Inferior alveolar nerve block success of 2% mepivacaine versus 4% articaine in patients with symptomatic irreversible pulpitis in mandibular molars: A randomized double-blind single-centre clinical trial.

AIM: The aim of this study was to assess inferior alveolar nerve block (IANB) success of 2% mepivacaine (Scandonest 2%, Septodont, France) and 4% articaine (Septanest 4%, Septodont) in patients with symptomatic irreversible pulpitis (SIP) in mandibular molars during access cavity preparation and instrumentation. METHODOLOGY: Three hundred and thirty patients with moderate-to-severe pain in mandibular molars with SIP randomly received either 3.6 ml 2% mepivacaine hydrochloride with 1:100 000 adrenalin or 3.4 ml 4% articaine hydrochloride with 1:100 000 adrenalin (n = 165). Intraoperative pain (IOP) intensity was assessed during access cavity preparation and canal instrumentation using 11-point Numerical Rating Scale (NRS). Overall success was considered if the patient felt no-to-mild pain without the need for supplemental anaesthesia throughout treatment; the incidence of need for supplemental anaesthesia was also recorded. Data were statistically analysed using Mann-Whitney U- and Chi-squared (χ2 ) tests. Relative risk (RR) and 95% confidence interval (CI) of anaesthetic failure were calculated. The effect of pre-disposing factors on outcome variables was assessed using multivariable regression analyses. None of the participants reported any adverse effects. RESULTS: Baseline variables were balanced between groups (p > .05). The IOP intensity during access cavity preparation and canal instrumentation was similar for both groups (p > .05). IOP intensity was associated with preoperative pain intensity and tooth type (p < .05). Overall anaesthetic success rate was 35.8% for mepivacaine and 41.2% for articaine (p > .05) with a relative risk of failure [95% CI] 1.09 [0.92, 1.30]. The need for supplemental anaesthesia occurred 43.6% and 38.2% with mepivacaine and articaine respectively (p > .05; RR [95% CI]: 1.14 [0.88, 1.48]). Preoperative pain level and age were associated with the need for supplemental anaesthesia. CONCLUSIONS: 2% mepivacaine and 4% articaine demonstrate similar IANB success rates for mandibular molars with SIP. Intraoperative pain experience during endodontic treatment can be associated with preoperative pain, tooth type and age.

Molecular Biomarkers and Signaling Pathways of Cancer Stem Cells in Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequently found cancer in the world, and it is frequently discovered when it is already far along in its development. About 20% of cases of CRC are metastatic and incurable. There is more and more evidence that colorectal cancer stem cells (CCSCs), which are in charge of tumor growth, recurrence, and resistance to treatment, are what make CRC so different. Because we know more about stem cell biology, we quickly learned about the molecular processes and possible cross-talk between signaling pathways that affect the balance of cells in the gut and cancer. Wnt, Notch, TGF-ß, and Hedgehog are examples of signaling pathway members whose genes may change to produce CCSCs. These genes control self-renewal and pluripotency in SCs and then decide the function and phenotype of CCSCs. However, in terms of their ability to create tumors and susceptibility to chemotherapeutic drugs, CSCs differ from normal stem cells and the bulk of tumor cells. This may be the reason for the higher rate of cancer recurrence in patients who underwent both surgery and chemotherapy treatment. Scientists have found that a group of uncontrolled miRNAs related to CCSCs affect stemness properties. These miRNAs control CCSC functions like changing the expression of cell cycle genes, metastasis, and drug resistance mechanisms. CCSC-related miRNAs mostly control signal pathways that are known to be important for CCSC biology. The biomarkers (CD markers and miRNA) for CCSCs and their diagnostic roles are the main topics of this review study.

P53 is a risk factor of de-novo hepatitis C-related hepatocellular carcinoma treated with direct-acting antivirals: a case-control study.

