The antimicrobial activity of tea tree oil (Melaleuca alternifolia) and its metal nanoparticles in oral bacteria.

Tea tree (Melaleuca alternifolia) oil (TTO) is an antimicrobial agent, and hence, its use in fabricating nanoparticles (NP) may be useful in providing more efficacious antimicrobial agents. The current research aimed to test the antimicrobial efficacy of TTO and its TTO-Metal-NPs against oral microbes: Porphyromonas gingivalis, Enterococcus faecalis, and Streptococcus mutans. The antimicrobial activity of TTO and zinc (Zn) and iron (Fe) nanoparticles (NPs) and the combined effects of antimicrobial agents were investigated using agar well diffusion assays. Fourier-transform infrared spectroscopy (FT-IR) was used to identify the phyto-constituents of TTO. Field emission scanning electron microscopy (FE-SEM), dynamic light scatter (DLS), and zeta potential were utilized to analyze the biogenic nanoparticles' morphology, size, and potential. The antimicrobial mode of action was determined by assessing the morphological changes under scanning electron microscopy (SEM). The TTO extracts converted Zn and Fe ions to NPs, having an average size of 97.50 (ZnNPs) and 102.4 nm (FeNPs). All tested agents had significant antibacterial efficacy against the tested oral microbes. However, the TTO extract was more efficacious than the NPs. Combination treatment of TTO with antibiotics resulted in partial additive effects against P. gingivalis and partial antagonistic effects against E. faecalis, S. mutans, and common mouthwashes (Oral B and chlorhexidine). TTO and NP-treated bacteria underwent morphological changes on treatment. M. alternifolia phytochemicals could be useful for further research and development of antimicrobial NPs. The current study highlights the variance in activity observed for different types of bacteria and antagonistic effects seen with common mouthwashes, which represent a threat to therapeutic efficacy and heighten the risk of clinical microbial resistance.

Exploring the potential of Ziziphus nummularia and luteolin-7-O-glucoside as tubulin inhibitors in cancer therapy and survival.

Cancer is responsible for approximately 10 million deaths worldwide, with 70% of the deaths occurring in low- and middle-income countries; as such safer and more effective anti-cancer drugs are required. Therefore, the potential benefits of Ziziphus nummularia and Ziziphus spina-christi as sources of anti-cancer agents were investigated. Z. nummularia and Z. spina-christi extracts were prepared using chloroform, ethanol, ethyl acetate, and water. The extracts' anti-cancer properties were determined using the MTT Cell Viability Assay in four cancer cell lines: breast (KAIMRC2 and MDA-MB-231), colorectal (HCT8), and liver (HepG2). The ApoTox-Glo Triplex Assay and high-content imaging (HCI)-Apoptosis Assay were used to assess KAIMRC2 and HCT8 cells further. In addition, KAIMRC2 cells were tested for microtubule staining, and AKT/mTOR protein expression was determined by western blot analysis. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the secondary metabolites in the ethanol and ethyl acetate extracts, followed by in silico techniques to predict molecular targets and interactions, safety, and pharmacokinetic profile for identified metabolites. Out of the eight extracts, the ethanolic extract of Z. nummularia, exhibited the most potent activity against KAIMRC2 cells with an IC50 value of 29.2 µg/ml. Cancer cell treatment with the ethanolic extract of Z. nummularia resulted in a dose-dependent decrease in cell viability with increased apoptosis and cytotoxic effects. Microtubule staining showed a disrupted microtubular network. The ethanolic extract treatment of KAIMRC2 cells led to upregulated expression of pAKT and pmTOR. In silico studies predicted luteolin-7-O-glucoside to be a ligand for tubulin with the highest docking score (- 7.686) and similar binding interactions relative to the native ligand. Further computational analysis of the metabolites showed acceptable pharmacokinetic and safety profiles, although ethanolic extract metabolites were predicted to have cardiotoxic effects. Ethanolic extraction is optimal for solubilizing active anticancer metabolites from Z. nummularia, which may act by causing M-phase arrest via inhibition of tubulin polymerization. Luteolin-7-O-glucoside is the lead candidate for further research and development as an anti-cancer agent. In addition, this study suggests that herbal treatment could switch on mechanisms of adaptation and survival in cancer cells.

