The critical impacts of cytokine storms in respiratory disorders.

Cytokine storm (CS) refers to the spontaneous dysregulated and hyper-activated inflammatory reaction occurring in various clinical conditions, ranging from microbial infection to end-stage organ failure. Recently the novel coronavirus involved in COVID-19 (Coronavirus disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been associated with the pathological phenomenon of CS in critically ill patients. Furthermore, critically ill patients suffering from CS are likely to have a grave prognosis and a higher case fatality rate. Pathologically CS is manifested as hyper-immune activation and is clinically manifested as multiple organ failure. An in-depth understanding of the etiology of CS will enable the discovery of not just disease risk factors of CS but also therapeutic approaches to modulate the immune response and improve outcomes in patients with respiratory diseases having CS in the pathogenic pathway. Owing to the grave consequences of CS in various diseases, this phenomenon has attracted the attention of researchers and clinicians throughout the globe. So in the present manuscript, we have attempted to discuss CS and its ramifications in COVID-19 and other respiratory diseases, as well as prospective treatment approaches and biomarkers of the cytokine storm. Furthermore, we have attempted to provide in-depth insight into CS from both a prophylactic and therapeutic point of view. In addition, we have included recent findings of CS in respiratory diseases reported from different parts of the world, which are based on expert opinion, clinical case-control research, experimental research, and a case-controlled cohort approach.

Nanocomposites of iron oxide, sodium alginate, and eugenol induce apoptosis via PI3K/Akt/mTOR signaling in Hep3 cells and in vivo hepatotoxicity in the zebrafish model.

Hepatic cancer is among the most recurrently detected malignancies worldwide and one of the main contributors to cancer-associated mortality. With few available therapeutic choices, there is an instant necessity to explore suitable options. In this aspect, Nanotechnology has been employed to explore prospective chemotherapeutic approaches, especially for cancer treatment. Nanotechnology is concerned with the biological and physical properties of nanoparticles in the therapeutic use of drugs. In the current work, formulation, and characterization of α-Fe2O3-Sodium Alginate-Eugenol nanocomposites (FSE NCs) using several approaches like SEM and TEM, UV-visible, FTIR, and PL spectroscopy, XRD, EDAX, and DLS studies have been performed. With an average size of 50 nm, the rhombohedral structure of NCs was identified. Further, their anticancer activity against Hep3B liver cancer cell lines has been performed by cell viability, dual staining, DCFH-DA, Annexin-V/-FITC/PI, cell cycle analysis methods, and PI3K/Akt/mTOR signaling proteins were studied to assess the anticancer effects of the NCs in Hep3B cells. Also, anti-cancer activity on animal modeling in-vivo using zebra fishes to hematological parameters, liver enzymes, and histopathology study effectiveness was noticed. Moreover, the NCs reduced the viability, elevated the ROS accumulation, diminished the membrane integrity, reduced the antioxidants, blocked the cell cycle, and triggered the PI3K/Akt/mTOR signaling axis that eventually resulted in cell death. As a result, FSE NCs possess huge potential for use as a possible anticancer candidate.

Syzygium cumini (L.) Extract-Derived Green Titanium Dioxide Nanoparticles Induce Caspase-Dependent Apoptosis in Hepatic Cancer Cells.

