Tenovin-1, a Selective SIRT1/2 Inhibitor, Attenuates High-fat Diet-induced Hepatic Fibrosis via Inhibition of HSC Activation in ZDF Rats.

Type 2 diabetes mellitus (T2DM) increases the risk of non-alcoholic fatty liver disease (NAFLD) progression to advanced stages, especially upon high-fat diet (HFD). HFD-induced hepatic fibrosis can be marked by oxidative stress, inflammation, and activation of hepatic stellate cells. Sirtuin 1/2 (SIRT1/2), NAD-dependent class III histone deacetylases, are involved in attenuation of fibrosis. In our conducted research, TGF-ß1-activated LX-2 cells, free fatty acid (FFA)-treated simultaneous co-culture (SCC) cells, and HFD-induced hepatic fibrosis in Zucker diabetic fatty (ZDF) rats, a widely used animal model in the study of metabolic syndromes, were used to evaluate the protective effect of Tenovin-1, a SIRT1/2 inhibitor. ZDF rats were divided into chow diet, HFD, and HFD + Tenovin-1 groups. Tenovin-1 reduced hepatic damage, inhibited inflammatory cell infiltration, micro/ macro-vesicular steatosis and prevented collagen deposition HFD-fed rats. Tenovin-1 reduced serum biochemical parameters, triglyceride (TG) and malondialdehyde (MDA) levels but increased glutathione, catalase, and superoxide dismutase levels. Tenovin-1 mitigated proinflammatory cytokines IL-6, IL-1ß, TNFα and fibrosis biomarkers in HFD rats, TGF-ß1-activated LX-2 and FFA treated SCC cells. Additionally, Tenovin-1 suppressed SIRT1/2 expression and inhibited JNK-1 and STAT3 phosphorylation in HFD rats and FFA-treated SCC cells. In conclusion, Tenovin-1 attenuates hepatic fibrosis by stimulating antioxidants and inhibiting inflammatory cytokines under HFD conditions in diabetic rats.

Rehabilitation of Flabby Ridges for Denture Fabrication: An Enigma for Dental Professionals.

Edentulism can be treated with a removable or fixed prosthesis to improve aesthetics, comfort, and function. The firmness of the residual ridge is crucial for providing sufficient support for soft tissue. However, a flabby ridge lacks adequate tissue support, which poses challenges for clinicians during impression-making and prosthesis fabrication. Conventional prosthodontic approaches are typically used to manage flabby ridges. This article describes two methods for recording flabby ridges: surgical and unique impression techniques. In the first case, the patient was partially edentulous with a flabby ridge in the lower anterior region. This was removed surgically, and a prosthesis was made conventionally. There has been no relapse in treatment after a follow-up of almost one year. In the second case, the flabby ridge was there in the upper anterior region, which was first excised surgically, but the residual ridge was there; hence, the impression was made by the window technique. After a follow-up of almost nine months, there was a relapse in treatment where a flabby ridge was present in the anterior as well as posterior regions. Hence, again, a window impression was recorded, and a new prosthesis was given to the patient, which yielded satisfactory results. In this article, we have presented two cases of flabby ridges that were successfully treated with surgical and non-surgical techniques followed by special impression techniques. Such analogous cases provide dental professionals with insight into the different lines of treatment, relapse, and further management.

Treatment Complications of Head and Neck Cancers and Rehabilitation Measures: A Narrative Review.

Head and neck cancers (HNCs) are malignant tumors mainly from squamous cells in the head and neck tissues. Treatment involves a multidisciplinary approach with surgery, radiotherapy, and chemotherapy. However, the long-term prognosis for patients with advanced-stage tumors is guarded, with a median survival time of approximately 24 months. HNC patients have very high rates of depression and anxiety and the highest suicide rate among all cancers due to the intense and challenging nature of the treatment, underscoring the importance of our collective efforts. Rehabilitation success depends on various factors, including tumor, patient, and treatment-related factors. Patients may require post-treatment oral rehabilitation measures, including implants, obturators, and flexible dentures. These measures are crucial, but they often need to be more utilized. Patients may face challenges in maintaining oral hygiene and managing mucositis. Additionally, it is essential to address other intricacies such as trismus, xerostomia, gustatory dysfunctions, neuropathy, speech impairments, and psychological disturbances. Unfortunately, there is little literature on post-treatment rehabilitative measures. Despite its crucial role in improving patients' quality of life, rehabilitation often receives inadequate attention compared to treatment. Our narrative review, which covers various factors that affect rehabilitation, including oral rehabilitation measures and post-treatment complications, is anticipated to deliver practical insights to professionals and inspire positive changes in their regular practice.

