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Purpose: The purpose of the study was to evaluate and compare the effect of beverages, denture cleanser and chlorhexidine gluconate solution on surface roughness of flexible denture base material. Materials and methods: Fifty flexible denture base resin specimens measuring 50±1mm in diameter and 0.5±0.05 mm in thickness were fabricated. The specimens were divided into five groups each containing ten specimens. The specimens were immersed in distilled water (Control group A); hot coffee (Group B); cold beverage (Group C); sodium perborate containing denture cleanser (Group D) and 2% chlorhexidine gluconate solution (Group E). The specimens were immersed for 10 min daily in mentioned solutions for up to 60 days. Surface roughness (Ra) was evaluated on the 1st, 20th and 60th day with the help of atomic force microscope. The statistical analysis was done using two-way ANOVA and Tukey's Post hoc test. Results: The two- way ANOVA revealed that the average Ra values varied significantly depending on the type of solution used for immersion (p<0.001) and the duration of immersion (p<0.001). Variation in surface roughness with cold beverage was highest (p=0.001). On the 60th day the surface roughness of flexible denture base resin material was higher with cold beverage (0.184 µm) and denture cleanser (0.203 µm) than that of distilled water (0.052 µm) hot coffee (0.030 µm) and 2% chlorhexidine gluconate (0.068 µm). Conclusion: Exposure to cold beverage, which was acidic in nature and peroxide containing denture cleanser, produces much rougher surface in the thermoplastic polyamide flexible denture base resin specimens.
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Indole based glycosides belong to the class of pharmacologically active molecules and found in diverse natural compounds. Herein, we report the synthesis of 1,2,3-triazole bridged chirally enriched diverse indole-chalcones based glycohybrids. Three series of glycohybrids were designed and efficiently synthesized using d-glucose, d-galactose and d-mannose derived 1-azido glycosides. The reactions sequence involved were, the synthesis of indole derived chalcones which were formed via Claisen-Schmidt condensation reaction and subsequently N-propargylation which leads to the production of N-propargylated indole-chalcones. The N-propargylated indole-chalcones get transformed into 1,2,3-triazole bridged indole-chalcone based glycohybrids by reacting with 1-azido sugar glycosides under click-chemistry reaction conditions. Further, the biological activity of synthesized glycohybrids (n = 27) was assessed in-vitro against MDA-MB231, MCF-7, MDA-MB453 cancer, and MCF-10A normal cell lines. The selected compounds showed potent anti-oncogenic properties against MCF-7 and MDA-MB231 breast cancer cell line with IC50 values of 1.05 µM and 11.40 µM respectively, with very good selectivity index (SI > 161). The active compounds show better binding affinity as compared to co-crystallized inhibitor 1-(tert-butyl)-3-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP1) with HCK (PTKs) proteins in molecular docking studies.
Subject(s)
Antineoplastic Agents , Chalcones , Drug Screening Assays, Antitumor , Indoles , Humans , Indoles/chemistry , Indoles/pharmacology , Indoles/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Chalcones/chemistry , Chalcones/pharmacology , Chalcones/chemical synthesis , Structure-Activity Relationship , Cell Proliferation/drug effects , Cell Line, Tumor , Molecular Structure , Glycosides/chemistry , Glycosides/chemical synthesis , Glycosides/pharmacology , Molecular Docking Simulation , Dose-Response Relationship, DrugABSTRACT
The Fucaceae family of marine brown algae includes Ascophyllum nodosum. Fucosterol (FSL) is a unique bioactive component that was identified through GC-MS analysis of the hydroalcoholic extract of A. nodosum. Fucosterol's mechanism of action towards hepatocellular cancer was clarified using network pharmacology and docking study techniques. The probable target gene of FSL has been predicted using the TargetNet and SwissTargetPred databases. GeneCards and the DisGNet database were used to check the targeted genes of FSL. By using the web programme Venny 2.1, the overlaps of FSL and HCC disease demonstrated that 18 genes (1.3%) were obtained as targeted genes Via the STRING database, a protein-protein interaction (PPI) network with 18 common target genes was constructed. With the aid of CytoNCA, hub genes were screened using the Cytoscape software, and the targets' hub genes were exported into the ShinyGo online tool for study of KEGG and gene ontology enrichment. Using the software AutoDock, a hub gene molecular docking study was performed. Ten genes, including AR, CYP19A1, ESR1, ESR2, TNF, PPARA, PPARG, HMGCR, SRC, and IGF1R, were obtained. The 10 targeted hubs docked with FSL successfully. The active components FSL of ASD, the FSL, are engaged in fatty liver disease, cancer pathways, and other signalling pathways, which could prove beneficial for the management of HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Molecular Docking Simulation , Network Pharmacology , Stigmasterol , Stigmasterol/analogs & derivatives , Humans , Stigmasterol/pharmacology , Stigmasterol/chemistry , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Protein Interaction Maps/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Computer SimulationABSTRACT
BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.
