Potential role of salivary vitamin D antimicrobial peptide LL-37 and interleukins in severity of dental caries: an exvivo study.

INTRODUCTION: Vitamin D performs various functions as a hormone by promoting calcium absorption but plays a major role in innate immunity,cell differentiation, cell maturation through its genomic effects via vitamin D receptor. The immune response also plays a major role in tooth surface and supporting structure destruction and playing a major factor in high caries formation. The inflammatory cytokines are released has proinflammatory cytokines and stimulate cells in disease process. Therefore, in the present study we have evaluated the association of salivary vitamin D, LL-37, interleukins 6 and 17A in various levels of severity of dental caries. METHOD: Ethical approval was obtained (NU/CEC/2020/0339), 377 individuals reporting to department of conservative dentistry and endodontics, AB Shetty memorial institute of dental sciences were included based on inclusion criteria. The individuals were further divided into caries free(N = 105) and caries active(N = 272) based on their caries prevalence. The salivary were collected and evaluated for vitamin D, LL-37,IL-17A and IL-6.Results were statistically analysed with SPSS vs 22 (IBM Corp, USA). Normally distributed data were expressed as mean ± SD. Skewed data were expressed as median and interquartile range. To compare (mean) outcome measures between the two groups unpaired independent t-test was applied and for values in median IQR, Mann Whitney U test was used. All statistical analysis for P value were two-sided and significance was set to P ≤ 0.05. RESULTS: The study showed that, the salivary vitamin D statistically decreased with increasing severity of caries which showed that vitamin D plays an important role in prevention of caries. Antimicrobial peptide LL-37 was higher in caries free group but was not statistically significant, salivary IL-6 level was higher in caries active group but intergroup comparison did not show significant difference. Salivary IL-17A did not show statistically significant between caries active and caries free group. CONCLUSION: The salivary levels of vitamin D may play a vital role in prevalence of dental caries and its severity which can be a underlying cause in presence of other etiological factors.

Genome-scale protein interaction network construction and topology analysis of functional hypothetical proteins in Helicobacter pylori divulges novel therapeutic targets.

The emergence and spread of multi-drug resistance among Helicobacter pylori (H. pylori) strain raise more stakes for genetic research for discovering new drugs. The quantity of uncharacterized hypothetical proteins in the genome may provide an opportunity to explore their property and promulgation could act as a platform for designing the drugs, making them an intriguing genetic target. In this context, the present study aims to identify the key hypothetical proteins (HPs) and their biological regulatory processes in H. pylori. This investigation could provide a foundation to establish the molecular connectivity among the pathways using topological analysis of the protein interaction networks (PINs). The giant network derived from the extended network has 374 nodes connected via 925 edges. A total of 43 proteins with high betweenness centrality (BC), 54 proteins with a large degree, and 23 proteins with high BC and large degrees have been identified. HP 1479, HP 0056, HP 1481, HP 1021, HP 0043, HP 1019, gmd, flgA, HP 0472, HP 1486, HP 1478, and HP 1473 are categorized as hub nodes because they have a higher number of direct connections and are potentially more important in understanding HP's molecular interactions. The pathway enrichment analysis of the network clusters revealed significant involvement of HPs in pathways such as flagellar assembly, bacterial chemotaxis and lipopolysaccharide biosynthesis. This comprehensive computational study revealed HP's functional role and its druggability characteristics, which could be useful in the development of drugs to combat H. pylori infections.

Salivary Calprotectin Levels and Bone Mineral Density in Post-Menopausal Women With and Without Chronic Periodontitis - An Evaluative Study.