Comparison of Buccal and Lingual-Based Triangular Flap During Mandibular Third Molar Extraction for Reducing Postoperative Complications: A Randomized Controlled Trial.

Background: Surgical removal of the mandibular third molar requires reflection of the mucoperiosteal flap. Several studies have suggested different varieties and innovative designs for flap reflection. We have designed a randomized controlled trial (RCT) to check the feasibility of two flap designs: lingual-based triangular flap (LBTF) and buccal-based triangular flap (BBTF) by calculating the duration of surgery and evaluating postoperative complications such as pain, swelling, and trismus. Materials and Method: It was a non-inferiority parallel-group RCT. The trial was registered in the Control Trial Register of India (CTRI/2021/10/037182) and was performed according to Consolidated Standards of Registered Trial (CONSORT) guidelines. Intraoperative surgery time and postoperative pain, swelling, and trismus were measured and analyzed by a two-sample t test. The Chi-square test was used to measure gender distribution in the study. Result: Of the total of 88 required subjects, gender distribution and performed surgical time were statistically insignificant with a p-value of 0.76 and 0.48, respectively. The pain was significantly higher in the LBTF group in the 5th and 7th postoperative days with a p-value of 0.02 and 0.028. The swelling was statistically higher during all the follow-ups except for the 28th day in the LBTF group with values of 0.006, 0.002 and 0.003, respectively. There was no significant difference in inter-incisional distance (IID) between the groups during postoperative check-ups. Conclusion: LBTF shows no edge over BBTF during mandibular third molar disimpaction.

Age Estimation of Children and Young Adults of Jharkhand Using Mineralization of Third Molars and Its Relation to Chronological Age: A Retrospective Analysis.

Background Dental age estimation plays an enormous role in the determination of an individual's identity and age in forensic and anthropological fields. The estimation of the chronological age of the individual is also important in the diagnosis, treatment planning, and treatment outcomes in the dental field. The third molar has some inimitable characteristics in terms of its size, shape, formation, and long path of eruption and usually erupts after puberty, which seems to be a reliable method of age estimation in adulthood. To establish the individual's identity, inference of age has gained considerable attention in forensics, and the aspect of dentistry has broadened nowadays. Thus the present study was conducted. Methodology The digital orthopantomograms of 720 patients who were exposed to X-rays for routine examination were assessed, and calcification of the tooth was observed. In order to ensure the blinding of the examiners, radiographs were numerically coded. Clinical stages of the tooth were categorised into erupted, pre-erupted, and missing. Statistical analysis was performed by IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY), with a level of significance set below 5%. Results The age of the patients whose OPGs were assessed ranged from 6 to 22 years, with a mean age of 18.93±3.129 years. Among the 720 participants, 370 (51.4%) were male and 350 (48.6%) were female. When the clinical status of the third molar among all the participants was assessed, in 148 (20.6%) subjects, third molars had erupted; in 188 (26.1%) subjects, the third molars were in the pre-erupted stage; and in 384 (53.30%), third molars were missing. When comparing the clinical status of the third molar in both arches and between genders, it was found that missing molars were common in females and the mandible arch, with statistically significant p-values. A comparison of Demirjian's stages between genders showed that the mean age to attain stage H was 21.37±0.774 years among males and 21.69±0.616 years among females. This means that the calcification of third-molar attainment occurs earlier in males compared with females. In a similar comparison between the upper and lower arches, it was found that calcification of the third molar was attained earlier in the maxillary arch compared to the mandibular arch. Conclusion It was concluded that the third molar is a versatile tooth and its path of mineralization can be used in orthodontics, pedodontics, and forensics to estimate chronological age, and chronological age significantly follows Demirjian's stages of third molar calcification. Third molar calcification occurred earlier in the maxillary arch and males, whereas several impacted molars were higher in females.

