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[Display omitted] • A DFT study of CUR interacting with B 40 and SiB 39 based carriers. • Interaction energy between CUR and B 40 is chemisorption. • B 40 and SiB 39 are electronically sensitive to CUR drug. • Molecular docking results illustrated that CUR/B 40 complexes have a good docking score with COX1, and TNF-alpha receptors. In this paper, density functional theory calculations have been employed to study the interaction of curcumin through β-diketone- and enol- forms with the borospherene molecule (B 40) and its silicon-doped variant (SiB 39) for application as a nanocarrier for designing a drug delivery system. The obtained results from binding energies analysis indicated that the enol form (state II: −1.32 eV) and β-diketone form (state III: −2.51 eV) of curcumin prefers a strong polar covalent B-O and Si-O bonds through carbonyl groups after the interaction with B 40 and SiB 39 fullerenes. The boron fullerene doped with silicon atom improves the adsorption of β-diketone form and has higher binding energy values and increased dipole moment. So, SiB 39 fullerene is more sensitive to the presence of β-diketone (state III: 76.84 %) and enol form is (state IV: 93.68 %) compared to the B 40 fullerene due to the alteration in energy gap. According to molecular docking analysis the β-diketone curcumin conjugated with SiB 39 (state III) and B 40 fullerenes (state I) revealed the best binding affinity with the tumor necrosis factor alpha (TNF-α) receptor (-8.9 kcal/mol) and the cyclooxygenase-1 (COX-1) receptor (-8.8 kcal/mol). The anticancer activities of β-diketone curcumin conjugated B 40 and SiB 39 fullerenes improved in comparison with curumin towards Epidermal growth factor and Human Epidermal Growth Factor Receptor 2 receptors. Molecular docking simulation analysis illustrated that the interaction of curcumin conjugated B 40 and SiB 39 fullerenes have great potential for the anticancer and anti-inflammatory activities in contrast to Curcumin. Thus, the molecular docking and density functional theory analysis confirm that curcumin decorated B 40 and SiB 39 fullerenes have significant potential to be explored further in cancer and inflammation treatments. [ABSTRACT FROM AUTHOR]

One of the best treatments for inflammatory diseases such as COVID−19, respiratory diseases and brain diseases is treatment with stem cells. Here we investigate the effect of stem cell therapy in the treatment of brain diseases.Preclinical studies have shown promising results, including improved functional recovery and tissue repair in animal models of neurodegenerative diseases, strokes,and traumatic brain injuries. However,ethical implications, safety concerns, and regulatory frameworks necessitate thorough evaluation before transitioning to clinical applications. Additionally, the complex nature of the brain and its intricate cellular environment present unique obstacles that must be overcome to ensure the successful integration and functionality of genetically engineered MSCs. The careful navigation of this path will determine whether the application of genetically engineered MSCs in brain tissue regeneration ultimately lives up to the hype surrounding it. [ABSTRACT FROM AUTHOR]

Understanding the function and mode of operation of microRNAs (miRNAs) in cancer is of growing interest. The short non-coding RNAs known as miRNAs, which target mRNA in multicellular organisms, are described as controlling essential cellular processes. The miR-181 family and miR-633 are well-known miRNAs that play a key role in the development and metastasis of tumor cells. They may facilitate either tumor-suppressive or oncogenic function in malignant cells, according to mounting evidence. Metastatic cells that are closely linked to cancer cell migration, invasion, and angiogenesis can be identified by abnormal levels of miR-181 and miR-633. Numerous studies have demonstrated their capacity to control drug resistance, cell growth, apoptosis, and the epithelial-mesenchymal transition (EMT) and metastasis process. Interestingly, the levels of miR-181 and miR-633 and their potential target genes in the basic cellular process can vary depending on the type of cancer cells and their gene expression profile. Such miRNAs' interactions with other non-coding RNAs such as long non-coding RNAs and circular RNAs can influence tumor behaviors. Herein, we concentrated on the multifaceted roles of miR-181 and miR-633 and potential targets in human tumorigenesis, ranging from cell growth and metastasis to drug resistance. [ABSTRACT FROM AUTHOR]

