Dental caries as a source of Helicobacter pylori infection in children: An RT-PCR study.

BACKGROUND: Findings on the presence of Helicobacter pylori in the oral cavity are conflicting. This bacterium can occur either transiently in the oral cavity or, in some situations, pose a threat to oral/gastric tissues. AIM: We investigated the presence of H. pylori in deep carious lesions of children and assessed its association with dental status and caries severity. DESIGN: This cross-sectional study involved 20 children aged 3-6 years attending the paediatric outpatient clinic. Demographic and oral hygiene-related data were obtained from parents/caregivers. Caries status and severity were assessed using the DMFT and ICDAS II indices respectively. Dentine samples were collected and stored in phosphate-buffered saline solution. These samples were assessed for H. pylori using reverse transcription polymerase chain reaction. DMFT and ICDAS II scores were compared between children with and without H. pylori. RESULTS AND CONCLUSION: H. pylori was detected in 70% of children with severe carious lesions (95% confidence interval: 46%-88%). The mean DMFT score was significantly higher in the group with H. pylori than in the group without (p = .001). The prevalence of H. pylori was greater in those with ICDAS II code 6 than in those with ICDAS II code 5 caries. Cavitated carious lesions can serve as a reservoir for H. pylori. Its presence was associated with higher caries status and caries severity (ICDAS II code 6). The presence of H. pylori in such cavities may tip the balance of plaque ecosystem in favour of Streptococcus mutans, the main bacterial source in dental caries.

Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein.

BACKGROUND: The Transmembrane Serine Protease 2 (TMPRSS2) of human cell plays a significant role in proteolytic cleavage of SARS-Cov-2 coronavirus spike protein and subsequent priming to the receptor ACE2. Approaching TMPRSS2 as a therapeutic target for the inhibition of SARS-Cov-2 infection is highly promising. Hence, in the present study, we docked the binding efficacy of ten naturally available phyto compounds with known anti-viral potential with TMPRSS2. The aim is to identify the best phyto compound with a high functional affinity towards the active site of the TMPRSS2 with the aid of two different docking software. Molecular Dynamic Simulations were performed to analyse the conformational space of the binding pocket of the target protein with selected molecules. RESULTS: Docking analysis using PyRx version 0.8 along with AutoDockVina reveals that among the screened phyto compounds, Genistein shows the maximum binding affinity towards the hydrophobic substrate-binding site of TMPRSS2 with three hydrogen bonds interaction ( - 7.5 kcal/mol). On the other hand, molecular docking analysis using Schrodinger identified Quercetin as the most potent phyto compound with a maximum binding affinity towards the hydrophilic catalytic site of TMPRSS2 ( - 7.847 kcal/mol) with three hydrogen bonds interaction. The molecular dynamics simulation reveals that the Quercetin-TMPRSS complex is stable until 50 ns and forms stable interaction with the protein ( - 22.37 kcal/mol of MM-PBSA binding free energy). Genistein creates a weak interaction with the loop residues and hence has an unstable binding and exits from the binding pocket. CONCLUSION: The compounds, Quercetin and Genistein, can inhibit the TMPRSS2 guided priming of the spike protein. The compounds could reduce the interaction of the host cell with the type I transmembrane glycoprotein to prevent the entry of the virus. The critical finding is that compared to Genistein, Quercetin exhibits higher binding affinity with the catalytic unit of TMPRSS2 and forms a stable complex with the target. Thus, enhancing our innate immunity by consuming foods rich in Quercetin and Genistein or developing a novel drug in the combination of Quercetin and Genistein could be the brilliant choices to prevent SARS-Cov-2 infection when we consider the present chaos associated with vaccines and anti-viral medicines.

Awareness and knowledge of oral manifestations in cardiovascular diseases among the general public.

Cardiovascular diseases (CVDs) are disorders affecting the heart and blood vessels. Periodontal problems, bleeding gums, dry mouth, and gingival hyperplasia are common oral manifestations seen in cardiovascular-related problems. To assess the extent of awareness and knowledge, the general public has toward the oral manifestation related to that of CVDs. A questionnaire was distributed among the general public in relation to that of the extent of awareness and knowledge of oral manifestations with regard to CVD. A total of 161 responses were collected from the survey. The collected data were compiled and analyzed by the SPSS software; the Pearson Chi-square test was done where P < 0.05 was considered statistically significant. The study showed that 65.22% of the population is aware of the types of CVD. About 59.63% of the population do not know that periodontal problems lead to cardiovascular problems. About 39.75% have vague knowledge about the maintenance of poor oral health causing cardiovascular problems. The study concluded that the general public is not much aware of the oral manifestations related to that of CVDs.

Molecular Studies on the Nephroprotective Potential of Celastrus paniculatus against Lead-Acetate-Induced Nephrotoxicity in Experimental Rats: Role of the PI3K/AKT Signaling Pathway.