Declining Trend in Antimicrobial Sensitivity in Respiratory Tract Bacterial Pathogens against Commonly Used Drugs at a Tertiary Care Hospital.

OBJECTIVES: Antimicrobial resistance (AMR) is a major health issue. To determine trends in bacterial organisms in respiratory tract infections (RTIs) and their antibiotic sensitivity at a tertiary care center in India, we performed this study. METHODS: Successive samples received from January 2017 to December 2021 from the respiratory tract (sputum, endotracheal secretion, and bronchoalveolar lavage) from intensive care units and medical inpatients were processed for bacterial growth. The identification of isolates and antibiotic sensitivity patterns was performed using an automated VITEK-2 system. Descriptive statistics are reported. RESULTS: We received 7,204 respiratory samples. Significant bacterial growth was in 3,000 (41.6%), and 2,992 (41.5%) were gram-negative. Klebsiella pneumoniae was the most prevalent, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Enterobacter aerogenes. Increasing secular trends were observed for Klebsiella and Pseudomonas and declining trends for Acinetobacter and Escherichia (p < 0.05). Antimicrobial sensitivity patterns showed that Klebsiella, Pseudomonas, Acinetobacter, E. coli, and Enterobacter had a high sensitivity with colistin and polymyxin (99-100%). Moderate sensitivity was observed with carbapenems (Acinetobacter: 47.5%, Enterobacter: 62.0%, Escherichia: 76.5%, Klebsiella: 72.3%, Pseudomonas: 66.7%) and tigecycline (Acinetobacter: 50.4%, Enterobacter: 68.0%, Escherichia: 81.1%, Klebsiella: 66.6%, Pseudomonas: 0%). Aminoglycosides had <50% sensitivity for various organisms, and <25% sensitivity was observed with third-generation cephalosporins and quinolones. Trend analysis showed persistent sensitivity of various pathogenic bacteria to colistin and polymyxin and declining pharmacological sensitivity in Acinetobacter (carbapenems and tigecycline), Escherichia (carbapenems, quinolones, and tigecycline), Klebsiella (carbapenems, quinolones, aminoglycosides, and tigecycline), and Pseudomonas (carbapenems and aminoglycosides) species (p < 0.05). CONCLUSION: Common respiratory tract gram-negative bacterial pathogens at a tertiary care hospital are K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli. All these bacteria demonstrate high sensitivity only with colistin and polymyxin. Significant AMR is observed to carbapenems, tigecycline, aminoglycosides, and third-generation cephalosporins. Secular trends show declining antimicrobial sensitivity among various bacterial pathogens.

Flagellin conjugated Per a 10 and its T cell peptides attenuate airway inflammation and restore cellular function.

Adjuvants were used to modulate response towards relevant immune cells. The present study aims to investigate FlaA-conjugated Per a 10 and T cell peptides in amelioration of allergic airway disease in mice. Mice given Per a 10 showed allergic features with higher cellular infiltration, IgE, Th-2 cytokines and alarmins. Fusion protein treatment reduced lung inflammation (p < 0.0001) and cellular infiltrates (p < 0.001) with higher IgG2a/IgE indicating resolution of disease. Immunotherapy with FPT1 and FPT3 reduces IL-4, IL-5 and IL-13 levels (p < 0.0001) with a fourfold increase in IFN-γ secretion in BALF. FPT1- and FPT3-treated mice have increased IL-10 and TGF-ß levels (p < 0.001) with CD4+Foxp3+ T cells (p < 0.01) indicating Treg response. There was enhanced expression of claudin-1 (1.7-fold) and occludin (fourfold) in lungs of FPT1- and FPT3-treated mice with reduced TSLP (p < 0.01) and IL-33 (p < 0.0001) secretion in BALF indicating recovery of epithelial function. Peptide-conjugated FlaA proteins showed protective immunity in mice and have potential for immunotherapy with restoration of cellular function.

The origin of intraluminal pressure waves in gastrointestinal tract.

