Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King.

The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 ± 5.45 µM) and potent (7.55 ± 1.64 µM) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have π-π interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.

Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King

@#The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 ± 5.45 μM) and potent (7.55 ± 1.64 μM) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have π-π interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.

Effect of prosthetic rehabilitation on oral health-related quality of life of patients with head and neck cancer: a systematic review.

BACKGROUND: To review the evidence on the oral health-related quality of life (OHRQoL) of head and neck cancer survivors after they have been treated with prosthetic rehabilitation. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were utilized as the framework in designing, implementing and reporting the current review. Search of literature was done electronically using Medline, Embase, and Cochrane databases. Intervention component of the patient, intervention, comparison, outcome (PICO) for the current review was the prosthetic rehabilitation performed on the surgically treated head and neck cancer patients (participants); and outcome was the OHRQoL. Methodological index for non-randomized studies was the assessment tool utilized to report on the quality of the included studies. RESULTS: The initial search had identified 799 records and the final level of screening included eight articles. Six studies were experimental in design and two were cross-sectional. Cumulative sample of the head and neck cancer cases from the selected studies was 354, with 35.9 (14.9) and 72.4 (8.7) years as the highest and lowest mean age recorded from the included studies. More male cases (69.5%) were reported than female cases (30.5%) and squamous cell carcinoma was the most commonly diagnosed malignancy. Maxillary reconstruction and implant supported prosthesis were the choice of treatment for most of the cases. Different versions of oral health impact profile (OHIP) constructs were preferred by six studies. While, one study utilized University of Washington quality of life questionnaire and the other utilized European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire. Arguably, three studies had compared the OHRQoL scores of head and neck cancer patients with healthy counterparts through a follow-up period ranging from 1 to 2 years. CONCLUSIONS: The included studies did not provide substantial evidence to demonstrate the improvement in OHRQoL of head and neck cancer patients after prosthetic rehabilitation. More prospective studies are needed with representative sample, robust methodology and a longer follow-up period. The current study provides a direction to the clinical decision-making process and the epidemiological research to enhance the patients and public health-related outcomes.

Does microbiome shift play a role in carcinogenesis? A systematic review.

Recent scientific advances have presented substantial evidence that there is a multifaceted relationship between the microbiome and cancer. Humans are hosts to multifarious microbial communities, and these resident microbes contribute to both health and disease. Circulating toxic metabolites from these resident microbes may contribute to the development and progression of cancer. The aim of this systematic review was to evaluate microbiome and microbial shift contribution to the development and progression of cancer. This systematic review provides an analytical presentation of the evidence linking various parts of the microbiota to cancer. Searches were performed in databases such as PubMed, Google Scholar, Scopus, EBSCO, E-Journals and Science Direct from the time of their establishment until May 2018 with the following search terms: cancer or human microbe or cancer and human microbiome AND shift in microbes in cancer. The merged data were assessed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cochrane's Risk of Bias Tool was used to assess the bias. Initially, 2,691 articles were identified, out of which 60 full-text articles were screened and re-evaluated. Among them, 14 were excluded based on inclusion/exclusion criteria; eventually, 46 articles were included in the systematic review. The reports of 46 articles revealed that microbial shift involving Candida species, Fusobacterium nucleatum, Porphyromonas gingivalis, Helicobacter pylori and Human papilloma virus (HPV) 16 & 18 were most commonly involved in various human cancers. In particular, organisms, such as Candida albicans, Fusobacterium nucleatum, Porphyromonas gingivalis and HPV-16 were found to be more prevalent in oral cancer. The present systematic review emphasizes that the role and diverse contributions of the microbiome in carcinogenesis will provide opportunities for the development of effective diagnostic and preventive methods.

Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development.