Subject(s)
Measles , Rubella , Humans , Infant , Child , Adolescent , Cross-Sectional Studies , Measles/prevention & control , Rubella/prevention & control , Measles Vaccine/therapeutic use , Vaccination , Rubella Vaccine/therapeutic use , India/epidemiology , Immunization ProgramsABSTRACT
Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF antibodies are often hindered in NSCLCs because of their limited distribution in the lungs and their adverse effects on normal tissues. These challenges can be overcome by delivering therapeutic antibodies in their mRNA form to lung endothelial cells, a primary target of VEGF-mediated pulmonary angiogenesis, to suppress the NSCLCs. In this study, we synthesized derivatives of poly(ß-amino esters) (PBAEs) and prepared nanoparticles to encapsulate the synthetic mRNA encoding bevacizumab, an anti-VEGF antibody used in the clinic. Optimization of nanoparticle formulations resulted in a selective lung transfection after intravenous administration. Notably, the optimized PBAE nanoparticles were distributed in lung endothelial cells, resulting in the secretion of bevacizumab. We analyzed the protein corona on the lung- and spleen-targeting nanoparticles using proteomics and found distinctive features potentially contributing to their organ-selectivity. Lastly, bevacizumab mRNA delivered by the lung-targeting PBAE nanoparticles more significantly inhibited tumor proliferation and angiogenesis than recombinant bevacizumab protein in orthotopic NSCLC mouse models, supporting the therapeutic potential of bevacizumab mRNA therapy and its selective delivery through lung-targeting nanoparticles. Our proof-of-principle results highlight the clinical benefits of nanoparticle-mediated mRNA therapy in anticancer antibody treatment in preclinical models.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Animals , Mice , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Endothelial Cells/metabolism , Nanomedicine , RNA, Messenger/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Vascular Endothelial Growth Factors , Polymers/therapeutic use , Lung/metabolism , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic useABSTRACT
All cells are equipped with intricate signaling networks to meet the energy demands and respond to the nutrient availability in the body. AMP-activated protein kinase (AMPK) is among the most potent regulators of cellular energy balance. Under ATP -deprived conditions, AMPK phosphorylates substrates and affects various biological processes, such as lipid/glucose metabolism and protein synthesis. These actions further affect the cell growth, death, and functions, altering the cellular outcomes in energy-restricted environments. AMPK plays vital roles in maintaining good health. AMPK dysfunction is observed in various chronic diseases, making it a promising target for preventing and alleviating such diseases. Herein, we highlight the different AMPK functions, especially in allergy, aging, and cancer, to facilitate the development of new therapeutic approaches in the future.