The gastrointestinal (GI) peristalsis is an involuntary wave-like contraction of the GI wall that helps to propagate food along the tract. Many GI diseases, e.g., gastroparesis, are known to cause motility disorders in which the physiological contractile patterns of the wall get disrupted. Therefore, to understand the pathophysiology of these diseases, it is necessary to understand the mechanism of GI motility. We present a coupled electromechanical model to describe the mechanism of GI motility and the transduction pathway of cellular electrical activities into mechanical deformation and the generation of intraluminal pressure (IP) waves in the GI tract. The proposed model consolidates a smooth muscle cell (SMC) model, an actin-myosin interaction model, a hyperelastic constitutive model, and a Windkessel model to construct a coupled model that can describe the origin of peristaltic contractions in the intestine. The key input to the model is external electrical stimuli, which are converted into mechanical contractile waves in the wall. The model recreated experimental observations efficiently and was able to establish a relationship between change in luminal volume and pressure with the compliance of the GI wall and the peripheral resistance to bolus flow. The proposed model will help us understand the GI tract's function in physiological and pathophysiological conditions.

Comparing finite viscoelastic constitutive relations and variational principles in modeling gastrointestinal soft tissue deformation.

The mechanical attributes of soft tissues within the gastrointestinal (GI) tract are crucial for the effective operation of the GI system, and alterations in these properties may play a role in motility-related disorders. Various constitutive modeling approaches have been suggested to comprehend the response of soft tissues to diverse loading conditions. Among these, hyperelastic constitutive models based on finite elasticity have gained popularity. However, these models fall short in capturing rate- and time-dependent tissue properties. In contrast, finite viscoelastic models offer a solution to overcome these limitations. Nevertheless, the development of a suitable finite viscoelastic model, coupled with a variational formulation for efficient finite element (FE) implementation, remains an ongoing challenge. This study aims to address this gap by developing diverse finite viscoelastic constitutive relations and applying them to characterize soft tissue. Furthermore, the research explores the creation of compressible, nearly incompressible, and incompressible versions of viscoelastic constitutive relations, along with their variational formulation, to facilitate efficient FE implementation. The proposed model demonstrates remarkable accuracy in replicating experimental results, achieving an R2 value exceeding 0.99.

Comparison of Glycated Hemoglobin (HbA1c) Values Estimated by High-Performance Liquid Chromatography and Spectrophotometry: A Pilot Study.

Background Invasive blood sample collection followed by high-performance liquid chromatography (HPLC) based analysis is the gold standard for estimating glycated hemoglobin level or HbA1c currently. Spectrophotometry could be an alternative that holds the potential to be translated into a portable, non-invasive device for glycated hemoglobin level estimation. This study compares HbA1c values obtained from HPLC and spectrophotometry. Methods Venous blood samples were collected from both diabetic and non-diabetic participants in a cross-sectional study. The samples were subjected to both HPLC and spectrophotometry-based estimation of HbA1c%. The results obtained were compared, and the relationship between the two estimations were assessed. Results About 15 diabetic and non-diabetic individuals participated in the study and 28 samples were included in the final analysis. The Pearson's correlation coefficient was 0.65 (95% CI, 0.37-0.82), indicating that there was a strong positive association. This was further supported by the findings from linear regression analysis with a p-value of <0.001. Conclusions The positive correlation between the HPLC and spectrophotometric values supports the hypothesis that spectrophotometry could be an alternative to conventional HPLC for the measurement of HbA1c. This needs to be further validated through larger, well-powered studies.

Iatrogenic breast pseudoaneurysm in a lactating female: A rare breast emergency treated with ultrasound guided thrombin administration.

Pseudoaneurysm development is a well-recognized consequence of arterial injury, frequently observed in procedures involving arterial groin access. Breast emergencies are infrequent but need prompt attention. We present a notable case of breast pseudoaneurysm postcore needle biopsy, incidentally, identified through subsequent magnetic resonance imaging. Remarkably, the patient's lactating status emerged as a unique risk factor. Our report thoroughly explores the pathogenesis, etiology, preventive measures, and treatment strategies specific to breast pseudoaneurysms. A comprehensive understanding of this phenomenon is essential for radiologists at large, with particular importance for specialists in breast imaging.

Peptide-triggered IL-12 and IFN-γ mediated immune response in CD4+ T-cells against Leishmania donovani infection.