Atypical chemokine receptor 4 (ACKR4), also known as CCX‐CKR, is a member of the chemokine receptor family that lacks typical G protein signaling activity. Instead, ACKR4 functions as a scavenger receptor that can bind and internalize a wide range of chemokines, influencing their availability and activity in the body. ACKR4 is involved in various physiological processes, such as immune cell trafficking and the development of thymus, spleen, and lymph nodes. Moreover, ACKR4 has been implicated in several pathological conditions, including cancer, heart and lung diseases. In cancer, ACKR4 plays a complex role, acting as a tumor suppressor or promoter depending on the type of cancer and the stage of the disease. For instance, ACKR4 may inhibit the growth and metastasis of breast cancer, but it may also promote the progression of hepatocellular carcinoma and gastric cancer. In inflammatory situations, ACKR4 has been found to modulate the recruitment and activation of immune cells, contributing to the pathogenesis of diseases such as myocardial infraction and pulmonary sarcoidosis. The study of ACKR4 is still ongoing, and further research is needed to fully understand its role in different physiological and pathological contexts. Nonetheless, ACKR4 represents a promising target for the development of novel therapeutic strategies for various diseases. Significance Statement: The exploration of Atypical Chemokine Receptor 4 (ACKR4/CCX‐CKR) represents a pivotal and timely endeavor in contemporary research, as it delves comprehensively into both the physiological and pathological landscapes. Investigating the multifaceted roles of ACKR4 across these contexts not only enhances our understanding of its fundamental biological functions but also sheds light on its potential implications in various diseases. This research contributes significantly to the current knowledge in cell biochemistry and function, offering insights that could pave the way for novel therapeutic interventions and diagnostic strategies. The comprehensive examination of ACKR4 aligns with the evolving landscape of molecular and cellular research, positioning it as a crucial player in unraveling the intricacies of cellular signaling and function, thereby advancing the frontiers of scientific knowledge in the field. [ABSTRACT FROM AUTHOR]

The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis. [ABSTRACT FROM AUTHOR]

The synthesis of polymers using environmentally friendly materials is on the rise. New chitosan, oxidized pectin, and tantalum metal–organic framework hydrogel were synthesized using chitosan and pectin, which are both available and environmentally friendly polymer materials. By scanning electron microscope images, energy-dispersive X-ray spectroscopy and EDAX mapping, X-ray diffraction pattern, Fourier transform infrared spectrum, and N2 adsorption/desorption isotherm curve, the structure of the synthesized polymer was confirmed. A specific surface area of about 26 m2/g was observed from the final system. The same morphology, and 51 nm particle size were other features of synthetic chitosan, oxidized pectin, and tantalum metal–organic framework hydrogel. The antimicrobial activity of the synthesized polymer was studied on Yersinia ruckeri, Vibrio fluvialis, Edwardsiella tarda, Lactococcus garvieae, and Streptococcus iniae as microbial agents of aquatic pathogens. The synthetic polymer studied in this research can be reported as a robust antimicrobial compound with an MBC of 4–128 mg/ml. A key aspect of this study is the synthesis of new polymers using environmentally friendly and controllable methods. Among other novelties of this study, it can be mentioned that it is effective against common pathogenic strains of humans and aquatic, which in some cases was more effective than available commercial drugs. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the world's most prevalent cancer among women. Microorganisms have been the richest source of antibiotics as well as anticancer drugs. Moricin peptides have shown antibacterial properties; however, the anticancer potential and mechanistic insights into moricin peptide-induced cancer cell death have not yet been explored. Methods: An investigation through in silico analysis, analytical methods (Reverse Phase-High Performance Liquid Chromatography (RP-HPLC), mass spectroscopy (MS), circular dichroism (CD), and in vitro studies, has been carried out to delineate the mechanism(s) of moricin-induced cancer cell death. An in-silico analysis was performed to predict the anticancer potential of moricin in cancer cells using Anti CP and ACP servers based on a support vector machine (SVM). Molecular docking was performed to predict the binding interaction between moricin and peptide-related cancer signaling pathway(s) through the HawkDOCK web server. Further, in vitro anticancer activity of moricin was performed against MDA-MB-231 cells. Results: In silico observation revealed that moricin is a potential anticancer peptide, and protein–protein docking showed a strong binding interaction between moricin and signaling proteins. CD showed a predominant helical structure of moricin, and the MS result determined the observed molecular weight of moricin is 4544 Da. An in vitro study showed that moricin exposure to MDA-MB-231 cells caused dose dependent inhibition of cell viability with a high generation of reactive oxygen species (ROS). Molecular study revealed that moricin exposure caused downregulation in the expression of Notch-1, NF-ƙB and Bcl2 proteins while upregulating p53, Bax, caspase 3, and caspase 9, which results in caspase-dependent cell death in MDA-MB-231 cells. Conclusions: In conclusion, this study reveals the anticancer potential and underlying mechanism of moricin peptide-induced cell death in triple negative cancer cells, which could be used in the development of an anticancer drug. [ABSTRACT FROM AUTHOR]