INTRODUCTION: Menopause is a normal developmental stage in a woman's life marking the permanent cessation of menstruation. Periodontitis and osteoporosis are noteworthy health concerns in post-menopausal women. Calprotectin is an inflammatory biomarker for precise diagnosis of periodontal disease. MATERIALS AND METHODS: This study was performed to evaluate the variations in salivary calprotectin levels and bone mineral density in post-menopausal women with and without chronic periodontitis. The study included 24 post-menopausal women aged 45-57 years and was divided into group 1 (12 post-menopausal women without chronic periodontitis) and group 2 (12 post-menopausal women with chronic periodontitis). Unstimulated salivary samples, panoramic radiographs and clinical examination were performed. RESULTS: The collected samples were combined with CALPRO antibody with horseradish peroxide (HRP) that results in the formation of antigen-antibody complex. Tetramethylbenzidine (TMB) solution was added that turned blue. Colour change was measured at 450nm. A human ELISA kit was used. Data collected were sent for statistical analysis. DISCUSSION: There was a statistically significant difference in salivary calprotectin levels between groups 1 and 2 ( P = 0.016) and no statistical difference in mean bone mineral density levels between the two groups ( P = 0.235). A positive correlation was seen between salivary calprotectin levels and bone mineral density in group 2 ( P = 0.013).

High expression of CD9 and Epidermal Growth Factor Receptor promotes the development of tongue cancer.

Tongue cancer is distinguished by aggressive behavior, a high risk of recurrence, lymph, and distant metastases. Hypoxia-Induced Factor 1 α functions as a CD9 transcription factor. CD9 is a transmembrane protein that may be found on the cell membrane. It can modulate the expression of the Epidermal Growth Factor Receptor (EGFR) pathway. ELISA was used to measure serum CD9, p-EGFR, and p-Akt levels in 70 tongue cancer patients and 35 healthy controls. RT-PCR was used to analyze the gene expression of the related genes. The gene as well as protein expression of CD9, EGFR/p-EGFR, and Akt/p-Akt was significantly higher in case subjects when compared with the controls. The expression of CD9 was higher in case subjects who were smokers/alcoholics when to control subjects who were smokers/alcoholics. Overexpression of CD9 due to hypoxic conditions leads to the activation of EGFR-signaling pathway resulting in cancer progression, resistance to chemotherapy. Hence, CD9 could be a potential target to suppress cancer progression.

Design and synthesis of positional isomers of 5 and 6-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles as possible antimicrobial and antitubercular agents.

In this Letter, we report the structure-activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles derivatives 7(a-j) and 8(a-j) synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The crystal structure of 7a was evidenced by X-ray diffraction study. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7b, 7e and 7h displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

Fatty acid transport proteins (FATPs) in cancer.

Lipids play pivotal roles in cancer biology. Lipids have a wide range of biological roles, especially in cell membrane synthesis, serve as energetic molecules in regulating energy-demanding processes; and they play a significant role as signalling molecules and modulators of numerous cellular functions. Lipids may participate in the development of cancer through the fatty acid signalling pathway. Lipids consumed in the diet act as a key source of extracellular pools of fatty acids transported into the cellular system. Increased availability of lipids to cancer cells is due to increased uptake of fatty acids from adipose tissues. Lipids serve as a source of energy for rapidly dividing cancerous cells. Surviving requires the swift synthesis of biomass and membrane matrix to perform exclusive functions such as cell proliferation, growth, invasion, and angiogenesis. FATPs (fatty acid transport proteins) are a group of proteins involved in fatty acid uptake, mainly localized within cells and the cellular membrane, and have a key role in long-chain fatty acid transport. FATPs are composed of six isoforms that are tissue-specific and encoded by a specific gene. Previous studies have reported that FATPs can alter fatty acid metabolism, cell growth, and cell proliferation and are involved in the development of various cancers. They have shown increased expression in most cancers, such as melanoma, breast cancer, prostate cancer, renal cell carcinoma, hepatocellular carcinoma, bladder cancer, and lung cancer. This review introduces a variety of FATP isoforms and summarises their functions and their possible roles in the development of cancer.

Association between iron profile status and insulin resistance in patients with type 2 diabetes mellitus.

