T-cell lymphomas, refer to a diverse set of lymphomas that originate from T-cells, a type of white blood cell, with limited treatment options. This investigation aimed to assess the efficacy and mechanism of a novel fluorinated nucleoside analogue (FNA), 2′-deoxy-2′-β-fluoro-4′-azidocytidine (FNC), against T-cell lymphoma using Dalton’s lymphoma (DL)-bearing mice as a model. Balb/c mice transplanted with the DL tumor model received FNC treatment to study therapeutic efficacy against T-cell lymphoma. Behavioral monitoring, physiological measurements, and various analyses were conducted to evaluate treatment effects for mechanistic investigations. The results of study indicated that FNC prevented DL-altered behavior parameters, weight gain and alteration in organ structure, hematological parameters, and liver enzyme levels. Moreover, FNC treatment restored organ structures, attenuated angiogenesis, reduced DL cell viability and proliferation through apoptosis. The mechanism investigation revealed FNC diminished MMP levels, induced apoptosis through ROS induction, and activated mitochondrial-mediated pathways leading to increase in mean survival time of DL mice. These findings suggest that FNC has potential therapeutic effects in mitigating DL-induced adverse effects. FNC represents an efficient and targeted treatment strategy against T-cell lymphoma. FNC’s proficient ability to induce apoptosis through ROS generation and MMP reduction makes it a promising candidate for developing newer and more effective anticancer therapies. Continued research could unveil FNC’s potential role in designing a better therapeutic approach against NHL.

The therapeutic potential of chemically synthesized AuNPs has been demonstrated in various types of cancer. However, gold nanoparticles (AuNPs) synthesized using typical chemical methods have concerns regarding their environmental safety and adverse impact on human well-being. To overcome this issue, we used an environmentally friendly approach in which gold nanoparticles were synthesized using Moringa oleifera leaf extract (MLE). The present research was mainly focused on the biosynthesis and characterization of gold nanoparticles (AuNPs) using Moringa oleifera leaf extract (MLE-AuNPs) and explore its anticancer potential against Dalton’s Lymphoma (DL) cells. Characterization of the MLE-AuNPs was conducted using UV-Vis Spectroscopy to confirm the reduction process, FTIR analysis to ascertain the presence of functional groups, and XRD analysis to confirm the crystallinity. SEM and TEM images were used to examine size and morphology. After characterization, MLE-AuNPs were evaluated for their cytotoxic effects on Dalton’s lymphoma cells, and the results showed an IC50 value of 75 ± 2.31 µg/mL; however, there was no discernible cytotoxicity towards normal murine thymocytes. Furthermore, flow cytometric analysis revealed G2/M phase cell cycle arrest mediated by the downregulation of cyclin B1 and Cdc2 and upregulation of p21. Additionally, apoptosis induction was evidenced by Annexin V Staining, accompanied by modulation of apoptosis-related genes including decreased Bcl-2 expression and increased expression of Bax, Cyt-c, and Caspase-3 at both the mRNA and protein levels. Collectively, our findings underscore the promising anti-cancer properties of MLE-AuNPs, advocating their potential as a novel therapeutic avenue for Dalton’s lymphoma.

Nucleoside analogs are a common form of chemotherapy that disrupts DNA replication and repair, leading to cell cycle arrest and apoptosis. Reactive oxygen species (ROS) production is a significant mechanism through which these drugs exert their anticancer effects. This study investigated a new nucleoside analog called FNC or Azvudine, and its impact on ROS production and cell viability in Dalton’s lymphoma (DL) cells. The study found that FNC treatment resulted in a time- and dose-dependent increase in ROS levels in DL cells. After 15 and 30 min of treatment with 2 and 1 mg/ml of FNC, mitochondrial ROS production was observed in DL cells. Furthermore, prolonged exposure to FNC caused structural alterations and DNA damage in DL cells. The results suggest that FNC’s ability to impair DL cell viability may be due to its induction of ROS production and indicate a need for further investigation.

Cold spraying of soft metals such as aluminium and its alloys often leads to clogging at nozzle throat affecting the productivity. Attempts were made to address clogging which includes a proper selection of nozzle material and nozzle cooling. Polymer based materials which has process temperature limitation (400 degrees C) are widely used to deposit aluminium. In this work, a systematic study was carried out using different nozzle materials and clogging is correlated with the wettability of feedstock. High-density graphite is identified as a materials solution which can replace expensive polybenzimidazole as nozzle material for depositing soft materials. (c) 2024 Published by Elsevier Ltd on behalf of Society of Manufacturing Engineers (SME).

