Characterization of HOXB13 expression patterns in localized and metastatic castration-resistant prostate cancer.

HOXB13 is a key lineage homeobox transcription factor that plays a critical role in the differentiation of the prostate gland. Several studies have suggested that HOXB13 alterations may be involved in prostate cancer development and progression. Despite its potential biological relevance, little is known about the expression of HOXB13 across the disease spectrum of prostate cancer. To this end, we validated a HOXB13 antibody using genetic controls and investigated HOXB13 protein expression in murine and human developing prostates, localized prostate cancers, and metastatic castration-resistant prostate cancers. We observed that HOXB13 expression increases during later stages of murine prostate development. All localized prostate cancers showed HOXB13 protein expression. Interestingly, lower HOXB13 expression levels were observed in higher-grade tumors, although no significant association between HOXB13 expression and recurrence or disease-specific survival was found. In advanced metastatic prostate cancers, HOXB13 expression was retained in the majority of tumors. While we observed lower levels of HOXB13 protein and mRNA levels in tumors with evidence of lineage plasticity, 84% of androgen receptor-negative castration-resistant prostate cancers and neuroendocrine prostate cancers (NEPCs) retained detectable levels of HOXB13. Notably, the reduced expression observed in NEPCs was associated with a gain of HOXB13 gene body CpG methylation. In comparison to the commonly used prostate lineage marker NKX3.1, HOXB13 showed greater sensitivity in detecting advanced metastatic prostate cancers. Additionally, in a cohort of 837 patients, 383 with prostatic and 454 with non-prostatic tumors, we found that HOXB13 immunohistochemistry had a 97% sensitivity and 99% specificity for prostatic origin. Taken together, our studies provide valuable insight into the expression pattern of HOXB13 during prostate development and cancer progression. Furthermore, our findings support the utility of HOXB13 as a diagnostic biomarker for prostate cancer, particularly to confirm the prostatic origin of advanced metastatic castration-resistant tumors. © 2023 The Pathological Society of Great Britain and Ireland.

Biomass patterns in Srivilliputhur Wildlife Sanctuary: exploring factors and gradients with machine learning approach.

Forest biomass plays a crucial role in the global carbon cycle as a significant contributor derived from both soil and trees. This study focuses on investigating tree carbon stock (TCS) and estimating aboveground biomass (AGB) based on elevation within the Srivilliputhur Wildlife Sanctuary forest, while also exploring the various factors that influence their contribution. Utilizing a non-destructive approach for carbon estimation, we found that the total tree biomass in this region ranged from 220.9 Mg/ha (in Z6) to 720.6 Mg/ha (Z2), while tree carbon stock ranged from 103.8 to 338.7 Mg/ha. While Kruskal-Wallis tests did not reveal a significant relationship (p = 0.09) between TCS and elevation, linear regression showed a weak correlation (R2 = 0.002, p < 0.05) with elevation. To delve deeper into the factors influencing TCS and biomass distribution, we employed a random forest (RF) machine learning algorithm, demonstrating that stand structural attributes, such as basal area (BA), diameter at breast height (DBH), and density, held a more prominent role than climatic variables, including temperature, precipitation, and slope. Generalized linear models (GLM) were also utilized, confirming that BA, mean DBH, and elevation significantly influenced AGB (p ≤ 0.001), with species richness, precipitation, and temperature having lower significance (p ≤ 0.01) comparatively. Overall, the RF model exhibited superior performance (R2 = 0.92, RMSE = 0.12) in terms of root mean square error (RMSE) compared to GLM (R2 = 0.88, RMSE = 0.35). These findings shed light on the intricate dynamics of biomass distribution and the importance of both stand structural and climatic factors in shaping forest ecosystems.

Biosynthesis of gold nanoparticles by Penicillium rubens and catalytic detoxification of ochratoxin A and organic dye pollutants.

