Risk factors of Oral cancer- A hospital based case control study

Oral cancer is a highly prevalent malignancy in Pakistan. Among various risk factors associated with this neoplasm, habits such as smoked and smokeless tobacco usage, betel quid, and betel nut consumption are the major culprits in our society. In the present study, we aimed to ascertain prevalent risk factors for OC in our population and to compare our findings with healthy controls to establish their significance. A hospital-based case control study was conducted at Dow University of Health Sciences, Pakistan from January 2015 ? September 2016. Information pertaining to unhealthy oral habits was obtained from 62 oral cancer patients (cases) and 62 healthy controls on specifically designed proforma by the principal investigator. Smokeless tobacco is strong, independent risk factor for oral cancer development in our study population. Buccal mucosa is the predominantly affected site (71%) which corresponds with high smokeless tobacco use. All studied habits increase risk of oral cancer as demonstrated by high odds ratio. Despite advancement in our knowledge and understanding of carcinogenic potential of these hazardous substances not enough efforts have been put forth to effectively control their widespread sale and consumption, particularly by the youth in our society

DETECTION AND CHARACTERIZATION OF LATENCY STAGE OF EBV AND HISTOPATHOLOGICAL ANALYSIS OF PROSTATIC ADENOCARCINOMA TISSUES

The pathophysiology of prostate cancer involves both genetic and acquired factors, including pathogens, such as viruses. A limited number of studies have shown the presence of Epstein-Barr virus (EBV) in prostate cancer tissues. However, there is a dearth of data exploring EBV latency profile in prostate cancer, and the relationship of EBV with histopathological features of prostate cancer. In this study, prostate cancer and benign prostatic hyperplasia (BPH) samples were screened for the presence of EBV, followed by the characterization of the EBV latency profile and analysis of histopathological parameters in EBV-positive and EBV-negative groups. A conventional PCR strategy was employed using virus-specific primers to screen EBV in 99 formalin-fixed paraffin-embedded (FFPE) prostate cancer and 33 BPH samples received for histopathological analysis during the years 2019–2020. Subsequently, cDNA samples were used in a qPCR array to analyze the expression of EBV latency-associated genes to map the latency profile EBV maintains in the samples. Finally, statistical analyses were performed to determine the correlation between EBV and several histopathological features of the samples. EBV was detected in 39% of prostate cancer and 24% of BPH samples. The histopathological analysis of prostate cancer samples identified all samples as prostatic adenocarcinoma of acinar type, while statistical analyses revealed EBV-positive samples to exhibit significantly higher (p < 0.05) Gleason major and total Gleason scores as compared to EBV-negative samples. In the EBV-positive samples, variable expression patterns of latency-associated genes were observed, where most of the samples exhibited EBV latency II/III-like profiles in prostate cancer, while latency-II-like profiles in BPH samples. This study suggests a high prevalence of EBV in prostate samples, where EBV exhibited latency II/III-like profiles. Furthermore, EBV-positive samples exhibited a higher Gleason score suggesting a possible link between EBV and the onset/progression of prostate cancers. However, future functional studies are required to understand the role of the EBV gene expression profile in the onset/progression of prostate cancer

ASSOCIATION BETWEEN THE BASELINE GENE EXPRESSION PROFILE IN PERIAPICAL GRANULOMA AND PERIAPICAL WOUND HEALING AFTER SURGICAL ENDODONTIC TREATMENT

In this study, we have investigated the association between the baseline gene expression profile in periapical granuloma and periapical wound healing after surgical endodontic treatment. Twenty-seven patients aged between 15 and 57 years underwent periapical surgery. The retrieved periapical tissue sample was used for mRNA expression analysis of COL1A1, VTN, ITGA5, IL-4, TNF, ANGPT, VEGFA, and CTGF. All patients were recalled after 6 and 12 months for periapical healing evaluation. Healing was then correlated with baseline gene expression. Healing was observed in 15 patients at the end of 6 months, which increased to 21 patients after 12 months. Six patients showed no healing even after 12 months. Analysis of baseline expression levels of the tested genes with healing status showed the mean relative expression of VTN, VEGFA, ANGPT, TNF, and CTGF to be significantly different (p < 0.05) between the healing group (6 and 12 months) (72.99%) and the non-healing (94.42%) group. Periapical Index scores 3–5 exhibited a positive correlation with ITGA-5 expression. Overexpression of ANGPT and a strong positive correlation between ITGA5 and PAI scores in the non-healing group of patients may suggest these genes to be a potential prognostic biomarker for periapical wound non-healing after surgical endodontic treatment