Cytotoxic nucleoside analogs (NAs) hold great promise in cancer therapeutics by mimicking endogenous nucleosides and interfering with crucial cellular processes. Here, we investigate the potential of the novel cytidine analog, 4′-azido-2′-deoxy-2′-fluoro(arbino)cytidine (FNC), as a therapeutic agent for Non-Hodgkin lymphoma (NHL) using Dalton’s lymphoma (DL) as a T-cell lymphoma model. FNC demonstrated dose- and time-dependent inhibition of DL cell growth and proliferation. IC-50 values of FNC were measured at 1 µM, 0.5 µM, and 0.1 µM after 24, 48, and 72 h, respectively. Further elucidation of FNC’s mechanism of action uncovers its role in inducing apoptosis in DL cells. Notable DNA fragmentation and nuclear condensation point to activated apoptotic pathways. FNC-induced apoptosis was concomitant with changes in cellular membranes, characterized by membrane rupture and altered morphology. The robust anticancer effects of FNC are linked to its capacity to induce reactive oxygen species (ROS) production, prompting oxidative stress-mediated apoptosis. Additionally, FNC disrupted mitochondrial membrane potential (MMP), leading to mitochondrial dysfunction, further promoting apoptosis. Dysregulation of apoptotic genes, with upregulation of Bax and downregulation of Bcl-2 and Bcl-xl, implicates the mitochondrial-mediated apoptosis pathway. Furthermore, FNC-induced G2/M phase cell cycle arrest was mediated through modulation of the cell cycle inhibitor p21. Overall, this study highlights the potential of FNC as a promising therapeutic agent for NHL.

Heat shock proteins are a widely distributed group of proteins. It is constitutively expressed in almost all organisms and shows little variation throughout evolution. Previously, HSPs, particularly Hsp70, were recognized as molecular chaperones that aid in the proper three-dimensional folding of newly synthesized polypeptides in cells. Recently, researchers have focused on the potential induction of immune cells, including macrophages, antigen-specific CD8+ cytotoxic T cells, and PBMCs. It induces the expression of CC chemokines such as MIP-1α and RANTES, which are responsible for the chemotactic movement and migration of immune cells at the site of infection to neutralize foreign particles in vivo and in vitro in several cell lines but their effect on tumor-associated macrophages is still not known. These cytokines are also known to influence the movement of several immune cells, including CD8+ cytotoxic T cells, toward inflammatory sites. Therefore, the effect of tumor-derived autologous Hsp70 on the expression of MIP-lα and RANTES in tumor-associated macrophages (TAMs) was investigated. Our results indicated that Hsp70 treatment-induced MIP-lα and RANTES expression was significantly greater in TAMs than in NMOs. According to the literature, the CC chemokine shares the same receptor, CCR5, as HIV does for their action, and therefore could provide better completion to the virus for ligand binding. Furthermore, Hsp70-preactivated TAMs induced increased IL-2 and IFN-γ expression in T cells during coculture for 48 h and upregulated the antitumor immune response of the host. Therefore, the outcome of our study could be useful for developing a better approach to restricting the growth and progression of tumors.

Objectives: The present study aimed to provide an insight into the acute toxicity of a novel fluorinated nucleoside analogue (FNA), FNC (Azvudine or2'-deoxy-2'-β-fluoro-4'-azidocytidine). FNC showed potent anti-viral and anti-cancer activities and approved drug for high-load HIV patients, despite, its acute toxicity study being lacking. Materials and Methods: OECD-423 guidelines were followed during this study and the parameters were divided into four categories - behavioral parameters, physiological parameters, histopathological parameters, and supplementary tests. The behavioral parameters included feeding, body weight, belly size, organ weight and size, and mice behavior. The physiological parameters consisted of blood, liver, and kidney indicators. In histopathological parameters hematoxylin and eosin staining was performed to analyse the histological changes in the mice organs after FNC exposure. In addition, supplementary tests were conducted to assess cellular viability, DNA fragmentation and cytokine levels (IL-6 and TNF-α) in response to FNC. Results: In the behavioral parameters FNC induced changes in the mice-to-mice interaction and activities. Mice's body weight, belly size, organ weight, and size remained unchanged. Physiological parameters of blood showed that FNC increased the level of WBC, RBC, Hb, and neutrophils and decreased the % count of lymphocytes. Liver enzymes SGOT (AST), and ALP was increased. In the renal function test (RFT) cholesterol level was significantly decreased. Histopathological analysis of the liver, kidney, brain, heart, lungs, and spleen showed no sign of tissue damage at the highest FNC dose of 25 mg/kg b.wt. Supplementary tests for cell viability showed no change in viability footprint, through our recently developed dilution cum-trypan (DCT) assay, and Annexin/PI. No DNA damage or apoptosis was observed in DAPI or AO/EtBr studies. Pro-inflammatory cytokines IL-6 and TNF-α increased in a dose-dependent manner. Conclusion: This study concluded that FNC is safe to use though higher concentration shows slight toxicity.

