Design anticancer potential of Zn(II)isoleucinedithiocarbamate complex on MCF-7 cell lines: synthesis, characterization, molecular docking, molecular dynamic, ADMET, and in-vitro studies.

Cisplatin is a cancer medication widely used today, but it still poses some problems due to its toxic properties in the body. To overcome this issue, a new complex has been developed as a potential anticancer drug prospect by minimizing its toxic consequences. A novel Zn(II)IleDTC complex containing isoleucine dithiocarbamate ligands has been produced and analyzed using a range of analytical and spectroscopic methods. The Zn(II) IleDTC complex were characterized using various methods, including UV-Vis spectroscopy, FT-IR, determination of melting point, conductivity, and HOMO-LUMO analysis. Furthermore, computational NMR spectrum analysis was conducted in this study. Molecular docking studies was conducted to evaluate the potential of Zn(II) isoleucine dithiocarbamate as an HIF1 inhibitor. The results showed that the Zn complex exhibited a good docking score of -6.6 and formed hydrogen bonds with ARG 17, VAL264, and GLU15, alkyl bonds with TRP27 and LEU32, and Pi-Alkyl bonds with PRO41 and ARG44. This suggests that the Zn(II) isoleucine dithiocarbamate complex could be a promising candidate for cancer treatment with potential HIF1 inhibition properties. To assess the dynamic stability and efficacy of protein-ligand interactions over time, molecular dynamics simulations was conducted for both individual proteins and protein complexes. The cytotoxicity evaluation of Zn(II) isoleucine dithiocarbamate against MCF-7 cells obtained an IC50 value of 362.70 µg/mL indicating moderate cytotoxicity and morphological changes of cancer cells causing cancer cells to undergo apoptosis. The Zn(II) isoleucine dithiocarbamate complex may have promising potential as an anticancer compound due to its significant inhibitory effect on the breast cancer cell line (MCF7). According to the ADMET study, the complex exhibits drug-like characteristics with low toxicity, further supporting its potential as a viable drug candidate.

Serum iron levels in tuberculosis patients and household contacts and its association with natural resistance-associated macrophage protein 1 polymorphism and expression.

BACKGROUND: Iron deficiency can impair immune function, increasing tuberculosis (TB) susceptibility and severity. The research aimed to investigate iron deficiency anemia in TB patients and household contacts and its association with natural resistance-associated macrophage protein 1 (NRAMP1) polymorphism and expression. METHODS: The levels of iron, ferritin, and transferrin were measured in the serum by ELISA (Enzyme-Linked Immunosorbent Assay). NRAMP1 polymorphisms were determined by polymerase chain reaction (PCR) and sequencing. NRAMP1 gene expression was measured by real-time PCR. Interferon-gamma release assay (IGRA) checked on household contacts to screen household contacts with positive IGRA as the control. RESULTS: This study involved 35 TB cases and 35 TB contacts. The results showed that the serum Fe levels were found to be lower in the TB case group (median 149.6 µmol/L) than in the positive IGRA household contacts group (median 628.53 µmol/L) with a p-value <0.001. Meanwhile, ferritin levels in TB cases tended to be higher, in contrast to transferrin, which was found to tend to be lower in TB cases than household contacts but did not show a significant difference. This study found no association between the polymorphism of exon 15 D543 and active TB. However, NRAMP1 gene expression was lower in TB cases than in positive IGRA household contacts (p = 0.011). Besides, there was a positive correlation between NRAMP1 gene expression and serum Fe levels (r = 0.367, p = 0.006). TB was associated with decreased NRAMP1 gene expression (OR 0.086 95% CI 0.02-0.366, p = 0.001). Besides, TB was associated with low Fe levels (OR 0.533 95% CI 0.453-0.629, p < 0.001). CONCLUSION: Comparing the TB case to the household contacts group, decreased serum Fe levels were discovered in the TB case group. This study also shows a correlation of NRAMP1 gene expression to Fe levels in TB patients and household contacts and describes that TB may lead to decreased Fe levels by downregulating NRAMP1 expression.

Anticancer potential of Cu(II)prolinedithiocarbamate complex: design, synthesis, spectroscopy, molecular docking, molecular dynamic, ADMET, and in-vitro studies.