Introduction: Individuals' burden of insulin resistance and metabolic syndrome, such as type 2 diabetes mellitus, is increasing. This indicates to intrigue into various facets of prevention, early screening, prognostication and feasible treatment alternatives in this arena. Aim: This study targets to evaluate iron profile status among people diagnosed with type 2 diabetes mellitus and normoglycemic in order to deduce association between iron parameters and insulin resistance, if any exist. Methodology: A case-control study of total 123 subjects, comprising males and females in the age group of 30 - 70 years were recruited for the study. Case group constituted 81 participants who were diagnosed with type 2 diabetes mellitus and control group constituted 42 healthy individuals who attended routine health check-ups in the hospital. Iron profile parameters including Serum Iron, Serum Ferritin, Total Iron binding Capacity and Glycemic profile parameter like fasting blood glucose, serum insulin were estimated. Transferrin saturation and HOMA-IR were calculated. Result: Ferritin and Transferrin saturation was found to be higher in cases than in controls with significance of p = 0.003 and p = 0.021 respectively and TIBC (total iron-binding capacity) was lesser in cases with p = 0.031. Comparison of Serum Iron values did not yield a significant result. Correlation study between ferritin and insulin resistance parameters yielded a satisfactory result in the cases (p<0.05) and controls (p<0.01) separately. Conclusion: This study implies that there is a clear link between iron profile status, notably ferritin, and the emergence of insulin resistance, and hence insulin production. This study supports the function of the micronutrient iron in the etiology of type 2 diabetes and its consequences.

Steroidal alkaloid solanidine impedes hypoxia-driven ATM phosphorylation to switch on anti-angiogenesis in lung adenocarcinoma.

PURPOSE: The declined oxygen tension in the cancer cell leads to the hypoxic adaptive response and favors establishment of tumor micro environment [TEM]. The complex TME consists of interwoven hypoxic HIF-1α and DNA damage repair ATM signaling. The ATM/HIF-1α phosphorylation switch on angiogenesis and abort apoptosis. Targeting this signaling nexus would be a novel therapeutic strategy for the treatment of cancer. BACKGROUND: Steroidal alkaloid solanidine is known for varied pharmacological role but with less molecular evidences. Our earlier findings on solanidine proven its anti-neoplastic activity by inducing apoptosis in lung cancer. In continued research, efforts have been made to establish the underlying molecular signaling in induction of DNA damage in prevailing hypoxic TME. METHODS: The solanidine induced DNA damage was assessed trough alkali COMET assay; signaling nexus and gene expression profile analysis through IB, qRT-PCR, Gelatin Zymography, IHC, IF and ELISA. Pathophysiological modulations assessed through tube formation, migration, invasion assays. Anti-angiogenic studies through CAM, rat aorta, matrigel assays and corneal neovascularization assay. Anti-tumor activity through in-vivo DLA ascites tumor model and LLC model. RESULTS: The results postulates, inhibition of hypoxia driven DDR proteins pATMser1981/pHIF-1αser696 by solanidine induces anti-angiogenesis. Systematic study of both non-tumorigenic and tumorigenic models in-vitro as well as in-vivo experimental system revealed the angio-regression mediated anticancer effect in lung cancer. These effects are due to the impeded expression of angiogenic mediators such as VEGF, MMP2&9 and inflammatory cytokines IL6 and TNFα to induce pathophysiological changes CONCLUSION: The study establishes new role of solanidine by targeting ATM/HIF-1α signaling to induce anti-angiogenesis for the first time. The study highlights the potentiality of plant based phytomedicine solanidine which can targets the multiple hallmarks of cancer by targeting interwoven signaling crosstalk. Such an approach through solanidine necessary to counteract heterogeneous complexity of cancer which could be nearly translated into drug.

Environmental pollutants and their effects on human health.

Numerous environmental contaminants significantly contribute to human disease, affecting climate change and public and individual health, resulting in increased mortality and morbidity. Because of the scarcity of information regarding pollution exposure from less developed nations with inadequate waste management, higher levels of poverty, and limited adoption of new technology, the relationship between pollutants and health effects needs to be investigated more. A similar situation is present in many developed countries, where solutions are only discovered after the harm has already been done and the necessity for safeguards has subsided. The connection between environmental toxins and health needs to be better understood due to difficulties in quantifying exposure levels and a lack of systematic monitoring. Different pollutants are to blame for both chronic and acute disorders. Additionally, research becomes challenging when disease problems are seen after prolonged exposure. This review aims to discuss the present understanding of the association between environmental toxins and human health in bridging this knowledge gap. The genesis of cancer and the impact of various environmental pollutants on the human body's cardiovascular, respiratory, reproductive, prenatal, and neural health are discussed in this overview.

