Crossroad between the Heat Shock Protein and Inflammation Pathway in Acquiring Drug Resistance: A Possible Target for Future Cancer Therapeutics.

The development of multidrug resistance (MDR) against chemotherapeutic agents has become a major impediment in cancer therapy. Understanding the underlying mechanism behind MDR can guide future treatment for cancer with better therapeutic outcomes. Recent studies evidenced that crossroads interaction between the heat shock proteins (HSP) and inflammatory responses under the tumor microenvironment plays a pivotal role in modulating drug responsiveness and drug resistance through a complex cytological process. This review aims to investigate the interrelationship between inflammation and HSP in acquiring multiple drug resistance and investigate strategies to overcome the drug resistance to improve the efficacy of cancer treatment. HSP plays a dual regulatory effect as an immunosuppressive and immunostimulatory agent, involving the simultaneous blockade of multiple signaling pathways in acquiring MDR. For example, HSP27 shows biological effects on monocytes by causing IL10 and TNFα secretion and blocking monocyte differentiation to normal dendritic cells and tumor-associated macrophages to promote cancer progression and chemoresistance. Thus, the HSP function and immune-checkpoint release modalities provide a therapeutic target for a therapeutically beneficial approach for enhancing anti-tumor immune responses. The interconnection between inflammation and HSP, along with the tumor microenvironment in acquiring drug resistance, has become crucial for rationalizing the effect of HSP immunomodulatory activity with immune checkpoint blockade. This relationship can overcome drug resistance and assist in the development of novel combinatorial cancer immunotherapy in fighting cancer with decreasing mortality rates.

Recent Developments of Silk-Based Scaffolds for Tissue Engineering and Regenerative Medicine Applications: A Special Focus on the Advancement of 3D Printing.

Regenerative medicine has received potential attention around the globe, with improving cell performances, one of the necessary ideas for the advancements of regenerative medicine. It is crucial to enhance cell performances in the physiological system for drug release studies because the variation in cell environments between in vitro and in vivo develops a loop in drug estimation. On the other hand, tissue engineering is a potential path to integrate cells with scaffold biomaterials and produce growth factors to regenerate organs. Scaffold biomaterials are a prototype for tissue production and perform vital functions in tissue engineering. Silk fibroin is a natural fibrous polymer with significant usage in regenerative medicine because of the growing interest in leftovers for silk biomaterials in tissue engineering. Among various natural biopolymer-based biomaterials, silk fibroin-based biomaterials have attracted significant attention due to their outstanding mechanical properties, biocompatibility, hemocompatibility, and biodegradability for regenerative medicine and scaffold applications. This review article focused on highlighting the recent advancements of 3D printing in silk fibroin scaffold technologies for regenerative medicine and tissue engineering.

Phytochemical Screening and Bioactivity Studies of Endophytes Cladosporium sp. Isolated from the Endangered Plant Vateria Indica Using In Silico and In Vitro Analysis.

Vateria indica is persistent tree used in Unani sources for the medication and classified as critically endangered. Thus, endophytes for alternative methods to explore these endangered Plants having rich source pharmaceuticals' active molecules for drug development and production. Endophytes comprises unexplored microbes as a potential source of rich pharmaceutically bioactive compounds attributable to their relationship with the host. In the current study, we have isolated endophyte fungi Cladosporium from the plant Vateria indica and performed phytochemical screening of its ethanolic extract to detect the phytochemicals using thin layer chromatography (TLC), gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), UV-visible spectrophotometry (UV-VIS), and Fourier transform infrared spectroscopy (FTIR). GC-MS analysis revealed the presence of an anticancer compound hydroxymethyl colchicine, antioxidant compound benzoic acid, and antimicrobial 2-(4-chlorophenoxy)-5-nitro in endophyte fungal extract of plant Vateria indica. Moreover, in silico analysis of bioactive compounds identified by GC-MS analysis using the Autodock Vina and SwissADME confirmed excellent anticancer activity methanone, [4-amino-2-[(phenylmethyl) amino]-5-thiazolyl] (4-fluorophenyl)- and hydroxymethyl colchicine against 6VO4 (Bfl-1 protein) as per Lipinski rule. Furthermore, we also demonstrated the excellent antioxidant of endophytic extract compared to plant extract by DPPH and ABTS assay, as well as antimicrobial activity against both Gram (+ ve) and Gram (- ve) bacteria. Moreover, the endophytic extract also showed its antimitotic activity with a mitotic index of 65.32, greater than the plant extract of 32.56 at 10 mg/ml. Thus endophytic fungi Cladosporium species isolated from plant Vateria indica might be used as a potential source for phytochemical anticancer hydroxymethyl colchicine, an antioxidant benzoic acid, and antimicrobial 2-(4-chlorophenoxy)-5-nitro.