Comparative clinical and epidemiological study of central nervous system tumors in Pakistan and global database

Introduction: Brain tumors encompass a broad group showing wide geographic and ethnic variation in incidence. In keeping view the critical dearth of epidemiological data on brain tumors from Pakistan we undertook this study, with the aim to first describe spectrum of brain tumors at our center, and then to compare our results with prevalence pattern in global population using TCGA clinical dataset. Material and methods: Data was retrospectively collected from Histopathology archives of Dow Diagnostic Reference and Research Lab (DDRRL), Dow University of Health Sciences (DUHS), Pakistan. Clinical data set for Low Grade Gliomas (LGG) and Glioblastoma (GBM) cohort (TCGA) was downloaded from cbioportal (www.cbioportal.org). All the analyses were performed in IBM SPSS v. 24 and P value 36 years). Significant difference was recorded between our centre and global dataset with respect to age (P < 0.0001), common histological subtype (P < 0.0001), and histological grade (P < 0.0001). Conclusion: Present study shows significant variation in CNS tumor prevalence pattern between our population and global data highlighting the need for epidemiological and scientific studies to delineate the environmental and genetic risk factors pertaining to our population

High Avidity Binding to DNA Protects Ubiquitylated Substrates from Proteasomal Degradation*

Protein domains that act as degradation and stabilization signals regulate the rate of turnover of proteasomal substrates. Here we report that the bipartite Gly-Arg repeat of the Epstein-Barr virus (EBV) nuclear antigen (EBNA)-1 acts as a stabilization signal that inhibits proteasomal degradation in the nucleus by promoting binding to cellular DNA. Protection can be transferred by grafting the domain to unrelated proteasomal substrates and does not involve changes of ubiquitylation. Protection is also afforded by other protein domains that, similar to the Gly-Arg repeat, mediate high avidity binding to DNA, as exemplified by resistance to detergent extraction. Our findings identify high avidity binding to DNA as a portable inhibitory signal that counteracts proteasomal degradation

Evaluation of loosely bound water loss from different compositions of glass ionomer cement

Background: Water is an essential component of glass ionomer cement. Water balance is probably the most important and least understood mechanism with the glass ionomer cement. Excessive water in glass ionomer produce weak cement while less amount of water produce cement which is relatively stronger initially but later results in the weakening of the cement. Water present in glass ionomer cement is classified according to its nature of being held in to the cement as tightly bound and loosely bound. The amount of loosely bound water loss from various composition of glass ionomer cement remains unknown.Methods: The study was conducted at the Department of Materials, Queen Mary University of London. Two different composition of glass ionomer cements were used in this experiment in which the amount of water absorbed by the different compositions of cement on 1, 3, 7 and 14 days were evaluated and the loss of water was measured after that period until the loss became constant. A total of 25 samples of each GIC composition, 5 samples were immersed in water for 24 hours, 5 in water for 3 days, 5 for 7 days and 5 for 14 days. The remaining 5 samples were directly placed into the desiccator without immersing it in the water. The total water content of both glass ionomer cements was calculated from its chemical composition. The samples were weighed every hour for first 3 hours and then every 24 hours until the weight of the sample became constant. Samples placed in water for 1, 3, 7 and 14 days were dried before weighing with a tissue.Results: The amount of water uptake in all the compositions was not that significant in relation to time. In case of Fuji IX, amount of water loss percentage did not vary with increasing time interval. The water loss was rapid in the first 24 hours but it slowed down with time and became constant after 3 days however in Ketac molar water loss slightly varied with time interval.Conclusion: It is concluded that the amount of water uptake in both glass ionomer cement is not significant in relation to time. The loss of loosely bound water becomes constant with time after 24 hours for both compositions of glass ionomer cements