BACKGROUND: The mechanisms underlying de-novo hepatocellular carcinoma (HCC) after direct-acting antivirals (DAAs) is still under investigation. This work aims to study P53 and hepatocyte growth factor (HGF) as possible diagnostics of de-novo hepatocellular carcinoma (HCC) following DAAs in comparison to alpha-fetoprotein (AFP). METHOD: This case-control study included 166 patients with liver cirrhosis divided into group-1: patients without HCC (n = 50), group-2: patients with de-novo HCC following DAAs, and achieved sustained virological response (n = 50), and group-3: patients with HCC without DAAs (n = 66). P53 antibody and HGF were determined using a quantitative sandwich enzyme immunoassay technique (Cusabio Co, Houston, USA). RESULTS: Patients with HCC showed significantly higher HGF. Patients with de-novo HCC following DAAs had significantly higher P53 than HCC without DAAs (P < 0.0001). The multiple logistic regression analysis showed that the P53 levels were significantly associated with susceptibility to de-novo HCC (P value = 0.004). The best overall formula was constructed for HCC diagnosis by entering significant markers into the regression model. A three markers model was developed = (1.22 + AFP X 0.002 + HGF X 0.001 + P53 X 0.001). The medians (percentiles) of combined three markers were 1.8 (1.0-2.1) in liver cirrhosis and 2.2 (2.0-2.9) in all HCC (P < 0.00001). The AUC of combined markers was greater than a single marker. The AUC was 0.87 to differentiate HCC from liver cirrhosis; AUC 0.91 to differentiate de-novo HCC after DAAs from liver cirrhosis. CONCLUSION: P53 may serve as a diagnostic marker for de-novo HCC after DAAs therapy. HGF may serve as a diagnostic marker for HCC but not specific for de-novo HCC after DAAs therapy.

Diagnostic performances of leucine-rich α-2-glycoprotein 1 and stem cell factor for diagnosis and follow-up of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequently diagnosed tumors worldwide with high mortality and morbidity. There is an urgent need for biomarkers to improve the outcomes and early detection of CRC. The sensitivity of traditional CRC tumor markers (carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)) is not ideal. The levels of leucine-rich-alpha-2-glycoprotein 1 (LRG1) and stem cell factor (SCF) were evaluated, but the combined value of both markers is unclear. This case-control study included four groups: CRC patients before treatments (n = 22), CRC patients after treatments (n = 26), 20 patients with benign tumor, and 20 healthy subjects. Levels of routine biochemical and hematological markers, traditional tumor markers (CA19.9 and CEA), and candidate markers (LRG1 and SCF) were determined. Univariate and multivariate logistic regression analysis and area receiver-operating characteristic analysis (ROC) were used for evaluation the diagnostic performances of single and combined markers. RESULTS: No significance difference in traditional tumor markers CEA, CA 19.9, and neutrophil-lymphocyte ratio (NLR) were found among study groups. SCF, LRG1, and platelet-lymphocyte ratio (PLR) were significantly decreased (p < 0.05) in non-treated CRC patients than after treated CRC. The combination between SCF and LRG1 showed highly significant difference in CRC patients compared with benign, healthy subjects, and among CRC groups (treated and non-treated) (p < 0.0001). The highest areas under curve (AUCs) were observed when LRG1 was used as a single predictor for discriminating CRC from healthy (0.87), benign (0.84), and non-treated CRC vs treated CRC (0.82). AUCs were jumped to 0.90, 0.84, and 0.84 when LRG1 and SCF were combined. CONCLUSION: Our study revealed that LRG1 and SCF were potential diagnostic and follow-up markers for CRC.

Development of a novel panel based on micro-RNAs (21, 29a, 200 and 335) and alpha-fetoprotein as diagnostic biomarkers for hepatocellular carcinoma associated with hepatitis C infection.