Exploring in vitro and in silico Biological Activities of Calligonum Comosum and Rumex Vesicarius: Implications on Anticancer and Antibacterial Therapeutics.

Introduction: The adverse effects of clinically used anti-cancer medication and the rise in resistive micro-organisms have limited therapeutic options. Multiple anti-cancer drugs are derived from medicinal herbs which also have shown anti-bacterial effects. This study aimed to identify the optimal extraction solvent for detecting the cytotoxic and anti-bacterial effects of Calligonum comosum (C. Comosum) and Rumex vesicarius (R. Vesicarius) extracts. Additionally, the study aimed to identify active metabolites and assess their potential as future drug candidates for anti-cancer and anti-bacterial therapeutics. Methods: Leaves from both plants were extracted using ethanol, ethyl acetate, chloroform, and water. The cytotoxic effects of the extracts were tested on liver, colon, and breast cancer cell lines. Apoptosis was assessed using High Content Imaging (HCI) and the ApoTox triplex Glo assay. The anti-bacterial effects were determined using agar-well diffusion. Liquid chromatography-mass spectrometry (LC-MS) was used to tentatively identify the secondary metabolites. In silico computational studies were conducted to determine the metabolites' mode of action, safety, and pharmacokinetic properties. Results: The ethanolic extract of C. Comosum exhibited potent cytotoxicity on breast cancer cell lines, with IC50 values of 54.97 µg/mL and 58 µg/mL for KAIMRC2 and MDA-MB-231, respectively. It also induced apoptosis in colon and breast cancer cell lines. All tested extracts of C. Comosum and R. Vesicarius demonstrated anti-bacterial activity against Staphylococcus aureus and Escherichia coli. Seven active metabolites were identified, one of which is Kaempferol 3-O-Glucoside-7-O-Rhamnoside, which showed strong (predicted) anti-cancer activity. Kaempferol 3-O-Glucoside-7-O-Rhamnoside and Quercetin-3-O-Glucuronide also exhibited potential anti-bacterial effects on gram-positive and negative bacteria. Conclusion: Ethanol extraction of C. Comosum solubilizes active metabolites with potential therapeutic applications in cancer treatment and bacterial infections. Kaempferol 3-O-Glucoside-7-O-Rhamnoside, in particular, shows promise as a dual therapeutic drug candidate for further research and development to improve its efficacy, safety, and pharmacokinetic profile.

The emergent role of artificial intelligence, natural learning processing, and large language models in higher education and research.

Artificial Intelligence (AI) has revolutionized various domains, including education and research. Natural language processing (NLP) techniques and large language models (LLMs) such as GPT-4 and BARD have significantly advanced our comprehension and application of AI in these fields. This paper provides an in-depth introduction to AI, NLP, and LLMs, discussing their potential impact on education and research. By exploring the advantages, challenges, and innovative applications of these technologies, this review gives educators, researchers, students, and readers a comprehensive view of how AI could shape educational and research practices in the future, ultimately leading to improved outcomes. Key applications discussed in the field of research include text generation, data analysis and interpretation, literature review, formatting and editing, and peer review. AI applications in academics and education include educational support and constructive feedback, assessment, grading, tailored curricula, personalized career guidance, and mental health support. Addressing the challenges associated with these technologies, such as ethical concerns and algorithmic biases, is essential for maximizing their potential to improve education and research outcomes. Ultimately, the paper aims to contribute to the ongoing discussion about the role of AI in education and research and highlight its potential to lead to better outcomes for students, educators, and researchers.

In silico Prediction of Malvaviscus arboreus Metabolites and Green Synthesis of Silver Nanoparticles - Opportunities for Safer Anti-Bacterial and Anti-Cancer Precision Medicine.

