Cytotoxic and antimicrobial mycophenolic acid derivatives from an endophytic fungus Penicillium sp. MNP-HS-2 associated with Macrozamia communis

Macrozamia communis and its associated endophytic fungi are untapped sources of bioactive metabolites with great potential for medicinal exploitation. Chemical investigation of the mycelial extract derived from an endophytic fungus Penicillium sp. MNP-HS-2 associated with M. communis fruit offered four mycophenolic acid derivatives recognized as previously undescribed natural products (1-4) together with nine known metabolites (5-13). Chemical structures of isolated compounds were determined based on extensive spectroscopic analyses, including 1D/2D NMR and HRESIMS. The absolute stereochemistry of alternatain E (1) was unambiguously established by comparing its experimental and calculated time-dependent density functional theory electronic circular dichroism spectra (TDDFT-ECD). All isolated compounds were assessed for their antimicrobial and cytotoxic activities, where mycophenolic acid methyl ester (7) displayed significant cytotoxic activity against seven different cell lines with IC50 values in the low micromolar to nanomolar range, whereas mycophenolene A (3) exhibited a potent antibacterial activity against Staphylococcus aureus (MIC = 2.1 µg/mL)

Potential Regulation of miRNA-29 and miRNA-9 by Estrogens in Neurodegenerative Disorders: An Insightful Perspective

Finding a link between a hormone and microRNAs (miRNAs) is of great importance since it enables the adjustment of genetic composition or cellular functions without needing gene-level interventions. The dicer-mediated cleavage of precursor miRNAs is an interface link between miRNA and its regulators; any disruption in this process can affect neurogenesis. Besides, the hormonal regulation of miRNAs can occur at the molecular and cellular levels, both directly, through binding to the promoter elements of miRNAs, and indirectly, via regulation of the signaling effects of the post-transcriptional processing proteins. Estrogenic hormones have many roles in regulating miRNAs in the brain. This review discusses miRNAs, their detailed biogenesis, activities, and both the general and estrogen-dependent regulations. Additionally, we highlight the relationship between miR-29, miR-9, and estrogens in the nervous system. Such a relationship could be a possible etiological route for developing various neurodegenerative disorders

A Literature review of traumatic brain injury biomarkers

Research into TBI biomarkers has accelerated rapidly in the past decade owing to the heterogeneous nature of TBI pathologies  and management, which pose challenges to TBI evaluation, management, and prognosis. TBI biomarker proteins resulting  from axonal, neuronal, or glial cell injuries are widely used and have been extensively studied. However, they might not pass  the blood-brain barrier with sufcient amounts to be detected in peripheral blood specimens, and further might not be detectable in the cerebrospinal fuid owing to fow limitations triggered by the injury itself. Despite the advances in TBI research,  there is an unmet clinical need to develop and identify novel TBI biomarkers that entirely correlate with TBI pathologies on  the molecular level, including mild TBI, and further enable physicians to predict patient outcomes and allow researchers to  test neuroprotective agents to limit the extents of injury. Although the extracellular vesicles have been identifed and studied  long ago, they have recently been revisited and repurposed as potential TBI biomarkers that overcome the many limitations  of the traditional blood and CSF assays. Animal and human experiments demonstrated the accuracy of several types of  exosomes and miRNAs in detecting mild, moderate, and severe TBI. In this paper, we provide a comprehensive review of  the traditional TBI biomarkers that are helpful in clinical practice. Also, we highlight the emerging roles of exosomes and  miRNA being the promising candidates under investigation of current research. </p

Dissecting sex-related cognition between Alzheimer’s disease and diabetes: from molecular mechanisms to potential therapeutic strategies

The brain is a sexually dimorphic organ that implies different functions and structures depending on sex. Current pharmacological approaches against different neurological diseases act distinctly in male and female brains. In all neurodegenerative diseases, including Alzheimer’s disease (AD), sex-related outcomes regarding pathogenesis, prevalence, and response to treatments indicate that sex differences are important for precise diagnosis and therapeutic strategy. Pathogenesis of AD includes vascular dementia, and in most cases, this is accompanied by metabolic complications with similar features as those assembled in diabetes. This review discusses how AD-associated dementia and diabetes affect cognition in relation to sex difference, as both diseases share similar pathological mechanisms. We highlight potential protective strategies to mitigate amyloid-beta (Aβ) pathogenesis, emphasizing how these drugs act in the male and female brains

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally