7-amino carboxycoumarin 2 inhibits lactate induced epithelial-to-mesenchymal transition via MPC1 in oral and breast cancer cells.

Lactate is an oncometabolite that play important role in tumor aggressiveness. Lactate from the tumor microenvironment (TME) is taken up by cancer cells as an energy resource via mitochondrial oxidative phosphorylation (or OXPHOS). In the present study, by using an online meta-analysis tool we demonstrated that in oral squamous cancer cells (OSCCs) glycolytic and OXPHOS governing genes are overexpressed, like in breast cancer. For experimental demonstration, we treated the OSCC cell line (SCC4) and breast cancer cells (MDA-MB-231) with sodium L-lactate and analyzed its effects on changes in EMT and migration. For the therapeutic intervention of lactate metabolism, we used AZD3965 (an MCT1 inhibitor), and 7ACC2 (an MPC inhibitor). Like breast cancer, oral cancer tissues showed increased transcripts of 12 genes that were previously shown to be associated with glycolysis and OXPHOS. We experimentally demonstrated that L-lactate treatment induced mesenchymal markers and migration of cancer cells, which was significantly neutralized by MPC inhibitor that is, 7ACC2. Such an effect on EMT status was not observed with AZD3965. Furthermore, we showed that lactate treatment increases the MPC1 expression in both cancer cells, and this might be the reason why cancer cells in the high lactate environment are more sensitive to 7ACC2. Overall, our present findings demonstrate that extracellular lactate positively regulates the MPC1 protein expression in cancer cells, thereby putting forward the notion of using 7ACC2 as a potential therapeutic alternative to inhibit malignant oxidative cancers. Future preclinical studies are warranted to validate the present findings.

Clinical Significance of MUC4 and Associated Proteins in Pancreatic and Periampullary Cancers.

OBJECTIVE: This study primarily aimed to assess the expression of MUC4 in patients with pancreatic ductal adenocarcinoma (PDAC) as compared with controls and assess its clinical relevance. MATERIALS AND METHODS: Serum MUC4 levels and MUC4 gene expression in snap-frozen tissue were analyzed through surface plasmon resonance and quantitative polymerase chain reaction, respectively. Tumor tissues and control tissues were analyzed for MUC4 and other mucins through immunohistochemistry. RESULT: MUC4 expression in tumor tissue was found to be significantly elevated in PDAC patients as compared with chronic pancreatitis tissues and normal pancreatic tissues. Periampullary carcinoma and cholangiocarcinoma tissue also showed increased expression of MUC4 and other mucins. CONCLUSIONS: Differential expression of MUC4 in pancreatic tumor tissues can help to differentiate PDAC from benign conditions.

Is Diclofenac Transbuccal Mucoadhesive Patch Superior to Oral Diclofenac for the Management of Postoperative Sequelae After Third Molar Surgery?

BACKGROUND: Pain, swelling, and trismus are the most common sequalae following the surgical removal of mandibular third molars. They pose significant challenges for clinicians, prompting the exploration of efficacious management approaches. PURPOSE: The purpose of this study was to assess the efficacy of transbuccal mucoadhesive patch of diclofenac sodium versus an oral tablet in controlling the aforesaid sequelae. STUDY DESIGN, SETTING, SAMPLE: A prospective split-mouth, single-blinded study was conducted in the Department of Oral and Maxillofacial Surgery at AMC Dental College and Hospital, Ahmedabad. The study sample included patients of either sex, aged 18 to 45 years, requiring surgical removal of bilaterally symmetrical mandibular third molars under local anesthesia. Patients who had consumed analgesics within 24 hours prior to the procedure were excluded. PREDICTOR VARIABLE: The primary predictor variable was the route of administration of nonsteroidal anti-inflammatory drug. The study group received transbuccal mucoadhesive patches containing 20 mg diclofenac sodium, whereas the control group received oral tablets of 50 mg. MAIN OUTCOME VARIABLE: Postoperative pain, measured with visual analog scale, was the primary outcome variable, whereas swelling, mouth opening, onset of analgesic effect, and adverse events were assessed as secondary outcome variables. COVARIATES: Two categories of covariates were considered. First, demographic: age and gender. Second, perioperative: pattern of impaction. ANALYSES: Intergroup comparison was made using a paired sample t-test and an independent sample t-test, while intragroup differences were assessed with a one-way ANOVA and a paired t-test. P value ≤ .05 was considered statistically significant. RESULTS: Out of 146 patients screened initially, the final study sample included 37 subjects with a mean age of 26.08 ± 5.09 years (21 (56.75%) males and 16 (43.25%) females). The study group exhibited a significantly lower postoperative pain score compared to the control group on days 0, 1, 2, and 3 postoperatively (P ≤ .05). No statistically significant difference was observed in reduction of facial swelling and improvement in mouth opening on 1st, 2nd, and 3rd days postoperatively between both the groups (P ≥ .05). The mean onset of analgesia was statistically significant in the study group (19.96 ± 5.40 minutes) compared to the control group (52.56 ± 6.33 minutes) (P < .001). CONCLUSION AND RELEVANCE: Transbuccal mucoadhesive patch of diclofenac sodium offers effective pain control with quicker analgesia and fewer side effects compared to an oral tablet.

