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Autophagy is a normal physiological process that aids the recycling of cellular nutrients, assisting the cells to cope with stressed conditions. However, autophagy's effect on cancer, including glioma, is uncertain and involves complicated molecular mechanisms. Several contradictory reports indicate that autophagy may promote or suppress glioma growth and progression. Autophagy inhibitors potentiate the efficacy of chemotherapy or radiation therapy in glioma. Numerous compounds stimulate autophagy to cause glioma cell death. Autophagy is also involved in the therapeutic resistance of glioma. This review article aims to detangle the complicated molecular mechanism of autophagy to provide a better perception of the two-sided role of autophagy in glioma and its therapeutic implications. The protein and epigenetic modulators of the cytoprotective and cytotoxic role of autophagy are described in this article. Moreover, several signaling pathways are associated with autophagy and its effects on glioma. We have reviewed the molecular pathways and highlighted the signaling axis involved in cytoprotective and cytotoxic autophagy. Additionally, this article discusses the role of autophagy in therapeutic resistance, including glioma stem cell maintenance and tumor microenvironment regulation. It also summarizes several investigations on the anti-glioma effects of autophagy modulators to understand the associated mechanisms and provide insights regarding its therapeutic implications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Temozolomide (TMZ) is the leading chemotherapeutic agent used for glioma therapy due to its good oral absorption and blood-brain barrier permeability. However, its anti-glioma efficacy may be limited due to its adverse effects and resistance development. O6-Methylguanine-DNA-methyltransferase (MGMT), an enzyme associated with TMZ resistance, is activated via the NF-κB pathway, which is found to be upregulated in glioma. TMZ also upregulates NF-κB signaling like many other alkylating agents. Magnolol (MGN), a natural anti-cancer agent, has been reported to inhibit NF-κB signaling in multiple myeloma, cholangiocarcinoma, and hepatocellular carcinoma. MGN has already shown promising results in anti-glioma therapy. However, the synergistic action of TMZ and MGN has not been explored. Therefore, we investigated the effect of TMZ and MGN treatment in glioma and observed their synergistic pro-apoptotic action in both in vitro and in vivo glioma models. To explore the mechanism of this synergistic action, we found that MGN inhibits MGMT enzyme both in vitro and in vivo glioma. Next, we established the link between NF-κB signaling and MGN-induced MGMT inhibition in glioma. MGN inhibits the phosphorylation of p65, a subunit of NF-κB, and its nuclear translocation to block NF-κB pathway activation in glioma. MGN-induced NF-κB inhibition results in the transcriptional inhibition of MGMT in glioma. TMZ and MGN combinatorial treatment also impedes p65 nuclear translocation to inhibit MGMT in glioma. We observed a similar effect of TMZ and MGN treatment in the rodent glioma model. Thus, we concluded that MGN potentiates TMZ-induced apoptosis in glioma by inhibiting NF-κB pathway-mediated MGMT activation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chemoresistance is a primary cause of breast cancer treatment failure, and protein-protein interactions significantly contribute to chemoresistance during different stages of breast cancer progression. In pursuit of novel biomarkers and relevant protein-protein interactions occurring during the emergence of breast cancer chemoresistance, we used a computational predictive biological (CPB) approach. CPB identified associations of adhesion molecules with proteins connected with different breast cancer proteins associated with chemoresistance. This approach identified an association of Integrin β1 (ITGB1) with chemoresistance and breast cancer stem cell markers. ITGB1 activated the Focal Adhesion Kinase (FAK) pathway promoting invasion, migration, and chemoresistance in breast cancer by upregulating Erk phosphorylation. FAK also activated Wnt/Sox2 signaling, which enhanced self-renewal in breast cancer. Activation of the FAK pathway by ITGB1 represents a novel mechanism linked to breast cancer chemoresistance, which may lead to novel therapies capable of blocking breast cancer progression by intervening in ITGB1-regulated signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Sox family of transcriptional factors play essential functions in development and are implicated in multiple clinical disorders, including cancer. Sox2 being their most prominent member and performing a critical role in reprogramming differentiated adult cells to an embryonic phenotype is frequently upregulated in multiple cancers. High Sox2 levels are detected in breast tumor tissues and correlate with a worse prognosis. In addition, Sox2 expression is connected with resistance to conventional anticancer therapy. Together, it can be said that inhibiting Sox2 expression can reduce the malignant features associated with breast cancer, including invasion, migration, proliferation, stemness, and chemoresistance. This review highlights the critical roles played by the Sox gene family members in initiating or suppressing breast tumor development, while primarily focusing on Sox2 and its role in breast tumor initiation, maintenance, and progression, elucidates the probable mechanisms that control its activity, and puts forward potential therapeutic strategies to inhibit its expression., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The damage to the skin is most prominent and