Introduction: Biogenic silver nanoparticles (AgNPs) may be a feasible therapeutic option in the research and development towards selectively targeting specific cancers and microbial infections, lending a role in precision medicine. In-silico methods are a viable strategy to aid in drug discovery by identifying lead plant bioactive molecules for further wet lab and animal experiments. Methods: Green synthesis of M-AgNPs was performed using the aqueous extract from the Malvaviscus arboreus leaves, characterized using UV spectroscopy, FTIR, TEM, DLS, and EDS. In addition, Ampicillin conjugated M-AgNPs were also synthesized. The cytotoxic potential of the M-AgNPs was evaluated using the MTT assay on MDA-MB 231, MCF10A, and HCT116 cancer cell lines. The antimicrobial effects were determined using the agar well diffusion assay on methicillin-resistant S. aureus (MRSA) and S. mutans, E. coli, and Klebsiella pneumoniae. Additionally, LC-MS was used to identify the phytometabolites, and in silico techniques were applied to determine the pharmacodynamic and pharmacokinetic profiles of the identified metabolites. Results: Spherical M-AgNPs were successfully biosynthesized with a mean diameter of 21.8 nm and were active on all tested bacteria. Conjugation with ampicillin increased the susceptibility of the bacteria. These antibacterial effects were most predominant in Staphylococcus aureus (p < 0.0001). M-AgNPs had potent cytotoxic activity against the colon cancer cell line (IC50=29.5 µg/mL). In addition, four secondary metabolites were identified, Astragalin, 4-hydroxyphenyl acetic acid, Caffeic acid, and Vernolic acid. In silico studies identified Astragalin as the most active antibacterial and anti-cancer metabolite, binding strongly to the carbonic anhydrase IX enzyme with a comparatively higher number of residual interactions. Discussion: Synthesis of green AgNPs presents a new opportunity in the field of precision medicine, the concept centered on the biochemical properties and biological effects of the functional groups present in the plant metabolites used for reduction and capping. M-AgNPs may be useful in treating colon carcinoma and MRSA infections. Astragalin appears to be the optimal and safe lead for further anti-cancer and anti-microbial drug development.

Proteomic Profiling Reveals Cytotoxic Mechanisms of Action and Adaptive Mechanisms of Resistance in Porphyromonas gingivalis: Treatment with Juglans regia and Melaleuca alternifolia.

The increasing trend in the rise of antibiotic-resistant bacteria pushes research to discover new efficacious antibacterial agents from natural and synthetic sources. Porphyromonas gingivalis is a well-known bacterium commonly known for causing periodontal disease, and it is associated with the pathogenesis of life-changing systemic conditions such as Alzheimer's. Proteomic research can be utilized to test new antibacterial drugs and understand the adaptive resistive mechanisms of bacteria; hence, it is important in the drug discovery process. The current study focuses on identifying the antibacterial effects of Juglans regia (JR) and Melaleuca alternifolia (MA) on P. gingivalis and uses proteomics to identify modes of action while exploring its adaptive mechanisms. JR and MA extracts were tested for antibacterial efficacy using the agar well diffusion assay. A proteomic study was conducted identifying upregulated and downregulated proteins compared to control by 2D-DIGE analysis, and proteins were identified using MADLI-TOF/MS. The bacterial inhibition for JR was 20.14 ± 0.2, and that for MA was 19.72 ± 0.5 mm. Out of 88 differentially expressed proteins, there were 17 common differentially expressed proteins: 10 were upregulated and 7 were downregulated in both treatments. Among the upregulated proteins were Arginine-tRNA ligase, ATP-dependent Clp protease proteolytic, and flavodoxins. In contrast, down-regulated proteins were ATP synthase subunit alpha and quinone, among others, which are known antibacterial targets. STRING analysis indicated a strong network of interactions between differentially expressed proteins, mainly involved in protein translation, post-translational modification, energy production, metabolic pathways, and protein repair and degradation. Both extracts were equi-efficacious at inhibiting P. gingivalis and displayed some overlapping proteomic profiles. However, the MR extract had a greater fold change in its profile than the JA extract. Downregulated proteins indicated similarity in the mode of action, and upregulated proteins appear to be related to adaptive mechanisms important in promoting repair, growth, survival, virulence, and resistance. Hence, both extracts may be useful in preventing P. gingivalis-associated conditions. Furthermore, our results may be helpful to researchers in identifying new antibiotics which may offset these mechanisms of resistance.