Effective strategies in the management of anterior mandibular fractures: a comprehensive systematic review.

This review examines the prevailing modalities for fractures of the anterior mandible, which represent a significant proportion of the maxillofacial injuries commonly treated by oral and maxillofacial surgeons. The article traces the historical shift from conservative techniques to the dominant management strategies of open reduction and fixation. Encompassing a range of studies, the review, in accordance with PRISMA 2020 recommendations, meticulously examines various fixation methods, assessing their efficacy in achieving stability of fracture, early healing, and mobilisation. The comparison of these methods highlights their unique advantages and limitations, and demonstrates the need for more nuanced and precise approaches. The review emphasises evidence-based methodology in the management of anterior mandibular fractures (AMF), highlighting the benefits offered by innovative techniques such as 3D miniplates. It also acknowledges the advantages provided by older fixation devices such as lag screws. The importance of postoperative outcomes and the need for tailored treatment strategies are recognised, considering the complex nature of these fractures.

Long non-coding RNAs in cancer: multifaceted roles and potential targets for immunotherapy.

Cancer remains a major global health concern with high mortality rates mainly due to late diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression in human cancer, functioning through various mechanisms including as competing endogenous RNAs (ceRNAs) and indirectly regulating miRNA expression. LncRNAs have been found to have both oncogenic and tumor-suppressive roles in cancer, with the former promoting cancer cell proliferation, migration, invasion, and poor prognosis. Recent research has shown that lncRNAs are expressed in various immune cells and are involved in cancer cell immune escape and the modulation of the tumor microenvironment, thus highlighting their potential as targets for cancer immunotherapy. Targeting lncRNAs in cancer or immune cells could enhance the anti-tumor immune response and improve cancer immunotherapy outcomes. However, further research is required to fully understand the functional roles of lncRNAs in cancer and the immune system and their potential as targets for cancer immunotherapy. This review offers a comprehensive examination of the multifaceted roles of lncRNAs in human cancers, with a focus on their potential as targets for cancer immunotherapy. By exploring the intricate mechanisms underlying lncRNA-mediated regulation of cancer cell proliferation, invasion, and immune evasion, we provide insights into the diverse therapeutic applications of these molecules.

MicroRNA Signatures for Pancreatic Cancer and Chronic Pancreatitis: Expression Profiling by NGS.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease due to the lack of early detection. Because chronic pancreatitis (CP) patients are a high-risk group for pancreatic cancer, this study aimed to assess the differential miRNA profile in pancreatic tissue of patients with CP and pancreatic cancer. METHODS: MiRNAs were isolated from formalin-fixed paraffin-embedded pancreatic tissue of 22 PDAC patients, 18 CP patients, and 10 normal pancreatic tissues from autopsy (C) cases and processed for next-generation sequencing. Known and novel miRNAs were identified and analyzed for differential miRNA expression, target prediction, and pathway enrichment between groups. RESULTS: Among the miRNAs identified, 166 known and 17 novel miRNAs were found exclusively in PDAC tissues, while 106 known and 10 novel miRNAs were found specifically in CP tissues. The pathways targeted by PDAC-specific miRNAs and differentially expressed miRNAs between PDAC versus CP tissues and PDAC versus control tissues were the proteoglycans pathway, Hippo signaling pathway, adherens junction, and transforming growth factor-ß signaling pathway. CONCLUSIONS: This study resulted in a set of exclusive and differentially expressed miRNAs in PDAC and CP can be assessed for their diagnostic value. In addition, studying the role of miRNA-target gene interactions in carcinogenesis may open new therapeutic avenues.