Six-month follow-up of salivary antioxidant defense outcomes of individuals using medicated toothpaste.

Objective: The objective of this study was to study the effect of medicated toothpaste on oral health, a 6-month follow-up. Methods: Four hundred and twenty-seven participants were screened and followed up for 6 months. The intraoral examination was performed to record caries, gingival bleeding, and plaque index. Saliva collected was evaluated for pH, total antioxidant capacity (TAC), malondialdehyde (MDA), and Vitamin C level for 6 months, and data were analyzed. Results: On the usage of medicated toothpaste with herbal extract for 6 months, the salivary pH levels were increased, the interquartile range for plaque, and the gingival bleeding index decreased. The percentage change in salivary TAC, MDA, and Vitamin C levels in the caries-free group of subgroup I was 174.8, 58.06, and 59.98, respectively, in subgroup II was 133.3, 52.08, and 58.51, and in subgroup III was 63.77, 45.11, and 47.77. The percentage change in salivary TAC, MDA, and Vitamin C levels in the caries-active group of subgroup I was 136.62, 57.27, and 72.83, subgroup II was 108.59, 37.50, and 61.55, and in subgroup III was 35.62, 30.82, and 54.10, respectively. Conclusion: The salivary pH levels increased on the usage of medicated toothpaste with herbal extract; plaque and the gingival bleeding index scores were decreased. The salivary antioxidant defense was increased in individuals using medicated toothpaste with herbal extracts which signifies an improvement in overall oral health in the 6-month follow-up.

Prognostic significance of tetraspanin CD9 and oncogenic epidermal growth factor receptor in tongue squamous cell carcinoma survival.

The most prevalent locations for head and neck cancer is the tongue. The surviving patients who are receiving therapy have considerably compromised speech, taste, chewing, and swallowing. CD9 is a cell surface protein that has contradictory role in cancer progression. The objective of the study is to analyze the Cluster of Differentiation 9(CD9), Epidermal Growth Factor Receptor (EGFR) and Phosphorylated Akt (p-Akt) expression in tongue cancer specimens and its clinical significance.50 tongue cancer sections were used to analyze the expression of CD9,EGFR and p-Akt by immunohistochemistry. Data regarding the histological grade of the tumor, age, sex, and habits were recorded, and relation with CD9,EGFR and p-Akt expression was assessed. Data were expressed as mean ± SEM. Categorical data was analyzed by Chi-square test. Student t-test was used to check the significance of data between two groups.A significant increase in the CD9,EGFR and p-Akt expression (1.8 ± 0.11, 2.06 ± 0.18 and 2.3 ± 0.15 respectively) was seen in the tongue cancer specimens. CD9 and p-Akt expression had a significant association with the histological grade (p < 0.004 and p < 0.006 respectively). CD9 expression was higher in patients with the combination of addiction/habit compared to patients with single addictions(1.08 ± 0.11 and 0.75 ± 0.47). Overall a poor rate of survival was observed in CD9 positive patients(p < 0.039). EGFR and p-Akt expression increased with increasing expression of CD9, suggesting its use as a biomarker to track the development of TSCC.

Utilizing the Potential of Antimicrobial Peptide LL-37 for Combating SARS-COV- 2 Viral Load in Saliva: an In Silico Analysis.