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Diabetes mellitus (DM), a metabolic and endocrine condition, poses a serious threat to human health and longevity. The emerging role of gut microbiome associated with bioactive compounds has recently created a new hope for DM treatment. UHPLC-HRMS methods were used to identify these compounds in a poly herbal ethanolic extract (PHE). The effects of PHE on body weight (BW), fasting blood glucose (FBG) level, gut microbiota, fecal short-chain fatty acids (SCFAs) production, and the correlation between DM-related indices and gut microbes, in rats were investigated. Chebulic acid (0.368%), gallic acid (0.469%), andrographolide (1.304%), berberine (6.442%), and numerous polysaccharides were the most representative constituents in PHE. A more significant BW gain and a reduction in FBG level towards normal of PHE 600 mg/kg treated rats group were resulted at the end of 28th days of the study. Moreover, the composition of the gut microbiota corroborated the study's hypothesis, as evidenced by an increased ratio of Bacteroidetes to Firmicutes and some beneficial microbial species, including Prevotella copri and Lactobacillus hamster. The relative abundance of Bifidobacterium pseudolongum, Ruminococcus bromii, and Blautia producta was found to decline in PHE treatment groups as compared to diabetic group. The abundance of beneficial bacteria in PHE 600 mg/kg treatment group was concurrently associated with increased SCFAs concentrations of acetate and propionate (7.26 nmol/g and 4.13 nmol/g). The findings of this study suggest a promising approach to prevent DM by demonstrating that these naturally occurring compounds decreased FBG levels by increasing SCFAs content and SCFAs producing gut microbiota.
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The occurrence of a second neoplasm possibly constitutes an adverse and uncommon complication after radiotherapy. The incidence of a second pituitary tumor in patients irradiated for adrenocorticotropic hormone secreting pituitary adenoma is rare. We report a case of a 40-year-old female with Cushing disease who underwent surgical management followed by radiotherapy. After 5 years of initial treatment, an increase in tumor size was evident at the same location, with a significant interval growth of the parasellar component of the lesion. Histology revealed an undifferentiated highly malignant sarcoma. In the span of next 2 years, the patient was followed with 2 repeat decompression surgeries and radiotherapy because of significant recurrent compressive symptoms by locally invasive malignant tumor. Despite the best efforts, the patient remained unresponsive to multiple treatment strategies (eg, surgical resections and radiotherapy) and succumbed to death.
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Dermoid cysts are the least commonly occurring developmental cysts in the oral and maxillofacial region. They may be congenital or acquired and are seen as asymptomatic swellings that are slow and progressive. It is very difficult to differentiate plunging ranulas from plunging dermoid cysts as both of them have very similar clinical features. However, since both entities have different treatment strategies, it is important to differentiate one from the other. A 57-year-old male patient reported to the Department of Oral Medicine and Radiology with a large swelling in the submental region. To the best of our knowledge, the present case report is the first one showing such an extensive lesion of plunging dermoid cyst mimicking plunging ranula in an elderly male patient. The report mainly focuses on the diagnostic challenges faced to reach the final diagnosis.
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PURPOSE: To evaluate the performance of complete-arch implant-supported fixed dental prostheses (FDPs) fabricated with polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) framework in clinical cases. MATERIALS AND METHODS: This systematic review followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses and was registered in the International Prospective Register of Systematic Reviews with the number CRD42023399494. The electronic database PubMed, Cochrane Library and EBSCOhost were assessed for clinical research and reports on complete-arch implant-supported FDPs fabricated with PEEK and PEKK framework. Human studies with a minimum follow-up of 1 year and published in an English language were the only ones included. RESULTS: The initial database and hand search provided 564 articles. Finally, 12 articles published between 2018 and 2022 were included in this systematic review. The mean follow-up ranged from 1 year to 6 years. The included studies reported 119 (114 PEEK, 5 PEKK) complete-arch implant-supported FDPs during 1 year follow-up. The cumulative survival rate of prostheses with PEEK as a framework was 97.3%. Prostheses fractures and complications were found with both PEEK and PEKK frameworks. No implant failure reported with both PEEK and PEKK prostheses. CONCLUSION: In short-term follow-up, the complete-arch implant-supported FDPs with PEEK as a framework showed a good survival rate and acceptable health of the supporting tissues. The PEEK framework had shown adhesion issues as the most common prosthetic complication. Limited data were available on PEKK as framework material, so further long-term clinical trials are required.