Elucidating the Role of miRNA-326 Modulating Hedgehog Signaling in Pancreatic Carcinoma.

BACKGROUND AND AIM: Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignancies worldwide characterized by poor prognosis. MicroRNAs (miRNAs) function as the key regulators in carcinogenesis and may act as noninvasive biomarkers in various malignancies including PDAC. The present study aimed to elucidate the role of miR-326, a known modulator of hedgehog (Hh) pathway in PDAC. MATERIALS AND METHODS: miR-326 circulating levels were assessed in 105 PDAC patients, 31 with chronic pancreatitis (CP) and 36 healthy controls by quantitative Polymerase chain reaction. The expression of miR-326 and smoothened (SMO) was checked in surgical PDAC tissue. SMO protein expression was analyzed by immunohistochemistry in different groups. Finally, the role of miR-326 as a modulator of Hh pathway was assessed in vitro. RESULTS: Our results demonstrate that miR-326 is downregulated in both blood and tissue of PDAC patients as compared with controls. In contrast, the target gene/protein expression of SMO is upregulated in PDAC. Moreover, the tumor stromal expression of SMO was found to be clinically associated with lymph-node metastasis and vascular encasement in PDAC. Overexpression of miR-326 in Panc1 cell line was found to induce downregulation of SMO suggesting the tumor suppressor role of miR-326 in PDAC. CONCLUSIONS: Taken together, miR-326 acts as a tumor suppressor in PDAC by modulating Hh pathway. It may be a promising target for the development of efficient drug therapies for the treatment of PDAC.

Involvement of DPP3 in modulating oncological features and oxidative stress response in esophageal squamous cell carcinoma.

Resistance to therapy in esophageal squamous cell carcinoma (ESCC) is a critical clinical problem and identification of novel therapeutic targets is highly warranted. Dipeptidyl peptidase III (DPP3) is a zinc-dependent aminopeptidase and functions in the terminal stages of the protein turnover. Several studies have reported overexpression and oncogenic functions of DPP3 in numerous malignancies. The present study aimed to determine the expression pattern and functional role of DPP3 in ESCC. DPP3 expression was assessed in normal and tumor tissues using quantitative real-time (qRT)-PCR and corroborated with ESCC gene expression datasets from Gene Expression Omnibus (GEO) and The cancer genome atlas (TCGA). DPP3 stable knockdown was performed in ESCC cells by shRNA and its effect on cell proliferation, migration, cell cycle, apoptosis, and activation of nuclear factor erythroid 2-related factor 2 (NRF2) pathway was assessed. The results suggested that DPP3 is overexpressed in ESCC and its knockdown leads to reduced proliferation, increased apoptosis, and inhibited migration of ESCC cells. Additionally, DPP3 knockdown leads to down-regulation of the NRF2 pathway proteins, such as NRF2, G6PD, and NQO1 along with increased sensitivity toward oxidative stress-induced cell death and chemotherapy. Conclusively, these results demonstrate critical role of DPP3 in ESCC and DPP3/NRF2 axis may serve as an attractive therapeutic target against chemoresistance in this malignancy.

Clinical significance of Notch pathway-associated microRNA-107 in pancreatic ductal adenocarcinoma.

Background & aim: MicroRNAs associated with the Notch pathway play a critical role in the progression of pancreatic carcinoma. Our aim was to study the clinical significance of miR-107 and NOTCH2 in pancreatic ductal adenocarcinoma (PDAC). Methods: The circulating miR-107 levels in PDAC and controls were determined by qPCR. NOTCH2 protein (target) expression in tissue of PDAC, periampullary carcinoma, chronic pancreatitis and normal pancreatic tissue was assessed by immunohistochemistry. Results: The circulating miR-107 levels were found to be significantly reduced in PDAC as compared with controls. Additionally, NOTCH2 protein expression was higher in PDAC tissue as compared with controls and was clinically associated with metastasis. Conclusion: Our findings demonstrate the utility of circulating miR-107 as a potential differentiating marker in PDAC.