BACKGROUND AND STUDY AIMS: MicroRNAs (miRNAs) play key roles in cancer biology; they are used as potential tools in cancer diagnosis. This study investigated the microRNA expression profile of patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Serum microRNA expression profiles (miRNA-29a, miRNA-200, miRNA-335 and miRNA-21) were analysed in 137 patients with HCC and liver cirrhosis and 49 healthy subjects (used as negative controls) using real-time quantitative reverse transcription polymerase chain reaction. Alpha-fetoprotein (AFP), as a routine tumour marker, was also assessed using enzyme-linked immunosorbent assay. RESULTS: The expression levels of miRNA-21, miRNA-335 and miRNA-200 were significantly up-regulated, whereas those of miRNA-29a were remarkably down-regulated in patients with HCC compared with those in healthy subjects. miRNA-200 had the most elevated area under the receiver operating characteristic curve (AUC) among single miRNAs used to predict HCC occurrence (AUC = 0.72). The highest discriminatory power was recorded using a panel based on the combination of four miRNAs, miRNA-200, miRNA-29a, miRNA-21 and miRNA-355, and AFP levels (AUC = 0.92). The four-miRNA panel combined with AFP levels exhibited high accuracy in predicting HCC with small tumour sizes of <2 cm (AUC = 0.90) and ≥2 cm (AUC = 0.93). The combination of the four-miRNA panel and AFP resulted in an AUC value of 0.83 for single lesions, which was lesser than that recorded for ≥2 lesions (AUC = 0.94, 0.95, respectively). CONCLUSION: The combination of the four-miRNA panel and AFP levels can be used as a sensitive and specific biomarker for HCC.

Allicin mitigates hepatic injury following cyclophosphamide administration via activation of Nrf2/ARE pathways and through inhibition of inflammatory and apoptotic machinery.

Treatment with anti-neoplastic agents, including cyclophosphamide (CP), is associated with several adverse reactions. Here, we distinguished the potential protective effect of allicin against CP-mediated hepatotoxicity in rats. To assess the effect of allicin, four experimental groups were used, with 7 rats per group, including control, allicin (10 mg/kg), CP (200 mg/kg), and allicin + CP-treated groups. All groups were treated for 10 days. Blood and liver samples were collected for biochemical, molecular, and histological analyses. Treatment with CP led to deformations in the liver tissue that were associated with higher liver function markers (alanine transaminase, aspartate transaminase, and alkaline phosphatase). Additionally, a disturbance in the redox balance was observed after CP exposure, as indicated by increased levels of oxidants, including malondialdehyde and nitric oxide, and the decreased levels of endogenous antioxidants, including glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. At the molecular level, CP treatment resulted in reduced expression of the Nrf2/ARE pathway and other genes related to this pathway, including NAD(P)H quinone dehydrogenase 1 and glutamate-cysteine ligase catalytic subunit. CP also led to a hyper-inflammatory response in hepatic tissue, with increased production of pro-inflammatory cytokines, including tumor necrosis factor-alpha and interlukin-1beta, and upregulation of nitric oxide synthase 2. CP also enhanced the immunoreactivity of the profibrogenic cytokine, transforming growth factor-beta, in liver tissue. Upregulation of caspase 3 and Bcl-2-associated X protein and downregulation of B-cell lymphoma 2 were also observed in response to CP treatment. Treatment with allicin reversed the molecular, biochemical, and histological changes that occurred with CP exposure. These results suggest that allicin can be used in combination with CP to avoid hepatotoxicity.

Rhamnolipids Nano-Micelles as a Potential Hand Sanitizer.

COVID-19 is a pandemic disease caused by the SARS-CoV-2, which continues to cause global health and economic problems since emerging in China in late 2019. Until now, there are no standard antiviral treatments. Thus, several strategies were adopted to minimize virus transmission, such as social distancing, face covering protection and hand hygiene. Rhamnolipids are glycolipids produced formally by Pseudomonas aeruginosa and as biosurfactants, they were shown to have broad antimicrobial activity. In this study, we investigated the antimicrobial activity of rhamnolipids against selected multidrug resistant bacteria and SARS-CoV-2. Rhamnolipids were produced by growing Pseudomonas aeruginosa strain LeS3 in a new medium formulated from chicken carcass soup. The isolated rhamnolipids were characterized for their molecular composition, formulated into nano-micelles, and the antibacterial activity of the nano-micelles was demonstrated in vitro against both Gram-negative and Gram-positive drug resistant bacteria. In silico studies docking rhamnolipids to structural and non-structural proteins of SARS-CoV-2 was also performed. We demonstrated the efficient and specific interaction of rhamnolipids with the active sites of these proteins. Additionally, the computational studies suggested that rhamnolipids have membrane permeability activity. Thus, the obtained results indicate that SARS-CoV-2 could be another target of rhamnolipids and could find utility in the fight against COVID-19, a future perspective to be considered.