The environmental pollution caused by chemical dyes is a growing concern nowadays. Limitations of traditional methods opened the route for nanotechnology; owing to the versatile properties of nanomaterials, gold nanoparticles (AuNPs) became a potential strategy for different applications. In the present study, biosynthesis of gold nanoparticles (BioAuNPs) was carried out by reacting chloroauric acid (HAuCl4) with cell-free filtrate of Penicillium rubens sp. nov. NCIM 1937. The AuNPs were then characterized by UV-visible spectroscopy, HR-TEM, FTIR, and DLS analysis to further examine their efficacious biosynthesis and morphological properties including size, shape, and stability. The biogenic AuNPs are polydisperse in nature, with a mean size of 14.92 ± 5 nm. These AuNPs exhibited promising antimicrobial activity against Escherichia coli NCIM-2065, Bacillus subtilis NCIM-2010, and Penicillium verrucosum MTCC 4935. In vitro quantitative HPLC results revealed that BioAuNPs significantly inhibited the biosynthesis of ochratoxin A (OTA). Microbial fuel cells (MFCs) are intriguing for power generation and wastewater treatment since they can directly transform chemical energy stored in organic matter to electricity by extracellular electron transfer (EET) via membrane proteins. AuNPs also showed excellent potential for dye degradation of organic pollutants, viz., methylene blue (MB), phenol red (PR), bromothymol blue (BTB), Congo red (CR), and 4-nitrophenol (4-NP). All dye removal efficiencies were estimated and fitted to pseudo-first-order processes using kinetic rate constants (Ka).The present study reveals a simple, original, and eco-friendly method for the synthesis of multifunctional biogenic AuNPs that could be effective in OTA detoxification in food products and organic pollutant removal during wastewater treatment for a sustainable environment.

Laparoscopic and hysteroscopic findings in women with sub-fertility and tuberculosis: A case series.

OBJECTIVE: Evaluation of hysteroscopic and laparoscopic findings in subfertile women predictive of tuberculosis. DESIGN: Retrospective case series analysis. SETTING: Tertiary hospital in India. POPULATION: A retrospective analysis of 16 784 subfertile women who had undergone diagnostic hysterolaparoscopy (DHL) was conducted between February 2014 and June 2021. METHODS: Histopathological evidence, acid-fast bacilli (AFB), culture and GeneXpert MTB/RIF assay were used to diagnose female genital tuberculosis (FGTB). Various hysteroscopic and laparoscopic findings were analysed, and a binary logistic regression assessed associations between these findings and positive diagnostic outcomes. MAIN OUTCOME MEASURES: Various hysteroscopic and laparoscopic findings correspond to tubercular manifestation. RESULTS: Of the 16,784 patients, 1083 had hysteroscopy and laparoscopy findings suggestive of tuberculosis, and 309 were diagnosed with FGTB based on diagnostic tests. Logistic regression identified variables strongly predictive of positive status outcomes; tuberculous abdomino-pelvic adhesions of various grades, isthmo-ampullary block, tubercle, tubo-ovarian mass, tuberculous hydrosalpinx, complete tubal destruction, tubal diverticula and rigid tube emerged as strong predictors. CONCLUSIONS: Logistic regression-derived predictors, alongside specific laparoscopic and hysteroscopic findings, can enhance diagnostic accuracy and clinical decision-making to start antitubercular therapy in subfertile women.

The anaphase-promoting complex/cyclosome co-activator, Cdh1, is a novel target of human papillomavirus 16 E7 oncoprotein in cervical oncogenesis.

The transforming properties of the high-risk human papillomavirus (HPV) E7 oncoprotein are indispensable for driving the virus life cycle and pathogenesis. Besides inactivation of the retinoblastoma family of tumor suppressors as part of its oncogenic endeavors, E7-mediated perturbations of eminent cell cycle regulators, checkpoint proteins and proto-oncogenes are considered to be the tricks of its transformative traits. However, many such critical interactions are still unknown. In the present study, we have identified the anaphase-promoting complex/cyclosome (APC) co-activator, Cdh1, as a novel interacting partner and a degradation target of E7. We found that HPV16 E7-induced inactivation of Cdh1 promoted abnormal accumulation of multiple Cdh1 substrates. Such a mode of deregulation possibly contributes to HPV-mediated cervical oncogenesis. Our mapping studies recognized the C-terminal zinc-finger motif of E7 to associate with Cdh1 and interfere with the timely degradation of FoxM1, a bona fide Cdh1 substrate and a potent oncogene. Importantly, the E7 mutant with impaired interaction with Cdh1 exhibited defects in its ability for overriding typical cell cycle transition and oncogenic transformation, thereby validating the functional and pathological significance of the E7-Cdh1 axis during cervical carcinoma progression. Altogether, the findings from our study discover a unique nexus between E7 and APC/C-Cdh1, thereby adding to our understanding of the mechanism of E7-induced carcinogenesis and provide a promising target for the management of cervical carcinoma.