Subject(s)
Dental Implants , Humans , Dental Restoration Failure , Dental Prosthesis, Implant-Supported , Polyethylene Glycols , KetonesABSTRACT
This study aimed to develop cetuximab (CTX) functionalized albumin nanoparticles (ALB-NPs) of oleanolic acid for EGFR targeted lung cancer therapy. The molecular docking methodology has been applied for a selection of suitable nanocarrier. Various physicochemical parameters like particle size, polydispersity, zeta potential, morphology, entrapment efficiency, and in-vitro drug release of all the ALB-NPs were analyzed. Furthermore, the in-vitro qualitative and quantitative cellular uptake study revealed that higher uptake of CTX conjugated ALB-NPs than nontargeted ALB-NPs in A549 cells. The in-vitro MTT assay revealed that the IC50 value of CTX-OLA-ALB-NPs (4.34 ± 1.90 µg/mL) was significantly reduced (p < 0.001) than OLA-ALB-NPs (13.87 ± 1.28 µg/mL) in A-549 cells. CTX-OLA-ALB-NPs caused apoptosis in A-549 cells at concentrations equivalent to its IC50 value and blocked the cell cycle in the G0/G1 phases. The hemocompatibility, histopathology and lung safety study confirmed the biocompatibility of the developed NPs. In vivo ultrasound and photoacoustic imaging confirmed the targeted delivery of the NPs to lung cancer. The findings demonstrated that CTX-OLA-ALB-NPs have potential for site-specific delivery of OLA for effective and targeted therapy of lung carcinoma.
Subject(s)
Lung Neoplasms , Nanoparticles , Oleanolic Acid , Humans , Oleanolic Acid/pharmacology , Molecular Docking Simulation , Early Detection of Cancer , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Cetuximab/therapeutic use , Albumins , ErbB Receptors/metabolism , Lung/metabolism , Nanoparticles/chemistry , Particle Size , Cell Line, Tumor , Drug Carriers/chemistryABSTRACT
In this paper, we developed a series of piperic acid (PA) analogs with the aim of overcoming the limitations associated with the natural products for the management of Alzheimer's disease (AD). A comprehensive SAR study was performed to enhance cholinesterase inhibition of PA. The acetylcholinesterase inhibition and its kinetic data suggested 6j as the lead molecule (AChE IC50 = 2.13 ± 0.015 µM, BChE = 28.19 ± 0.20%), in comparison to PA (AChE = 7.14 ± 0.98%) which was further selected for various biological studies in AD models. 6j, exhibited interaction with the peripheral anionic site of AChE, BBB permeability (Pe = 7.98), and antioxidant property (% radical scavenging activity = 35.41 ± 1.09, 2.43 ± 1.65, for 6j and PA at 20 M[Formula: see text], respectively). The result from the metal chelation study suggests that 6j did not effectively chelate iron. The molecular modeling studies suggested that 6j could effectively interact with Ser293, Phe295, Arg296, and Tyr34 of AChE. In the cell-based cytotoxicity studies, 6j exhibited cytocompatibility at the different tested concentrations. The acute toxicity data on mice suggested that compound 6j had no renal and hepatotoxicity at 500 mg/kg. Moreover, 6j could effectively reverse scopolamine-induced amnesia by improving spatial and cognitive memory in mice. The above results strongly suggest that compound 6j may act as a novel multi-targeted lead for AD therapy.
