Prospective of nanoscale metal organic frameworks [NMOFs] for cancer therapy.

Nano metal organic frameworks (NMOFs) belong to the group of nanoporous materials. Over the decades, the conducted researches explored the area for the potential applications of NMOFs in areas like biomedical, chemical engineering and materials science. Recently, NMOFs have been explored for their potential use in cancer diagnosis and therapeutics. The excellent physico-chemical features of NMOFs also make them a potential candiadate to facilitate drug design, delivery and storage against cancer cells. In this review, we have explored the characterstic features, synthesis methods, NMOFs based drug delivery, diagnosis and imaging in various cancer types. In addition to this, we have also pondered on the stability and toxicological concerns of NMOFs. Despite, a significant research has been done for the potential use of NMOFs in cancer diagonostic and therapeutics, more information regarding the stability, in-vivo clearance, toxicology, and pharmacokinetics is still needed to ehnace the use of NMOFs in cancer diagonostic and therapeutics.

A Study on the Effect of Vitamins A and C to Modulate the Expression of NKG2D Ligands in Hepatic and Colon Cancer Cells.

Recently, vitamins have been shown to act as epigenetic modifier. Cancer cells exhibit transcriptional downregulation of NK group 2D ligands (NKG2DLs) through repressive methylation and are largely resistant to NK cell-mediated eradication. We herein investigated the potential of recently reported epigenome modifying vitamins A, C, and E in inducing the expression of epigenetically silenced NKG2DLs in cancer cells. Based on the cell viability assay three concentrations, i.e., 25, 50, and 100 µg/ml of all vitamins were selected for treatment. Results showed that treatment of both vitamin A and C significantly upregulates expression of two major NKG2DLs namely MICA and MICB. Simultaneously, both, vitamin A and C significantly reduces the methylation process by downregulating DNA methyltransferases (DNMTs) expression level. Vitamin C, but not vitamin A, significantly upregulates TETs (DNA demethylases) expression. Further, we assessed the impact of both vitamins A and C on S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio levels and found no significant changes in SAM/SAH ratio. Overall, we clearly found that both vitamin A and C induces NKG2DLs mostly through repressing the expression of DNMTs, suggesting their potential role in improving the targeting of tumor cells by promoting the engagement and clearance of tumor cells with NK cells.

Urolithin A and B Alter Cellular Metabolism and Induce Metabolites Associated with Apoptosis in Leukemic Cells.

Leukemia is persistently a significant cause of illness and mortality worldwide. Urolithins, metabolites of ellagic acid and ellagitannins produced by gut microbiota, showed better bioactive compounds liable for the health benefits exerted by ellagic acid and ellagitannins containing pomegranate and walnuts. Here, we assessed the potential antileukemic activities of both urolithin A and urolithin B. Results showed that both urolithin A and B significantly inhibited the proliferation of leukemic cell lines Jurkat and K562, among which urolithin A showed the more prominent antiproliferative capability. Further, urolithin treatment alters leukemic cell metabolism, as evidenced by increased metabolic rate and notable changes in glutamine metabolism, one-carbon metabolism, and lipid metabolism. Next, we evidenced that both urolithins equally promoted apoptosis in leukemic cell lines. Based on these observations, we concluded that both urolithin A and B alter leukemic cell metabolome, resulting in a halt of proliferation, followed by apoptosis. The data can be used for designing new combinational therapies to eradicate leukemic cells.

LC-MS/MS-based metabolic profiling of Escherichia coli under heterologous gene expression stress.

Escherichia coli is frequently exploited for genetic manipulations and heterologous gene expression studies. We have evaluated the metabolic profile of E. coli strain BL21 (DE3) RIL CodonPlus after genetic modifications and subjecting to the production of recombinant protein. Three genetically variable E. coli cell types were studied, normal cells (susceptible to antibiotics) cultured in simple LB medium, cells harboring ampicillin-resistant plasmid pET21a (+), grown under antibiotic stress, and cells having recombinant plasmid pET21a (+) ligated with bacterial lactate dehydrogenase gene grown under ampicillin and standard isopropyl thiogalactoside (IPTG)-induced gene expression conditions. A total of 592 metabolites were identified through liquid chromatography-mass spectrometry/mass spectrometry analysis, feature and peak detection using XCMS and CAMERA followed by precursor identification by METLIN-based procedures. Overall, 107 metabolites were found differentially regulated among genetically modified cells. Quantitative analysis has shown a significant modulation in DHNA-CoA, p-aminobenzoic acid, and citrulline levels, indicating an alteration in vitamin K, folic acid biosynthesis, and urea cycle of E. coli cells during heterologous gene expression. Modulations in energy metabolites including NADH, AMP, ADP, ATP, carbohydrate, terpenoids, fatty acid metabolites, diadenosine tetraphosphate (Ap4A), and l-carnitine advocate major metabolic rearrangements. Our study provides a broader insight into the metabolic adaptations of bacterial cells during gene manipulation experiments that can be prolonged to improve the yield of heterologous gene products and concomitant production of valuable biomolecules.