A Comparative Evaluation of Smear Layer Removal by Using Four Different Irrigation Solutions like Root Canal Irrigants: An In Vitro SEM Study.

BACKGROUND: The present study aimed to evaluate and compare the efficacy of 17% ethylenediaminetetraacetic acid (EDTA), 18% etidronic acid, 10% citric acid, and 7% maleic acid in the removal of smear layer at the apical third of the root canals. MATERIALS AND METHODS: Sixty single-rooted teeth were equally divided into four study groups (n = 15), according to the type of irrigant used (17% EDTA, 18% etidronic acid, 10% citric acid, and 7% maleic acid) to remove the smear layer effectively from apical third of root canal. In each group, respective irrigant was used with 5.25% of sodium hypochlorite during instrumentation. Each study sample was then sectioned longitudinally and removal of smear layer was observed using a scanning electron microscope (SEM) at 2000×. RESULTS: A 7% maleic acid revealed better smear layer removal than all other three groups at apical third. A 10% citric acid was found to be more efficient than EDTA and etidronic acid. The intergroup comparison was performed using Mann-Whitney U test, and there was no significant difference between all the study groups, except maleic acid. CONCLUSION: The present study compared the effect of various irrigants as an adjunct with 5.25% of sodium hypochlorite for root canal irrigation during and after instrumentation. The use of irrigants aids in the removal of the smear layer from the root canals, thereby increasing the success rate of endodontic therapy. CLINICAL SIGNIFICANCE: This study supports the hypothesis that a thorough use of root canal irrigants can efficiently remove the smear layer which is the key for successful root canal treatment. The present study helps in choosing an appropriate irrigant that can ensure complete root canal debridement from all thirds, especially from the apical third of the root canal. How to cite this article: Mankeliya S, Singhal RK, Gupta A, et al. A Comparative Evaluation of Smear Layer Removal by Using Four Different Irrigation Solutions like Root Canal Irrigants: An In Vitro SEM Study. J Contemp Dent Pract 2021;22(5):527-531.

FoxM1: Repurposing an oncogene as a biomarker.

The past few decades have witnessed a tremendous progress in understanding the biology of cancer, which has led to more comprehensive approaches for global gene expression profiling and genome-wide analysis. This has helped to determine more sophisticated prognostic and predictive signature markers for the prompt diagnosis and precise screening of cancer patients. In the search for novel biomarkers, there has been increased interest in FoxM1, an extensively studied transcription factor that encompasses most of the hallmarks of malignancy. Considering the attractive potential of this multifarious oncogene, FoxM1 has emerged as an important molecule implicated in initiation, development and progression of cancer. Bolstered with the skill to maneuver the proliferation signals, FoxM1 bestows resistance to contemporary anti-cancer therapy as well. This review sheds light on the large body of literature that has accumulated in recent years that implies that FoxM1 neoplastic functions can be used as a novel predictive, prognostic and therapeutic marker for different cancers. This assessment also highlights the key features of FoxM1 that can be effectively harnessed to establish FoxM1 as a strong biomarker in diagnosis and treatment of cancer.

Phe28B10 Induces Channel-Forming Cytotoxic Amyloid Fibrillation in Human Neuroglobin, the Brain-Specific Hemoglobin.

Since its discovery, neuroglobin (Ngb), a neuron-specific oxygen binding hemoglobin, distinct from the classical myoglobin and blood hemoglobin, has attracted attention as an endogenous neuroprotectant. Recent reports suggest that Ngb protects neurons from brain stroke, ischemic stress-induced degeneration, and other brain disorders. Proteins with a specific role in neuroprotection are often associated with neurodegeneration, as well, depending on the cellular environment or specific cellular triggers that tilt the balance one way or the other. This investigation explored the potential role of Ngb in amyloid fibril-related neuronal disorder. Ngb was capable of amyloid formation in vitro at neutral pH and ambient temperature, in both apo and holo forms, albeit at a slower rate in the holo form, unlike other hemoglobins that exhibit such behavior exclusively in the apo states. Elevated temperature enhanced the rate of fibril formation significantly. The B-helix, which is known to play a major role in Ngb ligand binding kinetics, was found to be amyloidogenic with the Phe28B10 amino acid side chain as the key inducer of fibrillation. The Ngb amyloid fibril was also significantly cytotoxic to neuroblastoma cell lines, compared to those obtained from reference hemoglobins. The Ngb fibril probably promoted toxicity by inducing channel formation in the cell membrane, as investigated here using synthetic lipid bilayer membranes and the propidium iodide uptake assay. These findings imply that Ngb plays a role in neurodegenerative disorders in vivo, for which there seems to be indirect evidence by association. Ngb thus presents a novel prospect for understanding amyloid-related brain disorders beyond the limited set of proteins currently investigated for such diseases.