An aqueous extract of Syzygium cumini seeds was utilized to green synthesize titanium dioxide nanoparticles (TiO2 NPs). UV-Visible, DLS, FTIR, XRD, FESEM, TEM, SAED, EDAX, and photoluminescence spectroscopy techniques were employed to characterize the prepared TiO2 nanoparticles. The rutile crystal structure of TiO2 NPs was revealed by XRD study. The TEM and FESEM images of the TiO2 NPs revealed an average particle size of 50-100 nm. We employed EDAX to investigate the elemental compositions of TiO2 NPs. The O-Ti-O stretching bands appeared in the FTIR spectrum of TiO2 NPs at wavenumbers of 495 cm-1. The absorption edge peaks of TiO2 NPs were found in the UV-vis spectra at 397 nm. The MTT study revealed that TiO2 NPs effectively inhibited the growth of liver cancer Hep3 and Hep-G2 cells. The results of the corresponding fluorescent staining assays showed that TiO2 NPs significantly increased ROS generation, decreased MMP, and induced apoptosis in both liver cancer Hep3 and Hep-G2 cells. TiO2 nanoparticles lessened SOD, CAT, and GSH levels while augmenting MDA contents in Hep3 and Hep-G2 cells. In both Hep3 and Hep-G2 cells treated with TiO2 NPs, the Bax, CytC, p53, caspase-3, -8, and -9 expressions were remarkably augmented, while Bcl-2 expression was reduced. Overall, these findings revealed that formulated TiO2 NPs treatment considerably inhibited growth and triggered apoptosis in Hep3 and HepG2 cells.

ABO, Lewis blood group systems and secretory status with H.pylori infection in yemeni dyspeptic patients: a cross- sectional study.

BACKGROUND: The ABO and Lewis blood group antigens are potential factors in susceptibility to H. pylori infection. This research aimed to examine the prevalence of Helicobater pylori (H.pylori) infection and its association with ABO, Lewis blood group systems, and secretory status in Yemeni symptomatic patients. METHODS: In a cross-sectional study, 103 patients referred for endoscopy due to dyspepsia were included. H pylori infection was assessed using stool antigen and serum antibody rapid tests. ABO and Lewis blood group systems were examined using hemagglutination assay. Saliva samples were investigated for identification of the secretory phenotype using hemagglutination inhibition test. RESULTS: The prevalence of H. pylori infection was (80.6%), with a higher rate of infection in females than males. The ABO blood groups were found to be significantly different between males and females (p = 0.047). The O blood group was prevalent among H. pylori patients, especially secretors. There was a significant association between ABO blood groups and H. pylori infection (p = 0.001). The Le (a + b+) phenotype was the most common, followed by Le (a + b-), Le (a-b+), and Le (a-b-). Lewis blood group systems and secretory status of symptomatic patients were not associated with H. pylori infection. The results showed that serum Ab test for H. pylori achieved poor sensitivity (68%), specificity of 55%; positive predictive value (PPV) 86%, negative predictive value (NPV) 29% and accuracy 65.1%. CONCLUSION: The prevalence of H. pylori infection was high in Yemeni patients. This infection was linked to the O and Le (a + b+) secretor phenotype. The H. pylori stool Ag test is the most reliable noninvasive diagnostic method for detecting H. pylori infection.

Pluronic-F-127-Passivated SnO2 Nanoparticles Derived by Using Polygonum cuspidatum Root Extract: Synthesis, Characterization, and Anticancer Properties.

Nanotechnology has emerged as the most popular research topic with revolutionary applications across all scientific disciplines. Tin oxide (SnO2) has been gaining considerable attention lately owing to its intriguing features, which can be enhanced by its synthesis in the nanoscale range. The establishment of a cost-efficient and ecologically friendly procedure for its production is the result of growing concerns about human well-being. The novelty and significance of this study lie in the fact that the synthesized SnO2 nanoparticles have been tailored to have specific properties, such as size and morphology. These properties are crucial for their applications. Moreover, this study provides insights into the synthesis process of SnO2 nanoparticles, which can be useful for developing efficient and cost-effective methods for large-scale production. In the current study, green Pluronic-coated SnO2 nanoparticles (NPs) utilizing the root extracts of Polygonum cuspidatum have been formulated and characterized by several methods such as UV-visible, Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDAX), transmission electron microscope (TEM), field emission-scanning electron microscope (FE-SEM), X-ray diffraction (XRD), photoluminescence (PL), and dynamic light scattering (DLS) studies. The crystallite size of SnO2 NPs was estimated to be 45 nm, and a tetragonal rutile-type crystalline structure was observed. FESEM analysis validated the NPs' spherical structure. The cytotoxic potential of the NPs against HepG2 cells was assessed using the in vitro MTT assay. The apoptotic efficiency of the NPs was evaluated using a dual-staining approach. The NPs revealed substantial cytotoxic effects against HepG2 cells but failed to exhibit cytotoxicity in different liver cell lines. Furthermore, dual staining and flow cytometry studies revealed higher apoptosis in NP-treated HepG2 cells. Nanoparticle treatment also inhibited the cell cycle at G0/G1 stage. It increased oxidative stress and promoted apoptosis by encouraging pro-apoptotic protein expression in HepG2 cells. NP treatment effectively blocked the PI3K/Akt/mTOR axis in HepG2 cells. Thus, green Pluronic-F-127-coated SnO2 NPs exhibits enormous efficiency to be utilized as an talented anticancer agent.