Nanoparticles induce genetic, biochemical, and ultrastructure variations in Salvadora persica callus.

BACKGROUND: Salvadora persica is an endangered medicinal plant due to difficulties in its traditional propagation. It is rich in bioactive compounds that possess many pharmaceutical, antimicrobial activities and widely used in folk medicine. The current study aims at in vitro propagation of Salvadora persica and the application of different nanoparticles (NPs) to induce the synthesis of bioactive and secondary metabolites within the plant. The cellular and genetic responses to the application of different NPs were evaluated. RESULTS: The impact of nanoparticles NPs (ZnO, SiO2, and Fe3O4) on callus growth of Salvadora persica and the production of its active constituent benzyl isothiocyanate was examined, regarding some oxidative stress markers, antioxidant enzymes, and genetic variabilities. An encouraging impact of 0.5 mg/l ZnO NPs on benzyl isothiocyanate production was shown reaching up to 0.905 mg/g callus fresh weight in comparison to 0.539 mg/g in control callus. This was associated with decreasing hydrogen peroxide content and increasing superoxide dismutase and peroxidase activities. The deposition of the NPs on cellular organelles was detected using a transmission microscope. Fifteen Inter-Simple Sequence Repeats (ISSR) primers detected an overall, 79.1% polymorphism among different treatments. A reduction in genomic DNA template stability (GTS) was made and was more pronounced in higher doses of different NPs. CONCLUSION: This study is a stepping stone in developing a productive protocol for in vitro production of benzyl isothiocyanate from Salvadora persica using NPs as a valuable anticancer compound.

Effect of obturating systems, dowel materials, and adhesive luting techniques on the resistance to fracture of endodontically treated teeth.

PURPOSE: The aim of this study was to assess the role of obturating systems, dowel materials, and adhesive techniques on the resistance to fracture of endodontically treated teeth. MATERIAL AND METHODS: Eighty maxillary central incisors were selected and randomly divided into two groups according to the obturating system (n = 40); group I: gutta-percha and Roeko sealer; group II: RealSeal. Both groups were further subdivided into two subgroups; subgroup A: using ceramic dowels (Cosmopost); subgroup B using fiber dowels (Easy Post). Each subgroup was assigned to two divisions according to the adhesive luting technique; division V (total-etch) Variolink II resin cement; division U (self-adhesive) RelyX Unicem. Composite core build-up was made using a core former. Each specimen was loaded 2 mm from its incisal edge on the palatal side at a 135° angle with the long axis of the tooth using a universal testing machine with a load cell of 5 KN at a crosshead speed of 0.5 mm/min until fracture. Failure loads were recorded in N. Scanning electron microscopic examination at the dentin/resin interface (1000x) was performed. Three-way ANOVA was used to test the effect of obturating system, dowel material, adhesive technique, and their interactions (obturating system * dowel material, obturating system * adhesive, dowel material * adhesive, obturating system * dowel material * adhesive). Duncan's test was used for pairwise comparison. The significance level was set at p≤ 0.05. Statistical analysis was performed with SPSS 16.0. RESULTS: The mean resistance to fracture (617.4 N) was statistically significantly higher in the ceramic dowel with gutta-percha and Variolink (GP/C/V) group than in the other groups. The RealSeal and RelyX fiber dowel group's mean resistance was the lowest and was significantly lower than the other groups. CONCLUSIONS: In this study, three factors played a part in enhancing the resistance to fracture of endodontically treated teeth. High resistance to fracture was achieved when ceramic dowels were luted with total-etch technique in gutta-percha-obturated teeth.

Ferulic acid influences Nrf2 activation to restore testicular tissue from cadmium-induced oxidative challenge, inflammation, and apoptosis in rats.