High-risk HPV16E6 stimulates hADA3 degradation by enhancing its SUMOylation.

Despite significant research, our understanding of the molecular mechanisms of Human Papilloma Virus (HPV) induced cancers remains incomplete. Majority of invasive cervical cancers are caused by high-risk HPV 16 and 18. Two potent HPV oncoproteins, E6 and E7, promote human malignancies by disrupting the activities of key regulators of cell proliferation and apoptosis. Recent investigations have identified hADA3, a transcriptional coactivator protein as a target of high-risk HPV16E6. However, the mechanism of degradation of hADA3 by E6 and its contribution in HPV induced carcinogenesis is poorly understood. Here, we showed that E6-mediated proteolysis of hADA3 is responsible for maintaining low levels of hADA3 in HPV-positive cervical cancer cell lines. We demonstrate that HPV16E6 targets hADA3 for ubiquitin-mediated degradation via E6AP ubiquitin ligase. We also show that hADA3 undergoes accelerated SUMOylation in the presence of HPV16E6. Our data represent the first evidence that hADA3 is posttranslationally modified by SUMOylation, which makes it unstable and establishes a link between SUMOylation and E6-mediated ubiquitination of hADA3. Furthermore, depletion of Ubc9 prevented rapid degradation of hADA3 in E6 expressing cervical cancer cells and overexpression of hADA3 resulted in suppression of proliferation and migration abilities of SiHa cells. Overall, this study underscores the importance of posttranslational modifications in HPV16E6-mediated downregulation of hADA3 thereby unveiling a novel mechanism by which HPV induces oncogenesis.

Candida die-off: Adverse effect and neutralization with phytotherapy approaches.

Candida albicans is the main species that causes 3rd most common bloodstream infection candidiasis in hospitalization. Once it has been diagnosed and treated with antifungal medications accurately, large amounts of Candida cells are killed off rapidly known as Candida die-off or Jarisch-Herxheimer reactions. When Candida cells are killed off quickly, a large no. of toxic substances are released simultaneously. This flood of endotoxins is noxious (harmful) and causes the kidneys and liver to work overtime to try and remove them which causes worsening of symptoms in patients. As a complementary and holistic approach to addressing Candida die-off and its associated symptoms, plant-based remedies i.e., phytotherapy have been gaining increased attention. In this review paper, we have discussed major factors involved in provoking Candida die-off, their management by phytotherapy, challenges associated with the toxic effects due to die-off, and neutralization of Candida die-off through phytotherapy to manage this problem and challenges. In conclusion, this article serves as a meticulous compilation of knowledge on the intriguing subject of Candida die-off, presenting a distinct and informative perspective that has the potential to pave the way for new insights in the realm of plant-based antifungal therapeutics.

Modulators of Candida albicans Membrane Drug Transporters: A Lucrative Portfolio for the Development of Effective Antifungals.

The escalating prevalence of membrane drug transporters and drug efflux pumps in pathogenic yeast like Candida albicans necessitates a comprehensive understanding of their roles in MDR. The overexpression of drug transporter families, ABC and MFS, implicated in MDR through drug efflux and poses a significant challenge in the diagnosis and treatment of fungal infection. Various mechanisms have been proposed for MDR; however, the upregulation of ABC and MFS superfamily transporters is most noticeable in MDR. The direct inhibition of these transporters seems an efficient strategy to overcome this problem. The goal of the article is to present an overview of the prospect of utilizing these modulators of C. albicans drug transports as effective antifungal molecules against MDR addressing a critical gap in the field. The review tries to address to prevent drug extrusion by modulating the expression of drug transporters of C. albicans. The review discussed the progress in identifying potent, selective, and non-toxic modulators of these transporters to develop some effective antifungals and overcome MDR. We reviewed major studies in this area and found that recent work has shifted toward the exploration of natural compounds as potential modulators to restore drug sensitivity in MDR fungal cells. The focus of this review is to survey and interpret current research information on modulators of C. albicans drug transporters from natural sources emphasizing those compounds that are potent antifungal agents.