Proproliferative function of adaptor protein GRB10 in prostate carcinoma.

Growth factor receptor-binding protein 10 (GRB10) is a well-known adaptor protein and a recently identified substrate of the mammalian target of rapamycin (mTOR). Depletion of GRB10 increases insulin sensitivity and overexpression suppresses PI3K/Akt signaling. Because the major reason for the limited efficacy of PI3K/Akt-targeted therapies in prostate cancer (PCa) is loss of mTOR-regulated feedback suppression, it is therefore important to assess the functional importance and regulation of GRB10 under these conditions. On the basis of these background observations, we explored the status and functional impact of GRB10 in PCa and found maximum expression in phosphatase and tensin homolog (PTEN)-deficient PCa. In human PCa samples, GRB10 inversely correlated with PTEN and positively correlated with pAKT levels. Knockdown of GRB10 in nontumorigenic PTEN null mouse embryonic fibroblasts and tumorigenic PCa cell lines reduced Akt phosphorylation and selectively activated a panel of receptor tyrosine kinases. Similarly, overexpression of GRB10 in PTEN wild-type PCa cell lines accelerated tumorigenesis and induced Akt phosphorylation. In PTEN wild-type PCa, GRB10 overexpression promoted mediated PTEN interaction and degradation. PI3K (but not mTOR) inhibitors reduced GRB10 expression, suggesting primarily PI3K-driven regulation of GRB10. In summary, our results suggest that GRB10 acts as a major downstream effector of PI3K and has tumor-promoting effects in prostate cancer.-Khan, M. I., Al Johani, A., Hamid, A., Ateeq, B., Manzar, N., Adhami, V. M., Lall, R. K., Rath, S., Sechi, M., Siddiqui, I. A., Choudhry, H., Zamzami, M. A., Havighurst, T. C., Huang, W., Ntambi, J. M., Mukhtar, H. Proproliferatve function of adaptor protein GRB10 in prostate carcinoma.

COVID-19: Prospective Challenges and Potential Vaccines.

CONTEXT: RNA viruses exhibit an extraordinary ability to evolve in a changing environment and to switch from animal hosts to humans. The ongoing COVID-19 pandemic, recognized as a respiratory disease, is an example of zoonotic transmission of the RNA virus known as SARS-CoV-2. The development and regulatory approval of a vaccine against SARS-CoV-2 pose multiple preventive and therapeutic challenges, especially during an ongoing pandemic. OBJECTIVE: The review intended to examine the challenges and recent achievements in the development of vaccine candidates against COVID-19. DESIGN: The research team performed a literature review, searching relevant and up to date information from the literature. The sources of data included Google Scholar, PubMed, NCBI, and Yahoo. The search terms used were COVID-19 challenges, SARS-CoV-2 prospective challenges, RNA viruses adoptability, host switching by RNA viruses, COVID-19 vaccines. SETTING: The study took place at the digital libraries of contributing institutions. The data was combined, selected for further analysis and manuscript preparation at King Abdulaziz University. RESULTS: RNA viruses with high rate of genome alterations and evolution have better chances to survive in the adverse environmental conditions by adopting the alternate host species. The recent epidemics such as SARS, MERS, and COVID-19 are examples of zoonotic transmission of RNA viruses from animal species to the humans. However, the mechanisms involved in the switching-on to new host species need further investigations to control the zoonotic transmissions in near future. As of April 2020, 115 candidate vaccines were being evaluated; 78 of them had been found to be active, and a few of them are in Phase I trials. In the development of different types of vaccine candidates against COVID-19, multiple international pharmaceutical and biotechnology companies are involved. CONCLUSIONS: Emerging and re-emerging pathogenic RNA viruses pose a serious threat to human health. Little is known about the human-host adoptive mechanism for zoonotic transmission. Deep insights into the molecular mechanism responsible for the switching of animal or bird viruses to humans could provide target molecules or events to prevent such transmissions in the near future. Fast development and approval of efficacious and safe vaccines is key to the effort to provide preventive measures against COVID-19 and future viruses. However, the development and availability of a vaccine candidate is a time-consuming process and often can't be completed during an epidemic. Currently, several types of vaccines are under development, and most of them won't realistically be available in time for the present COVID-19 pandemic.