Leishmania donovani are intracellular, human blood parasites that cause visceral leishmaniasis or kala-azar. Cell-penetrating peptides (CPPs) have been shown to modulate intracellular processes and cargo delivery, whereas host defense peptides (HDPs) promote proliferation of both naïve and antigen activated CD4+ T-cells. We report newly designed tripeptides that were able to trigger proinflammatory cytokine (IL-12 and IFN-γ) secretion by CD4+CD44+ T-cells in response to Leishmania donovani infection. These peptides can be used to induce antigen specific TH1 responses to combat obstacles of cytotoxicity and drug resistance associated with current anti-leishmanial drugs. Furthermore, these peptides can also be used as adjuvants to develop an effective immunoprophylactic approach for immunity restoration against visceral leishmaniasis.

Squamous cell carcinoma of breast metastasising to upper lip.

Breast cancer is a heterogeneous set of carcinomas comprising a subgroup of invasive ductal carcinomas and numerous infrequent subtypes. Primary squamous cell carcinoma (SCC) breast is sporadic, accounting for less than 0.1% of all invasive subtypes. Primary metastases to soft tissues of the oral cavity are incredibly rare, amounting to 0.1% of oral malignancies. Diagnosing metastasis to the oral cavity is an enigma to clinicians without pathognomonic signs and symptoms. Here, we report a case of SCC breast, who developed metastatic deposits in the left upper lip after a disease-free survival of 1 year. There are no reports of SCC breast metastasising to the oral cavity, and probably, this is the first such case getting reported. The survival of such patients is abysmal, with most cases surviving less than a year post diagnosis. While treating patients with a history of malignancy, a high degree of clinical presentiment is required.

Unraveling Epigenetic Interplay between Inflammation, Thrombosis, and Immune-Related Disorders through a Network Meta-analysis.

Inflammation and thrombosis are two distinct yet interdependent physiological processes. The inflammation results in the activation of the coagulation system that directs the immune system and its activation, resulting in the initiation of the pathophysiology of thrombosis, a process termed immune-thrombosis. Still, the shared underlying molecular mechanism related to the immune system and coagulation has not yet been explored extensively. Inspired to answer this, we carried out a comprehensive gene expression meta-analysis using publicly available datasets of four diseases, including venous thrombosis, systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. A total of 609 differentially expressed genes (DEGs) shared by all four datasets were identified based on the combined effect size approach. The pathway enrichment analysis of the DEGs showed enrichment of various epigenetic pathways such as histone-modifying enzymes, posttranslational protein modification, chromatin organization, chromatin-modifying enzymes, HATs acetylate proteins. Network-based protein-protein interaction analysis showed epigenetic enzyme coding genes dominating among the top hub genes. The miRNA-interacting partner of the top 10 hub genes was determined. The predomination of epitranscriptomics regulation opens a layout for the meta-analysis of miRNA datasets of the same four diseases. We identified 30 DEmiRs shared by these diseases. There were 9 common DEmiRs selected from the list of miRNA-interacting partners of top 10 hub genes and shared significant DEmiRs from microRNAs dataset acquisition. These common DEmiRs were found to regulate genes involved in epigenetic modulation and indicate a promising epigenetic aspect that needs to be explored for future molecular studies in the context of immunothrombosis and inflammatory disease.

NRP1 interacts with endoglin and VEGFR2 to modulate VEGF signaling and endothelial cell sprouting.

Endothelial cells express neuropilin 1 (NRP1), endoglin (ENG) and vascular endothelial growth factor receptor 2 (VEGFR2), which regulate VEGF-A-mediated vascular development and angiogenesis. However, the link between complex formation among these receptors with VEGF-A-induced signaling and biology is yet unclear. Here, we quantify surface receptor interactions by IgG-mediated immobilization of one receptor, and fluorescence recovery after photobleaching (FRAP) measurements of the mobility of another coexpressed receptor. We observe stable ENG/NRP1, ENG/VEGFR2, and NRP1/VEGFR2 complexes, which are enhanced by VEGF-A. ENG augments NRP1/VEGFR2 interactions, suggesting formation of tripartite complexes bridged by ENG. Effects on signaling are measured in murine embryonic endothelial cells expressing (MEEC+/+) or lacking (MEEC-/-) ENG, along with NRP1 and/or ENG overexpression or knockdown. We find that optimal VEGF-A-mediated phosphorylation of VEGFR2 and Erk1/2 requires ENG and NRP1. ENG or NRP1 increase VEGF-A-induced sprouting, becoming optimal in cells expressing all three receptors, and both processes are inhibited by a MEK1/2 inhibitor. We propose a model where the maximal potency of VEGF-A involves a tripartite complex where ENG bridges VEGFR2 and NRP1, providing an attractive therapeutic target for modulation of VEGF-A signaling and biological responses.