Sodium alginate encapsulated iron oxide decorated with thymoquinone nanocomposite induces apoptosis in human breast cancer cells via PI3K-Akt-mTOR pathway.

The present study investigated the cytotoxicity and proapoptotic properties of iron oxide-sodium-alginate-thymoquinone nanocomposites against breast cancer MDA-MB-231 cells in vitro and in silico. This study used chemical synthesis to formulate the nanocomposite. Electron microscopies such as scanning (SEM) and transmission (TEM), Fourier transform infrared (FT-IR), Ultraviolet-Visible, Photoluminescence spectroscopy, selected area (electron) diffraction (SAED), energy dispersive X-ray analysis (EDX), and X-ray diffraction studies (XRD) were used to characterize the synthesized ISAT-NCs and the average size of them was found to be 55 nm. To evaluate the cytotoxic, antiproliferative, and apoptotic potentials of ISAT-NCs on MDA-MB-231 cells, MTT assays, FACS-based cell cycle studies, annexin-V-PI staining, ELISA, and qRT-PCR were used. PI3K-Akt-mTOR receptors and thymoquinone were predicted using in-silico docking studies. Cell proliferation is reduced in MDA-MB-231 cells due to ISAT-NC cytotoxicity. As a result of FACS analysis, ISAT-NCs had nuclear damage, ROS production, and elevated annexin-V levels, which resulted in cell cycle arrest in the S phase. The ISAT-NCs in MDA-MB-231 cells were found to downregulate PI3K-Akt-mTOR regulatory pathways in the presence of inhibitors of PI3K-Akt-mTOR, showing that these regulatory pathways are involved in apoptotic cell death. We also predicted the molecular interaction between thymoquinone and PI3K-Akt-mTOR receptor proteins using in-silico docking studies which also support PI3K-Akt-mTOR signaling inhibition by ISAT-NCs in MDA-MB-231 cells. As a result of this study, we can conclude that ISAT-NCs inhibit the PI3K-Akt-mTOR pathway in breast cancer cell lines, causing apoptotic cell death.

Effects of Albumin-Chlorogenic Acid Nanoparticles on Apoptosis and PI3K/Akt/mTOR Pathway Inhibitory Activity in MDA-MB-435s Cells.

In this study, we synthesized, characterized, and explored the anti-microbial and anti-cancer effects of albumin-chlorogenic acid nanoparticles (NPs). Characterization studies with a UV-vis spectrophotometer, FTIR, PL spectrum, TEM, FESEM, XRD, and DLA analysis showed patterns confirming the physio-chemical nature of biogenic nanocomposites. Further, anti-microbial studies using bacterial strains Staphylococcus aureus, Streptococcus pneumonia, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Vibrio cholera, and fungal strain Candida albicans showed significant (p < 0.05) anti-bacterial and anti-fungal activities. Next, we used MDA-MB-435s, a human cell line, to evaluate the anti-cancer effects of albumin-chlorogenic acid NPs. Cytotoxic studies revealed its IC50 concentration at 24 µg/mL after a 24 h treatment of MDA-MB-435s cells. We chose this IC50 dose to analyze albumin-chlorogenic acid NPs anti-cancer effects in vitro. MDA-MB-435s cells exposed to our NPs were studied via AO/EtBr staining, cell cycle analyses via PI staining, the status of whole genomic damage via comet assay, levels of apoptotic cells via annexin V/PI staining, ROS generation via DCFH-DA staining, an assay of antioxidant enzymes catalase, superoxide dismutase, and antioxidant GSH, via ELISA analyses of apoptotic markers caspase-3, 8, 9, Bax, Bcl-2, CytC, and p53, PI3/AKT/mTOR pathway. Our results collectively showed albumin-chlorogenic acid NPs induced apoptosis via p53-dependent and PI3/AKT/mTOR inhibition in MDA-MB-435s cells. Our results denote albumin-chlorogenic acid NPs can be used as an effective candidate for anti-microbial and anti-cancer applications; however, further in vivo confirmatory studies are warranted.

