Bioinformatics approach reveals the critical role of the NOD-like receptor signaling pathway in COVID-19-associated multiple sclerosis syndrome.

Multiple sclerosis (MS) is a kind of central nervous system (CNS) autoimmune disease, which mainly damages nerves, the brain, and the spinal cord. Recently, several clinical cases reported the relativity between Coronavirus Disease 2019 (COVID-19) and the development of MS, but the mechanism of how COVID-19 affects the occurrence of MS was still not clear. It is bioinformatics technology that we use to explore the potential association at the gene level. The genetic information related to the two diseases was collected from the DisGNET platform for functional protein network analysis and used STRING to identify the complete gene set. The protein-protein interaction (PPI) network was analyzed by STRING. Finally, in the GEO database, we selected peripheral blood mononuclear cell (PBMC) RNA sequencing data (GSE164805, GSE21942) from COVID-19 patients and MS patients to verify the potential cross mechanism between the two diseases. The similar gene set of immune or inflammation existed between the patients with COVID-19 and ones with MS, including L2RA, IFNG, IL1B, NLRP3, and TNF. Interaction network analysis among proteins revealed that IL1B, P2RX7, IFNB1, IFNB1, TNF, and CASP1 enhanced the network connectivity between the combined gene set of COVID-19 and MS associated with NOD-like receptor (NLR) signaling. The involvement of NLR signaling in both diseases was further confirmed by comparing peripheral blood monocyte samples from COVID-19 and MS patients. Activation of NLR signaling was found in both COVID-19 and MS. The PBMC samples analyses also indicated the involvement of the NLR signaling pathway. Taken together, our data analyses revealed that the NLR signaling pathway might play a critical role in the COVID-19-related MS.

Efficacy of EP Chemotherapy Followed by IP Chemotherapy Combined with Radiotherapy in the Treatment of Extensive-Stage Small-Cell Lung Cancer.

PURPOSE: To explore the efficacy and safety of etoposide + cisplatin (EP) and irinotecan + cisplatin (IP) sequential chemotherapy combined with radiotherapy in the treatment of extensive-stage small-cell lung cancer (SCLC). METHODS: A total of 108 patients with extensive-stage SCLC were divided into the EP+IP group (n=54, sequential IP chemotherapy), and the EP group (n=54, EP chemotherapy). The changes in the level of serum tumor markers and the number of circulating tumor cells (CTCs) in the peripheral blood were compared between the two groups of patients before and after treatment. The patients were followed up to record the survival status and tumor progression. RESULTS: The overall effective rate for bone metastases in the EP+IP group was significantly higher than that in the EP group. The EP+IP group displayed significantly lower levels of serum VEGF, Ki-67 and peripheral blood CTCs than the EP group. In addition, the follow-up results manifested that the median overall survival (OS) in the EP+IP group and the EP group were 16.2 months and 12.7 months, respectively, and the median progression-free survival (PFS) was 8.4 months and 5.9 months, respectively. The 2-year OS was 13.0% and 7.4%, respectively. Furthermore, the log-rank test illustrated that the OS and PFS in the EP+IP group were significantly superior to those in the EP group. CONCLUSIONS: EP and IP sequential chemotherapy combined with radiotherapy is more effective than EP chemotherapy combined with radiotherapy in the treatment of extensive-stage SCLC. The former can markedly reduce the levels of serum tumor markers and peripheral blood CTCs, increase the long-term survival of patients and reduce the occurrence of blood-related adverse reactions.

Rational design of ultra-small photoluminescent copper nano-dots loaded PLGA micro-vessels for targeted co-delivery of natural piperine molecules for the treatment for epilepsy.

In recent days, reported researches demonstrated that encapsulation of natural hydrophobic drug molecules (Piperine) into the biodegradable polymer system with nanoformulations opens a novel prospect in bio-nanomedicine field. Generally, the nanostructured materials embedded with the drug molecules could render enhanced efficiency in therapies. Piperine is a chief alkaloid compound of natural black pepper exhibits excellent anti-convulsant efficiency in the anti-epileptic treatment. Nonetheless, the poor water solubility of the piperine molecules has some difficulties in drug delivery and clinical applications. Herein we report the synthesis of Copper oxide quantum dots coated Hyaluronic acid (HA)/ Poly(lactic-co-glycolic acid) (PLGA) with for the effective delivery of piperine in the targeted drug delivery for epilepsy treatment. The physicochemical characterization was performed using the as prepared material. The crystal structure, surface morphology and the elemental composition were investigated from XRD, SEM, TEM and EDX analyses respectively. The surface morphology clearly stated the loading of CuO QDs loaded HA/PLGA microspheres. The capping of the polymer matrix was also studied using FTIR analysis. A Photoluminescence spectrum is also recorded. This study was illustrating that Piperine loaded CuQDs@HA/PLGA nanostructures exhibit improved neuroprotection and encourage the activation of astrocytes in chemical kindling model of epilepsy. This proposed material could be a novel and effective therapeutic platform for the targeted drug delivery systems.