Research News

https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(23)00166-9/fulltext

DOI: https://doi.org/10.1016/j.cell.2023.08.039

https://neuro.psychiatryonline.org/doi/10.1176/appi.neuropsych.20220136

Wound healing is a complex process that can be further complicated in chronic wounds, leading to prolonged healing times, high healthcare costs, and potential patient morbidity. Nanotechnology has shown great promise in developing advanced wound dressings that promote wound healing and prevent infection. The review article presents a comprehensive search strategy that was applied to four databases, namely Scopus, Web of Science, PubMed, and Google Scholar, using specific keywords and inclusion/exclusion criteria to select a representative sample of 164 research articles published between 2001 and 2023. This review article provides an updated overview of the different types of nanomaterials used in wound dressings, including nanofibers, nanocomposites, silver-based nanoparticles, lipid nanoparticles, and polymeric nanoparticles. Several recent studies have shown the potential benefits of using nanomaterials in wound care, including the use of hydrogel/nano silver-based dressings in treating diabetic foot wounds, the use of copper oxide-infused dressings in difficult-to-treat wounds, and the use of chitosan nanofiber mats in burn dressings. Overall, developing nanomaterials in wound care has complemented nanotechnology in drug delivery systems, providing biocompatible and biodegradable nanomaterials that enhance wound healing and provide sustained drug release. Wound dressings are an effective and convenient method of wound care that can prevent wound contamination, support the injured area, control hemorrhaging, and reduce pain and inflammation. This review article provides valuable insights into the potential role of individual nanoformulations used in wound dressings in promoting wound healing and preventing infections, and serves as an excellent resource for clinicians, researchers, and patients seeking improved healing outcomes.

T A, Prabhu A, Baliga V, Bhat S, Thenkondar ST, Nayak Y, Nayak UY. Transforming Wound Management: Nanomaterials and Their Clinical Impact. Pharmaceutics. 2023 May 22;15(5):1560. doi: 10.3390/pharmaceutics15051560. PMID: 37242802; PMCID: PMC10221108.

https://pubmed.ncbi.nlm.nih.gov/37242802/

Abstract

The dopaminergic neuromodulator system is fundamental to brain functions. Abnormal dopamine (DA) pathway is implicated in psychiatric disorders, including schizophrenia (SZ) and autism spectrum disorder (ASD). Mutations in Cullin 3 (CUL3), a core component of the Cullin-RING ubiquitin E3 ligase complex, have been associated with SZ and ASD. However, little is known about the function and mechanism of CUL3 in the DA system. Here, we show that CUL3 is critical for the function of DA neurons and DA-relevant behaviors in male mice. CUL3-deficient mice exhibited hyperactive locomotion, deficits in working memory and sensorimotor gating, and increased sensitivity to psychostimulants. In addition, enhanced DA signaling and elevated excitability of the VTA DA neurons were observed in CUL3-deficient animals. Behavioral impairments were attenuated by dopamine D2 receptor antagonist haloperidol and chemogenetic inhibition of DA neurons. Furthermore, we identified HCN2, a hyperpolarization-activated and cyclic nucleotide-gated channel, as a potential target of CUL3 in DA neurons. Our study indicates that CUL3 controls DA neuronal activity by maintaining ion channel homeostasis and provides insight into the role of CUL3 in the pathogenesis of psychiatric disorders.

SIGNIFICANCE STATEMENT This study provides evidence that Cullin 3 (CUL3), a core component of the Cullin-RING ubiquitin E3 ligase complex that has been associated with autism spectrum disorder and schizophrenia, controls the excitability of dopamine (DA) neurons in mice. Its DA-specific heterozygous deficiency increased spontaneous locomotion, impaired working memory and sensorimotor gating, and elevated response to psychostimulants. We showed that CUL3 deficiency increased the excitability of VTA DA neurons, and inhibiting D2 receptor or DA neuronal activity attenuated behavioral deficits of CUL3-deficient mice. We found HCN2, a hyperpolarization-activated channel, as a target of CUL3 in DA neurons. Our findings reveal CUL3’s role in DA neurons and offer insights into the pathogenic mechanisms of autism spectrum disorder and schizophrenia.