Nontoxic and Naturally Occurring Active Compounds as Potential Inhibitors of Biological Targets in Liriomyza trifolii.

In recent years, novel strategies to control insects have been based on protease inhibitors (PIs). In this regard, molecular docking and molecular dynamics simulations have been extensively used to investigate insect gut proteases and the interactions of PIs for the development of resistance against insects. We, herein, report an in silico study of (disodium 5'-inosinate and petunidin 3-glucoside), (calcium 5'-guanylate and chlorogenic acid), chlorogenic acid alone, (kaempferol-3,7-di-O-glucoside with hyperoside and delphinidin 3-glucoside), and (myricetin 3'-glucoside and hyperoside) as potential inhibitors of acetylcholinesterase receptors, actin, α-tubulin, arginine kinase, and histone receptor III subtypes, respectively. The study demonstrated that the inhibitors are capable of forming stable complexes with the corresponding proteins while also showing great potential for inhibitory activity in the proposed protein-inhibitor combinations.

The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy.

BACKGROUND: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life. METHOD: The current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)-like macrophage cell lines. Furthermore, using an in vivo rat model, the extracts' anti-inflammatory and wound-healing activity was investigated. In addition, in silico predictions of the myrrh constituents highlighted the pharmacokinetic properties, molecular targets, and safety profile, including cytochrome P 450 (CYP) inhibition and organ toxicity. RESULTS: Nine secondary metabolites were identified, and computational predictions suggested a good absorption profile, anticancer, anti-inflammatory, and wound-healing effects. The myrrh extract had moderate cytotoxic activity against both HL60 and K562 leukemia cell lines and the KAIMRC1 breast cancer cell line. Myrrh caused a dose-dependent effect on macrophages to increase the reactive oxygen species (ROS) levels, promote their polarization to classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes, and consequently induce apoptosis, highlighting its ability to modulate macrophage function, which could potentially aid in several desired therapeutic processes, including the resolution of inflammation, and autophagy which is an important aspect to consider in cancer treatment. The topical application of myrrh improved wound healing, with no delayed inflammatory response, and promoted complete re-epithelization of the skin, similar to the positive control. In conclusion, we provide evidence for the methanolic extract of myrrh having cytotoxic activity against cancer cells and anti-inflammatory wound-healing properties, which may be attributed to its role in modulating macrophage function. Furthermore, we suggest the active constituents responsible for these properties, which warrants further studies focusing on the precise roles of the active metabolites.

Distinct Mechanisms of Cytotoxicity in Novel Nitrogenous Heterocycles: Future Directions for a New Anti-Cancer Agent.

Electron-rich, nitrogenous heteroaromatic compounds interact more with biological/cellular components than their non-nitrogenous counterparts. The strong intermolecular interactions with proteins, enzymes, and receptors confer significant biological and therapeutic properties to the imidazole derivatives, giving rise to a well-known and extensively used range of therapeutic drugs used for infections, inflammation, and cancer, to name a few. The current study investigates the anti-cancer properties of fourteen previously synthesized nitrogenous heterocycles, derivatives of imidazole and oxazolone, on a panel of cancer cell lines and, in addition, predicts the molecular interactions, pharmacokinetic and safety profiles of these compounds. METHOD: The MTT and CellTiter-Glo® assays were used to screen the imidazole and oxazolone derivatives on six cancer cell lines: HL60, MDA-MB-321, KAIMRC1, KMIRC2, MCF-10A, and HCT8. Subsequently, in vitro tubulin staining and imaging were performed, and the level of apoptosis was measured using the Promega ApoTox-Glo® triplex assay. Furthermore, several computational tools were utilized to investigate the pharmacokinetics and safety profile, including PASS Online, SEA Search, the QikProp tool, SwissADME, ProTox-II, and an in silico molecular docking study on tubulin to identify the critical molecular interactions. RESULTS: In vitro analysis identified compounds 8 and 9 to possess the most significant potent cytotoxic activity on the HL60 and MDA-MB-231 cell lines, supported by PASS Online anti-cancer predictions with pa scores of 0.413 and 0.434, respectively. In addition, compound 9 induced caspase 3/7 dependent-apoptosis and interfered with tubulin polymerization in the MDA-MB-231 cell line, consistent with in silico docking results, identifying binding similarity to the native ligand colchicine. All the derivatives, including compounds 8 and 9, had acceptable pharmacokinetics; however, the safety profile was suboptimal for all the tested derivates except compound 4. CONCLUSION: The imidazole derivative compound 9 is a promising anti-cancer agent that switches on caspase-dependent apoptotic cell death and modulates microtubule function. Therefore, it could be a lead compound for further drug optimization and development.

