Assessment of Biological Damage Induced during Multidetector Computed Tomography (MDCT) Examination.

Computed tomography (CT) is known for its non-invasiveness, fast procedure, and also for providing detailed diagnostic information to physicians. It also utilises low-dose-rate ionising radiation (X-rays) as a source for imaging. Multidetector computed tomography (MDCT) is an advanced system that uses iodinated contrast media for more accurate diagnostic results. Studies suggest using these contrasts will lead to greater radiation adsorption with significant DNA damage. No studies have been taken comparing the physical dose with the biological effect. The present study sheds light on the same by assessing the biological effect of CT with and without contrast intervention. The present study is timebound; thus, 21 participants attending for CT thorax and abdomen with no history of any cancer were included. The same participants underwent both pre-contrast and post-contrast studies. The blood sample was taken before the procedure and used as a control. Physical parameters like DLP and CTDI obtained from the instrument were compared with the MN frequency obtained (CBMN Assay). The study showed a significant increase (p-value < 0.05) in the Physical and MN frequency in the Post-Contrast group compared to the pre-contrast group. Although a positive correlation was observed between pre and post-contrast groups, the results were not found to be statistically significant (p-value < 0.05). The study confirms increased physical dose and MN frequency upon contrast intervention. This study recommends the judicial use of MDCT in disease diagnostics.

Medium-Chain Fatty Acids and Breast Cancer Risk by Receptor and Pathological Subtypes.

Introduction: Medium-chain fatty acids contain 6-12 carbon atoms and are absorbed directly into the blood vessels, proceeding to the portal vein and, finally, to the liver, where they are immediately utilized for energy. We aimed to determine the medium-chain fatty acid levels in women with and without breast cancer. Materials and Methods: A total of 200 women (100 breast cancer subjects and 100 control subjects) were recruited for the study as per the inclusion and exclusion criteria. Blood samples were collected for biochemical estimations. Fatty acid methyl esters were isolated, and medium-chain fatty acid levels in plasma were analyzed using gas chromatography (GC-FID). Statistical analysis was performed using SPSS 20.0 software; p ≤ 0.05 was considered statistically significant. Results: The fatty acid analysis revealed a significant decrease in the levels of caprylic acid (C:8) and lauric acid (C:12) and a significant increase in the level of capric acid (C:10) in the breast cancer subjects when compared to the control group. The level of caproic acid (C:6) was not significantly increased in the breast cancer subjects. In particular, the HER2- and ER-positive breast cancer subjects showed a decrease in their caprylic acid and lauric acid levels compared to other receptors. Conclusions: The results of the current study imply that lower levels of caprylic and lauric acid may be associated with a higher risk of breast cancer. The relevance of medium-chain fatty acids for preventive and therapeutic interventions will be amplified by further research on the possibility that alteration in a patient's medium-chain fatty acid composition may mechanistically contribute to disease progression or breast cancer risk.

Tetraspanin CD9: A friend or foe of head and neck cancer (Review).

Head and neck cancers are diverse and complex diseases characterised by unregulated growth of tumour cells in various parts of the head and neck region, such as in the buccal mucosa, floor of the mouth, tongue, oropharynx, hypopharynx, oesophagus, nasopharynx and salivary glands. Partial or total glossectomy, radiation or chemotherapy greatly affect patient quality of life. However, even following treatment, patients may relapse. Nicotine­derived nitrosamines and alcohol are the major etiological factors underlying this deadly disease. These compounds induce DNA damage that may lead to mutation in crucial genes, such as p53 and p21, which are important to regulate cell proliferation, thus leading to cancer. CD9 is a tetraspanin, which are a group of transmembrane proteins that have a role in cell motility and adhesion. The present review aimed to explore the role of CD9 in head and neck cancer. Epidermal growth factor receptor activity and cell proliferation are regulated by the CD9­integrin/CD9­transforming growth factor interaction. Hence, CD9 can play a dual role in various types of cancer.

Pathway enrichment analysis of virus-host interactome and prioritization of novel compounds targeting the spike glycoprotein receptor binding domain-human angiotensin-converting enzyme 2 interface to combat SARS-CoV-2.

SARS-CoV-2 has become a pandemic causing a serious global health concern. The absence of effective drugs for treatment of the disease has caused its rapid spread on a global scale. Similarly to the SARS-CoV, the SARS-CoV-2 is also involved in a complex interplay with the host cells. This infection is characterized by a diffused alveolar damage consistent with the Acute Respiratory Disease Syndrome (ARDS). To explore the complex mechanisms of the disease at the system level, we used a network medicine tools approach. The protein-protein interactions (PPIs) between the SARS-CoV and the associated human cell proteins are crucial for the viral pathogenesis. Since the cellular entry of SARS-CoV-2 is accomplished by binding of the spike glycoprotein binding domain (RBD) to the human angiotensin-converting enzyme 2 (hACE2), a molecule that can bind to the spike RDB-hACE2 interface could block the virus entry. Here, we performed a virtual screening of 55 compounds to identify potential molecules that can bind to the spike glycoprotein and spike-ACE2 complex interface. It was found that the compound ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4-piperidine carboxylate (the S54 ligand) and ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4 piperazine carboxylate (the S55 ligand) forms hydrophobic interactions with Tyr41A, Tyr505B and Tyr553B, Leu29A, Phe495B, respectively of the spike glycoprotein, the hotspot residues in the spike glycoprotein RBD-hACE2 binding interface. Furthermore, molecular dynamics simulations and free energy calculations using the MM-GBSA method showed that the S54 ligand is a stronger binder than a known SARS-CoV spike inhibitor SSAA09E3 (N-(9,10-dioxo-9, 10-dihydroanthracen-2-yl) benzamide).Communicated by Ramaswamy H. Sarma.