Limiting the spread of virus during the recent pandemic outbreak was a major challenge. Viral loads in saliva, nasopharyngeal and oropharyngeal swabs were the major cause for droplet transmission and aerosols. Saliva being the major contributor for the presence of viral load is the major key factor; various mouthwashes and their combination were analyzed and utilized in health care centers to hamper the spread of virus and decrease viral load. The compositions of these mouthwashes to an extent affected the viral load and thereby transmission, but there is always a scope for other protocols which may provide better results. Here we evaluated the potential of antimicrobial peptide LL-37 in decreasing the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through an in silico work and evidence from other studies. This narrative review highlighted a brief nonsystematic methodology to include the selected articles for discussion. Accessible electronic databases (Medline, Scopus, Web of Science, SciELO, and PubMed) were used to find studies that reported the salivary viral load of SARS-CoV-2 published between December 2019 and June 2021. The following keywords were utilized for brief searching of the databases: "saliva," "viral load," and "SARS-CoV-2." Articles in English language, in vitro cell-line studies, ex vivo studies, and clinical trials explaining the viral load of SARS-CoV-2 in saliva and strategies to decrease viral load were included in this review. The search was complemented by manual searching of the reference lists of included articles and performing a citation search for any additional reviews. The antiviral potential of cationic host defense peptide LL-37 was evaluated using computational approaches providing in silico evidence. The analysis of docking studies and the display of positive interfacial hydrophobicity of LL-37 resulting in disruption of COVID-19 viral membrane elucidate the fact that LL-37 could be effective against all variants of SARS-CoV-2. Further experimental studies would be needed to confirm the binding of the receptor-binding domain with LL-37. The possibility of using it in many forms further to decrease the viral load by disrupting the viral membrane is seen.

Correlation of preferentially expressed antigen of melanoma (PRAME) gene expression with clinical characteristics in acute leukemia patients.

BACKGROUND: Preferentially expressed antigen of melanoma (PRAME) gene is regularly overexpressed in acute leukemia (AL) and other malignant diseases which are recognized by human leucocyte antigen (HLA-24) located in the human chromosome of 22q11 coded by 509 amino acids. To rule out the PRAME gene expression in AL patients and its correlation with clinical characteristics in the Indian population set up by RT-qPCR. RESULTS: A total of 42 samples collected, 29 (69.4%) were males, and 13 (30.95%) were females, with a mean and standard deviation for age were 39.07 ± 22.22 years. Of which AML were of 22 (52.38%) cases, ALL were of 14 (33.33%) cases, and 6 (14.2%) cases which included other forms of leukemia. PRAME gene expression was highly expressed in thirty-three 27 (64.28%) AL patients compared to the least expression in healthy individuals. No significant difference between the different forms of AL (p=0.3203) was observed. Cytogenetic analysis of normal karyotype (NK), abnormal karyotype (Ab. K), and culture failure (CF) displayed statistical non-significance (p=0.5801). Among cytogenetic abnormalities obtained, no significant differences between the groups were observed (p=0.8507). Chloride, potassium, and absolute lymphocyte count (ALC) was found to be statistically significant with p=0.0038**, p=0.0358*, and p=0.0216*, respectively, between all other clinical characteristics. There was no correlation between the PRAME gene expression and clinical parameters. CONCLUSION: PRAME gene expression in AL patients was highly expressed, comparable to studies reported globally with significant cytogenetic results. PRAME gene could be used as a potential diagnostic marker for monitoring the malignancies and minimal residual disease in AL.

Antiproliferative pharmacophore azo-hydrazone analogue BT-1F exerts death signalling pathway targeting STAT3 in solid tumour.

BACKGROUND: Anomalous activation of intra-cellular signalling cascades confers neoplastic properties on malignant cells. The JAK2/STAT3 proteins play a pivotal role in the pathogenesis of most of the solid malignancies. The over expression of STAT3 in these tumours results in an evasion of apoptosis and thereby pathogenesis. Hence, strategy to target STAT3 to regress tumour development is an emerging new concept. As an approach, anti-neoplastic drug, Azo-hydrozone analogue, BT-1F with potential anti-proliferative effect was evaluated to demonstrate its capacity to counteract STAT3 signal with mechanistic approach. METHODS: Cell based screening for cytotoxicity was performed through MTT, LDH and Trypan blue. The BT-1F induced anti-clonogenic property by clonogenic assay. The apoptotic capacity was examined by crystal violet staining, flow cytometry, Annexin-FITC, DAPI and TUNEL assay. The altered signalling events were studied using immunoblot. The drug-induced anti-tumour effect was evaluated in an in-vivo solid tumour model and molecular interaction was further validated by in-silico studies. RESULTS: The BT-1F exerts chemo-sensitivity specifically against EAC and A549 cells without altering its normal counterpart. The anti-proliferative/anti-clonogenic effect was due to the induction of apoptosis through inhibition of STAT3Tyr705 signal. Eventually downstream signalling proteins p53, Bax, Bad and Bcl-xL were significantly altered. Further in-vivo experimental results validated  in-vitro findings. The computational approaches assures the BT-1F efficiency in binding with STAT3. CONCLUSION: Systemic validation of STAT3 target drug, BT-1F in in-vitro, in-silico and in-vivo models has promising strategy for solid cancer treatment.