In-silico predicting as a tool to develop plant-based biomedicines and nanoparticles: Lycium shawii metabolites.

INTRODUCTION AND PURPOSE: In silico approach helps develop biomedicines and is useful for exploring the pharmacology of potential therapeutics using computer-simulated models. In vitro assays were used to determine the anti-microbial and cytotoxic efficacies of silver nanoparticles (AgNPs) synthesized with the shrub Lycium shawii. METHODS: In silico predicting was performed to assess the L. shawii metabolites identified using QTOF-LCMS for their pharmacological properties. L. shawii mediated AgNPs were synthesized and characterized (FTIR, TEM, SEM, DLS and EDX). The anti-bacterial efficacies of L. shawii extract, AgNPs, and penicillin-conjugated AgNPs (pen-AgNPs) were determined. The cytotoxicity of the AgNPs was measured against colorectal cancer cell line (HCT116), normal breast epithelium (MCF 10 A), and breast cancer cell line (MDA MB 231). RESULTS AND DISCUSSION: Five molecules (costunolide, catechin, emodin, lyciumaside, and aloe emodin 11-O-rhamnoside) were detected in the L. shawii extract. AgNPs (69 nm) were spherical with crystallographic structure. All three agents prepared showed inhibitory activity against the tested bacteria, the most efficacious being pen-AgNPs. High cytotoxicity of AgNPs (IC50 62 µg/ml) was observed against HCT116, IC50 was 78 µg/ml for MCF 10 A, and 250 µg/ml for MDA MB 231, of which cells showed apoptotic features under TEM examination. The in silico approach indicated that the carbonic anhydrase IX enzyme was the target molecule mediating anti-cancer and anti-bacterial activities and that emodin was the metabolite in action. CONCLUSIONS: Combining in vitro studies and in silico molecular target prediction helps find novel therapeutic agents. Among L. shawii metabolites, emodin is suggested for further studies as an agent for drug development against pathogenic bacteria and cancer.

Immunoinformatics design of B and T-cell epitope-based SARS-CoV-2 peptide vaccination.

SARS-COV-2 is a virulent respiratory virus, first identified in China (Wuhan) at the end of 2019. Scientists and researchers are trying to find any possible solution to this deadly viral disease. Different drug source agents have been identified, including western medicine, natural products, and traditional Chinese medicine. They have the potential to counteract COVID-19. This virus immediately affects the liver and causes a decrease in oxygen levels. In this study, multiple vacciome approaches were employed for designing a multi-epitope subunit vaccine for battling against SARS-COV-2. Vaccine designing, immunogenicity, allergenic, and physico-chemical assessment were performed by using the vacciome approach. The vaccine design is likely to be antigenic and produce potent interactions with ACE2 and NSP3 receptors. The developed vaccine has also been given to in-silico cloning models and immune response predictions. A total number of 12 CTL and 12 HTL antigenic epitopes were predicted from three selected covid-19 virulent proteins (spike protein, nucleocapsid protein, and membrane proteins, respectively) based on C-terminal cleavage and MHC binding scores. These predicted epitopes were amalgamated by AYY and GPGPG linkers, and a ß-defensins adjuvant was inserted into the N-terminus of this vaccine. This analysis shows that the recommended vaccine can produce immune responses against SARS-COV-2. Designing and developing of the mentioned vaccine will require further experimental validation.

