The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing.

Protein arginine methyltransferase 5 (PRMT5) is a promising cancer target, yet it is unclear which PRMT5 roles underlie this vulnerability. Here, we establish that PRMT5 inhibition induces a special class of unspliced introns, called detained introns (DIs). We used the depletion of CLNS1A, a PRMT5 cofactor that specifically enables Sm protein methylation, to interrogate the impact of DIs.

Mutant p53 exploits enhancers to elevate immunosuppressive chemokine expression and impair immune checkpoint inhibitors in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterized by activating KRAS mutations and TP53 alterations. TP53 missense mutations lose their wild-type tumor-suppressor function. Here, we studied whether p53 missense mutations have potential gain-of-function oncogenic roles and their impact on cancer-cell-intrinsic gene expression and the tumor immune microenvironment (TME) in PDAC.

The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing.

Protein arginine methyltransferase 5 (PRMT5) is a promising cancer target, yet it's unclear which PRMT5 roles underlie this vulnerability. Here, we establish that PRMT5 inhibition induces a special class of unspliced introns, called detained introns (DIs). To interrogate the impact of DIs, we depleted CLNS1A, a PRMT5 cofactor that specifically enables Sm protein methylation.

Mutant p53 Exploits Enhancers to Elevate Immunosuppressive Chemokine Expression and Impair Immune Checkpoint Inhibitors in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective treatments. It is characterized by activating KRAS mutations and p53 alterations. However, how these mutations dysregulate cancer-cell-intrinsic gene programs to influence the immune landscape of the tumor microenvironment (TME) remains poorly understood.

Salivary levels of NLRP3 protein are significantly raised in chronic periodontitis: A systematic review and meta-analysis of clinical studies.

Background: To date, there is no confirmatory diagnostic test that can identify the type of periodontal disease and the disease progress. With the advent of "molecular biomarkers," this systematic review and meta-analysis were designed with the sole purpose of identifying a novel biomarker, namely, nucleotide leucine rich repeat pyrin protein-3 (NLRP3) inflammasome which has already been extensively researched for chronic inflammatory and autoimmune diseases.

Types Of Studies Reviewed: Only case observational studies that evaluated the presence of human NLRP3 inflammasome in the saliva of patients with chronic periodontitis with no overlying systemic disease and compared the same to healthy patients to obtain quantitative data that can be statistically analyzed were included.

Effect of Laser Therapy on Postoperative Pain and Endodontic Retreatment: A Systematic Review and Meta-Analysis.

Background: Root canal re-treatment (RCR) cases are considered some of the most challenging cases in the field of endodontics, as they are mostly associated with various iatrogenic errors such as ledge formation, incomplete biomechanical preparation, file separation, and incomplete obturation. These iatrogenic errors lead to defective niches within root canals that may act as reservoirs for various viable microorganisms. Such residual microbial niches may cause postoperative pain even after thorough debridement and reshaping the canals, ultimately leading to a poor prognosis for the tooth.

Gingival Crevicular Fluid Levels of Neurokinin A and Substance P in Patients with Symptomatic Irreversible Pulpitis: A Systematic Review and Meta-Analysis.

Aims And Objectives: The levels of neuropeptides neurokinin A (NKA) and substance P (SP) in the gingival crevicular fluid of patients with symptomatic irreversible pulpitis (SIP) were evaluated using a comprehensive review and meta-analysis.

Materials And Methods: The data bases of Pubmed, Scopus, EBSCOhost, Science Direct, Proquest and Cochrane library databases were thoroughly searched. The quality of the study was evaluated using the Joanna Briggs Criteria.

Evaluation of postoperative pain using warm versus room temperature sodium hypochlorite as an irrigant in mandibular molars with irreversible pulpitis: A randomized controlled trial.

Introduction: The study evaluates and compare the effect of 3% warm NaOCl with NaOCl at room temperature in root canal irrigation on postoperative pain.

Materials And Methods: In this randomized controlled trial, mandibular molars with symptomatic irreversible pulpitis in healthy 18-year-old patients and above were included. The sample consisted of 56 patients evaluating the postoperative pain, allocated randomly into 2 groups of 3% NaOCl at two different temperatures, i.

Symptomatic Irreversible Pulpitis Induces Increased Levels of Human NLRP3 in Gingival Crevicular Fluid Compared to Saliva: A Case Control Observational Study.

Introduction: The goal of this case-control observational study was to compare the levels of the human nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing-3 (NLRP3) protein in the saliva and gingival crevicular fluid (GCF) of patients with symptomatic irreversible pulpitis (SIP) and healthy controls.