Here, we examined the protective effect of ferulic acid (FA) on cadmium chloride (CdCl2 )-mediated reproductive toxicity in male rats. Animals were divided into four groups: control, FA (20 mg/kg), CdCl2 (6.5 mg/kg), and FA + CdCl2 . CdCl2 treatment evoked a significant increase in testis cadmium concentration in addition to obvious increase in testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Moreover, CdCl2 -induced oxidative damage through exhausting the cellular defenses (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione) and downregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression accompanied by increases of malondialdehyde and nitric oxide contents. Testicular inflammation was evident indicated by increased levels of interleukin-1ß and tumor necrosis factor-α in CdCl2 -treated rats. CdCl2 exposure also decreased the expression of the proliferating cell nuclear antigen and augmented apoptotic events associated with prominent histopathological alterations. However, FA coadministration mitigated the impaired hormonal level, apoptotic and inflammatory injuries elicited by CdCl2, and maintained the oxidant/antioxidant balance in testicular tissue via Nrf2 activation. PRACTICAL APPLICATIONS: Cadmium is an environmental toxicant and known to cause adverse effects including reproductive toxicity. However, antioxidant application has been found to protect against heavy metals-mediated toxic effects. Here, we examined the potential protective efficacy of ferulic acid against cadmium-mediated testicular impairments through estimating the amount of cadmium in the testis, hormonal profile, oxidative status, inflammatory response, apoptotic and proliferating markers in addition to the histopathological alterations. The obtained findings revealed that ferulic acid supplementation was able to abolish the testicular damages coupled with cadmium exposure. The protective efficiency of ferulic acid may correlated with its strong antioxidant, anti-inflammatory, and antiapoptotic activities; suggesting that ferulic acid may be used to ameliorate cadmium-induced testicular deficits.

The protective efficacy of soursop fruit extract against hepatic injury associated with acetaminophen exposure is mediated through antioxidant, anti-inflammatory, and anti-apoptotic activities.

In the current report, we examined the potential beneficial role of soursop fruit extract (SSFE) on liver injury induced by a single paracetamol (APAP) overdose (2000 mg/kg). Thirty-five Wistar albino rats were randomly divided into five groups as follows: control, SSFE, APAP, SSFE+APAP, and silymarin (SIL)+APAP. APAP intoxication was found to elevate alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels. Moreover, it increased the levels of malondialdehyde, nitrites, and nitrates and depleted glutathione, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. APAP intoxication inactivated the nuclear factor erythroid 2-related factor 2 (Nrf2) defense pathway and upregulated the expression of heme oxygenase-1 (HO-1). APAP administration enhanced the activation of nuclear factor-kappa B (NF-κB), the elevation of tumor necrosis factor-alpha and interleukin 1-beta levels, and the upregulation of inducible nitric oxide synthase mRNA expression. In addition, APAP activated the overexpression of Bax protein, increased release of cytochrome c, and the downregulation of Bcl-2 protein. Finally, APAP-induced overexpression of transforming growth factor-beta (TGF-ß) further suggested enhanced liver damage. On the other hand, SSFE pretreatment attenuated these biochemical, molecular, and histopathological alterations in the liver, which might be partially due to the regulation of hepatic Nrf2/HO-1 and downregulation of NF-κB and TGF-ß.

The effect of different irrigating solutions on bond strength of two root canal-filling systems.

The bond strength of ActiV GP root canal filling system and gutta-percha/AH plus sealer when used after final rinse with different irrigation protocols was evaluated in this study. Forty roots were randomly divided into four groups (n = 10) according to the final irrigation regimen: group 1, 5 mL 17% EDTA; group 2, 5 mL 17% EDTA followed by 5 mL 2% chlorhexidine gluconate (CHX); group 3, 5 mL MTAD; and group 4, 5 mL MTAD followed by 5 mL 2% CHX. Each group was further subdivided into two subgroups (n = 5): in subgroup a, the root canals were filled using warm gutta-percha and AH plus sealer, and in subgroup b, the root canals were filled using the ActiV GP obturation system. Two-millimeter thick horizontal sections from the coronal and midthirds of each root were sliced for the push-out bond strength measurement. EDTA/CHX/ActiV GP (2.46 +/- 1.02 MPa) yielded significantly the highest mean bond strength value. The significantly lowest bond strength was recorded for EDTA/ActiV GP (1.12 +/- 0.72 MPa). It was concluded that the bond strength of ActiV GP was improved by using 2% CHX in the final irrigation after 17% EDTA, whereas CHX did not enhance the effect of MTAD on the bond strength of the material. The bond strength of gutta-percha/AH plus was adversely affected by MTAD and MTAD/CHX.