Therapeutic Potential of Albumin Nanoparticles Encapsulated Visnagin in MDA-MB-468 Triple-Negative Breast Cancer Cells.

Breast cancer is among the most recurrent malignancies, and its prevalence is rising. With only a few treatment options available, there is an immediate need to search for better alternatives. In this regard, nanotechnology has been applied to develop potential chemotherapeutic techniques, particularly for cancer therapy. Specifically, albumin-based nanoparticles are a developing platform for the administration of diverse chemotherapy drugs owing to their biocompatibility and non-toxicity. Visnagin, a naturally derived furanochromone, treats cancers, epilepsy, angina, coughs, and inflammatory illnesses. In the current study, the synthesis and characterization of albumin visnagin (AV) nanoparticles (NPs) using a variety of techniques such as transmission electron microscopy, UV-visible, Fourier transform infrared, energy dispersive X-ray composition analysis, field emission scanning electron microscopy, photoluminescence, X-Ray diffraction, and dynamic light scattering analyses have been carried out. The MTT test, dual AO/EB, DCFH-DA, Annexin-V-FITC/PI, Propidium iodide staining techniques as well as analysis of apoptotic proteins, antioxidant enzymes, and PI3K/Akt/mTOR signaling analysis was performed to examine the NPs' efficacy to suppress MDA-MB-468 cell lines. The NPs decreased cell viability increased the amount of ROS in the cells, disrupted membrane integrity, decreased the level of antioxidant enzymes, induced cell cycle arrest, and activated the PI3K/Akt/mTOR signaling cascade, ultimately leading to cell death. Thus, AV NPs possesses huge potential to be employed as a strong anticancer therapy alternative.

Clinical Characterization and Outcomes of Patients with Hypercreatinemia Affected by COVID-19.

The present study evaluated the clinical presentation and outcome of COVID-19 patients with underlying hypercreatinemia at the time of hospitalization. A retrospective observational study was conducted from the 23rd of March 2020 to the 15th of April 2021 in 1668 patients confirmed positive for COVID-19 in the Chest Disease Hospital in Srinagar, India. The results of the present study revealed that out of 1668 patients, 339 with hypercreatinemia had significantly higher rates of admission to the intensive care unit (ICU), severe manifestations of the disease, need for mechanical ventilation, and all-cause mortality. Multivariable analysis revealed that age, elevated creatinine concentrations, IL-1, D-Dimer, and Hs-Crp were independent risk factors for in-hospital mortality. After adjusted analysis, the association of creatinine levels remained strongly predictive of all-cause, in-hospital mortality (HR-5.34; CI-4.89-8.17; p ≤ 0.001). The amelioration of kidney function may be an effective method for achieving creatinemic targets and, henceforth, might be beneficial for improving outcomes in patients with COVID-19.

Study of Coagulation Disorders and the Prevalence of Their Related Symptoms among COVID-19 Patients in Al-Jouf Region, Saudi Arabia during the COVID-19 Pandemic.

