Ecklonia cava Polyphenols Have a Preventive Effect on Parkinson's Disease through the Activation of the Nrf2-ARE Pathway.

Parkinson's disease (PD) is a degenerative neurological disorder defined by the deterioration and loss of dopamine-producing neurons in the substantia nigra, leading to a range of motor impairments and non-motor symptoms. The underlying mechanism of this neurodegeneration remains unclear. This research examined the neuroprotective properties of Ecklonia cava polyphenols (ECPs) in mitigating neuronal damage induced by rotenone via the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. Using human neuroblastoma SH-SY5Y cells and PD model mice, we found that ECP, rich in the antioxidant polyphenol phlorotannin, boosted the gene expression and functionality of the antioxidant enzyme NAD(P)H quinone oxidoreductase-1. ECP also promoted Nrf2 nuclear translocation and increased p62 expression, suggesting that p62 helps sustain Nrf2 activation via a positive feedback loop. The neuroprotective effect of ECP was significantly reduced by Compound C (CC), an AMP-activated protein kinase (AMPK) inhibitor, which also suppressed Nrf2 nuclear translocation. In PD model mice, ECPs improved motor functions impaired by rotenone, as assessed by the pole test and wire-hanging test, and restored intestinal motor function and colon tissue morphology. Additionally, ECPs increased tyrosine hydroxylase expression in the substantia nigra, indicating a protective effect on dopaminergic neurons. These findings suggest that ECP has a preventative effect on PD.

Molecular Mechanism of Autophagy, Cytoplasmic Zoning by Lipid Membranes.

Autophagy is a highly conserved intracellular degradation mechanism. The most distinctive feature of autophagy is the formation of double-membrane structures called autophagosomes, which compartmentalize portions of the cytoplasm. The outer membrane of the autophagosome fuses with the vacuolar/lysosomal membrane, leading to the degradation of the contents of the autophagosome. Approximately 30 years have passed since the identification of autophagy-related (ATG) genes and Atg proteins essential for autophagosome formation, and the primary functions of these Atg proteins have been elucidated. These achievements have significantly advanced our understanding of the mechanism of autophagosome formation. This article summarizes our current knowledge on how the autophagosome precursor is generated, and how the membrane expands and seals to complete the autophagosome.

Sputum characteristics of patients with severe COVID-19: report of two cases with immunocytochemical detection of SARS-CoV-2 spike protein.

Patients with SARS-CoV-2 infection and with severe COVID-19 often have multiple coinfections, and their treatment is challenging. Here, we performed cytology analysis on sputum samples from two patients with severe COVID-19. The specimens were prepared using the rubbing method and stained with Papanicolaou stain. In both cases, several cells with frosted nuclei were observed, and the cytological findings per 100 cells were evaluated. The infected cells were mononuclear to multinuclear, showing chromatin aggregation at the nuclear margins, intranuclear inclusion bodies, eosinophilic cytoplasmic inclusion bodies, and mutual pressure exclusion of the nuclei. Immunocytochemical staining revealed that the cells were positive for AE1/AE3 and negative for CD68 expression, indicating their epithelial origin. Furthermore, infected cells with frosted nuclei were positive for surfactant protein A (SP-A) in Case 2, suggesting infection of type II alveolar pneumocytes or Clara cells. Moreover, in Case 2, the infected cells were positive for herpes simplex virus (HSV) I + II and SARS-CoV-2 spike protein, confirming double infection in these cells. In conclusion, sputum cytology is an important tool for determining the diversity of viral infection, and additional immunocytochemistry can be used for definitive diagnosis.

Generalized herpes zoster and cutaneous metastasis during chemotherapy for non-small cell lung cancer: A case report.

Although herpes zoster is known to occur in some patients with lung cancer, generalized (disseminated) herpes zoster is an uncommon form whereby hematogenous dissemination of the virus occurs and leads to the development of widespread cutaneous lesions. Similarly, skin is an uncommon site of metastasis in patients with lung cancer. Here, we report a clinical case of a 53-year-old male patient who developed generalized herpes zoster during chemotherapy for non-small cell lung cancer (squamous cell carcinoma) and subsequently developed cutaneous metastasis of lung cancer after generalized herpes zoster was cured by treatment with intravenous aciclovir. The coincidence of these two conditions, generalized herpes zoster and cutaneous metastasis, in the patient during lung cancer treatment might be associated with an impaired or dysregulated immune system partly due to repeated chemotherapy, indicating a poor prognosis. Close observation and accurate diagnosis of changes in the skin of patients with lung cancer are important when evaluating their immune status and considering their therapy and prognosis.