Chemicals can induce nephrotoxicity, with damage to different segments of the nephron and deterioration of renal function. Nephrotoxicity due to exposure to a toxin such as carbon tetrachloride, sodium oxalate, or heavy metals is the most common cause of kidney injury. The current study aimed to evaluate the protective effects of Celastrus paniculatus seed extract against lead-acetate-induced nephrotoxicity by evaluating the histopathology, immunohistochemistry, ultrastructure, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Twenty-four rats were divided into four groups (n = 6 per group): group 1 contained normal animals and served as the control; group 2 received lead acetate (30 mg/kg body weight (b.w.)/day, oral); group 3 received lead acetate and the standard drug N-acetylcysteine (NAC, 200 mg/kg b.w./day, oral); and group 4 received lead acetate and the ethanolic extract of C. paniculatus seed (EECP; 800 mg/kg b.w./day, oral). Treatment was given for 28 consecutive days. The data were analyzed using one-way analysis of variance with SIGMA PLOT 13 using SYSTAT software followed by Newman-Keul's test for comparison between the groups. EECP ameliorated the adverse changes caused by lead acetate. PI3K and AKT messenger RNA (mRNA) levels were diminished in lead-acetate-treated rats. Treatment with EECP inhibited the occurrence of shrunken cells, the atrophy of glomeruli, and degenerative changes in renal tubules caused by lead acetate. Interestingly, the PI3K and AKT mRNA levels were significantly increased in EECP-treated animals. Our results clearly evidence for the first time that C. paniculatus seed extract inhibits lead-acetate-induced detrimental changes in kidneys by regulating PI3K/AKT signaling pathways.

Novel Triterpenoids from Cassia fistula Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats.

Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from Cassia fistula stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (p < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (p < 0.05). Plasma insulin (p < 0.0001)/C-peptide (p < 0.0006), tissue glycogen (p < 0.0034), glycogen phosphorylase (p < 0.005), glucose 6-phosphatase (p < 0.0001) and lipid markers were significantly increased (p < 0.0001) in diabetic rats, whereas glucokinase (p < 0.0047), glycogen synthase (p < 0.003), glucose oxidation (p < 0.001), GLUT4 mRNA (p < 0.0463), GLUT4 protein (p < 0.0475) and the insulin-signaling molecules IR mRNA (p < 0.0195), IR protein (p < 0.0001), IRS-1 mRNA (p < 0.0478), p-IRS-1Tyr612 (p < 0.0185), Akt mRNA (p < 0.0394), p-AktSer473 (p < 0.0162), GLUT4 mRNA (p < 0.0463) and GLUT4 (p < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1-C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1-C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.

Molecular docking data of E3 ubiquitin-protein ligase WWP1 with compounds from a medicinal plant Justicia adhatoda L.

It is known that E3 ubiquitin-protein ligase WWP1 is linked to oral cancer. Therefore, it is of interest to document molecular docking data of E3 ubiquitin-protein ligase WWP1 with compounds ((Stigmasterol, Pyrazinamide, Vasicinone and Ethambutol)) from a medicinal plant Justicia adhatoda L for further consideration.

Molecular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus.

It is of interest to document the moelcular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus. Hence, we report the binding features of rutin, Luteolin, Salvianolic acid A, Rosmarinic acid and p-Coumaric acid with the target protein SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) for further consideration.

Molecular modeling of cornulin (CRNN) for docking with phytocompounds from Justicia adhatoda L.

Cornulin (CRNN) is linked with tumour progression. Therefore, it is of interest to document data on the molecular modeling of cornulin (CRNN) for docking with phytocompounds (Pyrazinamide, Anisotine, Vasicinone, Vasicoline) from Justicia adhatoda L. Thus, we document the optimal binding features of these compounds with the cornulin model for further consideration.

Molecular docking of alkaloid compounds with the matrix metalloproteinase 2.

Matrix metalloproteinase protein-2 (MMP-2) is linked to the human oral squamous cell carcinoma. Therefore, it is of interest to design new inhibitors for MMP-2 to combat the disease. Thus, we document the molecular docking features of Aristolochic acid, Cryptopleurine, Epipodophyllotoxin, and Fagaronine with MMP-2 for further consideration.

Molecular docking of potential inhibitors with the mTOR protein.

The mTOR (mammalian or mechanistic Target of Rapamycin) is linked with oral cancer. Therefore, it is of interest to study the molecular docking-based binding of paclitaxel (a FDA approved drug for oral cancer) and its analogues with mTOR. Hence, we report the binding features of 10-Deacetyltaxol, 7-Epi-10-deacetyltaxol, 7-Epi-Taxol and 6alpha-Hydroxypaclitaxel with mTOR for further consideration.

ß-sitosterol Mediated Silver Nanoparticles Induce Cytotoxicity in Human Colon Cancer HT-29 Cells.