Malaria is one of the most dangerous infectious diseases due to its high infection and mortality rates, especially in the tropical belt. Plasmodium falciparum (P. falciparum), the most virulent malaria parasite in humans, was recently reported to develop resistance against the final efficient antimalarial drug, artemisinin. Little is known about the resistance mechanisms, which further complicates the problem as a proper counteraction is unable to be taken. Hence, the understanding of drug mode of action and its molecular target is valuable knowledge that needs to be considered to develop the next generation of antimalarial drugs. P. falciparum protein kinase (Pf PK) is an attractive target for antimalarial chemotherapy due to its vital roles in all P. falciparum life stages. Moreover, overall structural differences and the presence of unique Pf PKs that are absent in human kinome, suggesting specific inhibition of Pf PK without affecting human cells is achievable. To date, at least 86 eukaryotic protein kinases have been identified in P. falciparum kinome, by which less than 40 were validated as potential targets at the erythrocytes stage. In this review, recent progress of the furthest validated Pf PKs; Pf Nek-1, Pf CDPK1, Pf CDPK4, Pf PKG, and Pf CLK-3 will be briefly discussed.

Current updates on dental perspectives of leprosy - Revisited.

The present review summarizes the current updates on dental perspectives on leprosy and the affording factors that are responsible for the prevalence of caries and periodontal diseases in leprosy. It also highlights immunopathological phenomena and reactional episodes of leprosy that occur due to daedal interactions between the perio-odontopathic bacteria and M. leprae. In addition, a brief introduction, historiography, classification and clinicopathological aspects are also been covered.

Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development

@#Malaria is one of the most dangerous infectious diseases due to its high infection and mortality rates, especially in the tropical belt. Plasmodium falciparum (P. falciparum), the most virulent malaria parasite in humans, was recently reported to develop resistance against the final efficient antimalarial drug, artemisinin. Little is known about the resistance mechanisms, which further complicates the problem as a proper counteraction is unable to be taken. Hence, the understanding of drug mode of action and its molecular target is valuable knowledge that needs to be considered to develop the next generation of antimalarial drugs. P. falciparum protein kinase (Pf PK) is an attractive target for antimalarial chemotherapy due to its vital roles in all P. falciparum life stages. Moreover, overall structural differences and the presence of unique Pf PKs that are absent in human kinome, suggesting specific inhibition of Pf PK without affecting human cells is achievable. To date, at least 86 eukaryotic protein kinases have been identified in P. falciparum kinome, by which less than 40 were validated as potential targets at the erythrocytes stage. In this review, recent progress of the furthest validated Pf PKs; Pf Nek-1, Pf CDPK1, Pf CDPK4, Pf PKG, and Pf CLK-3 will be briefly discussed.

Is toombak a risk factor for oral leukoplakia and oral squamous cell carcinoma ? A systematic review.

INTRODUCTION: Toombak is a form of smokeless tobacco that is not well known in Western Society but is widely used by the Sudanese population and many others in the sub-Sahara region. However, unlike other smokeless tobacco products, information on the carcinogenic potential of toombak is scarce. The present review explored any potential epidemiological association between the use of toombak and oral leukoplakia and oral squamous cell carcinoma (OSCC). METHODS: Databases including the Web of Science, SCOPUS, EMBASE and PubMed were searched for literature on the potential association between toombak and oral leukoplakia and OSCC. The search also included grey literature. The search period extended from 1990 to 2018. Following data mining, the study selection was conducted by two reviewers independently. RESULTS: Eight studies that satisfied the inclusion criteria were included. Based on these results, there was a threefoldto sevenfold increased risk of developing the oral leukoplakia and oral squamous cell carcinoma among toombak users compared with non-users. CONCLUSION: Based on the results of the systematic review, there is a strong epidemiological evidence to suggest toombak to be a major risk factor for both oral leukoplakia and OSCC. Further studies are necessary to evaluate the molecular pathway of toombak-induced oral carcinogenesis.

Role of salivary transcriptomics as potential biomarkers in oral cancer: A systematic review.

INTRODUCTION: Transcriptomes in saliva can be used as potential biomarkers for both diagnostic and response to treatment in oral squamous cell carcinoma (OSCC). In this review, we explored their application in this increasingly common disease. MATERIALS AND METHODS: PubMed, EMBASE, Scopus, Web of Science and grey literature from January 1990 to May 2017 were searched. Two independent reviewers performed the study selection according to eligibility criteria. RESULTS: A total of nine studies were included. Three studies showed increased expression of DUSP1, IL8, IL1B, OAZ1, SAT1, S100P and two showed increased expression of miRNA-31 among study groups compared to normal healthy controls. The sensitivity ranged from 14% to 100%, while the specificity ranged from 38% to 100%. miRNA-27b had the highest AUC (write in full) of 0.9643 and DUSP1 had the minimum AUC of 0.41. CONCLUSION: Salivary transcriptomics may play an effective role as a robust and non-invasive biomarker sighting tool for the diagnosis and management of OSCC.