Fatty acid desaturase 2 (FADS 2) rs174575 (C/G) polymorphism, circulating lipid levels and susceptibility to type-2 diabetes mellitus.

Several factors influence an individual's susceptibility in inter-individual lipid changes and its role in the onset of type-2 diabetes mellitus (T2DM). Considering the above fact, the present investigation focuses on determining the association between fatty acid desaturase 2 (FADS2) rs174575 (C/G) polymorphism, circulating lipid levels and susceptibility to type-2 diabetes mellitus. As per the inclusion and exclusion criteria a total of 429 subjects (non-diabetic-216; diabetic-213) were recruited for the study. Glycemic and lipid profile status were assessed using commercially available kits. Based on the previous reports SNP rs174575 of fatty acid desaturase gene (FADS2) was selected and identified using the dbSNP database. The amplified products were sequenced by means of Sanger sequencing method. Lipid profile status and apolipoprotein levels revealed statistically significant difference between the groups. Three models were assessed namely, recessive model (CC vs CG + GG), dominant model (CC + CG vs GG) and additive model (CC vs CG vs GG). The recessive model, displayed a statistically significant variations between the circulating lipid levels in T2DM. The multivariate model with genotype (G allele carriers), triglyceride (TG) and insulin served as a predictive model. The study results potentiate the functional link between FADS2 gene polymorphism, lipid levels and type-2 diabetes mellitus.

ω-6/ω-3 fatty acid ratio as an essential predictive biomarker in the management of type 2 diabetes mellitus.

OBJECTIVES: Intake of dietary fatty acid may play a major role in the prevention and management of lifestyle-related diseases such as type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to find an association between ω-6 to ω-3 fatty acid ratio and T2DM. METHODS: Fasting plasma glucose, glycated hemoglobin, and insulin were measured using commercially available kits. Fatty acid methyl esters were prepared using standard protocols. Delta-5 desaturase (D5D) and delta-6 desaturase (D6D) activities were determined from product-to-precursor ratios of individual fatty acids in plasma. Statistical analysis was performed using SPSS version 20. RESULTS: The ratio of ω-6 to ω-3 was higher in the group with diabetes (13:1) when compared with the group without diabetes (4:1) and was statistically significant (P < 0.0001). Further association studies showed that univariate model with the ω-6 to ω-3 ratio and a multivariate model with D5D, D6D, and ω-6 to ω-3 ratio could serve as predictive polyunsaturated fatty acid pathway models for T2DM. CONCLUSIONS: From the study results, it is evident that ω-6 to ω-3 fatty acid ratios can serve as essential predictive biomarkers in the management of patients with T2DM. This would not only help in management but would also aid in prevention of increased T2DM incidence in India. These results potentiate the need to maintain an ideal balance of ω-6 to ω-3, as prevention is always better than cure.

Aqueous extract from Madhuca indica bark protects cells from oxidative stress caused by electron beam radiation: in vitro, in vivo and in silico approach.

In an endeavor to find the novel natural radioprotector to secure normal cells surrounding cancerous cell during radiation exposure, Madhuca indica (M. indica) aqueous stem bark extract was evaluated for radioprotective activity using in vitro, in vivo, and in silico models. M. indica extract exhibited concentration dependent protective effect on electron beam radiation (EBR) induced damage to pBR322 DNA; the highest protection was achieved at 150 µg concentrations. Similarly, M. indica extract (400 mg/kg) administrated to mice prior to irradiation protected DNA from the radiation damage, which was confirmed by inhibiting comet parameters. The study showed a significant increase in the levels of glutathione and superoxide dismutase levels. The study also revealed that administration of M. Indica at the different dose to mice significantly reduced EBR induced MDA, sialic acid and nitric acid levels. Further extract prevented histophatological changes of skin and liver. In contrast, protein-protein interaction studies were performed to find the hub protein, involved in radiation-induced DNA damage. Among 437 proteins that are found expressed during radiation, p53 was found to be a master protein regulating the whole pathway. Molecular interaction between p53 and M. indica extract was predicted by quantitative structure-activity relationship and ADMET properties. Biomolecules such as quercetin, myricetin, and 7-hydroxyflavone were found to be promising inhibitors of p53 protein and may help in the protection of EBR induced DNA damage during cancer treatment.