Quantitative Evaluation of Pentraxin-3 in Peri-Miniscrew Implant Crevicular Fluid in Patients Undergoing Orthodontic Treatment: A Prospective Study.

OBJECTIVE: To assess the levels of Pentraxin-3 (PTX3) in peri-miniscrew implant crevicular fluid (PMICF) before and after orthodontic force application Material and Methods: This study included 40 miniscrew implants (MSI) sites in 11 orthodontic patients with high arch discrepancy requiring first premolar extraction using maximum anchorage mechanics for the retraction of anterior teeth. After alignment, the en-masse anterior retraction was carried out using the MSI-supported direct anchorage method. PMICF was collected from the crevice of MSI using Periopaper strips 1.2µl (Oraflow Inc. USA) after one hour, 24 hours, and three weeks of MSI insertion and after one hour, 24 hours, seven days, three weeks, and six weeks of the force application. Samples were quantitatively analyzed for PTX3 levels through enzyme-linked immunosorbent assay (ELISA). RESULTS: The trend in the change of PTX3 levels was evaluated using the Wilcoxon signed-rank test. The mean concentration of PTX3 immediately after MSI insertion was 1.19 ng/ml, significantly higher than after 3 weeks after MSI insertion (0.72 ng/ml), which may correspond to the baseline. After loading, the mean PTX3 concentration increased significantly with the peak at 24 hrs (1.28 ng/ml), followed by a gradual decline till the completion of the study (0.5 ng/ml). CONCLUSION: After MSI insertion, a rise in PTX3 levels in PMICF suggests an underlying inflammatory process. The slow decline in PTX3 level and return to the baseline after loading suggests an adaptive bone response to the stimulus.

Loss of TET2 with reduced genomic 5-hmC is associated with adverse-risk AML.

While considerable information exists on the ten-eleven translocation 2 (TET2) mutational landscape in AML, the information on TET2 expression is limiting. So, we aimed to study the TET2 expression at mRNA and protein levels in AML patients compared to healthy controls. To achieve this, we recruited 70 non-M3, de novo AML patients and 20 healthy controls. The expression of TET2 was checked at mRNA and protein levels by qPCR and ELISA respectively and the TET activity was checked by the 5-hmC assay. TET2 mRNA expression was correlated with clinicopathological parameters and overall survival. We found a significant downregulation of TET2 mRNA and protein and significantly lower DNA 5-hmC levels in AML patients compared to controls. TET2 downregulation was more in patients with high blast counts and patients of the adverse-risk ELN category. We also found a significant upregulation of DNMT1 and DNMT3a suggesting a hypermethylation phenotype in de novo AML.

Prediction of recurrence free survival for esophageal cancer patients using a protein signature based risk model.

BACKGROUND: Biomarkers to predict the risk of disease recurrence in Esophageal squamous cell carcinoma (ESCC) patients are urgently needed to improve treatment. We developed proteins expression-based risk model to predict recurrence free survival for ESCC patients. METHODS: Alterations in Wnt pathway components expression and subcellular localization were analyzed by immunohistochemistry in 80 ESCCs, 61 esophageal dysplastic and 47 normal tissues; correlated with clinicopathological parameters and clinical outcome over 86 months by survival analysis. Significant prognostic factors were identified by multivariable Cox regression analysis. RESULTS: Biomarker signature score based on cytoplasmic ß-catenin, nuclear c-Myc, nuclear DVL and membrane α-catenin was associated with recurrence free survival [Hazard ratio = 1.11 (95% CI = 1.05, 1.17), p < 0.001, C-index = 0.68] and added significant prognostic value over clinical parameters (p < 0.001). The inclusion of Slug further improved prognostic utility (p < 0.001, C-index = 0.71). Biomarker Signature Scoreslug improved risk classification abilities for clinical outcomes at 3 years, accurately predicting recurrence in 79% patients in 1 year and 97% in 3 years in high risk group; 73% patients within low risk group did not have recurrence in 1 year, with AUC of 0.76. CONCLUSIONS: Our comprehensive risk model predictive for recurrence allowed us to determine the robustness of our biomarker panel in stratification of ESCC patients at high or low risk of disease recurrence; high risk patients are stratified for more rigorous personalized treatment while the low risk patients may be spared from harmful side effects of toxic therapy.