Anthracene-Attached Persistent Tricyclic Aromatic Hydrocarbon Radicals.

Anthracene-attached tricyclic aromatic hydrocarbon radicals having different central polygons, Ant-5, Ant-6, and Ant-7, were synthesized to evaluate the role of an anthracene substituent group in the stability and reactivity of tricyclic aromatic hydrocarbon radicals. The bulky anthryl group effectively protects a carbon atom with high spin density, resulting in high persistence of the radicals. On the other hand, the combination of the anthryl group and the tricyclic aromatic scaffold makes the molecular structure drastically change from a twisted form to a folded form and an unpaired electron moves into the anthryl moiety, eventually affording a tail-to-tail σ-dimer.

Impact of dexmedetomidine on the tissue distribution, anesthetic action, and hemodynamic effects of mepivacaine.

The present study investigated the regional blood flow, tissue distribution, local anesthetic action, and hemodynamic effects of mepivacaine containing dexmedetomidine hydrochloride (DEX) in rats. Blood flow was measured after injection of 0.5% mepivacaine (M group), 12.5 µg/ml DEX (D group), or 0.5% mepivacaine containing 12.5 µg/ml DEX (DM group) into the upper lip. Mepivacaine distribution was autoradiographically observed in maxillary bone resected after injection of 0.5% 3H-mepivacaine (HM group) or 0.5% 3H-mepivacaine containing 12.5 µg/ml DEX (DHM group) into the palatal mucosa adjacent to the right maxillary first molar. Radioactivity was also measured using a liquid scintillation counter. SEP were measured to analyze anesthetic action. Blood pressure and heart rate were measured to compare hemodynamic effect. The addition of DEX significantly decreased blood flow compared to M group from 10 to 60 min after injection. The addition of DEX significantly increased the amount of radioactivity compared to HM group in the palatal mucosa from 5 to 60 min after injection and in the body of the maxilla from 2 to 60 min after injection. Maximum blood radioactivity was measured at 5 min after injection in HM group and 50 min after injection in DHM group. The addition of DEX significantly decreased peak-to-peak amplitudes compared to M group until 60 min after injection. No significant hemodynamic differences were observed. DEX enhances the action of mepivacaine in reducing regional blood flow prolongs its tissue retention, and increases the local anesthetic action without affecting hemodynamics on local administration.

Synthesis of carbocyclic pyrimidine nucleosides and their inhibitory activities against Plasmodium falciparum thymidylate kinase.

Plasmodium falciparum thymidylate kinase (PfTMK) is a promising antimalarial target due to its unique substrate specificity. Recently, we reported that 2',3'-dideoxycarbocyclic thymidine showed moderate inhibitory activity and reported the related structure-activity relationship for inhibitors against PfTMK. In this study, we have designed and synthesized enantioselective 2',3'-dideoxycarbocyclic pyrimidine nucleosides based on our previous results and screened them for inhibitory activity against PfTMK. The most potent inhibitor showed K(i)(TMP) and K(i)(dGMP) values of 14 and 20 µM, respectively. The fluorinated dideoxy derivative (-)-7, exhibited lower K(i)(TMP) and higher K(i)(dGMP) compared with that of the parent compound (K(i)(TMP), K(i)(dGMP) equals 20 and 7 µM, respectively). The modification of carbocyclic pyrimidine nucleosides is a promising strategy for developing powerful PfTMK inhibitors.

Carbocyclic thymidine derivatives efficiently inhibit Plasmodium falciparum thymidylate kinase (PfTMK).

During the course of our research into new anti-malaria drugs, Plasmodium falciparum thymidylate kinase (PfTMK) has emerged as an important drug target because of its unique substrate specificity. Compared with human thymidylate kinase (HsTMK), PfTMK shows broader substrate specificity, which includes both purine and pyrimidine nucleotides. PfTMK accepts both 2'-deoxyguanosine monophosphate (dGMP) and thymidine monosphosphate (TMP) as substrates. We have evaluated the inhibitory activity of seven carbocyclic thymidine analogs and report the first structure-activity relationship for these inhibitors against PfTMK. The 2',3' dideoxycarbocyclic derivative of thymidine showed the most potent inhibition of the enzyme. The K(i)(dTMP) and K(i)(dGMP) values were 20 and 7 µM respectively. Thus, further modifications of carbocyclic thymidine analogs represent a good strategy for developing more powerful thymidylate kinase inhibitors.