Methods: The 16 patients in the control group were matched with the 16 patients in the SIP group to create a total of 32 patients. In addition to saliva, GCF (n = 48) samples were collected from the involved tooth (n = 16), contralateral tooth (n = 16), and adjacent tooth (n = 16) in the SIP group.

Transcription factor antagonism regulates heterogeneity in embryonic stem cell states.

Gene expression heterogeneity underlies cell states and contributes to developmental robustness. While heterogeneity can arise from stochastic transcriptional processes, the extent to which it is regulated is unclear. Here, we characterize the regulatory program underlying heterogeneity in murine embryonic stem cell (mESC) states.

Anesthetic efficacy of supplemental intraligamentary injection in human mandibular teeth with irreversible pulpitis: a systematic review and meta-analysis.

Background: Inferior alveolar nerve block (IANB) is known to have a lower success rate for anesthesia in patients with irreversible pulpitis. This calls for supplementary techniques to effectively anesthetize such patients. This systematic review aimed to evaluate the published literature for determining the success rate of anesthesia induction using post-IANB intraligamentary (IL) injection in the mandibular teeth of patients with symptomatic irreversible pulpitis.

Periodontal health of the geriatric population in old-age homes of Delhi, India.

Background: Periodontal disease is one of the leading causes of tooth loss in the geriatric population. Assessment of periodontal disease in a population is an important step in planning effective prevention and control programs for periodontal disease. Therefore, a study was carried out in old-age homes of Delhi to assess the periodontal status of 65-74-year-old elderly and recommend interventions to improve their periodontal health.

Anesthetic efficacy of primary and supplemental buccal/lingual infiltration in patients with irreversible pulpitis in human mandibular molars: a systematic review and meta-analysis.

Achieving profound anesthesia in mandibular molars with irreversible pulpitis is a tedious task. This review aimed at evaluating the success of buccal/lingual infiltrations administered with a primary inferior alveolar nerve block (IANB) injection or as a supplemental injection after the failure of the primary injection in symptomatic and asymptomatic patients with irreversible pulpitis in human mandibular molars. The review question was "What will be the success of primary and supplemental infiltration injection in the endodontic treatment of patients with irreversible pulpitis in human mandibular molars?" We searched electronic databases, including Pubmed, Scopus, and Ebsco host and we did a comprehensive manual search.

Comparative evaluation of antibacterial efficacy of extract, aqueous ozone, diode laser, and 3% sodium hypochlorite in root canal disinfection: An study.

Aim: The present study aimed to individually evaluate and compare the aerobic and anaerobic antibacterial activity of extract, aqueous ozone, diode laser, and 3% sodium hypochlorite (NaOCl) as root canal irrigants.

Materials And Methods: Forty-eight patients were selected and randomly allocated to one of the four groups ( = 12 each) according to the irrigant to be used in each group. For each included tooth, the preirrigation and postirrigation (after irrigation with the test solution) samples were collected through sterile paper points and microbial culturing was done by swabbing on blood agar plates followed by incubation for aerobic and anaerobic bacteria.

Comparative Evaluation of the Marginal Fit of Inlays Fabricated by Conventional and Digital Impression Techniques: A Stereomicroscopic Study.

Context: Marginal fit being the prime concern of indirect restorations. Inlays can be either fabricated by conventional technique or computer-aided design and computer-aided manufacturing (CAD/CAM) techniques. CAD/CAM is the most evolving digital technique with faster, quicker, and precise results.

Effect of intracanal cryotherapy on postendodontic pain: a systematic review and meta-analysis of randomized controlled trials.

This systematic review aimed to qualitatively and quantitatively evaluate the effectiveness of cryotherapy in the reduction of postendodontic pain. The review question was, "What will be the success rate of cryotherapy technique among human patients with postendodontic pain?". The review protocol was framed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.

Assessment of Quality of Life of the Elderly Living in Rural and Urban Areas of Ambala District: A Comparative Study.

Context: Aging is a natural process which universally affects all the human beings in the society. As the geriatric population is quiet vulnerable, They might suffer from mental and physical disabilities which consequently threatens their independence. Quality of life among the geriatric population is a global concern as it reflects the status of health and of well being among the set population.

Ormocer: An aesthetic direct restorative material; An in vitro study comparing the marginal sealing ability of organically modified ceramics and a hybrid composite using an ormocer-based bonding agent and a conventional fifth-generation bonding agent.

Aims And Objectives: To compare the marginal sealing ability of ormocer with a hybrid composite using an ormocer based bonding agent and a conventional fifth generation bonding agent.

Materials And Methods: Fifty four human premolars were randomly distributed into four test groups of 12 teeth each and two control groups of 3 teeth each. Class I occlusal preparation of 1.