Exploring the Spectrum of Lymphadenopathy: Insights From a Three-Year Fine Needle Aspiration Cytology Study in a Tertiary Care Center.

Introduction Lymphadenopathy, characterized by the enlargement of lymph nodes, is a common concern encountered by physicians in outpatient settings. It is deemed significant and warrants evaluation due to the diverse range of potential causes, ranging from treatable infections to incurable metastatic malignancies. Fine needle aspiration cytology (FNAC) emerges as a crucial tool in addressing these concerns, acknowledged for its rapid diagnostic capabilities, simplicity, accuracy, and minimal invasiveness. Objectives This retrospective study aims to characterize the spectrum of lymphadenopathy cases observed in a tertiary care center over a specified period, shedding light on the prevalence, etiology, and clinical outcomes associated with this condition. Methods Electronic medical records of patients presenting with lymphadenopathy to the tertiary care center between May 2021 and June 2023 were reviewed. Data on patient demographics, clinical presentation, imaging findings, and cytopathological and histopathological diagnoses were analyzed. Results A total of 300 cases of lymphadenopathy were identified during the study period. The study population exhibited a diverse range of age groups, with a slight predilection for the age range of 11-20 years. The most common sites of lymphadenopathy were in the cervical group, and the predominant clinical presentations included tender lymph nodes and fever. Etiologically, infectious causes, such as accounted for the majority of cases, followed by inflammatory and neoplastic etiologies. Notably, 2.6 % of cases presented with non-specific lymphadenopathy, warranting further investigation. Diagnostic modalities, including imaging studies and histopathological examinations, played a crucial role in establishing accurate diagnoses. The study also highlights the challenges in differentiating benign from malignant lymphadenopathy, emphasizing the need for a comprehensive diagnostic approach. Conclusion This study provides a comprehensive overview of the lymphadenopathy spectrum in a tertiary care center, emphasizing the importance of a multidisciplinary approach for accurate diagnosis and management. The findings contribute to our understanding of the epidemiology and etiological patterns of lymphadenopathy, guiding clinicians in optimizing patient care and outcomes in a tertiary healthcare setting.

Deciphering the Association of Epstein-Barr Virus and Its Glycoprotein M Peptide with Neuropathologies in Mice.

The reactivation of ubiquitously present Epstein-Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M146-157 (gM146-157) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146-157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays. Disorganization of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages were observed in the brains of infected mice. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were found to be elevated in infected mouse brain tissue samples, whereas TNF-α exhibited a decline in the serum of these mice. Further, the altered levels of nuclear factor-kappa B (NF-kB) and neurotensin receptor 2 affirmed neuroinflammation in infected mouse brain samples. Similarly, the risk factor of AD, apolipoprotein E4 (ApoE4), was also found to be elevated at the protein level in EBV/gM146-157 challenged mice. Furthermore, we also observed an increased level of myelin basic protein in the brain cortex. Altogether, our results suggested an integral connection of EBV and its gM146-157 peptide to the neuropathologies.

A soft-computation hybrid method for search of the antibiotic-resistant gene in Mycobacterium tuberculosis for promising drug target identification and antimycobacterial lead discovery.

Tuberculosis (TB) control programs were already piloted before the COVID-19 pandemic commenced and the global TB response was amplified by the pandemic. To combat the global TB epidemic, drug repurposing, novel drug discovery, identification and targeting of the antimicrobial resistance (AMR) genes, and addressing social determinants of TB are required. The study aimed to identify AMR genes in Mycobacterium tuberculosis (MTB) and a new anti-mycobacterial drug candidate. In this research, we used a few software to explore some AMR genes as a target protein in MTB and identified some potent antimycobacterial agents. We used Maestro v12.8 software, along with STRING v11.0, KEGG and Pass Server databases to gain a deeper understanding of MTB AMR genes as drug targets. Computer-aided analysis was used to identify mtrA and katG AMR genes as potential drug targets to depict some antimycobacterial drug candidates. Based on docking scores of -4.218 and -6.161, carvacrol was identified as a potent inhibitor against both drug targets. This research offers drug target identification and discovery of antimycobacterial leads, a unique and promising approach to combating the challenge of antibiotic resistance in Mycobacterium, and contributes to the development of a potential futuristic solution.