The relationship of shammah (Arabian snuff) chewing to the risk of oral cancer and oral potentially malignant disorders.

INTRODUCTION: Shammah is a form of smokeless tobacco commonly used in the Arabian Peninsula. The data on the harmful effects of shammah on oral health, particularly oral malignancies, are scarce. The aim of this review was to explore the association between shammah use and development of oral potentially malignant disorders (OPMD) and/or oral cancer. MATERIALS AND METHODS: PubMed, EMBASE, Scopus, Web of Science and grey literature from January 1990 up to and including April 2018 were searched. Two independent reviewers performed the study selection according to eligibility criteria. RESULTS: A total of 10 studies that met the eligibility criteria were included. The odds of developing OPMD and/or oral cancer in relation to shammah use varied, with one study reporting a 39 increased risk (39, 95% CI: 14-105). The associated increased risk was relatively low among those that have stopped using shammah and ranged from threefold (3.65; 95% CI: 1.40-9.50) to 12-fold (12.6; 95% CI: 3.3-48.2). CONCLUSION: Shammah use seems to increase the risk of development of OPMD and/or oral cancer.

Association of nitric oxide with oral lichen planus.

BACKGROUND: The small signalling molecule nitric oxide (NO) has been postulated to have a mediator role in the pathogenesis of several diseases including oral lichen planus (OLP). This systematic review aimed to quantify the existing literature and assess the association of NO and OLP. METHODS: The focused question being addressed was "Is there an association between nitric oxide and OLP?" PubMed, EMBASE, Scopus, and Web of Science, and grey literature from January 1990 to August 2018 were searched. Two independent reviewers performed the study selection using specified eligibility criteria. RESULTS: Seven studies that met the eligibility criteria were included. All of these were case-control studies and 151 patients with OLP were evaluated (mostly females), with an age ranged from 20 to 75 years. The included studies showed a significant higher NO levels in OLP patients compared to the healthy controls, with two studies demonstrated a higher NO levels in erosive OLP compared to non-erosive OLP. CONCLUSION: These findings support that an association exists between higher NO concentration and OLP. However, larger high-quality studies with refined methodological design are needed to confirm the role of NO in the aetiology and pathogenesis of OLP.

Botulinum toxin in the management of myofascial pain associated with temporomandibular dysfunction.

INTRODUCTION: Critical evidence on the therapeutic efficacy of botulinum toxins (BTX) is still lacking for most pain conditions. The aim of this review was to evaluate the therapeutic efficacy of BTX in the management of temporomandibular myofascial pain. MATERIALS AND METHODS: Electronic databases PubMed, EMBASE, Scopus, Web of Science, and gray literature were searched for randomized clinical trials until February 2018 to answer a focused question "What is the effectiveness of botulinum toxin in the management of temporomandibular myofascial pain?" Two independent reviewers performed the study selection according to eligibility criteria. RESULTS: A total of seven studies that met the eligibility criteria were included. Two studies showed a significant improvement in temporomandibular myofascial pain, and one study showed equal efficacy of BTX in comparison with facial manipulation, while the remaining studies did not report any significant difference between BTX and control group. Due to heterogeneity in the methodology and outcome assessment, a meta-analysis and recalculation of risk could not be performed. CONCLUSION: Based on our findings, the therapeutic efficacy of BTX was unclear. Randomized controlled trials with better methodological criteria need to be carried out to evaluate the real effectiveness of BTX.

Iatrogenic arteriovenous fistula in the hand: a case report.

Peripheral intravenous cannulation is widely used in medicine. Arteriovenous fistulas are rare complications but their occurrence has never been reported in the hands. We report on a young patient who developed a high flow arteriovenous fistula on the dorsum of her hand two weeks after a failed peripheral intravenous cannulation attempt.