INTRODUCTION: The coronavirus (COVID-19) has affected millions of people around the world. COVID-19 patients, particularly those with the critical illness, have coagulation abnormalities, thrombocytopenia, and a high prevalence of intravascular thrombosis. OBJECTIVES: This work aims to assess the prevalence of coagulation disorders and their related symptoms among COVID-19 patients in the Al-Jouf region of Saudi Arabia. SUBJECTS AND METHODS: We conducted a retrospective study on 160 COVID-19 patients. Data were collected from the medical records department of King Abdulaziz Specialist Hospital, Sakaka, Al-Jouf, Saudi Arabia. The socio-demographic data, risk factors, coagulation profile investigation results, symptom and sign data related to coagulation disorders, and disease morbidity and mortality for COVID-19 patients were extracted from medical records, and the data were stored confidentially. RESULTS: Males represented the highest prevalence of COVID-19 infection at 65%; 29% were aged 60 or over; 28% were smokers; and 36% were suffering from chronic diseases, with diabetes mellitus representing the highest prevalence. Positive D-dimer results occurred in 29% of cases, with abnormal platelet counts in 26%. CONCLUSION: Our findings confirm that the dysregulation of the coagulation cascade and the subsequent occurrence of coagulation disorders are common in coronavirus infections. The results show absolute values, not increases over normal values; thus, it is hard to justify increased risk and presence based on the presented data.

Insight into Oncogenic Viral Pathways as Drivers of Viral Cancers: Implication for Effective Therapy.

As per a recent study conducted by the WHO, 15.4% of all cancers are caused by infectious agents of various categories, and more than 10% of them are attributed to viruses. The emergence of COVID-19 has once again diverted the scientific community's attention toward viral diseases. Some researchers have postulated that SARS-CoV-2 will add its name to the growing list of oncogenic viruses in the long run. However, owing to the complexities in carcinogenesis of viral origin, researchers across the world are struggling to identify the common thread that runs across different oncogenic viruses. Classical pathways of viral oncogenesis have identified oncogenic mediators in oncogenic viruses, but these mediators have been reported to act on diverse cellular and multiple omics pathways. In addition to viral mediators of carcinogenesis, researchers have identified various host factors responsible for viral carcinogenesis. Henceforth owing to viral and host complexities in viral carcinogenesis, a singular mechanistic pathway remains yet to be established; hence there is an urgent need to integrate concepts from system biology, cancer microenvironment, evolutionary perspective, and thermodynamics to understand the role of viruses as drivers of cancer. In the present manuscript, we provide a holistic view of the pathogenic pathways involved in viral oncogenesis with special emphasis on alteration in the tumor microenvironment, genomic alteration, biological entropy, evolutionary selection, and host determinants involved in the pathogenesis of viral tumor genesis. These concepts can provide important insight into viral cancers, which can have an important implication for developing novel, effective, and personalized therapeutic options for treating viral cancers.

Impact of GSTT1 and GSTM1 Polymorphisms in the Susceptibility to Philadelphia Negative Chronic Myeloid Leukaemia.

BACKGROUND: Our research aimed to clarify the role of genetic polymorphisms in GST (T1 and M1) in the development of Ph-ve CML. MATERIALS AND METHODS: We report on a case-control study with 126 participants, divided into 26 patients with Ph-ve CML (57.7% male, 42.3% female) and 100 healthy volunteers (51% male, 49% female) with no medical history of cancer as a control population. All Ph-ve CML patients were diagnosed according to standard hematologic and cytogenetic criteria based on CBC, confirmed by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) to determine the presence or absence of the BCRABL gene, followed by bone marrow (BM) examination. RESULTS: Of the 26 studied cases, 50% had the GSTT1 null genotype against 21% of the control group, a statistically significant difference (CI= 1.519 - 9.317; p-value= 0.004). The GSTM1 null genotype was detected in 23.1% of cases and 35% of controls, a difference not statistically significant (OR= 0.557; CI= 0.205-1.515; p-value= 0.252). The distribution of GSTT1 and GSTM1 polymorphisms was also examined according to gender, age and ethnic grouping; these findings revealed no statistically significant differences. CONCLUSION: Our study reveals a strong correlation between GSTT1 polymorphism and Ph-ve CML, whereas the data for GSTM1 polymorphisms indicates no role in the initial development of the disease. More studies are required to further clarify these and other genes' roles in disease development.