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AIMS: To examine the efficacy and safety of dapagliflozin in the treatment of hyperglycemia in cardiac surgery patients with type 2 diabetes (T2D). METHODS: Cardiac surgery patients with T2D (n = 250) were randomly assigned (1:1) to receive dapagliflozin plus basal-bolus insulin (DAPA group) or basal-bolus insulin alone (INSULIN group) in the early postoperative period. The primary outcome was mean difference in daily blood glucose (BG) concentrations between groups. The major safety outcomes were the occurrence of severe ketonemia/diabetic ketoacidosis (DKA) and hypoglycemia. All analyses were performed according to the intention-to-treat principle. RESULTS: The median age of the patients was 61 years (range, 55-61), and 219 (87.6%) were men. Overall, the randomization blood glucose was 165 mg/dL (SD, 37) and glycated hemoglobin was 7.7% (SD, 1.4). There were no differences in mean daily BG concentrations (149 vs. 150 mg/dL), mean percentage of readings within target BG of 70-180 mg/dL (82.7% vs. 82.5%), total daily insulin dose (mean, 39 vs. 40 units/day), number of daily insulin injections (median, 3.9 vs. 4), length of hospital stay (median, 10 vs. 10 days), or hospital complications (21.6% vs. 24.8%) between the DAPA and INSULIN groups. The mean plasma ketone levels were significantly higher in the DAPA group than in the INSULIN group at day 3 (0.71 vs. 0.30 mmol/L) and day 5 (0.42 vs. 0.19 mmol/L) of randomization. Six patients in the DAPA group developed severe ketonemia, but no patient developed DKA. There were no differences in the proportion of patients with BG < 70 mg/dL (9.6% vs. 7.2%) between the two groups. CONCLUSION: Dapagliflozin complementary to basal-bolus insulin does not improve glycemia further over and above the basal-bolus insulin alone in hospitalized cardiac surgery patients. Dapagliflozin significantly increases plasma ketones levels. Safety of dapagliflozin in hospitalized patients needs further investigation. Trial registration ClinicalTrials.gov NCT05457933.
Subject(s)
Cardiac Surgical Procedures , Diabetes Mellitus, Type 2 , Diabetic Ketoacidosis , Hyperglycemia , Male , Humans , Middle Aged , Female , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/surgery , Hypoglycemic Agents/therapeutic use , Blood Glucose , Inpatients , Treatment Outcome , Insulin/therapeutic use , Hyperglycemia/drug therapy , Hyperglycemia/etiology , Diabetic Ketoacidosis/drug therapy , HospitalsABSTRACT
PURPOSE: The purpose of this systematic review was to compare the clinical outcomes of dental implants in users of antihypertensive medication with those of nonusers. METHODS: This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and was registered in the International Prospective Register of Systematic Reviews under the number CRD42022319336. The electronic databases Medline (PubMed) and Central Cochrane were searched for relevant scientific literature published in English through May 2022. The focused question was, "Do patients taking antihypertensive medications have a similar impact on the clinical outcome and survival of dental implants compared with nonusers?". RESULTS: A total of 49 articles were found, of which 3 articles were finally selected for a qualitative synthesis. The three studies included 959 patients. In all three studies, the commonly used medication was renin-angiotensin system (RAS) inhibitors. Two studies mentioned implant survival rate, which was 99.4% in antihypertensive medication users and 96.1% in the nonusers. One study found a higher implant stability quotient (ISQ) in patients taking antihypertensive medication (75.7 ± 5.9) compared with patients not taking antihypertensive medication (73.7 ± 8.1). CONCLUSIONS: The limited available evidence showed that patient taking antihypertensive medications had comparable success rate and implant stability to patients not taking medications. The studies included patients taking different antihypertensive medications, so a drug-specific conclusion regarding the clinical outcome of dental implants is not possible. Further studies are needed, including patients taking certain antihypertensive medications, to determine their effects on dental implants.