Immobilization of enzymes for bioremediation: A future remedial and mitigating strategy.

Over the years, extensive urbanization and industrialization have led to xenobiotics contamination of the environment and also posed a severe threat to human health. Although there are multiple physical and chemical techniques for xenobiotic pollutants management, bioremediation seems to be a promising technology from the environmental perspective. It is an eco-friendly and low-cost method involving the application of microbes, plants, or their enzymes to degrade xenobiotics into less toxic or non-toxic forms. Moreover, bioremediation involving enzymes has gained an advantage over microorganisms or phytoremediation due to better activity for pollutant degradation with less waste generation. However, the significant disadvantages associated with the application of enzymes are low stability (storage, pH, and temperature) as well as the low possibility of reuse as it is hard to separate from reaction media. The immobilization of enzymes without affecting their activity provides a possible solution to the problems and allows reusability by easing the process of separation with improved stability to various environmental factors. The present communication provides an overview of the importance of enzyme immobilization in bioremediation, carrier selection, and immobilization methods, as well as the pros and cons of immobilization and its prospects.

Isolation and Phytochemical Screening of Endophytic Fungi Isolated from Medicinal Plant Mappia foetida and Evaluation of Its In Vitro Cytotoxicity in Cancer.

Isolated endophyte fungi from Mappia foetida have been explored as a potential source for the mass production of anticancer drug lead compounds in the current study. Since medical plants are not feasible economically for mass production of bioactive pharmaceutical important molecules using plant tissue culture due to factors like media design and fungal contamination, endophyte fungal mass culture have been an alternative for the relatively easy and inexpensive production. Two endophytic fungi isolated, Alternaria alternata and Fusarium species were mass cultured and their prepared alcoholic extract subjected to standard procedures to identify the phytochemical screening by gas chromatography-mass spectrometry (GCMS), high-performance liquid chromatography (HPLC), UV visible spectrophotometry (UV-VIS), and Fourier transform infrared spectroscopy (FTIR). GC-MS analysis revealed the presence of three major compounds in the extracts. The phytochemical screening confirmed the presence of an anticancer compound (camptothecin) in their extract. Moreover, the dose-dependent anticancer activity of ethanol extract was demonstrated against cervical carcinoma (HeLa), breast carcinoma (MCF-7), non-small cell lung carcinoma (H1975), and hepatocellular carcinoma cell line (Hep G2) by MTT assay where doxorubicin was used as the positive control. Furthermore, the microscopic examination also confirmed the cytotoxic effect of extract of endophytic fungi Alternaria alternata and Fusarium species against tested cancer cells. Hence, endophytic fungi Alternaria alternata and Fusarium species might be exploited for mass production of phytochemicals having anticancer activity.

Bimetallic p-ZnO/n-CuO nanocomposite synthesized using Aegle marmelos leaf extract exhibits excellent visible-light-driven photocatalytic removal of 4-nitroaniline and methyl orange.

In the current study, the photocatalytic activity of bimetallic ZnO-CuO hetero-nanocomposite was evaluated and compared with the monometallic ZnO and CuO nanoparticles using 4-nitroaniline (4-NA) and methyl orange (MO). Bimetallic ZnO-CuO hetero-nanocomposite, ZnO, and CuO nanostructure were synthesized utilizing leaf extract of Aegle marmelos and characterized by transmission electron microscopy, X-ray diffraction, and XPS. Benefiting from the p-n heterostructures formation, bimetallic ZnO-CuO hetero-nanocomposite exhibits an excellent photocatalytic activity against 4-NA as well as MO compared to pure ZnO and CuO. In particular, bimetallic ZnO-CuO hetero-nanocomposite expressed the highest photocatalytic activity by reducing 90% of 4-NA in 20 min and by degrading 96% of MO in 10 min, whereas 65% reduction of 4-NA in 30 min and 93% degradation of MO in 45 min was exhibited by CuO and 48% reduction of 4-NA in 30 min and 98% degradation of MO in 50 min was exhibited by ZnO. Moreover, bimetallic ZnO-CuO hetero-nanocomposite maintains excellent photocatalytic activity even after five cycles indicating its stability as photocatalyst and reusability. Based on the experimental findings, bimetallic ZnO-CuO hetero-nanocomposite could be used as a photocatalyst for wastewater treatment with excellent regeneration efficiency.