In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma.

Anthraquinones (AQs) are present in foods, dietary supplements, pharmaceuticals, and traditional treatments and have a wide spectrum of pharmacological activities. In the search for anti-cancer drugs, AQ derivatives are an important class. In this study, anthraquinone aglycons chrysophanol (Chr), emodin (EM) and FDA-approved anticancer drug fluorouracil were analyzed by molecular docking studies against receptor molecules caspase-3, apoptosis regulator Bcl-2, TRAF2 and NCK-interacting protein kinase (TNIK) and cyclin-dependent protein kinase 2 (CDK2) as novel candidates for future anticancer therapeutic development. The ADMET SAR database was used to predict the toxicity profile and pharmacokinetics of the Chr and EM. Furthermore, in silico results were validated by the in vitro anticancer activity against HCT-116 and HeLa cell lines to determine the anticancer effect. According to the docking studies simulated by the docking program AutoDock Vina 4.0, Chr and EM had good binding energies against the target proteins. It has been observed that Chr and EM show stronger molecular interaction than that of the FDA-approved anticancer drug fluorouracil. In the in vitro results, Chr and EM demonstrated promising anticancer activity in HCT-116 and HeLa cells. These findings lay the groundwork for the potential use of Chr and EM in the treatment of human colorectal and cervical carcinomas.

Resolvins Lipid Mediators: Potential Therapeutic Targets in Alzheimer and Parkinson Disease.

Inflammation and resolution are highly programmed processes involving a plethora of immune cells. Lipid mediators synthesized from arachidonic acid metabolism play a pivotal role in orchestrating the signaling cascades in the game of inflammation. The majority of the studies carried out so far on inflammation were aimed at inhibiting the generation of inflammatory molecules, whereas recent research has shifted more towards understanding the resolution of inflammation. Owing to chronic inflammation as evident in neuropathophysiology, the resolution of inflammation together with the class of lipid mediators actively involved in its regulation has attracted the attention of the scientific community as therapeutic targets. Both omega-three polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, orchestrate a vital regulatory role in inflammation development. Resolvins derived from these fatty acids comprise the D-and E-series resolvins. A growing body of evidence using in vitro and in vivo models has revealed the pro-resolving and anti-inflammatory potential of resolvins. This systematic review sheds light on the synthesis, specialized receptors, and resolution of inflammation mediated by resolvins in Alzheimer's and Parkinson's disease.

Illuminating the Molecular Intricacies of Exosomes and ncRNAs in Cardiovascular Diseases: Prospective Therapeutic and Biomarker Potential.

Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide. Accumulating evidences have highlighted the importance of exosomes and non-coding RNAs (ncRNAs) in cardiac physiology and pathology. It is in general consensus that exosomes and ncRNAs play a crucial role in the maintenance of normal cellular function; and interestingly it is envisaged that their potential as prospective therapeutic candidates and biomarkers are increasing rapidly. Considering all these aspects, this review provides a comprehensive overview of the recent understanding of exosomes and ncRNAs in CVDs. We provide a great deal of discussion regarding their role in the cardiovascular system, together with providing a glimpse of ideas regarding strategies exploited to harness their potential as a therapeutic intervention and prospective biomarker against CVDs. Thus, it could be envisaged that a thorough understanding of the intricacies related to exosomes and ncRNA would seemingly allow their full exploration and may lead clinical settings to become a reality in near future.

Synthesis, Characterization, and Antimicrobial and Antiproliferative Effects of CuO-TiO2-Chitosan-Escin Nanocomposites on Human Leukemic MOLT4 Cells.