Role of S100 A7 as a diagnostic biomarker in oral potentially malignant disorders and oral cancer.

Background: S100 proteins have been implicated in the tumorigenesis of different human cancers and in oral dysplasia, as they are keratinocytes. Materials and Methods: In the present study, we have attempted to compare the expression of S100-A7 within young-onset (age ≤45 years, Group 1) oral squamous cell carcinoma (OSCC), OSCC in older age groups (age >45 years Group 2), oral potentially malignant disorders (OPMDs, Group 3) and inflammatory lesions (Group 4). The tissue sections were scored based on the percentage of immunostained cells and staining intensity. Nuclear, cytoplasmic and membrane immunoreactivity were also scored. Results: The present study comprised 153 histopathologically diagnosed case subjects of OSCC >45 years (n = 41), OSCC <45 years (n = 36), OPMD (n = 40) and inflammatory lesions (n = 36). The present study revealed a statistically significant difference of distribution with regard to S100A7 staining (cytoplasmic and nuclear) between OPMDs and OSCC (P < 0.05). The nuclear, cytoplasmic and membrane staining as well as the staining intensity had significantly different scoring patterns among the OSCC group, OPMD group and the inflammatory lesions with the OSCC group having the highest scoring of the S100A7 staining (irrespective of the age). Conclusions: The present study concludes that S100A7 can be used as a diagnostic biomarker to differentiate between OPMDs and OSCC lesions. However, the marker is unable to distinguish between OSCCs in younger and older patients as the molecular pathogenesis of tumors in either of these age groups is probably similar.

Evaluation of Heterogeneous Nuclear Ribonucleoprotein D Expression as a Diagnostic Marker for Oral Squamous Cell Carcinoma.

The heterogeneous nuclear ribonucleoprotein D (hnRNPD) serves as a prognostic marker for oral squamous cell carcinoma (OSCC). We evaluated the diagnostic potential of hnRNPD to differentiate between OSCC and normal mucosa. Immunohistochemistry for hnRNPD and a routinely used diagnostic marker deltaNp63 (p40) was performed in 32 normal mucosae and 46 OSCC specimens. Subsequently, receiver-operating characteristic analysis was performed to evaluate the diagnostic potential of hnRNPD in comparison to that of p40. Immunostaining for p40 and hnRNPD was observed in 39 (84.78%) and 38 (82.60%) cases, respectively, in OSCC specimens. The poorly differentiated squamous cell carcinoma displayed 100% (eight cases) immunoreactivity for hnRNPD as compared to 87.5% (seven cases) for p40. Nuclear staining of p40 and hnRNPD was observed in all OSCC specimens. p40 staining was restricted to basal cells, whereas both basal and para-basal cells displayed hnRNPD staining in OSCC specimens. Areas under the curve for p40 and hnRNPD were 0.86 and 0.87, respectively. p40 and hnRNPD showed equal sensitivities (80.95%). However, hnRNPD displayed marginally higher (88.23%) specificity for tumor cells as compared to that of p40 (85.29%). Conclusion: In addition to being a well-established prognostic marker, hnRNPD can serve as a diagnostic marker for OSCC.

Alterations in Autophagy and Mammalian Target of Rapamycin (mTOR) Pathways Mediate Sarcopenia in Patients with Cirrhosis.

Background and aims: The pathophysiology of sarcopenia in cirrhosis is poorly understood. We aimed to evaluate the histological alterations in the muscle tissue of patients with cirrhosis and sarcopenia, and identify the regulators of muscle homeostasis. Methods: Computed tomography images at third lumbar vertebral level were used to assess skeletal muscle index (SMI) in 180 patients. Sarcopenia was diagnosed based on the SMI cut-offs from a population of similar ethnicity. Muscle biopsy was obtained from the vastus lateralis in 10 sarcopenic patients with cirrhosis, and the external oblique in five controls (voluntary kidney donors during nephrectomy). Histological changes were assessed by hematoxylin and eosin staining and immunohistochemistry for phospho-FOXO3, phospho-AKT, phospho-mTOR, and apoptosis markers (annexin V and caspase 3). The messenger ribonucleic acid (mRNA) expressions for MSTN, FoxO3, markers of ubiquitin-proteasome pathway (FBXO32, TRIM63), and markers of autophagy (Beclin-1 and LC3) were also quantified. Results: The prevalence of sarcopenia was 14.4%. Muscle histology in sarcopenics showed atrophic angulated fibers (P = 0.002) compared to controls. Immunohistochemistry showed a significant loss of expression of phospho-mTOR (P = 0.026) and an unaltered phospho-AKT (P = 0.089) in sarcopenic patients. There were no differences in the immunostaining for annexin-V, caspase-3, and phospho-FoxO3 between the two groups. The mRNA expressions of MSTN and Beclin-1 were higher in sarcopenics (P = 0.04 and P = 0.04, respectively). The two groups did not differ in the mRNA levels for TRIM63, FBXO32, and LC3. Conclusions: Significant muscle atrophy, increase in autophagy, MSTN gene expression, and an impaired mTOR signaling were seen in patients with sarcopenia and cirrhosis.