Concomitance of downregulated active caspase-3 and upregulated X-chromosome linked inhibitor of apoptosis protein as a sensitive diagnostic approach for breast cancer.

We aimed to explore the efficacy of active caspase-3 and X-chromosome linked inhibitor of apoptosis protein (XIAP) as diagnostic markers for breast cancer. Furthermore, we examined the relationship between the examined parameters and clinicopathological factors. The current study involved 96 patients diagnosed with breast cancer and 40 patients had benign breast diseases. The expression of active caspase-3 was analyzed by both ELISA and Western blot, whereas the expression of XIAP was determined by ELISA in cell lysates. Active caspase-3 was significantly downregulated, while XIAP was markedly upregulated in patients with breast cancer in comparison to benign group. A significant negative correlation was observed between active caspase-3 and XIAP in breast cancer patients. Low active caspase-3 expression was associated with high grade, whereas, the high XIAP level was correlated with poorly differentiated tumors and late tumor stages. The sensitivity and specificity were 73.96% and 80.0% for active caspase-3, and, 70.83% and 82.5% for XIAP. A combination of active caspase-3 and XIAP provided a promising sensitivity of 88.54% and specificity of 90.0%. Our data indicate that active caspase-3 and XIAP could be substantial diagnostic markers for breast cancer patients.

Synthesis and in vitro antitumor activity of novel acylspermidine derivative N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide (AAHD) against HepG2 cells.

Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.

Identification of variants in the mitochondrial lysine-tRNA (MT-TK) gene in myoclonic epilepsy-pathogenicity evaluation and structural characterization by in silico approach.

Variations in mitochondrial genes have an established link with myoclonic epilepsy. In the present study we evaluated the nucleotide sequence of MT-TK gene of 52 individuals from 12 unrelated families and reported three variations in 2 of the 13 epileptic patients. The DNA sequences coding for MT-TK gene were sequenced and mutations were detected in all participants. The mutations were further analyzed by the in silico analysis and their structural and pathogenic effects were determined. All the investigated patients had symptoms of myoclonus, 61.5% were positive for ataxia, 23.07% were suffering from hearing loss, 15.38% were having mild to severe dementia, 69.23% were males, and 61.53% had cousin marriage in their family history. DNA extracted from saliva was used for the PCR amplification of a 440 bp DNA fragment encompassing complete MT-TK gene. The nucleotide sequence analysis revealed three mutations, m.8306T>C, m.8313G>C, and m.8362T>G that are divergent from available reports. The identified mutations designate the heteroplasmic condition. Furthermore, pathogenicity of the identified variants was predicted by in silico tools viz., PON-mt-tRNA and MitoTIP. Secondary structure of altered MT-TK was predicted by RNAStructure web server. Studies by MitoTIP and PON-mt-tRNA tools have provided strong evidences of pathogenic effects of these mutations. Single nucleotide variations resulted in disruptive secondary structure of mutant MT-TK models, as predicted by RNAStructure. In vivo confirmation of structural and pathogenic effects of identified mutations in the animal models can be prolonged on the basis of these findings.

Synthetic strigolactone analogues reveal anti-cancer activities on hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic cancer via alteration of oxidative stress and inflammatory mechanism.

Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1ß (IL-1ß) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity.

The role of Gut Microbiota in the development of obesity and Diabetes.

Obesity and its associated complications like type 2 diabetes (T2D) are reaching epidemic stages. Increased food intake and lack of exercise are two main contributing factors. Recent work has been highlighting an increasingly more important role of gut microbiota in metabolic disorders. It's well known that gut microbiota plays a major role in the development of food absorption and low grade inflammation, two key processes in obesity and diabetes. This review summarizes key discoveries during the past decade that established the role of gut microbiota in the development of obesity and diabetes. It will look at the role of key metabolites mainly the short chain fatty acids (SCFA) that are produced by gut microbiota and how they impact key metabolic pathways such as insulin signalling, incretin production as well as inflammation. It will further look at the possible ways to harness the beneficial aspects of the gut microbiota to combat these metabolic disorders and reduce their impact.

