Search

Glioblastoma multiforme (GBM) is a grade IV, lethal, and the most common type of brain tumor. GBM can acquire resistance to temozolomide (TMZ) recommended for its treatment. Naringenin (NAG), a flavonoid generally found in grapefruit, has antioxidant, anti-proliferative, and anti-inflammatory properties. It has been reported that phytochemicals can reduce resistance and improve the efficacy of a chemo-resistant drug. The combinatorial effect of TMZ and NAG on cell proliferation was evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay, and the apoptosis in the U87MG and LN229 GBM cells were evaluated by change in fluorescence intensity. The effect of NAG and TMZ on anchorage-independent single-cell colony formation and cell migration was investigated. NAG and TMZ demonstrated enhanced cytotoxic effects on U87MG and LN229 cell lines. The combination index value being less than one indicated the synergistic action of the two drugs in restricting the growth of the cells. The NAG and TMZ together resulted in higher fluorescence intensity as compared to the alone drug. Further, the study showed a marked reduction in the migration of the cells and the formation of a single cell colony. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1952438 [ABSTRACT FROM AUTHOR]

Mosquito-borne viral diseases like chikungunya and dengue infections can cause severe illness and have become major public health concerns. Chikungunya virus (CHIKV) and dengue virus (DENV) infections share similar primary clinical manifestations and are transmitted by the same vector. Thus, the probability of their coinfection gets increased with more severe clinical complications in the patients. The present study was undertaken to elucidate the common human interacting partners of CHIKV and DENV proteins during coinfection. The viral–host protein–protein interactome was constructed using Cytoscape. Subsequently, significant host interactors were identified during coinfection. The network analysis elucidated 57 human proteins interacting with both CHIKV and DENV, represented as hub-bottlenecks. The functional and biological analyses of the 40 hub-bottlenecks revealed that they are associated with phosphoinositide 3-kinases (PI3K)/AKT, p53 signaling pathways, regulation of cell cycle and apoptosis during coinfection. Moreover, the molecular docking analysis uncovered the tight and robust binding of selected hub-bottlenecks with CHIKV/DENV proteins. Additionally, 23 hub-bottlenecks were predicted as druggable candidates that could be targeted to eradicate the host–viral interactions. The elucidated common host binding partners during DENV and CHIKV coinfection as well as indicated approved drugs can support the therapeutics development. [ABSTRACT FROM AUTHOR]

Glioblastoma is one of the most debilitating forms of brain tumour. It accounts for 17% of all the brain tumours and has resulted in 251,329 deaths in 2020 itself. Several studies performed on patient profiling have revealed that many genes tend to be overexpressed or mutated in many GBM patients and hamper the signalling and growth pathways. Additionally, there is a requirement to explore supplementary or alternative treatment that can aid in overcoming the resistance caused by standard care treatment (Temozolomide with radiation). The preliminary analysis on inhibitory potential of certain phytocompounds on the crucial genes involved in GBM has been studied in silico. The network of the genes critical for GBM has been analysed through several plugins of Cytoscape software like BiNGO and MCODE based on factors such as degree, closeness and betweenness. The network analysis gave out a cluster of 97 interactions with 16 interacting proteins. ERBB4 emerged as the seed protein indicating its crucial role in pathways. The BiNGO plugin gave out the gene ontology data describing the functions of the genes of the cluster. Additionally, the properties of ligands were studied by the PharmaGist server and 3D patterns of shared features by all or most input ligands of selected phytocompound were analysed and aligned. Upon docking the seed protein (ERBB4) individually with the best combination of aligned ligands yielded bromelain and EGCG as the compounds with best binding affinity of -9.8 and -9.2 kcal/mol respectively. This study has provided an important lead for further in vitro study to analyse the effect of combination of phytocompounds on the critical signalling pathways of GBM. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with hyperactive innate and adaptive immune systems that cause dermatological, cardiovascular, renal, and neuropsychiatric problems in patients. SLE's multifactorial nature and complex pathogenesis present significant challenges in its clinical classification. In addition, unpredictable treatment responses in patients emphasize the need for highly specific and sensitive SLE biomarkers that can assist in understanding the exact pathogenesis and, thereby, lead to the identification of novel therapeutic targets. Recent studies on microRNA (miRNA), a non-coding region involved in the regulation of gene expression, indicate its importance in the development of the immune system and thus in the pathogenesis of various autoimmune disorders such as SLE. miRNAs are fascinating biomarker prospects for SLE categorization and disease monitoring owing to their small size and high stability. In this paper, we have discussed the involvement of a wide range of miRNAs in the regulation of SLE inflammation and how their modulation can be a potential therapeutic approach. [ABSTRACT FROM AUTHOR]

Baclofen and Lamotrigine via PLGA nanoparticles were developed for nose-to-brain delivery for the treatment of Neuropathic pain. Nanoparticles were prepared using the modified nano-precipitation method. The prepared NPs were characterised and further in vitro and in vivo studies were performed. The Bcf-Ltg-PLGA-NPs were ∼177.7 nm with >75%(w/w) drugs encapsulated. In vitro dissolution studies suggested zero-order release profiles following the Korsmeyer-Peppas model. In vitro cytotoxicity and staining studies on mammalian cells showed dose dependant cytotoxicity where nanoparticles were significantly less toxic (>95% cell-viability). ELISA studies on RAW-macrophages showed Bcf-Ltg-PLGA-NPs as a potential pro-inflammatory-cytokines inhibitor. In vivo gamma-scintigraphy studies on rats showed intra-nasal administration of 99mTc-Bcf-Ltg-PLGA-NPs showed Cmax 3.6%/g at Tmax = 1.5h with DTE% as 191.23% and DTP% = 38.61% in brain. Pharmacodynamics evaluations on C57BL/6J mice showed a significant reduction in licks/bites during inflammation-induced phase II pain. The findings concluded that the combination of these drugs into a single nanoparticle-based formulation has potential for pain management. Baclofen and Lamotrigine loaded PLGA nanoparticles were prepared with a size of 177.7nm, PDI 0.057 and Zeta Potential −15.8 mV In vitro cell lines based studies showed dose dependant cytotoxicity and Bcf-Ltg-PLGA-NPs were found to be pro-inflammatory cytokines inhibitors In vivo Pharmacokinetic studies showed Cmax 3.6%/g at Tmax = 1.5 h with Drug Targeting Efficiency 191.23% and Drug Target Organ Transport 38.61% in the brain for prepared nanoparticles In vivo pharmacodynamics studies showed a significant reduction in licks/bites during inflammation-induced phase II pain [ABSTRACT FROM AUTHOR]