Breast cancer continues to be a major health issue for women all over the world. Cancer medications like cisplatin, which are widely used, still have negative side effects. The novel complex was created as a potential anticancer medication candidate that is both effective and safe, with few side effects. The Cu(II) complex using the prolinedithiocarbamate ligands was synthesized in situ. The Cu(II) complexes Characterization by UV-Vis, FT-IR spectroscopy and melting point determination, conductivity, and HOMO-LUMO were studied. Computational NMR spectrum analysis was performed. The interaction of Cu(II)prolineditiocarbamate complex with cancer cell target protein (MCF-7) was confirmed by molecular docking and molecular dynamic. The pharmacokinetic/ADMET properties were also performed on the complex. Results of the cytotoxic complex test against cancer cells (MCF-7) undergoing apoptosis with an IC50 value of 13.64 µg/mL showed high anticancer activity in MCF-7 cancer cells. The in-vivo data for Cu(II)prolineditiocarbamate complex was predicted using the Protox online tool with an LD50 value of 2500 mg/kg and belonging to the GHS toxicity class 5, which means the compound has a low acute toxicity effect. The Cu(II) prolineitiocarbamate complex may pave the way for the development of essential metal-based chemotherapy for the treatment of breast cancer.Communicated by Ramaswamy H. Sarma.

Expression of miRNA-29a-3p and IFN-γ as biomarkers in active and latent pulmonary tuberculosis.

Background: Diagnosis and management of latent tuberculosis (TB) infections are one of the challenges of eradicating pulmonary TB. A critical aspect of controlling pulmonary TB spread is early diagnosis. One TB biological marker type under evaluation is microRNAs (miRNAs). Mycobacterium tuberculosis infection causes epigenetic changes. The upregulation of miRNA-29a-3p suppresses the immune response by post-transcriptionally inhibiting interferon (INF)-γ expression in T cells, increasing susceptibility to pulmonary TB. This study aimed to assess miRNA-29a-3p expression as a biomarker of active and latent pulmonary TB infection. Methods: This case-control study included 50 individuals with active TB, 33 household contacts with a positive IFN-γ release assay (IGRA), and 30 healthy controls. An enzyme-linked immunosorbent assay-based IGRA was used to determine latent pulmonary TB infection in household contacts. Quantitative real-time PCR was used to quantify miRNA-29a-3p expression. Data analysis used analyses of variance and receiver operating characteristic (ROC) curves. Results: miRNA-29a-3p expression differed significantly between active TB, latent TB, and healthy participants (controls; p = <0.001. ROC curve analysis showed that miRNA-29a-3p expression had 86% sensitivity and 73% specificity with an area under the ROC curve (AUC) of 0.763 (95% confidence interval [CI]: 0.668-0.858). The miRNA-29a-3p ROC curve had 84.8% sensitivity and 70% specificity with an AUC of 0.808 (95% CI: 0.698-0.919) for latent TB. Additionally, miRNA-29a-3p expression was significantly correlated with active (p < 0.0001) and latent (p < 0.0001) pulmonary TB. However, miRNA-29a-3p expression was not significantly correlated with INF-γ levels in patients with active (R = 0.005; p = 0.62) and latent (R = 0.010; p = 0.38) pulmonary TB or healthy controls (R = 0.060; p = 0.19). Conclusion: miRNA-29a-3p expression was increased in patients with active and latent pulmonary TB. Therefore, miRNA-29a-3p represents a potential biomarker for latent and active pulmonary TB. However, IFN-γ levels were not correlated with miR-29a-3p expression.

A New Complex Design of Fe (II) Isoleucine Dithiocarbamate as a Novel Anticancer and Antivirus against SARSCOV-2 (COVID-19).

BACKGROUND: This study was carried out to synthesize a new complex of Fe(II) with isoleucine dithiocarbamate ligand and to determine its potential as an anticancer and antiviral agent for SARSCOV-2. METHODS: The synthesized complexes were then characterized by UV-vis and FT-IR spectroscopy and their melting points. The value of the conductivity of the complex compound is also determined. Anti-cancer activity was tested in vitro and molecular docking. Its potential as an antiviral against SARSCOV-2 was also carried out by molecular docking. Pharmacokinetics/ADMET properties were also carried out on the complex. RESULT: Spectral results showed the successful synthesis of Fe(II) isoleucine dithiocarbamate complex. The complex produced UV-vis spectra at 268 and 575 nm, and the IR data at 399-599 cm-1 showed the coordination between the Fe(II) atoms with sulphur, nitrogen and oxygen of the isoleucine dithiocarbamate ligand. Fe(II) isoleucine dithiocarbamate had a cytotoxicity effect on the MCF-7 cell line (IC50 =613 µg/mL). The complex significantly caused morphological changes in the breast cancer cell line, finally leading to cell apoptosis. CONCLUSION: Cytotoxic test of Fe(II) isoleucine dithiocarbamate showed moderate anticancer activity on MCF-7 cancer cells and showed antiviral activity against SARSCOV-2 by interfering with spike glycoprotein -ACE2 receptors, and inhibiting major proteases and 3Clpro.