Investigating the association between the autophagy markers LC3B, SQSTM1/p62, and dram and autophagy-related genes in glioma

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers\u27 expression in low-grade gliomas (LGGs) and high-grade gliomas (HGGs). In 39 glioma cases, we assessed the protein expression of autophagy markers LC3B, SQSTM1/p62, and DRAM by immunohistochemistry (IHC) and the mRNA expression of the autophagy genes PTEN, PI3K, AKT, mTOR, ULK1, ULK2, UVRAG, Beclin 1, and VPS34 using RT-qPCR. LC3B, SQSTM1/p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases, respectively. The expression of LC3B and SQSTM1/p62 was notably higher in HGGs compared to LGGs. VPS34 exhibited a significant differential expression, displaying increased fold change in HGGs compared to LGGs. Additionally, it exhibited robust positive associations with Beclin1 (rs = 0.768), UVRAG (rs = 0.802), and ULK2 (rs = 0.786) in HGGs. This underscores a potential association between autophagy and the progression of gliomas. We provide preliminary data for the functional analysis of autophagy using a cell culture model and to identify potential targets for therapeutic interventions

Interaction of Gamma-Herpesvirus Genome Maintenance Proteins with Cellular Chromatin

<div><p>The capacity of gamma-herpesviruses to establish lifelong infections is dependent on the expression of genome maintenance proteins (GMPs) that tether the viral episomes to cellular chromatin and allow their persistence in latently infected proliferating cells. Here we have characterized the chromatin interaction of GMPs encoded by viruses belonging to the genera Lymphocryptovirus (LCV) and Rhadinovirus (RHV). We found that, in addition to a similar diffuse nuclear localization and comparable detergent resistant interaction with chromatin in transfected cells, all GMPs shared the capacity to promote the decondensation of heterochromatin in the A03-1 reporter cell line. They differed, however, in their mobility measured by fluorescence recovery after photobleaching (FRAP), and in the capacity to recruit accessory molecules required for the chromatin remodeling function. While the AT-hook containing GMPs of LCVs were highly mobile, a great variability was observed among GMPs encoded by RHV, ranging from virtually immobile to significantly reduced mobility compared to LCV GMPs. Only the RHV GMPs recruited the bromo- and extra terminal domain (BET) proteins BRD2 and BRD4 to the site of chromatin remodeling. These findings suggest that differences in the mode of interaction with cellular chromatin may underlie different strategies adopted by these viruses for reprogramming of the host cells during latency.</p></div

Factors Affecting the Outcome of Periapical Surgery; a Prospective Longitudinal Clinical Study

Wound healing following periapical surgery is influenced by age, gender, smoking, periapical lesion size, type of root-end filling, method of root-end cavity preparation and the use of microsurgical or conventional technique. This study aimed to evaluate the influence of various preoperative factors such as age, gender, smoking, preoperative pain, and preoperative periapical lesion size on the outcome of surgical endodontic treatment. A thorough history, examination, and investigation were performed to establish patient age, gender, smoking status, periapical lesion size, and the presence of preoperative pain. Forty patients aged between 15–57 years presented with persistent chronic apical periodontitis of single-rooted anterior teeth after conventional re-root canal treatment were enrolled for periapical surgery. Following periapical surgery, all patients were recalled for evaluation of periapical healing after 12 months based on clinical and periapical X-ray examination due to inaccessibility of an advanced imaging system (CBCT). Chi-squared and Fisher’s exact test were applied, which revealed a statistically significant association of periapical healing with age (p = 0.025), smoking (p = 0.029), and lesion size (p p = 0.254). Patient age, smoking status, and size of the preoperative lesion had a strong influence on periapical healing after surgical endodontic treatment