Nanocomposites comprised of CuO-TiO2-chitosan-escin, which has adjustable physicochemical properties, provide a solution for therapeutic selectivity in cancer treatment. By controlling the intrinsic signaling primarily through the mitochondrial signaling pathway, we desired nanocomposites with enhanced anticancer activity by containing CuO-TiO2-chitosan-escin. The metal oxides CuO and TiO2, the natural polymer chitosan, and a phytochemical compound escin were combined to form CuO-TiO2-chitosan-escin nanocomposites. The synthesized nanocomposites were confirmed and characterized using FTIR spectroscopy, TEM, and UV-Vis absorption spectroscopy. A human leukemia cell line (MOLT-4) was used to assess the efficacy and selectivity of nanocomposites. Based on a cytotoxicity study, CuO-TiO2-chitosan-escin nanocomposites had inhibition concentrations (IC50) of 13.68, 8.9, and 7.14 µg/mL against human T lymphoblast cells after 24, 48, and 72 h of incubation, respectively. Compared with untreated MOLT-4 cells, CuO-TiO2-chitosan-escin nanocomposite-treated cells significantly increased (p < 0.05) caspase-3, -8, and -9 and decreased the levels of antioxidant enzymes GR, SOD, and GSH. Furthermore, MDA for lipid peroxidase and ROS levels significantly increased (p < 0.05) in the treated cells than in the untreated cells. Remarkably, CuO-TiO2-chitosan-escin nanocomposite-mediated control of cell cycles were mainly achieved through the activation of caspase-3, -8, and -9.

Synthesis, Characterization, and Antiproliferative Effect of CuO-TiO2-Chitosan-Amygdalin Nanocomposites in Human Leukemic MOLT4 Cells.

The main aim of this study was to synthesize copper oxide- (CuO-) titanium oxide- (TiO2-) chitosan-amygdalin nanocomposites (CTCANc) and to characterize them physically and biologically (antimicrobial and anticancer activity using MOLT4 blood cancer cell line) to endorse their useful applications as potential drug candidates in anticancer avenues. CuO-TiO2-chitosan-amygdalin nanocomposites were synthesized according to standard, reported methods. Physical characterization of the nanocomposites was performed using methods like X-ray diffractometer (XRD), and morphological and ultrastructural analysis of nanocomposites were done using electron microscope scanning and transmission. FTIR was recorded using a Perkin-Elmer spectrometer, and photoluminescence (PL) spectra were done using the spectrometer. Further, antibacterial activities were assessed using standard bacterial cultures. To demonstrate the nanocomposite's anticancer effects, MTT assay, morphological analysis, apoptosis studies using acridine orange/ethidium bromide (AO/EtBr) dual staining, reactive oxygen species (ROS) analysis, and levels of antioxidant enzymes were analyzed using the MOLT4 blood cancer cell line. Synthesized nanocomposites were characterized using XRD and showed various peaks, respectively, for CuO-TiO2, amygdalin, and chitosan. MTT assay indicated an IC50 value of 38.41 µg/ml concentration of CTCANc. Hence, 30 and 40 µg/ml were used for the subsequent experiments. Morphological analysis, staining for apoptosis using AO/EtBr, mitochondrial membrane potential (MMP or ΔΨm) analysis, ROS analysis, and determination of the SOD, CAT, MDA, and GSH levels were performed. Observations like a significant loss of morphology, induction of apoptosis, elevated ROS, and decreased MMP were significant in 30 and 40 µg/ml nanocomposite-treated cells when compared to control cells. The bimetallic nanocomposites exhibited typical nanocomposites characteristics and significant antibacterial and anticancer effects. The study results endorse the antibacterial, anticancer activity of CuO-TiO2-chitosan-amygdalin nanocomposites and strongly suggest that further in-depth research using CuO-TiO2-chitosan-amygdalin nanocomposites could reveal their efficacy in the clinical scenario.

Structural, Optical, Antibacterial, and Anticancer Properties of Cerium Oxide Nanoparticles Prepared by Green Synthesis Using Morinda citrifolia Leaves Extract.