Silver Nanoparticles Formation by Jatropha integerrima and LC/MS-QTOF-Based Metabolite Profiling.

The broad application of metal nanoparticles in different fields encourages scientists to find alternatives to conventional synthesis methods to reduce negative environmental impacts. Herein, we described a safe method for preparing silver nanoparticles (J-AgNPs) using Jatropha integerrima leaves extract as a reducing agent and further characterize its physiochemical and pharmacological properties to identify its therapeutic potential as a cytotoxic and antimicrobial agent. The biogenic synthesized J-AgNPs were physiochemically characterized by ultraviolet-visible spectroscopy, dynamic light scattering (DLS), transmission electron microscope (TEM), and energy-dispersive X-ray spectroscopy. HPLC-DAD, followed by LC/MS and the Fourier-transform infrared spectroscopy (FTIR), was applied to detect the biomolecules of J. integerrima involved in the fabrication of NPs. Furthermore, J-AgNPs and the ampicillin-nanocomposite conjugate were investigated for their potential antibacterial effects against four clinical isolates. Finally, cytotoxic effects were also investigated against cancer and normal cell lines, and their mechanism was assessed using TEM analysis and confocal laser scanning microscopy (LSM). Ag ions were reduced to spherical J-AgNPs, with a zeta potential of -34.7 mV as well as an average size of 91.2 and 22.8 nm as detected by DLS and TEM, respectively. HPLC GC/MC analysis identified five biomolecules, and FTIR suggested the presence of proteins besides polyphenolic molecules; together, these molecules could be responsible for the reduction and capping processes during NP formation. Additionally, J-AgNPs displayed a strong antibacterial effect, although the ampicillin conjugated form had a very weak antibacterial effect. Furthermore, the NPs caused a reduction in cell viability of all the treated cells by initiating ultrastructural changes and apoptosis, as identified by TEM and LSM analysis. Therefore, J-AgNPs can be formed using the leaf extract from the J. integerrima plant. Furthermore, J-AgNPs may serve as a candidate for further biochemical and pharmacological testing to identify its therapeutic value.

Protective effect of nano vitamin D against fatty degeneration in submandibular and sublingual salivary glands: A histological and ultrastructural study.

BACKGROUND: Poor nutritional habits and a low level of physical activity are associated with obesity, leading to increased caloric and fat intakes. A high-fat diet can significantly impact oral health through the accumulation of lipids in the salivary glands, which ultimately affect salivary gland function. Recently, an increasing number of supplement nano-formulations, such as nano vitamin D, have become available. However, only few studies have explored the effects of nano vitamin D on the maintenance of oral health. OBJECTIVE: This study aimed to compare the histological effects of nano vitamin D to those of regular vitamin D on fatty degeneration in submandibular and sublingual salivary glands using a rat model. METHODS: Twenty-four adult male albino Sprague-Dawley rats were divided into the following groups: untreated group, high-fat diet group, high-fat diet and regular vitamin D group, and high-fat diet and nano vitamin group.Thereafter, samples of the submandibular and sublingual salivary glands were dissected for histological and electron microscopic studies. Morphometric digital image analysis was used to quantitatively measure the changes in the size and number of acini and secretory granules. RESULTS: Regular vitamin D had a partial protective effect. However, vitamin D could fully restore cellular structures to their normal state, thereby protecting against fatty degeneration of the salivary tissue and immune cell infiltration, particularly in the submandibular serous tissue. Nano vitamin D was more efficacious than regular vitamin D at restoring the number and size of submandibular serous secretory granules. CONCLUSION: Employing nano vitamin D as a supplement to high-fat diets could protect against high-fat diet-induced salivary gland damage in rats.

Ethical Aspects concerning Instrument Separation and Perforations during Endodontic Treatment: A Cross-Sectional Study.