New nanocomposites containing zirconium were synthesized using microwave irradiation. Their structure was confirmed by vibrating sample magnetometer (VSM) curves, X-ray diffraction (XRD) patterns, scanning electron microscope (SEM) and transmission electron microscopy (TEM) images, Fourier transform infrared spectroscopy (FT-IR), and Brunauer–Emmett–Teller (BET) N2 adsorption/desorption isotherms. After the structure confirmation of the zirconium magnetic nanocomposite, the catalytic properties in the synthesis of pyrazole derivatives were investigated. Next, the biological activities of the zirconium magnetic nanocomposite, such as the antibacterial and antifungal activities, were investigated. The research results showed that the zirconium magnetic nanocomposite has high catalytic properties and can be used as a magnetic nanocatalyst for synthesizing heterocyclic compounds such as pyrazole derivatives in addition to having high biological properties. The unique properties of the nanoparticles can be attributed to their synthesis method and microwave radiation. [ABSTRACT FROM AUTHOR]

A Mitochondrial ROS was determined by microscopy with mitoSOX staining of moricin treated and untreated MDA-MB-231 cells treated with 6.25 µg/ml and 12.5 µg/ml moricin peptide. 4Effect of moricin peptide treatment on structural damages of mitochondria and lysosomes and induced mitochondrial ROS generations in MDA-MB-231 cells. [Extracted from the article]

The desirable characteristics of the hydrolytic enzymes for cellulose digestion include high catalytic activity and stress resistance ability under diverse condition during the process of bioconversion. In this view, for enhancing the thermal stability and functional specificity of enzymes, nanomaterials offer enormous potential. The waste bark of the Moringa plant, which is found to be rich in phytochemicals, has been used to synthesize MgO nanoparticles (MgO NPs) in the current study using an environmentally friendly and economical process. The newly synthesized MgO NPs has been characterized through various tools that included XRD, FT-IR, Raman spectroscopy, UV-Vis spectroscopy, SEM and TEM to evaluate physicochemical properties. Thereafter, impact of this phytochemically synthesized MgO NPs has been analyzed on the thermal stability and efficiency of the raw fungal cellulases. The different enzyme components demonstrated elevated thermal stability, such as filter paper activity (FPA) at 60 °C for 6.5 h, β-glucosidase (BGL) activity at 6.0 h, and endoglucanase (EG) activity at 50 °C for 4.0 h at a 20 mg concentration of MgO NPs. Such an improved nanomaterials assisted thermal efficiency of the enzyme systems can be further explored for numerous cellulase-enabled industrial purposes. [Display omitted] • Cellulose and lignin rich moringa bark is used for fabrication of MgO nanoparticles. • Characterizations of green synthesized MgO nanocatalyst have been performed. • Nanocatalysts is applied for thermal stability investigation of fungal cellulases. • This work has application in cellulose waste-based valorization for industries. [ABSTRACT FROM AUTHOR]

Zinc-based nanostructures are known for their numerous potential biomedical applications. In this context, the biosynthesis of nanostructures using plant extracts has become a more sustainable and promising alternative to effectively replace conventional chemical methods while avoiding their toxic impact. In this study, following a low-temperature calcination process, a green synthesis of Zn-hydroxide-based nanostructure has been performed using an aqueous extract derived from the leaves of Litchi chinensis, which is employed as a lignocellulose waste biomass known to possess a variety of phytocompounds. The biogenic preparation of Zn-hydroxide based nanostructures is enabled by bioactive compounds present in the leaf extract, which act as reducing and capping agents. In order to evaluate its physicochemical characteristics, the produced Zn-hydroxide-based nanostructure has been subjected to several characterization techniques. Further, the multifunctional properties of the prepared Zn-hydroxide-based nanostructure have been evaluated for antioxidant, antimicrobial, and anticancer activity. The prepared nanostructure showed antibacterial efficacy against Bacillus subtilis and demonstrated its anti-biofilm activity as evaluated through the Congo red method. In addition, the antioxidant activity of the prepared nanostructure has been found to be dose-dependent, wherein 91.52 % scavenging activity could be recorded at 200 μg/ml, with an IC 50 value of 45.22 μg/ml, indicating the prepared nanostructure has a high radical scavenging activity. Besides, the in vitro cytotoxicity investigation against HepG2 cell lines explored that the as-prepared nanostructure exhibited a higher cytotoxic effect and 73.21 % cell inhibition could be noticed at 25.6 μg/ml with an IC 50 of 2.58 μg/ml. On the contrary, it was found to be significantly lower in the case of HEK-293 cell lines, wherein ~47.64 % inhibition could be noticed at the same concentration. These findings might be further extended to develop unique biologically derived nanostructures that can be extensively evaluated for various biomedical purposes. [ABSTRACT FROM AUTHOR]