Nannan Gao, Zhipeng Liu, Hongsheng Wang, Chen Shen, Zhaoqi Dong, Wanpeng Cui, Wen-Cheng Xiong, Lin Mei: Deficiency of Cullin 3, a Protein Encoded by a Schizophrenia and Autism Risk Gene, Impairs Behaviors by Enhancing the Excitability of Ventral Tegmental Area (VTA) DA Neurons. J. Neuroscience. 43(36): 6249-67 (2023). DOI:10.1523/JNEUROSCI.0247-23.2023.

https://www.jneurosci.org/content/43/36/6249

https://doi.org/10.1176/appi.ajp.20230481

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease that is classically thought to impact the motor system. Over the past 20 years, research has started to consider the contribution of non-motor symptoms and features of the disease, and how they might affect ALS prognosis. Of the non-motor features of the disease, nutritional status (for example, malnutrition) and metabolic balance (for example, weight loss and hypermetabolism) have been consistently shown to contribute to more rapid disease progression and/or earlier death. Several complex cellular changes observed in ALS, including mitochondrial dysfunction, are also starting to be shown to contribute to bioenergetic failure. The resulting energy depletion in high energy demanding neurons makes them sensitive to apoptosis. Given that nutritional and metabolic stressors at the whole-body and cellular level can impact the capacity to maintain optimal function, these factors present avenues through which we can identify novel targets for treatment in ALS. Several clinical trials are now underway evaluating the effectiveness of modifying energy balance in ALS, making this article timely in reviewing the evidence base for metabolic and nutritional interventions.

Ludolph, A., Dupuis, L., Kasarskis, E. et al. Nutritional and metabolic factors in amyotrophic lateral sclerosis. Nat Rev Neurol 19, 511–524 (2023). https://doi.org/10.1038/s41582-023-00845-8

https://www.nature.com/articles/s41582-023-00845-8

Close-up side shot of hands shows microplastic waste contaminated with the seaside sand. Microplastics are contaminated in the sea. Concept of water pollution and global warming.

Are microplastics spreading infectious disease?

https://www.pnas.org/doi/10.1073/pnas.2311253120

https://www.nature.com/articles/s41380-022-01545-3.pdf

The development of effective drugs to treat coronavirus infections remains a significant challenge for the scientific community. Recent evidence reports on the sigma-1 receptor (S1R) as a key druggable host protein in the SARS-CoV-1 and SARS-CoV-2 interactomes and shows a potent antiviral activity against SARS-CoV-2 for the S1R antagonist PB28. To improve PB28 activity, we designed and tested a series of its analogues and identified a compound that is fourfold more potent against SARS-CoV-2 than PB28 itself. Interestingly, we found no direct correlation between S1R affinity and SARS-CoV-2 antiviral activity. Building on this, we employed comparative induced fit docking and molecular dynamics simulations to gain insights into the possible mechanism that occurs when specific ligand-protein interactions take place and that may be responsible for the observed antiviral activity. Our findings offer a possible explanation for the experimental observations, provide insights into the S1R conformational changes upon ligand binding and lay the foundation for the rational design of new S1R ligands with potent antiviral activity against SARS-CoV-2 and likely other viruses.

Abatematteo FS, Delre P, Mercurio I, Rezelj VV, Siliqi D, Beaucourt S, Lattanzi G, Colabufo NA, Leopoldo M, Saviano M, Vignuzzi M, Mangiatordi GF, Abate C. A conformational rearrangement of the SARS-CoV-2 host protein sigma-1 is required for antiviral activity: insights from a combined in-silico/in-vitro approach. Sci Rep. 2023 Aug 7;13(1):12798. doi: 10.1038/s41598-023-39662-w. PMID: 37550340; PMCID: PMC10406941.

https://pubmed.ncbi.nlm.nih.gov/37550340/