Effects of synbiotic supplement on body weight and fasting blood glucose levels in obesity: A randomized placebo-controlled trial.

BACKGROUND: Obesity and diabetes are related. The role of gut microbiota disruption in obesity has been reported as a cause of several metabolic diseases including diabetes. OBJECTIVES: Evaluate the effects of synbiotic supplementation (a combination of probiotic and prebiotic) on body weight (BW), Body Mass Index (BMI), and Fasting Blood Glucose (FBG) in obese subjects. METHODS: This study was a randomized, double-blind placebo-controlled. Participants were allocated with randomization into 2 groups: the obese group with synbiotic supplementation and the obese group with placebo; each group consists of 8 participants. BW, BMI, and FBG level were measured at baseline, 8 weeks after supplementation, and 4 weeks after terminating the supplementation. RESULTS: There were no significant change of body weight and BMI after 8 weeks synbiotics supplementation and 4 weeks after supplement discontinuation, but there were significant increases in body weight by 3.38 kg and BMI by 1.37 kg/m2 in the control group. Fasting blood glucose levels were significantly decreased by 6.125 mg/dL after synbiotic supplementation. FBG did not resume 4 weeks after terminating the supplementation. In contrast, there was a significant increase of FBG in control group on week 8 and was further increased 4 weeks after placebo was discontinued. CONCLUSIONS: Synbiotic supplementation may prevent increase of body weight and BMI in obesity and this may be related with lower fasting blood glucose levels.

RbAp48 is essential for viability of vertebrate cells and plays a role in chromosome stability.

RbAp46/48, histone chaperone, is a family of evolutionarily conserved WD40 repeat-containing proteins, which are involved in various chromatin-metabolizing processes, but their in vivo functional relevance is yet unclear. In order to examine the biological role of pRbAp48 in chicken DT40 cells, we generated a tetracycline-inducible system for conditional RbAp48-knockout cells. Depletion of RbAp48 led to delayed S phase progression associated with slow DNA synthesis and nascent nucleosome formation, followed by accumulation in G2/M phase, finally leading to cell death. Prior to cell death, these cells exhibited aberrant mitosis such as highly condensed and abnormal chromosome alignment on the metaphase plate, leading to chromosome missegregation. Depletion of RbAp48 also caused dissociation of heterochromatin protein 1 (HP1) from pericentromeric heterochromatin. Furthermore, depletion of RbAp48 from cells led to elevated levels of acetylation and slightly decreased levels of methylation, specifically at Lys-9 residue of histone H3. These results suggest that RbAp48 plays an important role in chromosome stability for proper organization of heterochromatin structure through the regulation of epigenetic mark.

WD dipeptide motifs and LXXLL motif of chicken HIRA are essential for interactions with the p48 subunit of chromatin assembly factor-1 and histone deacetylase-2 in vitro and in vivo.

We cloned cDNA encoding chicken HIRA, a homolog of Saccharomyces cerevisiae transcriptional corepressors Hir1p and Hir2p, possessing seven WD dipeptide motifs and a LXXLL motif in its N-terminal and C-terminal regions, respectively. It binds to CAF-1p48, HDAC-1 and 2, but not to CAF-1p60, p46 polypeptide and HDAC-3. The immunoprecipitation experiment involving truncated and missense mutants of HIRA and CAF-1p48 revealed not only that even one of seven WD dipeptide motifs in the N-terminal half of HIRA are necessary for the interaction with CAF-1p48, but also that those of CAF-1p48 are necessary for the interaction with HIRA. These findings indicate that the proper propeller structures of both HIRA and CAF-1p48 are necessary for their in vitro interaction. The immunoprecipitation experiment involving truncated and missense mutants of HIRA and HDAC-2 revealed that the LXXLL motif in the C-terminal half of HIRA and a C-terminal region of HDAC-2 are necessary for their in vitro interaction. Moreover, the WD dipeptide motifs and LXXLL motif of HIRA are essential for the interaction with CAF-1p48 and HDAC-2 in vivo. Taken together, these results indicate that HIRA should participate differentially in a number of DNA-utilizing processes through interactions of its distinct regions with these proteins.