BACKGROUND: Silver nanoparticles (AgNP) are commonly used metallic nanoparticles in health care systems. Colon cancer incidence is increasing worldwide. In this study, AgNP was synthesized using ß-sitosterol and its cytotoxic potential was evaluated in human colon cancer (HT-29) cells. METHODS: Characterization of AgNP was analyzed by TEM and spectrophotometry analysis. HT-29 cells were treated with different concentrations (2, 4, 6, 8 and 10 ng/ml) of AgNPs and cytotoxicity was evaluated by MTT assay. The apoptosis was analyzed by the flow cytometry. The expression of p53 protein was analyzed by western blotting. RESULTS: ß-sitosterol mediated AgNP are spherical in shape and induced concentration-dependent cytotoxicity in HT-29 cells. AgNP caused apoptosis related morphological changes as evidenced by annexin positive staining. AgNP treatments also induced the p53 expression in HT-29 cells. CONCLUSION: Our present result suggests that ß-sitosterol mediated AgNP induce apoptosis in colon cancer cells and this finding may pave the way for further experimental analysis in vivo.

Molecular docking analysis of amyloid precursor protein with compounds from the Australian cowplant.

Amyloid precursor protein is linked with Alzheimer's disease (AD). The Australian cowplant Gymnema sylvestre is known in Indian and Chinese medicine. Therefore, it is of interest to screen the Amyloid precursor protein with compounds from the Australian cowplant. We report five compounds (Gymnemasaponin 5, Gymnemasin D, Gymnemoside A, Gymnemoside E, Gymnemoside F) derived from the Australian cowplant as the poteinal inhibitors of Amyloid precursor protein with optimal binding features for further consideration.

Molecular docking analysis of docetaxel analogues as duel lipocalin 2 inhibitors.

Lipocalin 2 (Lcn2, also called as neutrophil gelatinase-associated lipocalin) is a member of the lipocalin family and a known target for breast cancer. Therefore, it is of interest to use Docetaxel as a scaffold to design molecules with improved efficiency from naturally derived phytochemicals. We document 10 analogues (4Deacetyltaxol, 7Acetyltaxol, Cabazitaxel, Cephalomannine, Docetaxal, Deacetyltaxol, Docetaxeltrihydrate, Ortataxel, Paclitaxel, Taxoline) having optimal binding with Lipocalin 2 in comparison with Docetaxel. This data is highly useful for consideration in the design and development of drugs for breast cancer.

Molecular docking data of piperine with Bax, Caspase 3, Cox 2 and Caspase 9.

Several apoptotic signalling proteins such as Bax, Caspase 3, Cox 2 and Caspase 9 are known to be associated with colorectal cancer (CRC). It is of interest to study the interaction of these proteins with piperine a known drug candidate. We document the binding energy, hydrogen bond interaction and hydrophobic interaction between the piperine and apoptotic proteins for further consideration.

Molecular docking analysis of Bcl-2 with phyto-compounds.

The Bcl-2 protein is liked in several cancers and drug resistance to therapy is also known in this context. There are many Bcl-2 inhibitors under clinical trials. It is of further interest to design new Bcl2 inhibitors from phyto compounds such as artesunate, bruceantin, maytansin, Salvicine, indicine N-oxide, kamebanin and oxyacanthine. We report the optimal binding features of these compounds with Bcl-2 for further consideration towards in vitro and in vivo validation.

Molecular docking analysis of piperine with CDK2,CDK4,Cyclin D and Cyclin T proteins.

Piperine is a component of Piper nigrum (Black pepper). It is well known in ayurvedic formulations. Piperine is a bioenhancer as it reduces the activity of drug-metabolizing enzymes in rodents and thereby enhancing the plasma concentrations of several drugs, including the Pglycoprotein substrates. Therefore, it is of interest to understand the molecular docking interactions of piperine with several cell cycle proteins such as Cyclin dependent kinase 2 (CDK2), Cyclin-dependent kinase 4 (CDK4), Cyclin D and Cyclin T for further consideration in drug discovery related to oral cancer.

Docking analysis of importin-11 homology model with the phyto compounds towards colorectal cancer treatment.

Colorectal cancer (CRC) is the most familiar malignancy worldwide. Hence, searching for novel therapeutic options is of highest priority. Therefore, it is of interest to design inhibitors to the protein target importin-11, which transports ß-catenin linked to colon cancer cells. However, the structure of importin-11 is not known. Hence, we use a homology model of importin-11 to dock potential interactions with five phyto compounds using molecular interaction features for further consideration.

Molecular docking analysis of alkaloid compounds with beta-catenin towards the treatment of colon cancer.

It is known that beta-catenin is associated with fibromatosis, sarcoma and mesenchymal tumor. Therefore, it is of interest to design an effective inhibtitor to the target protein beta-catenin. In this study, we report the molecular docking analysis of alkaloid compounds (aristolochicacid, cryptopleurine, demecolcine, fagaronine and thalicarpine) with beta-catenin for further consideration towards the design and development of potential inhintors for the treatmnet of colon cancer.