Currently, new advancements in the area of nanotechnology opened up new prospects in the field of medicine that could provide us with a solution for numerous medical complications. Although a several varieties of nanoparticles is being explored to be used as nanomedicines, cerium oxide nanoparticles (CeO2 NPs) are the most attractive due to their biocompatibility and their switchable oxidation state (+3 and +4) or in other words the ability to act as prooxidant and antioxidant depending on the pH condition. Green synthesis of nanoparticles is preferred to make it more economical, eco-friendly, and less toxic. The aim of our study here is to formulate the CeO2 NPs (CeO2 NPs) using Morinda citrifolia (Noni) leaf extract and study its optical, structural, antibacterial, and anticancer abilities. Their optical and structural characterization was accomplished by employing X-ray diffractography (XRD), TEM, EDAX, FTIR, UV-vis, and photoluminescence assays. Our CeO2 NPs expressed strong antibacterial effects against Gram-positive S. aureus and S. pneumonia in addition to Gram-negative E. coli and K. pneumonia when compared with amoxicillin. The anticancer properties of the green synthesized CeO2 NPs against human acute lymphoblastic leukemia (ALL) MOLT-4 cells were further explored by the meticulous study of their ability to diminish cancer cell viability (cytotoxicity), accelerate apoptosis, escalate intracellular reactive oxygen species (ROS) accumulation, decline the mitochondria membrane potential (MMP) level, modify the cell adhesion, and shoot up the activation of proapoptotic markers, caspase-3, -8, and -9, in the tumor cells. Altogether, the outcomes demonstrated that our green synthesized CeO2 NPs are an excellent candidate for alternative cancer therapy.

Synthesis of Zinc Oxide (ZnO)-Titanium Dioxide (TiO2)-Chitosan-Farnesol Nanocomposites and Assessment of Their Anticancer Potential in Human Leukemic MOLT-4 Cell Line.

Leukemia is the most prevalent cancer in children and one of the most common and deadly cancers that affect adults. Several metal oxide nanoparticles, biopolymers, and phytochemicals have been discovered to target cancer cells selectively while inflicting low to no damage to healthy cells. Among the existing nanoparticle synthesis methodologies, biologically synthesized nanoparticles using phytochemicals have emerged as a straightforward, economical, and environmentally sound strategy. The synergistic antitumor potential of ZnO-TiO2-chitosan-farnesol nanocomposites (NCs) against leukemia MOLT-4 cells was investigated in the current study. After synthesizing the NCs, characterization of the same was carried out using XRD, DLS, FESEM, TEM, PL, EDX, and FTIR spectroscopy. To analyze its anticancer activity, MOLT-4 cells were cultured and treated at diverse dosages of NCs. The cell viability upon treatment was examined by MTT assay. The morphological and nuclear modifications were observed by dual staining. ROS and MMP levels were observed by DCFH-DA staining and Rh-123 dye, respectively. Furthermore, the caspase 3, 8, and 9 levels were examined by performing ELISA. The XRD patterns exhibited a hexagonal structure of the NCs. In the DLS spectrum, the hydrodynamic diameter of the NCs was observed to be 126.2 nm. The electrostatic interface between the ZnO-TiO2-chitosan-farnesol NCs was confirmed by the FTIR spectra. A significant loss of cell viability in a dosage-dependent trend confirmed the cytotoxic effect of the NCs. An elevated ROS level and MMP depletion suggested apoptosis-associated cell death via the intrinsic pathway, which was confirmed by elevated expressions of caspase 3, 8, and 9 markers. Thus, the results showed that the synthesized NCs demonstrated a remarkable anticancer potential against leukemic cells and can be potentially valuable in cancer treatments. The findings from this study conclude that this is a new approach for modifying the physicochemical characteristics of ZnO-TiO2-chitosan-farnesol composites to increase their properties and synergistically exhibit anticancer properties in human leukemic cancer cells.