AIM: During endodontic treatment, dentists may face various unwanted procedural accidents, at any stage of the treatment that might compromise endodontic treatment outcome and bring obstacles to dentists as well. This study aimed to address and analyze several ethical concerns relating to the behavioural conduct of dentists towards endodontic instrument separation as well as perforation of the crown and/or root during root canal treatment in Riyadh, Saudi Arabia. METHOD: Hundred and eleven questionnaires were distributed among dentists working in Riyadh in university clinics and government and private sectors. Data were collected, reviewed, and statistically analyzed by Fisher's exact and chi-square tests at a 5% significance level, using SPSS software. RESULTS: 54.5% of the respondents have encountered instrument separation. 53.2% stated that they would inform the patient about the instrument separation. 43.6% of the respondents had experienced perforation during root canal treatment, and 54.9% reported that they would inform the patient of the accident. CONCLUSION: Within the limitation of this survey, we concluded that most of the dental professionals did not hesitate to adhere to the correct ethical conduct, and they would inform the patient if an incident occurred.

Evaluating the Role of CXCR3 in Pain Modulation: A Literature Review.

CXCR3 is a well-known receptor involved in immune cell recruitment and inflammation. Pathological inflammation leads to pain stimulation and hence nociception. Therefore, we decided to review the recent research on CXCR3 to identify its precise role in the modulation of pain in a variety of clinical conditions targeting various regions of the body. Studies were selected from PubMed Medline, which relate CXCR3 to the progression of diseases with either bone cancer pain, neuropathic pain, cystitis pain, osteoarthritis and rheumatoid arthritis pain, dental pain, in particular, periodontitis and pulpitis. In all the diseases studied, a high prevalence of CXCR3 and/or its ligand were identified where CXCR3 is a key player in the pathophysiological process of many inflammatory conditions. CXCR3 and its ligands, particularly CXCL10, modulate nociception via actions in the dorsal root ganglia and dorsal horn of the spinal cord, in cases of bone cancer pain, neuropathic, and joint pain. However, with the other studied disease, no direct link to pain has been made, although it contributes to the pathological progression of the diseases and hence would be a causal factor for the pain. Furthermore, CXCR3 appears to play a role in desensitizing the opioid receptor in the descending modulatory pathway within the brain stem as well as modulating opioid-induced hyperalgesia in the dorsal horn of the spinal cord. Further research is required for understanding the exact mechanisms of CXCR3 in pain modulation centrally and peripherally. A greater understanding of the immunological activities and pharmacological consequence of CXCR3 and its ligands could help in the discovery of newer drugs for modulating pain arising from pathogenic or inflammatory sources. Given the significance of the CXCR3 for nociception, its utilization may prove to be beneficial as a target for analgesia.

Type 2 Diabetes, Obesity, and Cancer Share Some Common and Critical Pathways.

Diabetes and cancer are among the most frequent and complex diseases. Epidemiological evidence showed that the patients suffering from diabetes are significantly at higher risk for a number of cancer types. There are a number of evidence that support the hypothesis that these diseases are interlinked, and obesity may aggravate the risk(s) of type 2 diabetes and cancer. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic agents. With so many known challenges, it is critical to understand the relationships and the commonly shared causes between type 2 diabetes and cancer, which is difficult to unravel and understand. Furthermore, the real complexity arises from contended corroborations that specific drug(s) (individually or in combination) during the treatment of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidence from the studies where the origin, biological background, the correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. We have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases, diabetes and cancer.

The Assessment of Drug Utilization Study of Anticancer Drugs Using WHO Prescribing Indicators in a Government Tertiary Care Hospital of the Hyderabad - Karnataka Region of India.

