Potential application of heat shock proteins as therapeutic targets in Parkinson's disease.

Parkinson's disease (PD) is a common chronic neurodegenerative disease, and the heat shock proteins (HSPs) are proved to be of great value for PD. In addition, HSPs can maintain protein homeostasis, degrade and inhibit protein aggregation by properly folding and activating intracellular proteins in PD. This study mainly summarizes the important roles of HSPs in PD and explores their feasibility as targets. We introduced the structural and functional characteristics of HSPs and the physiological functions of HSPs in PD. HSPs can protect neurons from damage by degrading aggregates with three mechanisms, including the aggregation and removing α-Synuclein (α-Syn) aggregates, promotion the autophagy of abnormal proteins, and inhibition the apoptosis of degenerated neurons. This study underscores the importance of HSPs as targets in PD and helps to expand new mechanisms in PD treatment strategies.

Complement Receptor 3 Pathway and NMDA Receptor 2B Subunit Involve Neuropathic Pain Associated with Spinal Cord Injury.

Background: Neuropathic pain (NP) after spinal cord injury (SCI-evoked NP) is clinically challenging; the underlying mechanisms are not fully understood, leading to a lack of promising treatment options. NP occurs in only a subset of patients with SCI. The injured spinal cord exhibits a series of histopathological changes, and the complement system has been shown to play an important role in these processes. In addition, NMDA receptor subunit 2B (NR2B) is involved in the development and maintenance of NP. This preliminary study was performed to investigate the correlations of the complement receptor 3/complement component 3 (CR3/C3) pathway and NR2B with SCI-evoked NP. Methods: A trauma-induced SCI animal model was established and SCI-evoked NP was evaluated by behavioural analysis. Transcriptome analysis was performed to identify genes in the CR3/C3 pathway related to synaptic modification, while the expression and distribution of NR2B in the injured spinal cord, and the relation to NP, were examined by immunohistochemical analysis. Results: Nine of seventeen SCI rats (52.9%) developed NP. C3 mRNA expression was significantly decreased in SCI-evoked NP rats and significantly increased in the non-NP SCI rats. C1q mRNA and CR3 mRNA expression were significantly increased in all SCI rats, but higher levels of expression were observed in the non-NP SCI rats. NR2B mRNA expression was significantly increased in the SCI-evoked NP rats and significantly decreased in the non-NP SCI rats. In addition, significantly elevated expression of NR2B-positive cells was seen in lamina II of the superficial dorsal horn in SCI-evoked NP rats in comparison with non-NP SCI rats. Conclusion: NP occurred in only a subset of SCI rats, and the CR3/C3 pathway and NR2B were involved in SCI-evoked NP. Further studies are required to determine the mechanisms underlying the SCI-evoked NP associated with the CR3/C3 pathway and NR2B.

Iridium-catalyzed direct asymmetric reductive amination utilizing primary alkyl amines as the N-sources.

Direct asymmetric reductive amination is one of the most efficient methods for the construction of chiral amines, in which the scope of the applicable amine coupling partners remains a significant challenge. In this study we describe primary alkyl amines effectively serve as the N-sources in direct asymmetric reductive amination catalyzed by the iridium precursor and sterically tunable chiral phosphoramidite ligands. The density functional theory studies of the reaction mechanism imply the alkyl amine substrates serve as a ligand of iridium strengthened by a (N)H-O(P) hydrogen-bonding attraction, and the hydride addition occurs via an outer-sphere transition state, in which the Cl-H H-bonding plays an important role. Through this concise procedure, cinacalcet, tecalcet, fendiline and many other related chiral amines have been synthesized in one single step with high yields and excellent enantioselectivity.

Promising Immunotherapies against COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a severe pandemic and deeply affected the livelihood of people worldwide. In response to the pandemic, researchers have been rapidly studying different aspects of COVID-19, such as virus detection, vaccinations, and epidemiological aspects of the disease. It has been reported that SARS-CoV-2 can induce uncontrolled inflammation and cause a lack of antiviral response, thereby aggravating the disease. Therefore, recovery of immune functions is key to COVID-19 treatment. Many clinical trials are exploring suitable therapies, and some progress has been made. Early administration of interferons may prevent COVID-19 exacerbation and/or promotes recovery from the diseases. Inhibitors of inflammation can prevent cytokine storms and multi-organ damage. Convalescent plasma containing neutralizing antibodies has played an important role in therapeutic options at the beginning of the pandemic owing to the lack of other effective methods. To aid the development of treatment options for COVID-19, this review focuses on immunotherapies, including treatment with interferons, inhibition of pro-inflammatory mechanisms, and the use of convalescent plasma.