NFκB (RelA) mediates transactivation of hnRNPD in oral cancer cells.

Heterogeneous Ribonucleoprotein D (hnRNPD) is an RNA binding protein involved in post-transcriptional regulation of multiple mediators of carcinogenesis. We previously demonstrated a strong association of hnRNPD over expression with poor outcome in Oral Squamous Cell Carcinoma (OSCC). However, hitherto the precise molecular mechanism of its overexpression in oral cancer was not clear. Therefore, in an attempt to elucidate the transcriptional regulation of hnRNPD expression, we cloned 1406 bp of 5' flanking region of human hnRNPD gene along with 257 bp of its first exon upstream to promoterless luciferase reporter gene in pGL3-Basic. Transfection of the resulting construct in SCC-4 cells yielded 1271 fold higher luciferase activity over parent vector. By promoter deletion analysis, we identified a canonical TATA box containing 126 bp core promoter region that retained ~ 58% activity of the full length promoter. In silico analysis revealed the presence of four putative NFκB binding motifs in the promoter. Sequential deletion of these motifs from the full-length promoter reporter construct coupled with luciferase assays revealed an 82% decrease in promoter activity after deletion of the first (-1358/-1347) motif and 99% reduction after the deletion of second motif (-1052/-1041). In-vivo binding of NFκB (RelA) to these two motifs in SCC-4 cells was confirmed by ChIP assays. Site directed mutagenesis of even one of these two motifs completely abolished promoter activity, while mutagenesis of the remaining two motifs had marginal effect on the same. Consistent with these findings, treatment of SCC-4 cells with PDTC, a known inhibitor of NFκB dramatically reduced the levels hnRNPD mRNA and protein. Finally, the expression of hnRNPD and NFκB in clinical specimen from 37 oral cancer patients was assessed and subjected to Spearmen's Correlation analysis which revealed a strong positive correlation between the two. Thus, results of the present study for the first time convincingly demonstrate NFκB (RelA) mediated transcriptional upregulation of hnRNPD expression in oral cancer.

Overexpression of prothymosin-α in glioma is associated with tumor aggressiveness and poor prognosis.

Prothymosin-α (PTMA), a nuclear protein, is strikingly associated with unfavorable clinical outcomes in many cancers. However, no information about its clinical relevance in glioma was available. Therefore in the present study, we evaluated the prognostic utility of this protein in a cohort of 81 glioma patients. The PTMA expression was assessed by immunohistochemical analysis, quantitative PCR, and Western blotting. Furthermore, the association of PTMA with clinicopathological features and molecular alterations were assessed in the patient cohort and validated in multiomics datasets, The Cancer Genome Atlas (TCGA; n=667) and Chinese Glioma Genome Atlas (CGGA; n=1013). We observed an increase in PTMA expression with increasing histological grades of this malignancy. PTMA immunostaining also displayed a strong positive association with the MIB-1 index. Univariate analysis revealed a superior prognostic value of PTMA to predict overall survival (OS) as compared with the routinely used markers (p53, isocitrate dehydrogenase (IDH) 1 (IDH1), α-thalassemia/intellectual disability syndrome X-linked (ATRX), and Ki-67). Interestingly, in Cox regression analysis it emerged as an independent predictor of OS (hazard ratio (HR) = 13.71, 95% CI = 5.96-31.52, P<0.0001). Thus, our results demonstrate the potential prognostic utility of PTMA in glioma which may prove useful in the management of this deadly malignancy.