BACKGROUND: Cancer is a major burden and threat to global society. A wide range of chemotherapeutic agents is extensively used to treat cancer at different stages. Inappropriate drug use may also lead to the raised cost of medical care, adverse drug effects, and patient mortality. Hence, in recent years, drug utilisation studies have become a potential tool to be used in the evaluation of different health care systems including cancer. AIMS: The objectives of the study were to identify the various types of cancer, the commonly prescribed drugs, rational use of anticancer drugs, and analyse the prescribing indicators in a tertiary care government hospital of India. MATERIAL AND METHODS: Newly diagnosed cancer and/or known case of carcinoma of either sex which required treatment/on treatment with chemotherapy aged > 18 yrs admitted in Radiotherapy Department from April 2016 to September 2016 were included in the study and analysed for prescribing indicators. RESULTS: The head & neck cancers were the prevalent cancers observed with more preponderance among males. Most of the patients were prescribed with a single anticancer drug. Cisplatin was the most commonly used cytotoxic drug followed by carboplatin, and antimetabolites. The most commonly used adjuvant drugs in our study were anti-emetics and anti-peptic ulcer drugs. Over 82% of anticancer agents were taken from the essential drug list and were prescribed in generic names, indicating rational use. CONCLUSION: Over 82% of anticancer agents were taken from the essential drug list and were prescribed in generic names, indicating rational use.

The comparative evaluation of knowledge, attitude, and practice of different health-care professionals about the pharmacovigilance system of India.

In India, the under-reporting of adverse drug reactions (ADRs) by health professionals is recognized as one of the leading reasons of poor ADR signal detection. The knowledge of ADRs and positive attitude of health-care professionals toward ADRs reporting is vital for decreasing the irrational use of an inappropriate pharmacy. The present study was directed to assess the knowledge, attitude, and practice (KAP) of pharmacovigilance (PV) among the physicians, nurses, and pharmacists of a teaching tertiary care hospital of India. A structured questionnaire was designed using previous studies and standardized. Questions were categorized into three groups: Group 1 tested the knowledge (K1-K8), Group 2 tested attitude (A1-A6), and Group 3 tested the level of practice of PV (P1-P5) of the participant. Such 250 questionnaires were distributed to different health-care professionals of VIMS, Ballari. The participants were graded in three categories as poor, unsatisfactory, and satisfactory depending on the mean score. The data were interpreted by calculating the frequencies, one-way ANOVA and Scheffe's test. Furthermore, factors that discourage them from taking part in the PV program were recorded. A total of 182 questionnaires were statistically analyzed. It was found that KAP of PV among doctors, nurses, and pharmacists was unsatisfactory. Our study showed that knowledge, attitude, and level of practice of PV among doctors, nurses, and pharmacists stand inadequate. Educational interventions periodically can improve these parameters of PV.

Growth of Neisseria gonorrhoeae in the female mouse genital tract does not require the gonococcal transferrin or hemoglobin receptors and may be enhanced by commensal lactobacilli.

Neisseria gonorrhoeae is capable of utilizing a variety of iron sources in vitro, including human transferrin, human lactoferrin, hemoglobin, hemoglobin-haptoglobin complexes, heme, and heterologous siderophores. Transferrin has been implicated as a critical iron store for N. gonorrhoeae in the human male urethra. The demonstration that gonococci can infect the lower genital tracts of estradiol-treated BALB/c mice in the absence of human transferrin, however, suggests that other usable iron sources are present in the murine genital tract. Here we demonstrate that gonococcal transferrin and hemoglobin receptor mutants are not attenuated in mice, thereby ruling out transferrin and hemoglobin as essential for murine infection. An increased frequency of phase variants with the hemoglobin receptor "on" (Hg(+)) occurred in ca. 50% of infected mice; this increase was temporally associated with an influx of neutrophils and detectable levels of hemoglobin in the vagina, suggesting that the presence of hemoglobin in inflammatory exudates selects for Hg(+) phase variants during infection. We also demonstrate that commensal lactobacilli support the growth of N. gonorrhoeae in vitro unless an iron chelator is added to the medium. We hypothesize that commensal lactobacilli may enhance growth of gonococci in vivo by promoting the solubilization of iron on mucosal surfaces through the production of metabolic intermediates. Finally, transferrin-binding lipoprotein (TbpB) was detected on gonococci in vaginal smears, suggesting that although gonococci replicate within the genital tracts of mice, they may be sufficiently iron-stressed to express iron-repressible proteins. In summary, these studies support the potential role of nontransferrin, nonhemoglobin iron sources during gonococcal infection of the female genital tract.