Role of hesperetin in LDL-receptor expression in hepatoma HepG2 cells.

BACKGROUND: High plasma concentration of low-density lipoprotein cholesterol (LDL-c) plays a significant role in the incidence of atherosclerosis and coronary heart diseases. The aim of this study was to investigate the mechanism by which the citrus flavonoid, hesperetin, regulates the LDL receptor (LDLr) gene in the human liver using the human hepatoma cell line, HepG2. METHODS: Luciferase reporter gene assays were performed (in the absence of lipoprotein) to measure the activity of the LDLr promoter and the promoters of the sterol regulatory element binding protein (SREBP) transcription factors that control the LDLr promoter. RESULTS: Only SREBP-1 promoter activity was significantly increased 4 h after exposure to 200 µM hesperetin. However, after 24 h incubation with 200 µM hesperetin, the activities of all the promoter-constructs, SREBP-1a, -1c, -2 and LDLr, were significantly increased. The effects of 200 µM hesperetin on elevating LDLr mRNA levels were possibly due to regulation of LDLr gene transcription by SREBP-la and SREBP-2. CONCLUSIONS: We conclude that 200 µM hesperetin was likely to have stimulated LDLr gene expression in human hepatoma HepG2 cells via increased phosphorylation of PI3K andERK1/2, which increased SREBP-1a and SREBP-2 mRNA levels and enhanced the maturation of the encoded proteins. This may lead to lower plasma LDL cholesterol; therefore, diets supplemented with hesperidin might provide cardio-protective effects and reduce mortality and morbidity from coronary heart diseases.

The hepatoprotective activity of olive oil and Nigella sativa oil against CCl4 induced hepatotoxicity in male rats.

BACKGROUND: Liver disease is the major cause of serious health problem leading to morbidity and mortality worldwide and the problem has increased in search for hepatotherapeutic agents from plants. The present study was designed to compare the probable hepatoprotective activity of olive oil and N. sativa oil on CCl4 induced liver damage in male rats. METHODS: Forty males of a new model of albino rats (Wistar strain) (175-205 g) were divided into four groups. The 1st Group (G1) was the negative control group, the remaining rats were injected with CCl4 (1 ml/kg body weight) with equal amount of olive oil on the 1st and 4th day of every week for 4 weeks. The 2nd group (G2) was the positive control, the 3rd group (G3) and the fourth group (G4) were treated orally with N. sativa oil and olive oils using stomach tube. RESULTS: The positive control group showed an increase in hepatic enzymes, total bilirubin, creatinine, uric acid, lipid peroxide total cholesterol, triglyceride, low density lipoprotein, very low density lipoproteins, interleukin-6, and a decrease in antioxidant enzymes, high density lipoprotein cholesterol, a decrease in total protein and albumin an when compared with negative control group. Histology of the CCl4 treated group revealed inflammation and damage of liver cells. Treating the hepatotoxic rats with olive oil and N. sativa oil showed a significant improvement in all biochemical tests compared with the positive CCl4 control group. In addition, the liver tissues of olive oil treated group showed mild improvement in inflammatory infiltration and in N. sativa oil treated group showed normal hepatocytes with no evidence of inflammation. CONCLUSION: This study revealed that olive oil and N. sativa oil have a protective effect against CCl4-induced hepatotoxicity in male rats. Nigella sativa oil was more effective than olive oil.

Label-free and ultrasensitive electrochemical transferrin detection biosensor based on a glassy carbon electrode and gold nanoparticles.