In vivo study on the release of nickel, chromium, and zinc in saliva and serum from patients treated with fixed orthodontic appliances.

BACKGROUND: Fixed orthodontic appliances can release metal ions such as nickel, chromium, and zinc into saliva and blood, which can cause contact dermatitis, hypersensitivity, and cytotoxicity. This study was undertaken to assess the release of nickel, chromium, and zinc in saliva and serum of patients undergoing fixed orthodontic treatment. MATERIALS AND METHODS: This in vivo study was conducted on 80 participants with an age range of 15-40 years. Thirty were included as controls and 50 participants were treated with fixed orthodontic appliances. Saliva and blood samples were collected at five different periods, before insertion of fixed orthodontic appliance and at 1 week, 3 months, 1 year, and 1.5 years after insertion of appliance, respectively. The metal ion content in the samples were analyzed by atomic absorption spectrophotometry. Mean levels of nickel, chromium, and zinc in saliva and serum were compared between groups using independent sample t-test and before and after results using paired t-test. P < 0.05 was considered as statistically significant. RESULTS: At the end of 1.5 years, the mean salivary levels of nickel, chromium, and zinc in controls were 5.02 ppb, 1.27 ppb, and 10.24 ppb, respectively, as compared to 67 ppb, 30.8 ppb, and 164.7 ppb at the end of 1.5 years. This was statistically significant with P < 0.001. A significant increase in the metal ion levels were seen in participants with before and after insertion of appliance (P < 0.001). CONCLUSION: Orthodontic appliances do release considerable amounts of metal ions such as nickel, chromium, and zinc in saliva and serum. However, it was within permissible levels and did not reach toxic levels.

Estimation of Antioxidant Levels in Saliva and Serum of Chronic Periodontitis Patients with and without Ischemic Heart Disease.

OBJECTIVE: To investigate whether there is a relationship between periodontitis and ischemic heart disease by estimation of total antioxidant status in saliva and serum. MATERIALS AND METHODS: A total of 80 samples were collected and divided equally into 4 groups of healthy controls, chronic periodontitis patients, ischemic heart disease patients with periodontitis, and ischemic heart disease patients without periodontitis. Saliva and venous blood samples were collected and analyzed for levels of total antioxidant capacity, superoxide dismutase, glutathione peroxidase, and catalase. RESULTS: There were significant (p < 0.05) differences in the mean serum levels of total antioxidant capacity (p < 0.001), superoxide dismutase (p < 0.001), glutathione peroxidase (p < 0.006), and catalase (p < 0.001) within the 4 groups, whereas the mean salivary levels were significant only for glutathione peroxidase (p = 0.001). Both of these serum and salivary antioxidant levels were lower in disease groups of IHD + CP, IHD + H, and CP as compared to healthy controls, with different patterns. CONCLUSION: Antioxidant capacity is significantly hampered in chronic periodontitis and ischemic heart disease patients with or without periodontitis as compared to healthy controls. The salivary and serum antioxidants may not follow the same increase or decrease as a result of increased oxidant stress due to disease.

Synthesis of some new substituted triazolo [4,3-a][1,4] benzodiazepine derivatives as potent anticonvulsants.

Novel 8-chloro-6-(2-fluorophenyl)-1-(aryl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines (5a-f) were prepared by treating 7-chloro-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepine-2-thione with various aromatic acid hydrazides. The newly prepared compounds were characterized by spectral analysis. Compounds were tested for anticonvulsant activity. Four of the tested compounds such as 5a, 5d, 5e and 5f exhibited excellent anticonvulsant activity in comparison with standard drug, diazepam.