Insight into OroxylinA-7-O-ß-d-Glucuronide-Enriched Oroxylum indicum Bark Extract in Oral Cancer HSC-3 Cell Apoptotic Mechanism: Role of Mitochondrial Microenvironment.

Oroxylum indicum, of the Bignoniaceae family, has various ethnomedical uses such as an astringent, anti-inflammatory, anti-bronchitis, anti-helminthic and anti-microbial, including anticancer properties. The druggability of OI stem bark extract was determined by its molecular docking interactions with PARP and Caspase-3, two proteins involved in cell survival and death. Note that 50 µg/mL of Oroxylum indicum extract (OIE) showed a significant (p < 0.05%) toxicity to HSC-3 cells. MTT aided cell viability and proliferation assay demonstrated that 50 µg/mL of OIE displayed significant (p < 0.5%) reduction in cell number at 4 h of incubation time. Cell elongation and spindle formation was noticed when HSC-3 cells were treated with 50 µg/mL of OIE. OIE initiated DNA breakage and apoptosis in HSC-3 cells, as evident from DNA ladder assay and calcein/EB staining. Apoptosis potential of OIE is confirmed by flow cytometer and triple-staining (live cell/apoptosis/necrosis) assay. Caspase-3/7 fluorescence quenching (LANCE) assay demonstrated that 50 µg/mL of OIE significantly enhanced the RFU of caspases-3/7, indicating that the apoptosis potential of OIE is probably through the activation of caspases. Immuno-cytochemistry of HSC-3 cells treated with 50 µg/mL of OIE showed a significant reduction in mitochondrial bodies as well as a reduction in RFU in 60 min of incubation time. Immunoblotting studies clearly showed that treatment of HSC-3 cells with OI extract caused caspase-3 activation and PARP deactivation, resulting in apoptotic cell death. Overall, our data indicate that OIE is an effective apoptotic agent for human squamous carcinoma cells and it could be a future cancer chemotherapeutic target.

Association of Sperm Aneuploidy Frequency and DNA Fragmentation Index in Infertile Men.

BACKGROUND: For improving the evaluation of male infertility, many parameters were studied and reported in earlier literature. The aim of this study was to estimate the frequency of sperm aneuploidy and DNA fragmentation in infertile men and to assess the correlation between sperm aneuploidy and DNA fragmentation. METHODS: In this study 100 infertile men were included, cases with azoospermia were 68%, oligospermia 18%, severe oligospermia 6%, and oligoasthenoteratospermia (OAT) 8%. Ten normozoospermic men who had two normal children were included as a control. The sperm aneuploidy test by Fluorescence In Situ Hybridization (FISH) and sperm DNA fragmentation index by TdT (Terminal deoxynucleotidyl transferase)-mediated dUTP nick end labelling (TUNEL) were carried out. To determine the aneuploidy status and DNA fragmentation index, frequency was used. The correlation between sperm aneuploidy and sperm DNA fragmentation along with age was assessed by using Spearman's correlation coefficient. The p<0.05 was considered significant. RESULTS: The age of 100 subjects ranged between 22-48 years (35.5±5.1). Sperm aneuploidy frequency and DNA fragmentation rate were found to be higher in infertile men compared to control men (n=10). There was a significant relationship between age and sex chromosomal aneuploidy (p<0.05) and significant difference between sperm aneuploidy and damaged DNA (p<0.05). CONCLUSION: FISH and TUNEL assay results showed increased sperm aneuploidy frequency, and DNA fragmentation index in infertile men compared with the fertile men. There is significant relationship observed between sperm aneuploidy and DNA fragmentation. These two parameters are important and they must be investigated for clinical practice.

Haematopoietic, Antioxidant and Membrane Stabilizing Property of Diallyl Disulphide in Irradiated Mice.

INTRODUCTION: Diallyl disulphide is an organo-sulphur compound which is present in garlic and responsible for the characteristic odor of garlic. It is known for its anticancer and invitro membrane stabilizing properties. AIM: The main aim was to evaluate the haematopoietic, antioxidant and membrane stabilizing property of diallyl disulfide in irradiated mice. MATERIALS AND METHODS: Mice were grouped into 6 groups as control, drug control, radiation control and drug pre-treatment groups (i.e. drug administration + radiation group) The mice were fed orally for 15 consecutive days and on the 15(th) day, one hour after drug administration, the mice were irradiated with 6Gy electron beam radiation. The changes in blood cell count, total antioxidant levels, malondialdehyde and reduced glutathione levels were determined. The immunomodulatory response of DADS to the radiological effects was determined by the estimation of IL-6 levels. RESULTS: A significant improvement in pre-drug treatment group when compared to control groups in the haemoglobin, red blood cell count, white blood cell count, haematocrit and platelet counts was observed. There is an increased level of interleukin-6 in the drug treated groups compared to the radiation control. An increase in the malondialdehyde levels and decrease in the glutathione levels in the irradiated group indicate increased lipid peroxidation and oxidative stress, whereas, there is a significant reduction in the malondialdehyde levels and increased glutathione levels in the drug pre-treatment groups showing membrane stabilization. CONCLUSION: Thus DADS proves to be an effective haematopoietic and antioxidative agent to counter radiation induced haematopoietic suppression and oxidative stress.