The microenvironment of lymphoid organs can aid healthy immune function through provision of both structural and molecular support. In mice, fibroblastic reticular cells (FRCs) create an essential T-cell support structure within lymph nodes, while human FRCs are largely unstudied. Here, we show that FRCs create a regulatory checkpoint in human peripheral T-cell activation through 4 mechanisms simultaneously utilised. Human tonsil and lymph node–derived FRCs constrained the proliferation of both naïve and pre-activated T cells, skewing their differentiation away from a central memory T-cell phenotype. FRCs acted unilaterally without requiring T-cell feedback, imposing suppression via indoleamine-2,3-dioxygenase, adenosine 2A Receptor, prostaglandin E2, and transforming growth factor beta receptor (TGFβR). Each mechanistic pathway was druggable, and a cocktail of inhibitors, targeting all 4 mechanisms, entirely reversed the suppressive effect of FRCs. T cells were not permanently anergised by FRCs, and studies using chimeric antigen receptor (CAR) T cells showed that immunotherapeutic T cells retained effector functions in the presence of FRCs. Since mice were not suitable as a proof-of-concept model, we instead developed a novel human tissue–based in situ assay. Human T cells stimulated using standard methods within fresh tonsil slices did not proliferate except in the presence of inhibitors described above. Collectively, we define a 4-part molecular mechanism by which FRCs regulate the T-cell response to strongly activating events in secondary lymphoid organs while permitting activated and CAR T cells to utilise effector functions. Our results define 4 feasible strategies, used alone or in combinations, to boost primary T-cell responses to infection or cancer by pharmacologically targeting FRCs. [ABSTRACT FROM AUTHOR]

• Computational-based estimation of drug solubility in supercritical CO 2. • The used models are Random Forest (RF), KNN and Extra Tree (ET). • The ET model had the best result with a R2 score of 0.9999. In this study, we implemented and compared various non-mechanistic based models for prediction of drug solubility in supercritical solvent. The data were collected from references and the models were built considering various operational circumstances. Small data sets, like the solubility data used in this study, have always been one of the challenges for modeling in machine learning method. In this study, in order to solve the regression problem related to the solubility of drugs, which includes 32 laboratory data, we implemented and studied models that are naturally compatible with very small data like solubility data of drugs in solvents. These models included Random Forest (RF), KNN and Extra Tree (ET). After obtaining the best settings for each model, their final results were compared in terms of accuracy for predicting drug solubility. The ET model had the best result with a score of 0.9999 on the R2 criterion. Random forests with 0.978 and KNN with 0.972 also had acceptable regression results. Finally, the trained model was used to display and evaluate the effect of input parameters like pressure and temperature on drug solubility to understand the process. [ABSTRACT FROM AUTHOR]

Solid waste management and waste valorization are key concerns and challenges around the globe. Solid wastes generated by food industries are found in a diverse variety, are key sources of enormously valuable compounds, and can be effectively transformed into useful products for broad industrial applications. Biomass-based catalysts, industrial enzymes, and biofuels are some of the very prominent and sustainable products that are developed using these solid wastes. The aims of the current study are therefore centered on the multiple valorizations of coconut waste (CWs) to develop biochar as a catalyst and its application in fungal enzyme production in solid-state fermentation (SSF). Biochar as a catalyst using CWs has been prepared via a calcination process lasting 1 h at 500 °C and characterized through X-ray diffraction, Fourier-transformed infrared spectroscopy, and scanning electron microscope techniques. The produced biochar has been implemented for boosting enzyme production through SSF. In addition, studies have been performed on enzyme production with varying time and temperature, and it is found that the maximum 92 IU/gds BGL enzyme could be produced at a 2.5 mg concentration of biochar-catalyst at 40 °C in 72 h. [Display omitted] • Sustainable valorization of coconut waste (CWs) has been presented. • CWs derived biochar-catalyzed cellulose degrading enzymes is produced via SSF. • Enhancements in fungal enzymes production have been recorded using biochar. • The study has potential in industrial and waste management applications. [ABSTRACT FROM AUTHOR]