Deposition of Ni-Cr through cold spraying has potential implications in power sector as a potential candidate for high temperature oxidation and corrosion resistance coating. In this work, cold spray deposition of Ni-Cr at different stagnation temperatures varying from 600 degrees C to 800 degrees C using air as process gas instead of expensive nitrogen and helium gases is realised. The bonding state at the inter-splat boundaries was simulated and the same was correlated with the results obtained from mechanical and thermal cycling studies. Coatings deposited at higher temperature exhibit superior performance due to the formation of strong inter-splat boundaries, thus reflected in porosity and oxidation resistance. Deposition conditions (V-P / V-Cr) used in this study meets the requirement for inter-splat bonding. The fraction of bonded inter-splat boundaries achieved at 20 bar 800 degrees C was estimated to be similar to 100 % thus reflects in functional properties such as porosity, microstructure, superior oxidation and spallation resistances.

Cold spray bonding mechanism is often correlated with adiabatic shear instability and jetting at inter-splat boundaries. In this work, the role of in-flight temperature on the deposition characteristics is synergistically addressed with the in-flight velocity of the impacting powders. The fraction of inter-splat bonding and the properties of the coatings are correlated as a function of total energy of the powder upon impact rather than inflight velocity alone. Fraction of inter-splat bonding is used to obtain normalised electrical conductivity and normalised elastic modulus for variety of materials ranging from low melting point zinc (Zn) to high melting point tungsten (W). Onset of deposition is characterized with the dimension less parameter estimated by normalising the total energy of the impacting powder with the Ebond (critical energy). The data is correlated with the experimental results. For instance, the critical velocity (VCr) and critical energy (Ebond) for bonding of copper are estimated to be 451 m/s and 27.25 & mu;J respectively. One can tailor the process condition to deposit the metallic powder in cold spraying by selecting either in-flight velocity or in-flight temperature. The synergistic effect of velocity and temperature can be corroborated with the bonding state in cold sprayed coatings.

Cold spray is the only solid-state coating technique to deposit thick metallic coatings. Deposition of metallic and metallic alloy powders is carried out at the temperature lower than the melting point. Since spraying of Al-based aerospace alloys are associated with nozzle clogging, successful deposition is restricted to nitrogen or helium as the main process gas with a polymer nozzle. Deposition of the alloys using air as process gas at elevated stagnation temperatures (up to 600 degrees C) has benefits in the repair and refurbishment sector, especially in aerospace. In this study, the effect of elevated stagnation temperatures (from 400 to 600 degrees C) using air as the main process gas on the deposition characteristics of aerospace grade Al-alloys (Cp-Al, Al-2024, Al-6061 and Al-7075) is studied. Deposition of the alloys at various stagnation temperatures is studied using FEM and correlated with the coating thickness. The deposition behaviour is studied using various parameters such as lattice misfit calculations and solid solution strengthening calculations. The ease of cold spray deposition of Al-aerospace alloys is systematically studied and listed as Al-6061 > Cp-Al > Al-7075 > Al-2024 for the first time.

PKCα is a molecule with many functions that play an important role in cell survival and death to maintain cellular homeostasis. Alteration in the normal functioning of PKCα is responsible for the complicated etiology of many pathologies, including cancer, cardiovascular diseases, kidney complications, neurodegenerative diseases, diabetics, and many others. Several studies have been carried out over the years on this kinase's function, and regulation in normal physiology and pathological conditions. A lot of data with antithetical results have therefore accumulated over time to create a complex framework of physiological implications connected to the PKCα function that needs comprehensive elucidation. In light of this information, we critically analyze the multiple roles played by PKCα in basic cellular processes and their molecular mechanism during various pathological conditions. This review further discusses the current approaches to manipulating PKCα signaling amplitude in the patient's favour and proposed PKCα as a therapeutic target to reverse pathological states.