Unveiling the Gut Microbiome: How Junk Food Impacts the Gut.

The human gut microbiome, a complex community of microorganisms, profoundly influences human health and disease. Bacteroidetes and Firmicutes make up the majority of the normal human gut microbiota. These microorganisms wield considerable influence over our physiological functions, impacting both our well-being and our susceptibility to disease. The surge of interest in the gut microbiome over the past decade has been remarkable. Once overlooked, the gastrointestinal tract's microbiota has gained recognition for its significance in maintaining optimal health. The food industry has capitalized on this, flooding the market with "probiotic" and "fermented" products. This article aims to provide a critical review of the current literature on the gut microbiome and its significance in human health, with a particular focus on the impact of dietary choices, especially junk food, on the composition and function of the gut microbiota. Microbes possess the remarkable ability to unlock nutrients from otherwise indigestible substances. The gut microbiome of individuals who consume healthy foods and those who prefer junk food varies significantly. Healthy diets promote a diverse and beneficial gut microbiome, while junk food consumption often leads to a less diverse microbiome with negative consequences for health.

Incidental Finding of Invasive Ductal Carcinoma on Mastectomy in the Case of Lymphocytic Mastitis: A Case Report.

A rare inflammatory breast disorder called lymphocytic mastitis is characterized by lymphocyte infiltrates in the mammary parenchyma. Due to their rarity, incidental observations of invasive ductal carcinoma in lymphocytic mastitis present diagnostic and management challenges. We present a case of a 52-year-old female with a history of painfully swollen breasts for three months who underwent a core needle biopsy, consistent with lymphocytic mastitis on histopathology. Due to persistent and worsening symptoms, a mastectomy was performed. During the examination, an incidental finding of infiltrating ductal carcinoma was identified in the mastectomy specimen. This unexpected discovery led to further investigations and altered the patient's treatment plan. The detection of invasive ductal carcinoma in the presence of lymphocytic mastitis highlights the importance of continuous surveillance and thorough examination. In the circumstances of lymphocytic mastitis, it is vital to take the likelihood of concurrent malignancy into account, especially when symptoms persist or reappear after appropriate management. This case report seeks to raise awareness among physicians of this exceptional association and drive further research that will explain its pathophysiology while enhancing management strategies.

Emerging Applications of Liquid Biopsies in Ovarian Cancer.

Liquid biopsy is a new diagnostic tool in precision oncology that can be used as a complementary or alternative method to surgical biopsies. It is a cutting-edge sampling technique that examines distinct cancer components, such as exosomes and circulating tumor cells discharged into the peripheral circulation, to identify tumor biomarkers through various methods, including polymerase chain reaction (PCR). Liquid biopsy has several benefits, including its non-invasiveness and practicality, which permit serial sampling and long-term monitoring of dynamic tumor changes. Ovarian cancer (OC), the most lethal gynecologic malignancy in the world, is typically diagnosed at stages II and III, which makes recovery and treatment extremely difficult. Relapsed OC and chemotherapy resistance of ovarian tumor cells are other clinical challenges. Although liquid biopsy is not a routinely used diagnostic test, it should be utilized in the diagnosis and prognosis of OC for early detection and treatment. It is less intrusive than conventional tissue biopsies, allowing for the continuous collection of serial blood samples to track cancer development in real time. Before therapeutic application, more investigation is required to pinpoint the particular release processes, the source tissue, and the biological significance of the bulk of liquid biopsy contents.

Clinical Performance of Composite Resin Restorations of Primary Incisors with Extensive Carious Lesions Retained by Glass Fiber Post or Biological Post.