Nintedanib-induced osteomyelitis of the jaw against the background of COVID-19 infection.

PURPOSE: Various medications are administered to treat Coronavirus Disease 2019 (COVID-19) infection and prevent its complications. Some medicines have complications and long-term effects, which may mimic other conditions, making precise diagnosis difficult. This report aims to bring to light one such complication, medication-related osteonecrosis of the jaw (MRONJ), secondary to a commonly prescribed medication for preventing lung fibrosis post-COVID-19 infection. METHOD: A 33-year-old male reported to our department with the typical clinical and radiological features of Mucormycosis of the upper jaw post-COVID-19 infection. However, on detailed evaluation of his history (controlled diabetic and short duration of steroid therapy) and review of the mycology staining, bacteriology, culture, and histopathological reports, we came to a negative diagnosis for Mucormycosis. The patient was, however, on treatment for the prevention of lung fibrosis with Nintedanib (tyrosine kinase inhibitor) 150 mg twice a day for one month. RESULT: In the absence of predisposing factors and negative laboratory findings for mucormycosis, we arrived at a diagnosis of MRONJ, attributable to Nintedanib therapy given to prevent lung fibrosis post-COVID-19 infection. CONCLUSION: The use of Nintedanib has recently increased due to the high incidence of lung fibrosis post-COVID-19 infection. However, Nintedanib should be considered a causative agent for osteonecrosis of the jaw in the absence of other obvious predisposing factors. Therefore, Nintedanib must be administered after a thorough consideration of risk factors.

Comparative evaluation of colistin broth disc elution (CBDE) and broth microdilution (BMD) in clinical isolates of Pseudomonas aeruginosa with special reference to heteroresistance.

PURPOSE: Antimicrobial resistance (AMR) in Pseudomonas aeruginosa has been ever-increasing. Among other reasons, colistin resistance might be attributed to limited routine testing by approved methods. Both broth microdilution (BMD) and colistin broth disc elution (CBDE) methods have been advocated, with limited data on the performance of these methods in the Indian settings. This prospective study was conducted to determine colistin resistance in P. aeruginosa, compare the BMD and CBDE methods with special reference to heteroresistance. MATERIALS AND METHODS: A total of 100 isolates of P. aeruginosa from admitted patients were included. Antimicrobial susceptibility testing was done against standard antibiotics by disc diffusion test. Minimum inhibitory concentration (MIC) against polymyxins was studied by BMD and CBDE (for colistin only). Heteroresistance to colistin was studied by population analysis profile (PAP). CBDE and BMD were compared by performance calculations. Discrepancy in results were analyzed based on heteroresistance. RESULTS: Majority of the P. aeruginosa isolates were from pus samples (62, 62 â€‹%). Disc diffusion method revealed maximum susceptibility towards aztreonam (74, 74 â€‹%) followed by meropenem (68, 68 â€‹%) and piperacillin-tazobactam (65, 65 â€‹%). Polymyxin B resistance was seen in 6 â€‹% (6) while colistin resistance was seen in 9 â€‹% (9) isolates by BMD. CBDE revealed 8 â€‹% (8) resistance to colistin, having 97 â€‹% essential agreement and 95 â€‹% categorical agreement with BMD. Further, by PAP analysis, 9 isolates were resistant to colistin which included 9 resistant isolates by BMD. On discrepancy analysis, 1 isolate was found to be heteroresistant to colistin. No heteroresistance was seen in the isolates that were susceptible by all the methods. CONCLUSIONS: Heteroresistance to colistin in P. aeruginosa accounted for the discrepancy in results where CBDE method failed to detect heteroresistant isolate. As heteroresistance is a least studied phenotype, it's exact prevalence should be studied so that challenges in susceptibility testing could be addressed.