In this study, we developed a label-free and ultrasensitive electrochemical biosensor for the detection of transferrin (Tf), an important serum biomarker of atransferrinemia. The biosensor was fabricated by using glassy carbon electrode (GCE) and modified with gold nanoparticles (AuNPs) via electroless deposition. The electrochemical characteristics of the GCE-AuNPs biosensors were characterized using cyclic voltammetry and electrochemical impedance spectroscopy analysis. Differential pulse voltammetry was used for quantitative evaluation of the Tf-antigen by recording the increase in the anodic peak current of GCE-AuNPs biosensor. The GCE-AuNPs biosensor demonstrates superior sensing performance for Tf-antigen fortified in buffer, with a wide linear range of 0.1 to 5000 µg/mL and a limit of detection of 0.18 µg/mL. The studied GCE-AuNPs biosensor showed excellent sensitivity, selectivity, long-term storage stability and simple sensing steps without pretreatment of clinical samples. This GCE-AuNPs biosensor indicates great potential for developing a Tf detection platform, which would be helpful in the early diagnosis of atransferrinemia. The developed GCE-AuNPs biosensor holds great potential in biomedical research related to point of care for the early diagnosis and monitoring of diseases associated with aberrant serum transferrin levels. These findings suggest that the GCE-AuNPs biosensor has great potential for detecting other serum biomarkers.

Brace-related Stress and Quality of Life Parameters between Chêneau and Boston Braces: A Cross-sectional Comparative Study on Adolescent Idiopathic Scoliosis in Saudi Arabia.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is the most prevalent spinal deformity affecting healthy children. Although AIS typically lacks symptomatic manifestations, its resultant deformities can affect patients' quality of life (QoL). Evaluating QoL and stress levels is crucial in determining the optimal brace type for AIS patients; however, research comparing the effectiveness of different brace types in this regard is lacking. Therefore, this study aimed to evaluate the impact of Boston versus Chêneau braces on QoL and stress levels in AIS patients. METHODS: This cross-sectional study was conducted at a medical institution in Riyadh, Saudi Arabia, involving 52 eligible patients selected through stratified random sampling based on type of brace as the main stratum. The inclusion criteria were idiopathic scoliosis, age ≥ 10 years, bracing for at least 3 months, and no history of cancer. QoL was evaluated according to the revised Scoliosis Research Society 22-item questionnaire (SRS-22r) and stress levels according to the eight-item Bad Sobernheim stress questionnaire (BSSQ-Brace). Independent-sample t-tests were used to compare brace-related QoL and stress level according to participants' sex and brace type. RESULTS: Overall, 32 participants were treated with Boston braces (seven men and 25 women), with a median (IQR) age of 11.00 years (10.00-13.00), and 20 participants were treated with Chêneau braces (three men, 17 women), with a median (IQR) age of 12.50 years (10.00-14.25). The total SRS-22 score was not significantly different between the brace groups (p = 0.158). However, patients in the Boston brace group reported significantly higher satisfaction levels (median = 4.00, IQR = 3.50-4.50) than did those in the Chêneau brace group (median = 3.25, IQR = 2.38-4.13, p = 0.013, moderate effect size = 0.345, 95% CI = 0.060 to 0.590). Furthermore, the BSSQ-brace total score was significantly higher in the Boston brace group (median = 9.00, IQR = 8.00-12.00) than in the Chêneau brace group (median = 7.50, IQR = 4.75-10.00, p = 0.007, moderate effect size = 0.376, 95% CI = 0.130 to 0.590), indicating higher stress levels in the Chêneau brace group. CONCLUSION: The QoL in AIS patients undergoing brace treatment was comparable across groups. Nonetheless, patients who used Chêneau braces experienced higher stress levels and lower treatment satisfaction rates than did those who used Boston braces. These findings can inform clinical decisions regarding prescription of bracing types and highlight the need for further in-depth research.

Fabrication of an affordable and sensitive corticosteroid-binding globulin immunosensor based on electrodeposited gold nanoparticles modified glassy carbon electrode.

Herein, we fabricated an ultrasensitive electrochemical immunosensor for the quantitative detection of corticosteroid-binding globulin (CBG). CBG is a protein that regulates glucocorticoid levels and is an important biomarker for inflammation. A decrease in CBG levels is a key biomarker for inflammatory diseases, such as septic shock. To enhance the electrochemical performance and provide a large surface area for anti-CBG immobilization, we functionalized the glassy carbon electrode surface with AuNPs. Electrochemical characterization methods including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to examine the construction of the fabricated immunosensor. The electrochemical signal demonstrated a remarkable sensitivity to the CBG antigen, with a detection range from 0.01 to 100 µg/mL and a limit of detection of 0.012 µg/mL, making it suitable for both clinical and research applications. This label-free immunosensor offers significant advantages, including high sensitivity, low detection limits and excellent selectivity, making it a promising tool for detecting CBG in complex biological samples. Its potential applications include early disease diagnosis, treatment monitoring and studying CBG-related physiological processes.

