalence was 54.2%. Severe to extremely severe depression, anxiety, and stress symptoms were detected in 11.2%, 14.9%, and 9.1% of the participants, respectively. Younger age, non-Malay ethnicity, living alone, and higher income categories were significantly higher in the fatigued group. Higher DASS-21 scores on all domains were associated with higher FAS scores. Meanwhile, high scores for perceived tiredness from complying with the COVID-19 Standard Operating Procedure (SOP), perceived risk of infection from COVID-19, perceived hardship due to the pandemic, perceived public complacency during the pandemic, and perceived changes due to the pandemic were associated with a higher FAS score. This study provides valuable information for policymakers and mental health professionals worldwide on pandemic fatigue and its associated factors, including mental health status in Malaysia.

TPD52 expression increases neutral lipid storage within cultured cells.

Tumor protein D52 (TPD52) is amplified and/or overexpressed in cancers of diverse cellular origins. Altered cellular metabolism (including lipogenesis) is a hallmark of cancer development, and protein-protein associations between TPD52 and known regulators of lipid storage, and differential TPD52 expression in obese versus non-obese adipose tissue, suggest that TPD52 might regulate cellular lipid metabolism. We found increased lipid droplet numbers in BALB/c 3T3 cell lines stably expressing TPD52, compared with control and TPD52L1-expressing cell lines. TPD52-expressing 3T3 cells showed increased fatty acid storage in triglyceride (from both de novo synthesis and uptake) and formed greater numbers of lipid droplets upon oleic acid supplementation than control cells. TPD52 colocalised with Golgi, but not endoplasmic reticulum (ER), markers and also showed partial colocalisation with lipid droplets coated with ADRP (also known as PLIN2), with a proportion of TPD52 being detected in the lipid droplet fraction. Direct interactions between ADRP and TPD52, but not TPD52L1, were demonstrated using the yeast two-hybrid system, with ADRP-TPD52 interactions confirmed using GST pulldown assays. Our findings uncover a new isoform-specific role for TPD52 in promoting intracellular lipid storage, which might be relevant to TPD52 overexpression in cancer.

TPD52 represents a survival factor in ERBB2-amplified breast cancer cells.

TPD52 and ERBB2 co-expression has been persistently reported in human breast cancer and animal models of this disease, but the significance of this is unknown. We identified significant positive associations between relative TPD52 and ERBB2 transcript levels in human diagnostic breast cancer samples, and maximal TPD52 expression in the hormone receptor (HR)- and ERBB2-positive sub-group. High-level TPD52 expression was associated with significantly reduced metastasis-free survival, within the overall cohort (log rank test, P = 8.6 × 10(-4), n = 375) where this was an independent predictor of metastasis-free survival (hazard ratio, 2.69, 95% confidence interval 1.59-4.54, P = 2.2 × 10(-4), n = 359), and the HR- and ERBB2-positive sub-group (log rank test, P = 0.035, n = 47). Transient TPD52 knock-down in the ERBB2-amplified breast cancer cell lines SK-BR-3 and BT-474 produced significant apoptosis, both singly and in combination with transient ERBB2 knock-down. Unlike ERBB2 knock-down, transient TPD52 knock-down produced no reduction in pAKT levels in SK-BR-3 or BT-474 cells. We then derived multiple SK-BR-3 cell lines in which TPD52 levels were stably reduced, and measured significant inverse correlations between pERBB2 and TPD52 levels in viable TPD52-depleted and control cell lines, all of which showed similar proliferative capacities. Our results therefore identify TPD52 as a survival factor in ERBB2-amplified breast cancer cells, and suggest complementary cellular functions for TPD52 and ERBB2.

Molecular identification of adenovirus causing respiratory tract infection in pediatric patients at the University of Malaya Medical Center.

BACKGROUND: There are at least 51 adenovirus serotypes (AdV) known to cause human infections. The prevalence of the different human AdV (HAdV) serotypes varies among different regions. Presently, there are no reports of the prevalent HAdV types found in Malaysia. The present study was undertaken to identify the HAdV types associated primarily with respiratory tract infections (RTI) of young children in Malaysia. METHODS: Archived HAdV isolates from pediatric patients with RTI seen at the University of Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia from 1999 to 2005 were used. Virus isolates were inoculated into cell culture and DNA was extracted when cells showed significant cytopathic effects. AdV partial hexon gene was amplified and the sequences together with other known HAdV hexon gene sequences were used to build phylogenetic trees. Identification of HAdV types found among young children in Malaysia was inferred from the phylograms. RESULTS: At least 2,583 pediatric patients with RTI sought consultation and treatment at the UMMC from 1999 to 2005. Among these patients, 48 (< 2%) were positive for HAdV infections. Twenty-seven isolates were recovered and used for the present study. Nineteen of the 27 (approximately 70%) isolates belonged to HAdV species C (HAdV-C) and six (approximately 22%) were of HAdV species B (HAdV-B). Among the HAdV-C species, 14 (approximately 74%) of them were identified as HAdV type 1 (HAdV-1) and HAdV type 2 (HAdV-2), and among the HAdV-B species, HAdV type 3 (HAdV-3) was the most common serotype identified. HAdV-C species also was isolated from throat and rectal swabs of children with hand, foot, and mouth disease (HFMD). Two isolates were identified as corresponding to HAdV-F species from a child with HFMD and a patient with intestinal obstruction. CONCLUSIONS: HAdV-1 and HAdV-2 were the most common HAdV isolated from pediatric patients who sought treatment for RTI at the UMMC from 1999 to 2005. HAdV-B, mainly HAdV-3, was recovered from approximately 22% of the patients. These findings provide a benchmark for future studies on the prevalence and epidemiology of HAdV types in Malaysia and in the region.

Reemergence of endemic Chikungunya, Malaysia.

Chikungunya virus infection recently reemerged in Malaysia after 7 years of nondetection. Genomic sequences of recovered isolates were highly similar to those of Malaysian isolates from the 1998 outbreak. The reemergence of the infection is not part of the epidemics in other Indian Ocean countries but raises the possibility that chikungunya virus is endemic in Malaysia.