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Pancreatic cancer is the seventh most prevalent cause of mortality globally. Since time immemorial, plant-derived products have been in use as therapeutic agents due to the existence of biologically active molecules called secondary metabolites. Flavonoids obtained from plants participate in cell cycle arrest, induce autophagy and apoptosis, and decrease oxidative stress in pancreatic cancer. The present study involves network pharmacology-based study of the methanolic leaf extract of Trema orientalis (MLETO) Linn. From the high-resolution mass spectrometry (HRMS) analysis, 21 nucleated flavonoids were screened out, of which only apigeniflavan was selected for further studies because it followed Lipinski's rule and showed no toxicity. The pharmacokinetics and physiochemical characteristics of apigeniflavan were performed using the online web servers pkCSM, Swiss ADME, and ProTox-II. This is the first in silico study to report the efficiency of apigeniflavan in pancreatic cancer treatment. The targets of apigeniflavan were fetched from SwissTargetPrediction database. The targets of pancreatic cancer were retrieved from DisGeNET and GeneCards. The protein-protein interaction of the common genes using Cytoscape yielded the top five hub genes: KDR, VEGFA, AKT1, SRC, and ESR1. Upon molecular docking, the lowest binding energies corresponded to best docking score which indicated the highest protein-ligand affinity. Kyoto Encyclopaedia of Genes and Genomes (KEGG) database was employed to see the involvement of hub genes in pathways related to pancreatic cancer. The following, pancreatic cancer pathway, MAPK, VEGF, PI3K-Akt, and ErbB signaling pathways, were found to be significant. Our results indicate the involvement of the hub genes in tumor growth, invasion and proliferation in the above-mentioned pathways, and therefore necessitating their downregulation. Moreover, apigeniflavan can flourish as a promising drug for the treatment of pancreatic cancer in future.
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Programmed cell death protein 1 (PD-1), expressed on tumor-infiltrating T cells, is a T cell exhaustion marker. The mechanisms underlying PD-1 upregulation in CD4 T cells remain unknown. Here we develop nutrient-deprived media and a conditional knockout female mouse model to study the mechanism underlying PD-1 upregulation. Reduced methionine increases PD-1 expression on CD4 T cells. The genetic ablation of SLC43A2 in cancer cells restores methionine metabolism in CD4 T cells, increasing the intracellular levels of S-adenosylmethionine and yielding H3K79me2. Reduced H3K79me2 due to methionine deprivation downregulates AMPK, upregulates PD-1 expression and impairs antitumor immunity in CD4 T cells. Methionine supplementation restores H3K79 methylation and AMPK expression, lowering PD-1 levels. AMPK-deficient CD4 T cells exhibit increased endoplasmic reticulum stress and Xbp1s transcript levels. Our results demonstrate that AMPK is a methionine-dependent regulator of the epigenetic control of PD-1 expression in CD4 T cells, a metabolic checkpoint for CD4 T cell exhaustion.
Subject(s)
CD4-Positive T-Lymphocytes , Neoplasms , Programmed Cell Death 1 Receptor , Animals , Female , Mice , AMP-Activated Protein Kinases/metabolism , CD8-Positive T-Lymphocytes , Methionine/metabolism , Mice, Knockout , Neoplasms/metabolism , Programmed Cell Death 1 Receptor/metabolism , Racemethionine/metabolism , Up-RegulationABSTRACT
Purpose: Excessively produced heat could lead to clinical failure of osseointegration. This study was done to compare the heat generated during osteotomy with the conventional drill, trephine, and alveolar expander . Materials and methods: This in vitro study was performed on ten bovine femoral bones. In each femoral bone, three osteotomy sites were prepared at a distance of 1.5cm using the conventional drill, trephine, and alveolar expander. During osteotomy, the site was irrigated with a copius amount of normal saline. Osteotomy sites of 3.6 mm in diameter and 11.5 mm in length were prepared using the conventional drill and bone trephines. The alveolar expander used for preparing the osteotomy site was 3.5mm, the nearest dimensions available. The temperature rise was measured using a thermocouple thermometer. Repeated measures ANOVA and Fisher's least significant difference pairwise comparison test was done for statistical analysis. Results: Repeated measures ANOVA revealed a significant difference in the heat generation with the conventional drill, trephine, and alveolar expander (p<0.001). The mean heat generated was maximum with the trephine (28.26±0.246 0C) followed by the conventional drill (27.27±0.297 0C) and least with alveolar expander (25.64±0.142 0C). Pairwise comparison showed a significant difference in heat generated during osteotomy with conventional drill compared to trephine (P=0.023), conventional drill compared to alveolar expander (P=0.014), and trephine compared to alveolar expander (P<0.001). Conclusion: The heat generated with trephine was maximum compared to the alveolar expander and conventional drills. If in case trephine is to be used, both internal and external irrigation must be used. Less heat generation during osteotomy by alveolar expander seems very promising and advantageous for better osseointegration.