The Expression of the RUVBL1 Component of the R2TP Complex Correlates with Poor Prognosis in DLBCL.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin's lymphoma (NHL) accounting for 30% of adult NHL worldwide and 50% in developing countries like India. DNA damage and Myc-induced transformation are well-known contributing factors towards development of DLBCL. A recently identified HSP90 co-chaperone complex R2TP has been shown to contribute towards DNA damage and Myc-induced transformation. This study aimed to analyse the immunohistochemical (IHC) expression of R2TP complex components RUVBL1, PIH1D1, and RPAP3 in DLBCL patients and correlate with prognosis. METHODS: DLBCL (n = 54) histological slides were retrieved from archives, and detailed histomorphological and clinical features were noted. IHC staining of R2TP complex components RUVBL1, PIH1D1, and RPAP3 was performed on 54 cases (FFPE) of DLBCL. Expression data were correlated with survival and clinical features. RESULTS: Out of the 54 DLBCL cases, 59.26% (n = 32) stained positive for RUVBL1. The RUVBL1 expression was associated with poor prognosis in both progression-free survival (PFS) (p = 0.0146) and overall survival (OS) (p = 0.0328). The expression was positively correlated with bone marrow involvement (p = 0.0525). The expression of PIH1D1 was observed in 68.51% (n = 32) of DLBCL cases, and positive correlation was observed with international prognostic index score (p = 0.0246); however, no correlation was observed with PFS or OS. Finally, RPAP3 was found immunopositive in only 1 case of DLBCL. CONCLUSIONS: Immunopositivity for RUVBL1 is associated with poor prognosis along with a higher relapse rate amongst the DLBCL patients. PIH1D1 immunopositivity correlated with a higher IPI score.

Effects of submucosally administered platelet-rich plasma on the rate of tooth movement.

OBJECTIVES: To evaluate the effects of submucosally administered platelet-rich plasma (PRP) on the rate of maxillary canine retraction. Levels of soluble receptor activator of nuclear factor-κb ligand (sRANKL) and osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) were also measured over 2 months. MATERIALS AND METHODS: This split-mouth trial involved 20 sites in 10 subjects randomly assigned to PRP (experimental) side and control side. After alignment, the freshly prepared PRP was injected submucosally distal to the experimental side maxillary canine, and retraction was performed using NiTi closed-coil springs (150 g) on 0.019 × 0.025-inch stainless steel wire. The rate of canine movement was assessed using digital model superimposition at 0, 30, and 60 days. The OPG and sRANKL were assayed using enzyme-linked immunosorbent assay from GCF collected at 0, 1, 7, 21, 30, and 60 days. RESULTS: Twenty sites were analyzed using paired t test. The rate of tooth movement increased significantly by 35% on the PRP side compared with the control side in the first month (P = .0001) and by 14% at the end of the second month (P = .015). Using the Mann-Whitney U test, OPG levels were found to be significantly decreased on the 7th (P = .003) and 30th day on the PRP side (P = .01), while sRANKL became detectable by the third week postinjection on the PRP side (P = .069). CONCLUSIONS: Submucosal injection of platelet-rich plasma significantly increased tooth movement during the 60-day observation period. Local injection of PRP significantly altered the levels of OPG and sRANKL in GCF.

Pleiotropic role of PARP1: an overview.

Poly (ADP-ribose) polymerase 1 (PARP1) protein is encoded by the PARP1 gene located on chromosome 1 (1q42.12) in human cells. It plays a crucial role in post-translational modification by adding poly (ADP-ribose) (PAR) groups to various proteins and PARP1 itself by utilizing nicotinamide adenine dinucleotide (NAD +) as a substrate. Since the discovery of PARP1, its role in DNA repair and cell death has been its identity. This is evident from an overwhelmingly high number of scientific reports in this regard. However, PARP1 also plays critical roles in inflammation, metabolism, tumor development and progression, chromatin modification and transcription, mRNA stability, and alternative splicing. In the present study, we attempted to compile all the scattered scientific information about this molecule, including the structure and multifunctional role of PARP1 in cancer and non-cancer diseases, along with PARP1 inhibitors (PARPis). Furthermore, for the first time, we have classified PARP1-mediated cell death for ease of understanding its role in cell death pathways.