Aim: Intracanal posts enhance the resistance of the restoration to mechanical loads and masticatory forces in primary teeth with extensive carious breakdown. This study was done to investigate the clinical performance of composite resin restoration retained by either glass fiber post or biological post in the restoration of primary anterior teeth with extensive carious lesions. Materials and methods: A total of 21 children (with 82 primary anterior teeth) who met the inclusion criteria were involved in the study. The 82 primary maxillary incisors were randomly allocated into two equal groups: groups I (glass fiber post) and II (biological post). All the teeth underwent pulpectomy, followed by glass fiber post or biological post, followed by celluloid strip crown restoration. Clinical analysis of all the teeth in the two groups was performed at 1, 3, 6, 9, and 12 months to assess the success of treatment procedures. Statistical Package for the Social Sciences (SPSS) software version "17" was used for statistical analysis. Pearson's Chi-squared test and Fisher's exact test were utilized to evaluate the success of both treatment procedures. The significance level was predetermined at p < 0.05. Results: At the end of the 12-month follow-up period, 89.4 and 84.2% of composite resin restorations of primary incisors with extensive carious lesions were retained by glass fiber and biological posts, respectively. The intergroup comparison revealed no statistically significant differences pertaining to retention loss, marginal discoloration, and marginal adaptation at all follow-up intervals (p > 0.05). Conclusion and clinical significance: Since biological posts are inexpensive and economical, they may replace the commercial post systems available to pediatric dentists. How to cite this article: Jaiswal N, Garg N, Pathivada L, et al. Clinical Performance of Composite Resin Restorations of Primary Incisors with Extensive Carious Lesions Retained by Glass Fiber Post or Biological Post. Int J Clin Pediatr Dent 2023;16(6):850-857.

Armamentarium in Drug Delivery for Colorectal Cancer.

Colorectal cancer (CRC) is the second most common cause of cancer related deaths in the United States. However, more than half of all incidence and mortality are caused by risk factors such as smoking, unhealthy diet, excessive alcohol consumption, inactivity, and excess weight, and thus can be protected. CRC morbidity and mortality can also be reduced by proper screening and monitoring. Over the last few years the amalgamation of nanotechnology with healthcare system has brought about the potential to administer the delivery of certain therapeutic drugs to cancer cells without affecting normal tissues. Recent strategies combine the diagnostic and therapeutic approaches to improve the overall performance of cancer nanomedicines. Targeted cancer nanotherapeutics provides many more opportunities for the selective detection of toxic chemicals within cancer cells. The distinctive features of nanoparticles, such as their small size, large surface to volume ratio, and the ability of nanoparticles to achieve several interactions of ligands at surface, offer great benefits of nanomedicines to treat various types of cancers. This review highlights the molecular mechanisms of colorectal carcinogenesis and discusses various key concepts in the development of nanotherapeutics targeted for CRC treatment.

TNF Signaling Is Required for Castration-Induced Vascular Damage Preceding Prostate Cancer Regression.

The mainstay treatment for locally advanced, recurrent, or metastatic prostate cancer (PrCa) is androgen deprivation therapy (ADT). ADT causes prostate cancers to shrink in volume, or regress, by inducing epithelial tumor cell apoptosis. In normal, non-neoplastic murine prostate, androgen deprivation via castration induces prostate gland regression that is dependent on TNF signaling. In addition to this direct mechanism of action, castration has also been implicated in an indirect mechanism of prostate epithelial cell death, which has been described as vascular regression. The initiating event is endothelial cell apoptosis and/or increased vascular permeability. This subsequently leads to reduced blood flow and perfusion, and then hypoxia, which may enhance epithelial cell apoptosis. Castration-induced vascular regression has been observed in both normal and neoplastic prostates. We used photoacoustic, power Doppler, and contrast-enhanced ultrasound imaging, and CD31 immunohistochemical staining of the microvasculature to assess vascular integrity in the period immediately following castration, enabling us to test the role of TNF signaling in vascular regression. In two mouse models of androgen-responsive prostate cancer, TNF signaling blockade using a soluble TNFR2 ligand trap reversed the functional aspects of vascular regression as well as structural changes in the microvasculature, including reduced vessel wall thickness, cross-sectional area, and vessel perimeter length. These results demonstrate that TNF signaling is required for vascular regression, most likely by inducing endothelial cell apoptosis and increasing vessel permeability. Since TNF is also the critical death receptor ligand for prostate epithelial cells, we propose that TNF is a multi-purpose, comprehensive signal within the prostate cancer microenvironment that mediates prostate cancer regression following androgen deprivation.