ABSTRACT
In pancreatic cancer, healthy cells in the pancreas begin to malfunction and proliferate out of control. According to our conventional knowledge, many plants contain several novel bioactive compounds, having pharmaceutical applications for the treatment of disease like pancreatic cancer. The methanolic fraction of fruit extract of Trema orientalis L. (MFETO) was analysed through HRMS. In this in silico study, pharmacokinetic and physicochemical properties of the identified flavonoids from MFETO were screened out by ADMET analysis. Kaempferol and catechin followed Lipinski rules and showed no toxicity in Protox II. Targets of these compounds were taken from SwissTarget prediction and TCMSP whilst targets for pancreatic cancer were taken from GeneCards and DisGeNET databases. The protein-protein interaction (PPI) network of common genes was generated through STRING and then exported to the Cytoscape to get top 5 hub genes (AKT1, SRC, EGFR, TNF, and CASP3). The interaction between compounds and hub genes was analysed using molecular docking, and high binding affinity between them can be visualised by Biovia discovery studio visualizer. Our study shows that, five hub genes related to pancreatic cancer play an important role in tumour growth induction, invasion and migration. Kaempferol effectively check cell migration by inhibiting ERK1/2, EGFR-related SRC, and AKT pathways by scavenging ROS whilst catechin inhibited TNFα-induced activation and cell cycle arrest at G1 and G2/M phases by induction of apoptosis of malignant cells. Kaempferol and catechin containing MFETO can be used for formulation of potent drugs for pancreatic cancer treatment in future.
Subject(s)
Catechin , Drugs, Chinese Herbal , Neoplasms , Trema , Humans , Catechin/pharmacology , Kaempferols/pharmacology , Molecular Docking Simulation , Network Pharmacology , ErbB Receptors , Pancreatic NeoplasmsABSTRACT
Vitamin D3 is a secosteroid, broad-spectrum immunomodulatory, antioxidant, and anti-inflammatory hormone produced either by the internal subcutaneous pathway in the presence of ultraviolet B (UVB) rays or by the external pathway in the form of supplements. Vitamin D3 deficiency is a common and reversible contributor to mortality and morbidity among critically ill patients, including Coronavirus Disease 2019 (COVID-19) and other viral infections. The major functions of vitamin D3 are inhibiting the proinflammatory pathways, including nuclear factor kappa B (NF-kB), inflammatory cytokines, such as interleukin-6 (ILs-6), interleukin-18 (ILs-18), and tumour necrosis factor (TNF), preventing the loss of neural sensation in COVID-19, maintaining respiratory homeostasis, and acting as an antiviral, antimalarial, and antihypertensive agent. Vitamin D3 has an important role in reversing the COVID-19 infection in patients who have previously suffered from a neurological disease, such as Alzheimer's disease, Parkinson disease, motor neuron disease, multiple sclerosis, Creutzfeldt-Jakob disease, stroke, cardiovascular problems, headache, sleep-associated disorder, and others. Moreover, vitamin D3 plays a key role in regulating the gene expression of different pro-inflammatory cytokines. In addition to the information provided above, the current review article provides the most recent information on Vitamin D against COVID-19 with comorbid neurological disorders. Furthermore, we present the most recent advancement and molecular mechanism of action of vitamin D3. Diabetes, cardiovascular disease, and neurological disorders are comorbid conditions, and vitamin D3 is a critical regulator of COVID-19 infection during these conditions. In the midst of the COVID-19 epidemic, factors such as sex, latitudes, nutrition, demography, pollution, and gut microbiota warrants for additional research on vitamin D supplements.