Synthesis of carbon nanotubes-chitosan nanocomposite and immunosensor fabrication for myoglobin detection: An acute myocardial infarction biomarker.

The use of single-walled carbon nanotubes (SWCNTs) in biomedical applications is limited due to their inability to disperse in aqueous solutions. In this study, dispersed -COOH functionalized CNTs with N-succinylated chitosan (CS), greatly increasing the water solubility of CNTs and forming a uniformly dispersed nanocomposite solution of CNTs@CS. Coupling reagent EDC/NHS was used as a linker with the -COOH groups present on the N-succinylated chitosan which significantly improved the affinity of the CNTs for biomolecules. Myoglobin (Mb) is a promising biomarker for the precise assessment of cardiovascular risk, type 2 diabetes, metabolic syndrome, hypertension and several types of cancer. A high level of Mb can be used to diagnose the mentioned pathogenic diseases. The CNTs@CS-FET demonstrates superior sensing performance for Mb antigen fortified in buffer, with a wide linear range of 1 to 4000 ng/mL. The detection limit of the developed Mb immunosensor was estimated to be 4.2 ng/mL. The novel CNTs@CS-FET immunosensor demonstrates remarkable capability in detecting Mb without being affected by interferences from nonspecific antigens. Mb spiked serum showed a recovery rate of 100.262 to 118.55 % indicating great promise for Mb detection in clinical samples. The experimental results confirmed that the CNTs@CS-FET immunosensor had excellent selectivity, reproducibility and storage stability.

An affordable label-free ultrasensitive immunosensor based on gold nanoparticles deposited on glassy carbon electrode for the transferrin receptor detection.

In recent decades, there has been a concerning and consistent rise in the incidence of cancer, posing a significant threat to human health and overall quality of life. The transferrin receptor (TfR) is one of the most crucial protein biomarkers observed to be overexpressed in various cancers. This study reports on the development of a novel voltammetric immunosensor for TfR detection. The electrochemical platform was made up of a glassy carbon electrode (GCE) functionalized with gold nanoparticles (AuNPs), on which anti-TfR was immobilized. The surface characteristics and electrochemical behaviors of the modified electrodes were comprehensively investigated through scanning electron microscopy, XPS, Raman spectroscopy FT-IR, electrochemical cyclic voltammetry and impedance spectroscopy. The developed immunosensor exhibited robust analytical performance with TfR fortified buffer solution, showing a linear range (LR) response from 0.01 to 3000 µg/mL, with a limit of detection (LOD) of 0.01 µg/mL and reproducibility (RSD <4 %). The fabricated sensor demonstrated high reproducibility and selectivity when subjected to testing with various types of interfering proteins. The immunosensor designed for TfR detection demonstrated several advantageous features, such as being cost-effective and requiring a small volume of test sample making it highly suitable for point-of-care applications.

Molecular docking, molecular dynamics simulation and MM-GBSA studies of the activity of glycyrrhizin relevant substructures on SARS-CoV-2 RNA-dependent-RNA polymerase.

SARS-CoV-2 is the causative agent of Coronavirus Disease (COVID-19), which is a life-threatening disease. The World Health Organization has classified COVID-19 as a severe worldwide public health pandemic due to its high death rate, quick transmission, and lack of medicines. To counteract the recurrence of the severe acute respiratory syndrome, active antiviral medications are urgently required. Glycyrrhizin was documented with activity on different viral proteins, including SARS-CoV-2; in this study, the activity of glycyrrhizin and its substructures (604 molecules) were screened on SARS-CoV-2 RNA-dependent-RNA polymerase using molecular docking, molecular dynamic (MD) simulation, and MM/GBSA. Sixteen molecules exhibited docking energy higher than -7 kcal/mol; four compounds (10772603, 101088272, 154730753 and glycyrrhizin) showed the highest binding energy, and good stability during MD simulation. The glycyrrhizin compound exhibited favorable docking energy (-7.9 kcal/mol), and it was the most stable complex during MD simulation. The predicted binding free energy of the glycyrrhizin complex was -57 ± 8 kcal/mol. These findings suggest that this molecule, after more validation, could become a good candidate for developing and manufacturing an anti-SARS-CoV-2 medication.Communicated by Ramaswamy H. Sarma.