evident as it is our first line of defense and unremittingly under attack by biological and environmental factors. The restoration of the skin is dependent on the extent of the injury. To explore the prospects of new biomimetic material, bi-layered skin construct is fabricated in vitro with nonmulberry silk protein sericin and chitosan hydrogels using human dermal fibroblasts and keratinocytes. The in vitro analysis of the hydrogels showed enhanced adhesion, proliferation, and migration of skin cells with coordinated interaction amongst themselves leading to the synthesis of collagen IV and matrix metalloproteinase (MMP2 and MMP9). The in vivo evaluation indicates the regeneration of skin with densely packed collagen and formation of matured blood vessels in the animals implanted with sericin containing hydrogels. Moreover, the local and systemic immune response determined in vivo exhibits the biosafety of sericin based hydrogels. In addition, the cross-sectional analysis of the implanted hydrogels displays infiltration of the skin tissue cells into the hydrogels marking their biocompatibility and non-toxicity. The cumulative analysis of the in vitro and in vivo observations demonstrates that the sericin based hydrogels are non-inflammatory, supports the regeneration and repair of the skin tissue., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Epithelial to mesenchymal transition (EMT) and extracellular matrix (ECM) remodeling, are the two elemental processes promoting glioblastoma (GBM). In the present work we propose a mechanistic modelling of GBM and in process establish a hypothesis elucidating critical crosstalk between heat shock proteins (HSPs) and matrix metalloproteinases (MMPs) with synergistic upregulation of EMT-like process and ECM remodeling., Methods: The interaction and the precise binding site between the HSP and MMP proteins was assayed computationally, in-vitro and in GBM clinical samples., Results: A positive crosstalk of HSP27 with MMP-2 and MMP-9 was established in both GBM patient tissues and cell-lines. This association was found to be of prime significance for ECM remodeling and promotion of EMT-like characteristics. In-silico predictions revealed 3 plausible interaction sites of HSP27 interacting with MMP-2 and MMP-9. Site-directed mutagenesis followed by in-vitro immunoprecipitation assay (IP) with 3 mutated recombinant HSP27, confirmed an interface stretch containing residues 29-40 of HSP27 to be a common interaction site for both MMP-2 and MMP-9. This was further validated with in-vitro IP of truncated (sans AA 29-40) recombinant HSP27 with MMP-2 and MMP-9., Conclusion: The association of HSP27 with MMP-2 and MMP-9 proteins along with the identified interacting stretch has the potential to contribute towards drug development to inhibit GBM infiltration and migration., General Significance: Current findings provide a novel therapeutic target for GBM opening a new horizon in the field of GBM management., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recently, the progress in biomaterials for biomedical applications brings the focus of the research community toward nanomaterials. The nanofibrous matrices offer certain advantages (structural similarity to extracellular matrix, high surface area-to-volume ratio, increased elasticity, biostability, and strength) compared to other prevalent type of materials. This affirms their superiority and flexibility to be used in regenerative medicine. We have fabricated nonmulberry (Antheraea mylitta) silk protein sericin-based nanofibrous matrices (fiber thickness; 80-400 nm) with improved mechanical strength and desired stability (>4 weeks) as required for tissue reconstruction. These matrices support the adhesion, proliferation, and cellular interconnection of human keratinocytes. These are minimally hemolytic, nonimmunogenic, and capable of wound healing in vivo. Antibiotic (cephalexin hydrate [CH])-loaded nanofibrous matrices accelerate the full-thickness wound repair with minimal inflammation and without any signs of infection. The histological analysis authenticates skin restoration with re-epithelialization, generation of associated skin appendages, and synthesis of dense collagen fibrils. In addition, analysis of inflammatory genes and immunohistochemical assays have proved their biocompatibility and wound healing potential. Angiogenesis is also prevalent in the animal tissue treated with nanofibrous matrices. The results of in vitro and in vivo experimentations indicate a clear prospect of the fabricated sericin-based nanofibrous matrices to be used for skin regeneration., Statement of Significance: Nonmulberry silk protein sericin-based nanofibrous matrix is a useful biomaterial for wound healing, collagen production, and skin tissue repair. It has been used in different formulations including hydrogels and nanofibrous membranes with chitosan (CS) and polyvinyl alcohol (PVA). No experiments have been carried out to evaluate sericin-based nanofibrous membranes for skin tissue engineering application. The present study shows that the nanofibrous matrices fabricated by electrospinning nonmulberry silk protein sericin with CS and PVA mimic the architectural environment of the extracellular matrix fibrils. These matrices are minimally hemolytic, are nonimmunogenic, and support better growth of human keratinocytes in vitro and wound healing in vivo with re-epithelialization of the skin tissue and angiogenesis. This work indicates that these nonmulberry sericin-based nanofibrous matrices with CS may be used as an ideal physical environment and biological cues for the promotion of skin tissue reconstruction and repair., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)